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Search for "stereocontrol" in Full Text gives 119 result(s) in Beilstein Journal of Organic Chemistry.
Recent developments in the engineered biosynthesis of fungal meroterpenoids
- Zhiyang Quan and
- Takayoshi Awakawa
Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50
- chair–chair stereocontrol, the structure basis of InsA7 should be unique. A structural comparison of InsB2 and InsA7 will help to clarify the differences in their structural bases. Recent advances in artifical intelligence (AI) have even made the structural modeling of membrane-bound proteins possible
Graphical Abstract
Figure 1: Examples of bioactive fungal meroterpenoids.
Figure 2: The diversity of DMOA-derived meroterpenoid biosyntheses.
Figure 3: The combinatorial biosynthesis of diterpene pyrone meroterpenoids. The production of subglutinol A ...
Figure 4: The biosynthetic reaction from the common intermediate 21 to ascochlorin (22) and ascofuranone (23)...
Figure 5: The multistep oxidations catalyzed by AusE and PrhA from the common intermediate 24.
Figure 6: Reactions of SptF with native substrates 31 and 32.
Figure 7: A) Reactions of SptF with unnatural substrates. B) Reactions of SptF variants with 31.
Figure 8: The reaction of the αKG enzyme AndA and its variants generated via saturated mutagenesis.
Figure 9: The synthetic biological production of daurichromenic acid and its halogenated derivative.
α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping
- Angel Palillero-Cisneros,
- Paola G. Gordillo-Guerra,
- Fernando García-Alvarez,
- Olivier Jackowski,
- Franck Ferreira,
- Fabrice Chemla,
- Joel L. Terán and
- Alejandro Perez-Luna
Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103
- 5 and 8a in 77–88% yields, albeit as poorly selective mixtures of diastereoisomers. This lack of stereocontrol is not surprising, given the well-known difficulty to control the relative configuration between the two adjacent stereocenters created during aldol condensations with zinc enolates
Graphical Abstract
Scheme 1: Air-promoted radical chain reaction of dialkylzinc reagents with α,β-unsaturated carbonyl compounds....
Scheme 2: Enolate formation by zinc radical transfer (SH2 on dialkylzinc reagents).
Scheme 3: Preparation of α-(aminomethyl)acrylate 10.
Scheme 4: Reaction of α-(aminomethyl)acrylate 10 with Et2Zn in the presence of air.
Scheme 5: Chemical correlation to determine the configuration of the major diastereomer of (RS)-14b.
Scheme 6: Air-promoted tandem 1,4-addition–aldol condensation reactions of Et2Zn with α-(aminomethyl)acrylate...
Scheme 7: Diagnostic experiments for a radical mechanism and for enolate formation.
Scheme 8: Diagnostic experiments with N-benzyl enoate 10.
Scheme 9: Reactivity manifolds for the air-promoted tandem 1,4-addition–electrophilic substitution reaction b...
Synthesis of ether lipids: natural compounds and analogues
- Marco Antônio G. B. Gomes,
- Alicia Bauduin,
- Chloé Le Roux,
- Romain Fouinneteau,
- Wilfried Berthe,
- Mathieu Berchel,
- Hélène Couthon and
- Paul-Alain Jaffrès
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
Graphical Abstract
Figure 1: Chemical structure of some natural ether lipids (ELs).
Figure 2: Synthesis of lyso-PAF and PAF from 1-O-alkylglycerol [64].
Figure 3: Synthesis of lyso-PAF from 1,3-benzylideneglycerol 3.1 [69].
Figure 4: A) Synthesis of the two enantiomers of octadecylglycerol (4.6 and 4.10) from ᴅ-mannitol (4.1); B) s...
Figure 5: Four-step synthesis of PAF 5.6 from (S)-glycidol [73].
Figure 6: Synthesis of 1-O-alkylglycerol A) from solketal, B) from ᴅ- or ʟ-tartaric acid and the intermediate ...
Figure 7: Synthesis of EL building blocks starting from substituted glycidol 7.1a–c [82].
Figure 8: Synthesis of PAF 8.5 by using phosphoramidite 8.2 [86].
Figure 9: Synthesis of oleyl-PAF 9.7 from ʟ-serine [88].
Figure 10: Synthesis of racemic analogues of lyso-PAF 10.8 and PAF 10.9 featuring a phenyl group between the g...
Figure 11: Synthesis of racemic deoxy-lyso-PAF 11.7 and deoxy-PAF 11.8 [91].
Figure 12: Synthesis of racemic thio-PAF 12.8 [93].
Figure 13: Racemic synthesis of 13.6 to illustrate the modification of the glycerol backbone by adding a methy...
Figure 14: Racemic synthesis of 14.5 as an illustration of the introduction of methyl substituents on the glyc...
Figure 15: Synthesis of functionalized sn-2-acyl chains of PC-EL; A) Steglich esterification or acylation reac...
Figure 16: Synthesis of racemic mc-PAF (16.3), a carbamate analogue of PAF [102].
Figure 17: A) Synthesis of (R)-17.2 and (S)-17.6 starting from (S)-solketal (17.1); B) synthesis of N3-PAF (17...
Figure 18: Modification of the phosphocholine polar head to produce PAF analogues [81].
Figure 19: Racemic PAF analogues 19.3 and 19.5 characterized by the absence of the phosphate group [107].
Figure 20: Synthesis of PIP3-PAF (20.7) [108].
Figure 21: Large-scale synthesis of C18-edelfosine (21.8) [116].
Figure 22: Synthesis of C16-edelfosine (22.10) starting from isopropylidene-ʟ-glyceric acid methyl ester (22.1...
Figure 23: Phosphocholine moiety installation by the use of chlorophosphite 23.2 as key reagent [119].
Figure 24: Synthesis of rac-1-alkyl-2-O-methylglycerol (AMG) [120].
Figure 25: Synthesis of stereocontrolled 1-alkyl-2-O-methyl glycerol 25.9 (AMG) from dimethyl ᴅ-tartrate [81].
Figure 26: A) Racemic synthesis of thioether 26.4 [129,130], B) structure of sulfone analogue 26.5 [129].
Figure 27: Stereocontrolled synthesis of C18-edelfosine thioether analogue 27.8 [118].
Figure 28: Synthesis of thioether 28.4 that include a thiophosphate function [134].
Figure 29: Synthesis of ammonium thioether 29.4 and 29.6 [135].
Figure 30: Synthesis of the N-methylamino analogue of edelfosine 30.6 (BN52211) [138].
Figure 31: Synthesis of 1-desoxy analogues of edelfosine; A) with a saturated alkyl chain; B) synthesis of the...
Figure 32: Stereocontrolled synthesis of edelfosine analogue (S)-32.8 featuring a C18:1 lipid chain [142].
Figure 33: Synthesis of edelfosine analogues with modulation of the lipid chain; A) illustration with the synt...
Figure 34: Synthesis of phospholipid featuring a carbamate function to link the lipid chain to the glycerol un...
Figure 35: Synthesis of sesquiterpene conjugates of phospho glycero ether lipids [148].
Figure 36: Racemic synthesis of methyl-substituted glycerol analogues 36.7 and 36.10: A) synthesis of diether ...
Figure 37: Racemic synthesis of ilmofosine (37.6) [155,156].
Figure 38: A) Stereoselective synthesis of 38.5 via a stereoselective hydroboration reaction; B) synthesis of ...
Figure 39: Racemic synthesis of SRI62-834 (39.6) featuring a spiro-tetrahydrofurane heterocycle in position 2 ...
Figure 40: Racemic synthesis of edelfosine analogue 40.5 featuring an imidazole moiety in sn-2 position [160].
Figure 41: Racemic synthesis of fluorine-functionalized EL: A) Synthesis of 41.6 and B) synthesis of 41.8 [161-163].
Figure 42: A) Synthesis of the β-keto-ester 42.6 that also features a decyl linker between the phosphate and t...
Figure 43: Synthesis of phosphonate-based ether lipids; A) edelfosine phosphonate analogue 43.7 and B) thioeth...
Figure 44: Enantioselective synthesis of phosphonates 44.3 and 44.4 [171].
Figure 45: Racemic synthesis of phosphinate-based ether lipid 45.10 [172].
Figure 46: Racemic synthesis of edelfosine arsonium analogue 46.5 [173].
Figure 47: Synthesis of edelfosine dimethylammonium analogue 47.2 [118].
Figure 48: Synthesis of rac-C18-edelfosine methylammonium analogue 48.4 [176].
Figure 49: A) Synthesis of edelfosine N-methylpyrrolidinium analogue 49.2 or N-methylmorpholinium analogue 49.3...
Figure 50: A) Synthesis of edelfosine’s analogue 50.4 with a PE polar group; B) illustration of a pyridinium d...
Figure 51: A) Synthesis of 51.4 featuring a thiazolium cationic moiety; B) synthesis of thiazolium-based EL 51...
Figure 52: Synthesis of cationic ether lipids 52.3, 52.4 and 52.6 [135,183].
Figure 53: Synthesis of cationic carbamate ether lipid 53.5 [184].
Figure 54: Synthesis of cationic sulfonamide 54.5 [185].
Figure 55: Chemical structure of ONO-6240 (55.1) and SRI-63-119 (55.2).
Figure 56: Synthesis of non-ionic ether lipids 56.2–56.9 [188].
Figure 57: Synthesis of ether lipid conjugated to foscarnet 57.6 [189].
Figure 58: A) Synthesis of ether lipid conjugated to arabinofuranosylcytosine; B) synthesis of AZT conjugated ...
Figure 59: Synthesis of quercetin conjugate to edelfosine [191].
Figure 60: Synthesis of 60.8 (Glc-PAF) [194].
Figure 61: A) Synthesis of amino ether lipid 61.7 functionalized with a rhamnose unit and its amide analogue 6...
Figure 62: A) Synthesis of glucose ether lipid 62.4; B) structure of ether lipid 62.5 possessing a maltose uni...
Figure 63: A) Synthesis of glucuronic methyl ester 63.8; B) structure of cellobiose 63.9 and maltose 63.10 ana...
Figure 64: A) Synthesis of maltosyl glycerolipid 64.7; B) structure of lactose analogue 64.8 prepared followin...
Figure 65: A) Asymmetric synthesis of the aglycone moiety starting from allyl 4-methoxyphenyl ether; B) glycos...
Figure 66: A) Synthesis of ohmline possessing a lactose moiety. B) Structure of other glyco glycero lipids pre...
Figure 67: A) Synthesis of lactose-glycerol ether lipid 67.5; B) analogues possessing a maltose (67.6) or meli...
Figure 68: Synthesis of digalactosyl EL 68.6, A) by using trityl, benzyl and acetyl protecting groups, B) by u...
Figure 69: A) Synthesis of α-ohmline; B) structure of disaccharide ether lipids prepared by using similar meth...
Figure 70: Synthesis of lactose ether lipid 70.3 and its analogue 70.6 featuring a carbamate function as linke...
Figure 71: Synthesis of rhamnopyranoside diether 71.4 [196].
Figure 72: Synthesis of 1-O-hexadecyl-2-O-methyl-3-S-(α-ᴅ-1'-thioglucopyranosyl)-sn-glycerol (72.5) [225].
Figure 73: A) Preparation of lipid intermediate 73.4; B) synthesis of 2-desoxy-C-glycoside 73.10 [226].
Figure 74: Synthesis of galactose-pyridinium salt 74.3 [228].
Figure 75: Synthesis of myo-inositol derivative Ino-C2-PAF (75.10) [230].
Figure 76: A) Synthesis of myo-inositol phosphate building block 76.7; B) synthesis of myo-inositolphosphate d...
Figure 77: A) Synthesis of phosphatidyl-3-desoxy-inositol 77.4; B) synthesis of phosphono-3-desoxyinositol 77.9...
Figure 78: A) Structure of diether phosphatidyl-myo-inositol-3,4-diphosphate 78.1; B) synthesis of phosphatidy...
Figure 79: A) Synthesis of diether-phosphatidyl derivative 79.4 featuring a hydroxymethyl group in place of a ...
Figure 80: Synthesis of Glc-amine-PAF [78].
Figure 81: Synthesis of glucosamine ether lipid 81.4 and its analogues functionalized in position 3 of the ami...
Figure 82: Synthesis of fully deprotected aminoglucoside ether lipid 82.5 [246].
Figure 83: Synthesis of C-aminoglycoside 83.12 using Ramberg–Bäcklund rearrangement as a key step [250].
Figure 84: A) List of the most important glyco lipids and amino glyco lipids included in the study of Arthur a...
Figure 85: Synthesis of mannosamine ether lipid 85.6 [254].
Figure 86: A) Synthesis of glucosamine ether lipids with a non-natural ʟ-glucosamine moiety; B) synthesis of e...
Figure 87: A) Structure of the most efficient anticancer agents 87.1–87.4 featuring a diamino glyco ether lipi...
Figure 88: A) Synthesis of diamino glyco ether lipid 87.4; B) synthesis of bis-glycosylated ether lipid 88.10 [256]....
Figure 89: Synthesis of triamino ether lipid 89.4 [260].
Figure 90: Synthesis of chlorambucil conjugate 90.7 [261].
Figure 91: Three main methods for the preparation of glycerol ether lipid 91.3; A) from solketal and via a tri...
Figure 92: Four different methods for the installation of the phosphocholine polar head group; A) method using...
Figure 93: Illustration of two methods for the installation of saccharides or aminosaccharides; A) O-glycosyla...
Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update
- Anup Biswas
Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72
- stereocenter in cyclic sulfamidate derivatives. N-Alkyl and N-benzyl-substituted pyrroles responded to the process with appreciable enantioefficiency. However, pyrrole was not proved to be the efficient substrate in terms of stereocontrol [27] (Scheme 4a). In the very next year, pyrrole was successfully
Graphical Abstract
Scheme 1: First organocatalyzed asymmetric aza-Friedel–Crafts reaction.
Scheme 2: Aza-Friedel–Crafts reaction between indoles and cyclic ketimines.
Scheme 3: Aza-Friedel–Crafts reaction utilizing trifluoromethyldihydrobenzoazepinoindoles as electrophiles.
Scheme 4: Aza-Friedel–Crafts reaction utilizing cyclic N-sulfimines as electrophiles.
Scheme 5: Aza-Friedel–Crafts reaction involving N-unprotected imino ester as electrophile.
Scheme 6: Aza-Friedel–Crafts and lactonization cascade.
Scheme 7: One-pot oxidation and aza-Friedel–Crafts reaction.
Scheme 8: C1 and C2-symmetric phosphoric acids as catalysts.
Scheme 9: Aza-Friedel–Crafts reaction using Nps-iminophosphonates as electrophiles.
Scheme 10: Aza-Friedel–Crafts reaction between indole and α-iminophosphonate.
Scheme 11: [2.2]-Paracyclophane-derived chiral phosphoric acids as catalyst.
Scheme 12: Aza-Friedel–Crafts reaction through ring opening of sulfamidates.
Scheme 13: Isoquinoline-1,3(2H,4H)-dione scaffolds as electrophiles.
Scheme 14: Functionalization of the carbocyclic ring of substituted indoles.
Scheme 15: Aza-Friedel–Crafts reaction between unprotected imines and aza-heterocycles.
Scheme 16: Anilines and α-naphthols as potential nucleophiles.
Scheme 17: Solvent-controlled regioselective aza-Friedel–Crafts reaction.
Scheme 18: Generating central and axial chirality via aza-Friedel–Crafts reaction.
Scheme 19: Reaction between indoles and racemic 2,3-dihydroisoxazol-3-ol derivatives.
Scheme 20: Exploiting 5-aminoisoxazoles as nucleophiles.
Scheme 21: Reaction between unsubstituted indoles and 3-alkynylated 3-hydroxy-1-oxoisoindolines.
Scheme 22: Synthesis of unnatural amino acids bearing an aza-quaternary stereocenter.
Scheme 23: Atroposelective aza-Friedel–Crafts reaction.
Scheme 24: Coupling of 5-aminopyrazole and 3H-indol-3-ones.
Scheme 25: Pyrophosphoric acid-catalyzed aza-Friedel–Crafts reaction on phenols.
Scheme 26: Squaramide-assisted aza-Friedel–Crafts reaction.
Scheme 27: Thiourea-catalyzed aza-Friedel–Crafts reaction.
Scheme 28: Squaramide-catalyzed reaction between β-naphthols and benzothiazolimines.
Scheme 29: Thiourea-catalyzed reaction between β-naphthol and isatin-derived ketamine.
Scheme 30: Quinine-derived molecule as catalyst.
Scheme 31: Cinchona alkaloid as catalyst.
Scheme 32: aza-Friedel–Crafts reaction by phase transfer catalyst.
Scheme 33: Disulfonamide-catalyzed reaction.
Scheme 34: Heterogenous thiourea-catalyzed aza-Friedel–Crafts reaction.
Scheme 35: Total synthesis of (+)-gracilamine.
Scheme 36: Total synthesis of (−)-fumimycin.
Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles
- Péter Kisszékelyi and
- Radovan Šebesta
Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44
- Indonesian sponge Haliclona sp. [108]. Their synthesis takes advantage of the same tandem procedure that gives β-ketoester 219. The asymmetric conjugate 1,4-addition and subsequent acylation provided good stereocontrol and the authors could revise the thus far incorrectly assigned configuration of the target
Graphical Abstract
Scheme 1: General scheme depicting tandem reactions based on an asymmetric conjugate addition followed by an ...
Scheme 2: Cu-catalyzed tandem conjugate addition of R2Zn/aldol reaction with chiral acetals.
Scheme 3: Cu-catalyzed asymmetric desymmetrization of cyclopentene-1,3-diones using a tandem conjugate additi...
Scheme 4: Stereocontrolled assembly of dialkylzincs, cyclic enones, and sulfinylimines utilizing a Cu-catalyz...
Scheme 5: Cu-catalyzed tandem conjugate addition/Mannich reaction (A). Access to chiral isoindolinones and tr...
Scheme 6: Cu-catalyzed tandem conjugate addition/nitro-Mannich reaction (A) with syn–anti or syn–syn selectiv...
Figure 1: Various chiral ligands utilized for the tandem conjugate addition/Michael reaction sequences.
Scheme 7: Cu-catalyzed tandem conjugate addition/Michael reaction: side-product formation with chalcone (A) a...
Scheme 8: Zn enolate trapping using allyl iodides (A), Stork–Jung vinylsilane reagents (B), and allyl bromide...
Scheme 9: Cu-catalyzed tandem conjugate addition/acylation through Li R2Zn enolate (A). A four-component coup...
Scheme 10: Selected examples for the Cu-catalyzed tandem conjugate addition/trifluoromethylthiolation sequence....
Scheme 11: Zn enolates trapped by vinyloxiranes: synthesis of allylic alcohols.
Scheme 12: Stereoselective cyclopropanation of Mg enolates formed by ACA of Grignard reagents to chlorocrotona...
Scheme 13: Domino aldol reactions of Mg enolates formed from coumarin and chromone.
Scheme 14: Oxidative coupling of ACA-produced Mg enolates.
Scheme 15: Tandem ACA of Grignard reagents to enones and Mannich reaction.
Scheme 16: Diastereodivergent Mannich reaction of Mg enolates with differently N-protected imines.
Scheme 17: Tandem Grignard–ACA–Mannich using Taddol-based phosphine-phosphite ligands.
Scheme 18: Tandem reaction of Mg enolates with aminomethylating reagents.
Scheme 19: Tandem reaction composed of Grignard ACA to alkynyl enones.
Scheme 20: Rh/Cu-catalyzed tandem reaction of diazo enoates leading to cyclobutanes.
Scheme 21: Tandem Grignard-ACA of cyclopentenones and alkylation of enolates.
Scheme 22: Tandem ACA of Grignard reagents followed by enolate trapping reaction with onium compounds.
Scheme 23: Mg enolates generated from unsaturated lactones in reaction with activated alkenes.
Scheme 24: Lewis acid mediated ACA to amides and SN2 cyclization of a Br-appended enolate.
Scheme 25: Trapping reactions of aza-enolates with Michael acceptors.
Scheme 26: Si enolates generated by TMSOTf-mediated ACA of Grignard reagents and enolate trapping reaction wit...
Scheme 27: Trapping reactions of enolates generated from alkenyl heterocycles (A) and carboxylic acids (B) wit...
Scheme 28: Reactions of heterocyclic Mg enolates with onium compounds.
Scheme 29: Synthetic transformations of cycloheptatrienyl and benzodithiolyl substituents.
Scheme 30: Aminomethylation of Al enolates generated by ACA of trialkylaluminum reagents.
Scheme 31: Trapping reactions of enolates with activated alkenes.
Scheme 32: Alkynylation of racemic aluminum or magnesium enolates.
Scheme 33: Trapping reactions of Zr enolates generated by Cu-ACA of organozirconium reagents.
Scheme 34: Chloromethylation of Zr enolates using the Vilsmeier–Haack reagent.
Scheme 35: Tandem conjugate borylation with subsequent protonation or enolate trapping by an electrophile.
Scheme 36: Tandem conjugate borylation/aldol reaction of cyclohexenones.
Scheme 37: Selected examples for the tandem asymmetric borylation/intramolecular aldol reaction; synthesis of ...
Scheme 38: Cu-catalyzed tandem methylborylation of α,β-unsaturated phosphine oxide in the presence of (R,Sp)-J...
Scheme 39: Cu-catalyzed tandem transannular conjugated borylation/aldol cyclization of macrocycles containing ...
Scheme 40: Stereoselective tandem conjugate borylation/Mannich cyclization: selected examples (A) and a multi-...
Scheme 41: Some examples of Cu-catalyzed asymmetric tandem borylation/aldol cyclization (A). Application to di...
Scheme 42: Atropisomeric P,N-ligands used in tandem conjugate borylation/aldol cyclization sequence.
Scheme 43: Selected examples for the enantioselective Cu-catalyzed borylation/intramolecular Michael addition ...
Scheme 44: Selected examples for the preparation of enantioenriched spiroindanes using a Cu-catalyzed tandem c...
Scheme 45: Enantioselective conjugate borylation of cyclobutene-1-carboxylic acid diphenylmethyl ester 175 wit...
Scheme 46: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 47: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 48: Cu-catalyzed tandem conjugate silylation/aldol condensation. The diastereoselectivity is controlled...
Scheme 49: Chiral Ru-catalyzed three-component coupling reaction.
Scheme 50: Rh-Phebox complex-catalyzed reductive cyclization and subsequent reaction with Michael acceptors th...
Scheme 51: Rh-catalyzed tandem asymmetric conjugate alkynylation/aldol reaction (A) and subsequent spiro-cycli...
Scheme 52: Rh-bod complex-catalyzed tandem asymmetric conjugate arylation/intramolecular aldol addition (A). S...
Scheme 53: Co-catalyzed C–H-bond activation/asymmetric conjugate addition/aldol reaction.
Scheme 54: (Diisopinocampheyl)borane-promoted 1,4-hydroboration of α,β-unsaturated morpholine carboxamides and...
Figure 2: Some examples of total syntheses that have been recently reviewed.
Scheme 55: Stereoselective synthesis of antimalarial prodrug (+)-artemisinin utilizing a tandem conjugate addi...
Scheme 56: Amphilectane and serrulatane diterpenoids: preparation of chiral starting material via asymmetric t...
Scheme 57: Various asymmetric syntheses of pleuromutilin and related compounds based on a tandem conjugate add...
Scheme 58: Total synthesis of glaucocalyxin A utilizing a tandem conjugate addition/acylation reaction sequenc...
Scheme 59: Installation of the exocyclic double bond using a tandem conjugate addition/aminomethylation sequen...
Scheme 60: Synthesis of the taxol core using a tandem conjugate addition/enolate trapping sequence with Vilsme...
Scheme 61: Synthesis of the tricyclic core of 12-epi-JBIR-23/24 utilizing a Rh-catalyzed asymmetric conjugate ...
Scheme 62: Total synthesis of (−)-peyssonoside A utilizing a Cu-catalyzed enantioselective tandem conjugate ad...
Asymmetric synthesis of a stereopentade fragment toward latrunculins
- Benjamin Joyeux,
- Antoine Gamet,
- Nicolas Casaretto and
- Bastien Nay
Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32
- analogue synthesis, starting from (+)-β-citronellene. Key stereoselective transformations involve an asymmetric Krische allylation, an aldol reaction under 1,5-anti stereocontrol, and a Tishchenko–Evans reduction accompanied by a peculiar ester transposition, allowing to install key stereogenic centers of
- the natural products. Keywords: allylation; aldol reaction; latrunculins; stereocontrol; total synthesis; Introduction Latrunculins constitute a class of marine polyketide natural products isolated from Sponges like Negombata (= Latrunculia) magnifica [1][2]. They are characterized by the presence
- formed by the oxidation of an allyl moiety introduced by the asymmetric allylation of an aldehyde derived from (+)-β-citronellene. At this stage, we can speculate that the stereocontrol of this reaction could either follow a polar Felkin–Anh model [14][15][16] based on chiral aldehyde partner 8 [17], or
Graphical Abstract
Figure 1: Structure of latrunculins (the red dots show the natural product stereopentade).
Figure 2: General strategy for latrunculin cycle disconnections (left), previous works towards linear precurs...
Scheme 1: Synthesis of fragment 15 from (+)-β-citronellene (10).
Scheme 2: Synthesis of fragment 8 from ʟ-cysteine ethyl ester hydrochloride (16).
Scheme 3: Synthesis of fragment 21 through a stereoselective aldol reaction.
Scheme 4: 1,3-Anti-diastereoselective reduction of 21 with PNBz transposition, and final determination of the...
Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series
- Cécile Alleman,
- Charlène Gadais,
- Laurent Legentil and
- François-Hugues Porée
Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23
- ), where the eight-membered ring was accessed through a SmI2-mediated cyclization cascade reaction of a dialdehyde [69]. In this approach, an original way was proposed to form in a single step the tricyclic core of pleuromutilin (1) with a stereocontrol at the four contiguous stereocenters [69][70]. The
Graphical Abstract
Figure 1: Examples of terpenes containing a bicyclo[3.6.0]undecane motif.
Figure 2: Commercially available first and second generation Grubbs and Hoveyda–Grubbs catalysts.
Figure 3: Examples of strategies to access the fusicoccan and ophiobolin tricyclic core structure by RCM.
Scheme 1: Synthesis of bicyclic core structure 12 of ophiobolin M (13) and cycloaraneosene (14).
Scheme 2: Synthesis of the core structure 21 of ophiobolins and fusicoccanes.
Scheme 3: Ring-closing metathesis attempts starting from thioester 22.
Scheme 4: Total synthesis of ent-fusicoauritone (28).
Figure 4: General structure of ophiobolins and congeners.
Scheme 5: Total synthesis of (+)-ophiobolin A (8).
Scheme 6: Investigation of RCM for the synthesis of ophiobolin A (8). Path A) RCM with TBDPS-protected alcoho...
Scheme 7: Synthesis of the core structure of cotylenin A aglycon, cotylenol (50).
Scheme 8: Synthesis of tricyclic core structure of fusicoccans.
Scheme 9: Total synthesis of (−)-teubrevin G (59).
Scheme 10: Synthesis of the core skeleton 63 of the basmane family.
Scheme 11: Total synthesis of (±)-schindilactone A (68).
Scheme 12: Total synthesis of dactylol (72).
Scheme 13: Ring-closing metathesis for the total synthesis of (±)-asteriscanolide (2).
Scheme 14: Synthesis of the simplified skeleton of pleuromutilin (1).
Scheme 15: Total synthesis of (−)-nitidasin (93) using a ring-closing metathesis to construct the eight-member...
Scheme 16: Total synthesis of (±)-naupliolide (97).
Scheme 17: Synthesis of the A-B ring structure of fusicoccane (101).
Scheme 18: First attempts of TRCM of dienyne substrates.
Scheme 19: TRCM on optimized substrates towards the synthesis of ophiobolin A (8).
Scheme 20: Tandem ring-closing metathesis for the synthesis of variecolin intermediates 114 and 115.
Scheme 21: Synthesis of poitediol (118) using the allylsilane ring-closing metathesis.
Scheme 22: Access to scaffold 122 by a NHK coupling reaction.
Scheme 23: Key step to construct the [5-8] bicyclooctanone core of aquatolide (4).
Scheme 24: Initial strategy to access aquatolide (4).
Scheme 25: Synthetic plan to cotylenin A (130).
Scheme 26: [5-8] Bicyclic structure of brachialactone (7) constructed by a Mizoroki–Heck reaction.
Scheme 27: Influence of the replacement of the allylic alcohol moiety.
Scheme 28: Formation of variecolin intermediate 140 through a SmI2-mediated Barbier-type reaction.
Scheme 29: SmI2-mediated ketyl addition. Pleuromutilin (1) eight-membered ring closure via C5–C14 bond formati...
Scheme 30: SmI2-mediated dialdehyde cyclization cascade of [5-8-6] pleuromutilin scaffold 149.
Scheme 31: A) Modular synthetic route to mutilin and pleuromutilin family members by Herzon’s group. B) Scaffo...
Scheme 32: Photocatalyzed oxidative ring expansion in pleuromutilin (1) total synthesis.
Scheme 33: Reductive radical cascade cyclization route towards (−)-6-epi-ophiobolin N (168).
Scheme 34: Reductive radical cascade cyclization route towards (+)-6-epi-ophiobolin A (173).
Scheme 35: Radical 8-endo-trig-cyclization of a xanthate precursor.
Figure 5: Structural representations of hypoestin A (177), albolic acid (178), and ceroplastol II (179) beari...
Scheme 36: Synthesis of the common [5-8-5] tricyclic intermediate of hypoestin A (177), albolic acid (178), an...
Scheme 37: Asymmetric synthesis of hypoestin A (177), albolic acid (178), and ceroplastol II (179).
Figure 6: Scope of the Pauson–Khand reaction.
Scheme 38: Nazarov cyclization revealing the fusicoauritone core structure 192.
Scheme 39: Synthesis of fusicoauritone (28) through Nazarov cyclization.
Scheme 40: (+)-Epoxydictymene (5) synthesis through a Nicholas cyclization followed by a Pauson–Khand reaction...
Scheme 41: Synthesis of aquatolide (4) by a Mukaiyama-type aldolisation.
Scheme 42: Tandem Wolff/Cope rearrangement furnishing the A-B bicyclic moiety 204 of variecolin.
Scheme 43: Asymmetric synthesis of the A-B bicyclic core 205 and 206 of variecolin.
Scheme 44: Formation of [5-8]-fused rings by cyclization under thermal activation.
Scheme 45: Construction of the [5-8-6] tricyclic core structure of variecolin (3) by Diels–Alder reaction.
Scheme 46: Synthesis of the [6-4-8-5]-tetracyclic skeleton by palladium-mediated cyclization.
Scheme 47: Access to the [5-8] bicyclic core structure of asteriscanolide (227) through rhodium-catalyzed cycl...
Scheme 48: Total syntheses of asterisca-3(15),6-diene (230) and asteriscanolide (2) with a Rh-catalyzed cycliz...
Scheme 49: Photocyclization of 2-pyridones to access the [5-8-5] backbone of fusicoccanes.
Scheme 50: Total synthesis of (+)-asteriscunolide D (245) and (+)-aquatolide (4) through photocyclization.
Scheme 51: Biocatalysis pathway to construct the [5-8-5] tricyclic scaffold of brassicicenes.
Scheme 52: Influence of the CotB2 mutant over the cyclization’s outcome of GGDP.
Synthetic study toward tridachiapyrone B
- Morgan Cormier,
- Florian Hernvann and
- Michaël De Paolis
Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183
- electrocyclization of compounds 1a and b [19][20][21][22]. Interestingly, Baldwin and Moses demonstrated the irradiation or sunlight-promoted cycloisomerization of a similar tetraenyl framework into the bicyclo[3.1.0]hexane core through a 6π-conrotatory stereocontrol [23][24]. To date, the known strategies to
Graphical Abstract
Scheme 1: Routes to crispatene, photodeoxytridachione, aureothin, and tridachiapyrone B.
Scheme 2: Desymmetrization of 2.
Scheme 3: Addition of lithiocyclopentadiene to pyrone 2.
Scheme 4: Plan to reach 2,5-cyclohexadienone 5.
Scheme 5: Preparation of 2,5-cyclohexadienone 5.
Scheme 6: Attempts to perform the conjugate addition.
Scheme 7: Updated route to tridachiapyrone B.
Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A
- Takumi Matsumoto,
- Takefumi Kuranaga,
- Yuto Taniguchi,
- Weicheng Wang and
- Hideaki Kakeya
Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166
- communication in the microbial world. Herein, we report the solid-phase total synthesis and structural confirmation of longicatenamide A. First, commercially unavailable building blocks were chemically synthesized with stereocontrol. Second, the peptide chain was elongated via Fmoc-based solid-phase peptide
- with stereocontrol. Then, the peptide chain was elongated by Fmoc-based solid-phase peptide synthesis. Finally, the cyclization of the peptide chain followed by simultaneous cleavage of all protecting groups in the solution phase afforded target compound 1. The comparison of the chromatograms of
Graphical Abstract
Figure 1: Structures of longicatenamides A–D (1–4).
Scheme 1: Retrosynthesis of longicatenamycin A (1).
Scheme 2: Synthesis of building block 10.
Scheme 3: Synthesis of building block 7.
Scheme 4: Total synthesis of longicatenamycin A (1).
Figure 2: LC–MS extracted ion chromatograms (EICs) of synthesized and natural 1. Column: Imtakt Cadenza CD-C1...
Supramolecular approaches to mediate chemical reactivity
- Pablo Ballester,
- Qi-Qiang Wang and
- Carmine Gaeta
Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152
- and stereocontrol of the reaction depends on the conformational rigidity of the macrocyclic framework and a synergy between the thiourea and tertiary amine sites. Recently, many efforts were focused on the synthesis and applications of mechanically interlocked molecules (MIMs), such as catenanes and
Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives
- Oleg A. Levitskiy,
- Olga I. Aglamazova,
- Yuri K. Grishin and
- Tatiana V. Magdesieva
Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121
- base platform creates an optimal balance between the covalent binding with the substrate (which does not “kill” its reactivity but precludes its redox destruction) with non-covalent interactions in the metal chiral coordination environment governing the reaction’s stereocontrol. Cyclic voltammograms
Graphical Abstract
Figure 1: Cyclic voltammograms obtained for complexes 1 (black), 2 (blue), 3 (green), 4 (red) (MeCN, 0.05 M Bu...
Scheme 1: Synthesis of complex 4.
Figure 2: Key correlations in the NOESY spectrum of complex (S)-4 and the corresponding characteristic fragme...
Scheme 2: Reductive three-membered ring-opening and follow-up chemical steps.
Figure 3: Correlations in the HMBC spectra of 6a and 6b and spin coupling constants in the 1H NMR spectrum of ...
Scheme 3: Electrochemically induced ring-opening followed by intramolecular cyclization.
Scheme 4: One-pot multistep approach to the cysteine derivatives.
Figure 4: Characteristic correlations in the NOESY spectra of diastereomeric complexes 10 and the correspondi...
Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions
- Hao Guo,
- Yu-Fei Ao,
- De-Xian Wang and
- Qi-Qiang Wang
Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51
- tertiary amine sites were found to be crucial for achieving efficient activation and stereocontrol. As shown in control experiments, catalysis with the acyclic analogues having the same structural motifs were non-selective. Keywords: chiral macrocycles; cooperative asymmetric catalysis; decarboxylative
- cavity environment may be good for stereocontrol. The diphenylethylenediamine-linking macrocycles M5 and M6, however, gave very low ees (Table 1, entries 5 and 6). The hetero-macrocycles M7–M12 did not afford better selectivity as well (Table 1, entries 7–12). It is interesting to note that M9–M12 led to
- stereocontrol. On the other hand, compound 3c led to a much slower conversion and also nearly racemic product formation, indicating that the thiourea units must have engaged in activation and being cooperative with the tertiary amine sites. With the reaction outcomes and pronounced macrocyclic effect observed
Graphical Abstract
Figure 1: Design of PKS-inspired multifunctional amino-thiourea macrocycle catalysts.
Scheme 1: Synthesis of tetraamino-bisthiourea chiral macrocycles M1–M12. The synthesis of M1, M5, M7, and M8 ...
Scheme 2: Substrate scope of isatin imines. Reaction conditions: 6 (0.2 mmol), 7a (0.3 mmol), and 5 mol % M3 ...
Scheme 3: Substrate scope of MAHTs. Reaction conditions: 6a (0.2 mmol), 7 (0.3 mmol), and 5 mol % M3 in 2 mL ...
Figure 2: Proposed catalytic mechanism.
Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study
- Angel Ho,
- Austin Pounder,
- Krish Valluru,
- Leanne D. Chen and
- William Tam
Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30
- catalyzed by rhodium/diene to afford the 1,2,4-trisubstituted naphthalene framework 8 with complete regio- and stereocontrol (Scheme 1) [62][63]. In 2015, the Nishimura group reported the first iridium-catalyzed addition of salicylaldehydes 14 to bicyclic alkenes 11 (Scheme 1) [64]. Although a variety of
Graphical Abstract
Scheme 1: Previously reported metal-catalyzed reactions of heterobicyclic alkenes and applications towards th...
Scheme 2: Iridium-catalyzed hydroacylation of C1-substituted OBDs 13a–k with salicylaldehyde 14.
Scheme 3: Competition reaction of different C1-substituted OBDs.
Figure 1: Potential energy profile of the PCM solvation model for the hydrometalation/reductive elimination p...
Figure 2: Potential energy profile of the PCM solvation model for the carbometalation/reductive elimination p...
Figure 3: Potential energy profile of the PCM solvation model for the endo hydrometalation/reductive eliminat...
Figure 4: Potential energy profile of the PCM solvation model for the Ir/diene-catalyzed hydroacylation of Me...
Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds
- Alemayehu Gashaw Woldegiorgis and
- Xufeng Lin
Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185
- and could considerably improve the stereocontrol of the reaction [21]. The axially chiral arylquinazolinones form the backbones of a large number of natural products and biologically active compounds as well as chiral ligands [83]. Nevertheless, a simple chiral phosphoric acid-catalyzed
- gram scale was carried out without loss of chemical yields and stereoselectivities under optimized conditions. The authors also found that the excellent stereocontrol was due to the simultaneous interaction between the bifunctional phosphoric acid and the intermediate formed in the reaction via
Graphical Abstract
Figure 1: Representative examples of axially chiral biaryls, heterobiaryls, spiranes and allenes as ligands a...
Figure 2: Selected examples of axially chiral drugs and bioactive molecules.
Figure 3: Axially chiral functional materials and supramolecules.
Figure 4: Important chiral phosphoric acid scaffolds used in this review.
Scheme 1: Atroposelective aryl–aryl-bond formation by employing a facile [3,3]-sigmatropic rearrangement.
Scheme 2: Atroposelective synthesis of axially chiral biaryl amino alcohols 5.
Scheme 3: The enantioselective reaction of quinone and 2-naphthol derivatives.
Scheme 4: Enantioselective synthesis of multisubstituted biaryls.
Scheme 5: Enantioselective synthesis of axially chiral quinoline-derived biaryl atropisomers mediated by chir...
Scheme 6: Pd-Catalyzed atroposelective C–H olefination of biarylamines.
Scheme 7: Palladium-catalyzed directed atroposelective C–H allylation.
Scheme 8: Enantioselective synthesis of axially chiral (a) aryl indoles and (b) biaryldiols.
Scheme 9: Asymmetric arylation of indoles enabled by azo groups.
Scheme 10: Proposed mechanism for the asymmetric arylation of indoles.
Scheme 11: Enantioselective synthesis of axially chiral N-arylindoles [38].
Scheme 12: Enantioselective [3 + 2] formal cycloaddition and central-to-axial chirality conversion.
Scheme 13: Organocatalytic atroposelective arene functionalization of nitrosonaphthalene with indoles.
Scheme 14: Proposed reaction mechanism for the atroposelective arene functionalization of nitrosonaphthalenes.
Scheme 15: Asymmetric construction of axially chiral naphthylindoles [65].
Scheme 16: Enantioselective synthesis of axially chiral 3,3’-bisindoles [66].
Scheme 17: Atroposelective synthesis of 3,3’-bisiindoles bearing axial and central chirality.
Scheme 18: Enantioselective synthesis of axially chiral 3,3’-bisindoles bearing single axial chirality.
Scheme 19: Enantioselective reaction of azonaphthalenes with various pyrazolones.
Scheme 20: Enantioselective and atroposelective synthesis of axially chiral N-arylcarbazoles [73].
Scheme 21: Atroposelective cyclodehydration reaction.
Scheme 22: Atroposelective construction of axially chiral N-arylbenzimidazoles [78].
Scheme 23: Proposed reaction mechanism for the atroposelective synthesis of axially chiral N-arylbenzimidazole...
Scheme 24: Atroposelective synthesis of axially chiral arylpyrroles [21].
Scheme 25: Synthesis of axially chiral arylquinazolinones and its reaction pathway [35].
Scheme 26: Synthesis of axially chiral aryquinoline by Friedländer heteroannulation reaction and its proposed...
Scheme 27: Povarov cycloaddition–oxidative chirality conversion process.
Scheme 28: Atroposelective synthesis of oxindole-based axially chiral styrenes via kinetic resolution.
Scheme 29: Synthesis of axially chiral alkene-indole frame works [45].
Scheme 30: Proposed reaction mechanism for axially chiral alkene-indoles.
Scheme 31: Atroposelective C–H aminations of N-aryl-2-naphthylamines with azodicarboxylates.
Scheme 32: Synthesis of brominated atropisomeric N-arylquinoids.
Scheme 33: The enantioselective syntheses of axially chiral SPINOL derivatives.
Scheme 34: γ-Addition reaction of various 2,3-disubstituted indoles to β,γ-alkynyl-α-imino esters.
Scheme 35: Regio- and stereoselective γ-addition reactions of isoxazol-5(4H)-ones to β,γ-alkynyl-α-imino ester...
Scheme 36: Synthesis of chiral tetrasubstituted allenes and naphthopyrans.
Scheme 37: Asymmetric remote 1,8-conjugate additions of thiazolones and azlactones to propargyl alcohols.
Scheme 38: Synthesis of chiral allenes from 1-substituted 2-naphthols [107].
Synthetic strategies toward 1,3-oxathiolane nucleoside analogues
- Umesh P. Aher,
- Dhananjai Srivastava,
- Girij P. Singh and
- Jayashree B. S
Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182
Graphical Abstract
Figure 1: Representative modified 1,3-oxathiolane nucleoside analogues.
Figure 2: Mechanism of antiviral action of 1,3-oxathiolane nucleosides, 3TC (1) and FTC (2), as chain termina...
Figure 3: Synthetic strategies for the construction of the 1,3-oxathiolane sugar ring.
Scheme 1: Synthesis of 4 from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na.
Scheme 2: Synthesis of 8 from protected glycolic aldehyde 3b and 2-mercaptoacetic acid (3o).
Scheme 3: Synthesis of 20 from ᴅ-mannose (3c).
Scheme 4: Synthesis of 20 from 1,6-thioanhydro-ᴅ-galactose (3d).
Scheme 5: Synthesis of 8 from 2-(tert-butyldiphenylsilyloxy)methyl-5-oxo-1,2-oxathiolane (3m).
Scheme 6: Synthesis of 20a from ʟ-gulose derivative 3f.
Scheme 7: Synthesis of 31 from (+)-thiolactic acid 3p and 2-benzoyloxyacetaldehyde (3a).
Scheme 8: Synthesis of 35a from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g) hydrate.
Scheme 9: Synthetic routes toward 41 through Pummerer reaction from methyl 2-mercaptoacetate (3j) and bromoac...
Scheme 10: Strategy for the synthesis of 2,5-substituted 1,3-oxathiolane 41a using 4-nitrobenzyl glyoxylate an...
Scheme 11: Synthesis of 44 by a resolution method using Mucor miehei lipase.
Scheme 12: Synthesis of 45 from benzoyloxyacetaldehyde (3a) and 2-mercaptoacetaldehyde bis(2-methoxyethyl) ace...
Scheme 13: Synthesis of 46 from 2-mercaptoacetaldehyde bis(2-methoxyethyl) acetal (3nc) and diethyl 3-phosphon...
Scheme 14: Synthesis of 48 from 1,3-dihydroxyacetone dimer 3l.
Scheme 15: Approach toward 52 from protected alkene 3rb and lactic acid derivative 51 developed by Snead et al....
Scheme 16: Recent approach toward 56a developed by Kashinath et al.
Scheme 17: Synthesis of 56a from ʟ-menthyl glyoxylate (3h) hydrate by DKR.
Scheme 18: Possible mechanism with catalytic TEA for rapid interconversion of isomers.
Scheme 19: Synthesis of 35a by a classical resolution method through norephedrine salt 58 formation.
Scheme 20: Synthesis of 63 via [1,2]-Brook rearrangement from silyl glyoxylate 61 and thiol 3nb.
Scheme 21: Combined use of STS and CAL-B as catalysts to synthesize an enantiopure oxathiolane precursor 65.
Scheme 22: Synthesis of 1 and 1a from glycolaldehyde dimer 64 and 1,4-dithiane-2,5-diol (3q) using STS and CAL...
Scheme 23: Synthesis of 68 by using Klebsiella oxytoca.
Scheme 24: Synthesis of 71 and 72 using Trichosporon taibachii lipase and kinetic resolution.
Scheme 25: Synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution.
Figure 4: Pathway for glycosidic bond formation.
Scheme 26: First synthesis of (±)-BCH-189 (1c) by Belleau et al.
Scheme 27: Enantioselective synthesis of 3TC (1).
Scheme 28: Synthesis of cis-diastereomer 3TC (1) from oxathiolane propionate 44.
Scheme 29: Synthesis of (±)-BCH-189 (1c) via SnCl4-mediated N-glycosylation of 8.
Scheme 30: Synthesis of (+)-BCH-189 (1a) via TMSOTf-mediated N-glycosylation of 20.
Scheme 31: Synthesis of 3TC (1) from oxathiolane precursor 20a.
Scheme 32: Synthesis of 83 via N-glycosylation of 20 with pyrimidine bases.
Scheme 33: Synthesis of 85 via N-glycosylation of 20 with purine bases.
Scheme 34: Synthesis of 86 and 87 via N-glycosylation using TMSOTf and pyrimidines.
Scheme 35: Synthesis of 90 and 91 via N-glycosylation using TMSOTf and purines.
Scheme 36: Synthesis of 3TC (1) via TMSI-mediated N-glycosylation.
Scheme 37: Stereoselective N-glycosylation for the synthesis of 1 by anchimeric assistance of a chiral auxilia...
Scheme 38: Whitehead and co-workers’ approach for the synthesis of 1 via direct N-glycosylation without an act...
Scheme 39: ZrCl4-mediated stereoselective N-glycosylation.
Scheme 40: Plausible reaction mechanism for stereoselective N-glycosylation using ZrCl4.
Scheme 41: Synthesis of enantiomerically pure oxathiolane nucleosides 1 and 2.
Scheme 42: Synthesis of tetrazole analogues of 1,3-oxathiolane nucleosides 97.
Scheme 43: Synthetic approach toward 99 from 1,3-oxathiolane 45 by Camplo et al.
Scheme 44: Synthesis of 100 from oxathiolane phosphonate analogue 46.
Scheme 45: Synthetic approach toward 102 and the corresponding cyclic thianucleoside monophosphate 102a by Cha...
Scheme 46: Synthesis of emtricitabine (2) from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g).
Scheme 47: Synthesis of 1 and 2, respectively, from 56a–d using iodine-mediated N-glycosylation.
Scheme 48: Plausible mechanism for silane- and I2-mediated N-glycosylation.
Scheme 49: Pyridinium triflate-mediated N-glycosylation of 35a.
Scheme 50: Possible pathway for stereoselective N-glycosylation via in situ chelation with a metal ligand.
Scheme 51: Synthesis of novel 1,3-oxathiolane nucleoside 108 from oxathiolane precursor 8 and 3-benzyloxy-2-me...
Scheme 52: Synthesis of 110 using T-705 as a nucleobase and 1,3-oxathiolane derivative 8 via N-glycosylation.
Scheme 53: Synthesis of 1 using an asymmetric leaving group and N-glycosylation with bromine and mesitylene.
Scheme 54: Cytidine deaminase for enzymatic separation of 1c.
Scheme 55: Enzymatic resolution of the monophosphate derivative 116 for the synthesis of (−)-BCH-189 (1) and (...
Scheme 56: Enantioselective resolution by PLE-mediated hydrolysis to obtain FTC (2).
Scheme 57: (+)-Menthyl chloroformate as a resolving agent to separate a racemic mixture 120.
Scheme 58: Separation of racemic mixture 1c by cocrystal 123 formation with (S)-(−)-BINOL.
Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides
- Pratibha Sharma,
- Raakhi Gupta and
- Raj K. Bansal
Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173
- –91%) with excellent levels of stereocontrol (≈92% ee, >20:1 dr in all cases). The ketone group in the cascade product was reduced asymmetrically to a chiral secondary hydroxy group (Table 1) [26]. In this case, the role of Ph3CCO2H as additive is to furnish the conjugate base Ph3CO2− anion which
Graphical Abstract
Scheme 1: Asymmetric aza-Michael addition catalyzed by cinchona alkaloid derivatives.
Scheme 2: Intramolecular 6-exo-trig aza-Michael addition reaction.
Scheme 3: Asymmetric aza-Michael/Michael addition cascade reaction of 2-nitrobenzofurans and 2-nitrobenzothio...
Scheme 4: Asymmetric aza-Michael addition of para-dienone imide to benzylamine.
Scheme 5: Asymmetric synthesis of chiral N-functionalized heteroarenes.
Visible-light-mediated copper photocatalysis for organic syntheses
- Yajing Zhang,
- Qian Wang,
- Zongsheng Yan,
- Donglai Ma and
- Yuguang Zheng
Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169
- with diverse chiral ligands to provide a chiral environment for asymmetric control. Despite the remarkable achievements in this field, copper-based catalytic asymmetric reactions still remain a challenging task because of the difficulty of stereocontrol of the highly reactive radical intermediates
Graphical Abstract
Scheme 1: Photoredox catalysis mechanism of [Ru(bpy)3]2+.
Scheme 2: Photoredox catalysis mechanism of CuI.
Scheme 3: Ligands and CuI complexes.
Scheme 4: Mechanism of CuI-based photocatalysis.
Scheme 5: Mechanisms of CuI–substrate complexes.
Scheme 6: Mechanism of CuII-base photocatalysis.
Scheme 7: Olefinic C–H functionalization and allylic alkylation.
Scheme 8: Cross-coupling of unactivated alkenes and CF3SO2Cl.
Scheme 9: Chlorosulfonylation/cyanofluoroalkylation of alkenes.
Scheme 10: Hydroamination of alkenes.
Scheme 11: Cross-coupling reaction of alkenes, alkyl halides with nucleophiles.
Scheme 12: Cross-coupling of alkenes with oxime esters.
Scheme 13: Oxo-azidation of vinyl arenes.
Scheme 14: Azidation/difunctionalization of vinyl arenes.
Scheme 15: Photoinitiated copper-catalyzed Sonogashira reaction.
Scheme 16: Alkyne functionalization reactions.
Scheme 17: Alkynylation of dihydroquinoxalin-2-ones with terminal alkynes.
Scheme 18: Decarboxylative alkynylation of redox-active esters.
Scheme 19: Aerobic oxidative C(sp)–S coupling reaction.
Scheme 20: Copper-catalyzed alkylation of carbazoles with alkyl halides.
Scheme 21: C–N coupling of organic halides with amides and aliphatic amines.
Scheme 22: Copper-catalyzed C–X (N, S, O) bond formation reactions.
Scheme 23: Arylation of C(sp2)–H bonds of azoles.
Scheme 24: C–C cross-coupling of aryl halides and heteroarenes.
Scheme 25: Benzylic or α-amino C–H functionalization.
Scheme 26: α-Amino C–H functionalization of aromatic amines.
Scheme 27: C–H functionalization of aromatic amines.
Scheme 28: α-Amino-C–H and alkyl C–H functionalization reactions.
Scheme 29: Other copper-photocatalyzed reactions.
Scheme 30: Cross-coupling of oxime esters with phenols or amines.
Scheme 31: Alkylation of heteroarene N-oxides.
Halides as versatile anions in asymmetric anion-binding organocatalysis
- Lukas Schifferer,
- Martin Stinglhamer,
- Kirandeep Kaur and
- Olga García Macheño
Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145
- only a spectator linking the substrate and catalyst in the presence of an external nucleophile, halides can also be tuned to participate as the nucleophile in certain reactions. In theory, the close association of the catalyst and the anionic nucleophile might allow for better stereocontrol. An early
- % ee [63]. Evolution of catalyst designs: from bidentate to supramolecular multidentate anion-binding catalysts Despite the evident potential that anion-binding catalysis showed in the pioneering publications – especially in regard to exerting high stereocontrol –, the strategy was still faced with
Graphical Abstract
Figure 1: a) Binding interactions in the chloride channel of E. coli. and b) examples of chloride, cyanide, n...
Figure 2: a) H-bond vs anion-binding catalysis and b) activation modes in anion-binding catalysis.
Scheme 1: First proposed anion-binding mechanism in the thiourea-catalyzed acetalization of benzaldehyde.
Scheme 2: a) Thiourea-catalyzed enantioselective acyl-Pictet–Spengler reaction of tryptamine-derived imines 4...
Scheme 3: Proposed mechanism of the thiourea-catalyzed enantioselective Pictet–Spengler reaction of hydroxyla...
Scheme 4: a) Thiourea-catalyzed intramolecular Pictet–Spengler-type cyclization of hydroxylactam-derived N-ac...
Scheme 5: Enantioselective Reissert-type reactions of a) (iso)quinolines with silyl ketene acetals, and b) vi...
Figure 3: Role of the counter-anion: a) Anion acting as a spectator and b) anion participating directly as th...
Scheme 6: Enantioselective selenocyclization catalyzed by squaramide 28.
Scheme 7: Desymmetrization of meso-aziridines catalyzed by bifunctional thiourea catalyst 31.
Scheme 8: Anion-binding-catalyzed desymmetrization of a) meso-aziridines catalyzed by chiral triazolium catal...
Scheme 9: Bis-urea-catalyzed enantioselective fluorination of a) β-bromosulfides and b) β-haloamines by Gouve...
Scheme 10: a) Bifunctional thiourea anion-binding – basic/nucleophilic catalysts. Selected applications in b) ...
Scheme 11: Thiourea-catalyzed enantioselective polycyclization reaction of hydroxylactams 51 through cation–π ...
Scheme 12: Enantioselective aza-Sakurai cyclization of hydroxylactams 56 implicating additional cation–π and L...
Scheme 13: Enantioselective tail-to-head cyclization of neryl chloride derivatives.
Scheme 14: Cation–π interactions in anion binding-catalyzed asymmetric addition reactions: a) addition of indo...
Scheme 15: Bisthiourea catalyzed oxa-Pictet–Spengler reaction of indole-based alcohols and aromatic aldehydes ...
Scheme 16: Anion-binding catalyst development in the enantioselective addition of silyl ketene acetals to 1-ch...
Scheme 17: a) Macrocyclic bis-thiourea catalyst in a diastereoselective glycosylation reaction. b) Competing SN...
Scheme 18: a) Folding mechanism of oligotriazoles upon anion recognition. b) Representative tetratriazole 82 c...
Scheme 19: Switchable chiral tetratriazole catalyst 86 in the enantioselective addition of silyl ketene acetal...
Progress and challenges in the synthesis of sequence controlled polysaccharides
- Giulio Fittolani,
- Theodore Tyrikos-Ergas,
- Denisa Vargová,
- Manishkumar A. Chaube and
- Martina Delbianco
Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129
- ]. Nevertheless, the complexity and diversity of polysaccharides makes synthetic processes extremely laborious and time consuming. Several aspects are crucial to plan a successful polysaccharide synthesis. Properly designed starting materials and/or catalysts are required to ensure regio- and stereocontrol during
- synthetic steps. In general, BBs are equipped with a reactive anomeric LG to allow for glycosylation and suitable PGs to ensure regio- and stereocontrol [25]. Even though, in most cases, BB preparation follows straightforward protection/deprotection strategies, the low selectivity and yield of certain
- released from the solid support and subjected to global deprotection. Similar to chemical polymerization, the removal of the PGs is a significant bottleneck. Additionally, several transformations remain challenging due to the poor reactivity or limited stereocontrol of certain BBs [33][34][35][36][37]. To
Graphical Abstract
Figure 1: Overview of the methods available for the synthesis of polysaccharides. For each method, advantages...
Figure 2: Overview of the classes of polysaccharides discussed in this review. Each section deals with polysa...
Scheme 1: Enzymatic and chemical polymerization approaches provide cellulose oligomers with a non-uniform dis...
Scheme 2: AGA of a collection of cellulose analogues obtained using BBs 6–9. Specifically placed modification...
Figure 3: Chemical structure of the different branches G, X, L, F commonly found in XGs. Names are given foll...
Scheme 3: AGA of XG analogues with defined side chains. The AGA cycle includes coupling (TMSOTf), Fmoc deprot...
Figure 4: Synthetic strategies and issues associated to the formation of the β(1–3) linkage.
Scheme 4: Convergent synthesis of β(1–3)-glucans using a regioselective glycosylation strategy.
Scheme 5: DMF-mediated 1,2-cis glycosylation. A) General mechanism and B) examples of α-glucans prepared usin...
Scheme 6: Synergistic glycosylation strategy employing a nucleophilic modulation strategy (TMSI and Ph3PO) in...
Scheme 7: Different approaches to produce xylans. A) Polymerization techniques including ROP, and B) enzymati...
Scheme 8: A) Synthesis of arabinofuranosyl-decorated xylan oligosaccharides using AGA. Representative compoun...
Scheme 9: Chemoenzymatic synthesis of COS utilizing a lysozyme-catalyzed transglycosylation reaction followed...
Scheme 10: Synthesis of COS using an orthogonal glycosylation strategy based on the use of two different LGs.
Scheme 11: Orthogonal N-PGs permitted the synthesis of COS with different PA.
Scheme 12: AGA of well-defined COS with different PA using two orthogonally protected BBs. The AGA cycle inclu...
Scheme 13: A) AGA of β(1–6)-N-acetylglucosamine hexasaccharide and dodecasaccharide. AGA includes cycles of co...
Figure 5: ‘Double-faced’ chemistry exemplified for ᴅ-Man and ʟ-Rha. Constructing β-Man linkages is considerab...
Figure 6: Implementation of a capping step after each glycosylation cycle for the AGA of a 50mer oligomannosi...
Scheme 14: AGA enabled the synthesis of a linear α(1–6)-mannoside 100mer 93 within 188 h and with an average s...
Scheme 15: The 151mer branched polymannoside was synthesized by a [30 + 30 + 30 + 30 + 31] fragment coupling. ...
Figure 7: PG stereocontrol strategy to obtain β-mannosides. A) The mechanism of the β-mannosylation reaction ...
Scheme 16: A) Mechanism of 1,2-cis stereoselective glycosylation using ManA donors. Once the ManA donor is act...
Figure 8: A) The preferred 4H3 conformation of the gulosyl oxocarbenium ion favors the attack of the alcohol ...
Scheme 17: AGA of type I rhamnans up to 16mer using disaccharide BB 115 and CNPiv PG. The AGA cycle includes c...
Figure 9: Key BBs for the synthesis of the O-antigen of Bacteroides vulgatus up to a 128mer (A) and the CPS o...
Figure 10: Examples of type I and type II galactans synthesized to date.
Figure 11: A) The DTBS PG stabilizes the 3H4 conformation of the Gal oxocarbenium ion favoring the attack of t...
Figure 12: Homogalacturonan oligosaccharides synthesized to date. Access to different patterns of methyl-ester...
Figure 13: GlfT2 from Mycobacterium tuberculosis catalyzes the sequential addition of UPD-Galf donor to a grow...
Figure 14: The poor reactivity of acceptor 137 hindered a stepwise synthesis of the linear galactan backbone a...
Scheme 18: AGA of a linear β(1–5) and β(1–6)-linked galactan 20mer. The AGA cycle includes coupling (NIS/TfOH)...
Figure 15: The 92mer arabinogalactan was synthesized using a [31 + 31 + 30] fragment coupling between a 31mer ...
Scheme 19: Synthesis of the branched arabinofuranose fragment using a six component one-pot synthesis. i) TTBP...
Figure 16: A) Chemical structure and SNFG of the representative disaccharide units forming the GAG backbones, ...
Figure 17: Synthetic challenges associated to the H/HS synthesis.
Scheme 20: Degradation of natural heparin and heparosan generated valuable disaccharides 150 and 151 that can ...
Scheme 21: A) The one-step conversion of cyanohydrin 156 to ʟ-iduronamide 157 represent the key step for the s...
Scheme 22: A) Chemoenzymatic synthesis of heparin structures, using different types of UDP activated natural a...
Scheme 23: Synthesis of the longest synthetic CS chain 181 (24mer) using donor 179 and acceptor 180 in an iter...
Scheme 24: AGA of a collection of HA with different lengths. The AGA cycle includes coupling (TfOH) and Lev de...
N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles
- Joseane A. Mendes,
- Paulo R. R. Costa,
- Miguel Yus,
- Francisco Foubelo and
- Camilla D. Buarque
Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86
- allylic bromides in the presence of zinc or indium metals is a well-known reaction [66][67]. It is possible to control and predict the stereochemistry of the addition to get the corresponding homoallylamine derivative with a high level of stereocontrol. The reaction of chiral imine 14 with an excess of
- stereoselective synthesis is especially interesting, highlighting the 1,3-dipolar cycloaddition reactions with azomethine ylides as an example of transformation that take place with great stereocontrol, and allow the synthesis of polyfunctionalized pyrrolidines in a single reaction step [91][92]. On the other
- carried out in the presence of the electrophile (chiral imine 79). Surprisingly, both diastereomeric aldimines 79 (RS and SS) gave similar results concerning the stereochemical outcome, suggesting that the chiral sulfonamide moiety was not involved in the stereocontrol during this tandem Barbier addition
Graphical Abstract
Scheme 1: General strategy for the enantioselective synthesis of N-containing heterocycles from N-tert-butane...
Scheme 2: Methodologies for condensation of aldehydes and ketones with tert-butanesulfinamides (1).
Scheme 3: Transition models for cis-aziridines and trans-aziridines.
Scheme 4: Mechanism for the reduction of N-tert-butanesulfinyl imines.
Scheme 5: Transition models for the addition of organomagnesium and organolithium compounds to N-tert-butanes...
Scheme 6: Synthesis of 2,2-dibromoaziridines 15 from aldimines 14 and bromoform, and proposed non-chelation-c...
Scheme 7: Diastereoselective synthesis of aziridines from tert-butanesulfinyl imines.
Scheme 8: Synthesis of vinylaziridines 22 from aldimines 14 and 1,3-dibromopropene 23, and proposed chelation...
Scheme 9: Synthesis of vinylaziridines 27 from aldimines 14 and α-bromoesters 26, and proposed transition sta...
Scheme 10: Synthesis of 2-chloroaziridines 28 from aldimines 14 and dichloromethane, and proposed transition s...
Scheme 11: Synthesis of cis-vinylaziridines 30 and 31 from aldimines 14 and bromomethylbutenolide 29.
Scheme 12: Synthesis of 2-chloro-2-aroylaziridines 36 and 32 from aldimines 14, arylnitriles 34, and silyldich...
Scheme 13: Synthesis of trifluoromethylaziridines 39 and proposed transition state of the aziridination.
Scheme 14: Synthesis of aziridines 42 and proposed state transition.
Scheme 15: Synthesis of 1-substituted 2-azaspiro[3.3]heptanes, 1-phenyl-2-azaspiro[3.4]octane and 1-phenyl-2-a...
Scheme 16: Synthesis of 1-substituted 2,6-diazaspiro[3.3]heptanes 48 from chiral imines 14 and 1-Boc-azetidine...
Scheme 17: Synthesis of β-lactams 52 from chiral imines 14 and dimethyl malonate (49).
Scheme 18: Synthesis of spiro-β-lactam 57 from chiral (RS)-N-tert-butanesulfinyl isatin ketimine 53 and ethyl ...
Scheme 19: Synthesis of β-lactam 60, a precursor of (−)-batzelladine D (61) and (−)-13-epi-batzelladine D (62)...
Scheme 20: Rhodium-catalyzed asymmetric synthesis of 3-substituted pyrrolidines 66 from chiral imine (RS)-63 a...
Scheme 21: Asymmetric synthesis of 1,3-disubstituted isoindolines 69 and 70 from chiral imine 67.
Scheme 22: Asymmetric synthesis of cis-2,5-disubstituted pyrrolidines 73 from chiral imine (RS)-71.
Scheme 23: Asymmetric synthesis of 3-hydroxy-5-substituted pyrrolidin-2-ones 77 from chiral imine (RS)-74.
Scheme 24: Asymmetric synthesis of 4-hydroxy-5-substituted pyrrolidin-2-ones 80 from chiral imines 79.
Scheme 25: Asymmetric synthesis of 3-pyrrolines 82 from chiral imines 14 and ethyl 4-bromocrotonate (81).
Scheme 26: Asymmetric synthesis of γ-amino esters 84, and tetramic acid derivative 86 from chiral imines (RS)-...
Scheme 27: Asymmetric synthesis of α-methylene-γ-butyrolactams 90 from chiral imines (Z,SS)-87 and ethyl 2-bro...
Scheme 28: Asymmetric synthesis of methylenepyrrolidines 92 from chiral imines (RS)-14 and 2-(trimethysilylmet...
Scheme 29: Synthesis of dibenzoazaspirodecanes from cyclic N-tert-butanesulfinyl imines.
Scheme 30: Stereoselective synthesis of cyclopenta[c]proline derivatives 103 from β,γ-unsaturated α-amino acid...
Scheme 31: Stereoselective synthesis of alkaloids (−)-angustureine (107) and (−)-cuspareine (108).
Scheme 32: Stereoselective synthesis of alkaloids (−)-pelletierine (112) and (+)-coniine (117).
Scheme 33: Synthesis of piperidine alkaloids (+)-dihydropinidine (122a), (+)-isosolenopsin (122b) and (+)-isos...
Scheme 34: Stereoselective synthesis of the alkaloids(+)-sedamine (125) from chiral imine (SS)-119.
Scheme 35: Stereoselective synthesis of trans-5-hydroxy-6-substituted-2-piperidinones 127 and 129 from chiral ...
Scheme 36: Stereoselective synthesis of trans-5-hydroxy-6-substituted ethanone-2-piperidinones 132 from chiral...
Scheme 37: Stereoselective synthesis of trans-3-benzyl-5-hydroxy-6-substituted-2-piperidinones 136 from chiral...
Scheme 38: Stereoselective synthesis of trans-5-hydroxy-6-substituted 2-piperidinones 139 from chiral imine 138...
Scheme 39: Stereoselective synthesis of ʟ-hydroxypipecolic acid 145 from chiral imine 144.
Scheme 40: Synthesis of 1-substituted isoquinolones 147, 149 and 151.
Scheme 41: Stereoselective synthesis of 3-substituted dihydrobenzo[de]isoquinolinones 154.
Scheme 42: Enantioselective synthesis of alkaloids (S)-1-benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (...
Scheme 43: Enantioselective synthesis of alkaloids (−)-cermizine B (171) and (+)-serratezomine E (172) develop...
Scheme 44: Stereoselective synthesis of (+)-isosolepnosin (177) and (+)-solepnosin (178) from homoallylamine d...
Scheme 45: Stereoselective synthesis of tetrahydroquinoline derivatives 184, 185 and 187 from chiral imines (RS...
Scheme 46: Stereoselective synthesis of pyridobenzofuran and pyridoindole derivatives 193 from homopropargylam...
Scheme 47: Stereoselective synthesis of 2-substituted 1,2,5,6-tetrahydropyridines 196 from chiral imines (RS)-...
Scheme 48: Stereoselective synthesis of 2-substituted trans-2,6-disubstituted piperidine 199 from chiral imine...
Scheme 49: Stereoselective synthesis of cis-2,6-disubstituted piperidines 200, and alkaloid (+)-241D, from chi...
Scheme 50: Stereoselective synthesis of 6-substituted piperidines-2,5-diones 206 and 1,7-diazaspiro[4.5]decane...
Scheme 51: Stereoselective synthesis of spirocyclic oxindoles 210 from chiral imines (RS)-53.
Scheme 52: Stereoselective synthesis of azaspiro compound 213 from chiral imine 211.
Scheme 53: Stereoselective synthesis of tetrahydroisoquinoline derivatives from chiral imines (RS)-214.
Scheme 54: Stereoselective synthesis of (−)-crispine A 223 from chiral imine (RS)-214.
Scheme 55: Synthesis of (−)-harmicine (228) using tert-butanesulfinamide through haloamide cyclization.
Scheme 56: Stereoselective synthesis of tetraponerines T1–T8.
Scheme 57: Stereoselective synthesis of phenanthroindolizidines 246a and (−)-tylophorine (246b), and phenanthr...
Scheme 58: Stereoselective synthesis of indoline, tetrahydroquinoline and tetrahydrobenzazepine derivatives 253...
Scheme 59: Stereoselective synthesis of (+)-epohelmin A (258) and (+)-epohelmin B (260) from aldimine (RS)-79.
Scheme 60: Stereoselective synthesis of (−)-epiquinamide (266) from chiral aldimine (SS)-261.
Scheme 61: Synthesis synthesis of (–)-hippodamine (273) and (+)-epi-hippodamine (272) using chiral sulfinyl am...
Scheme 62: Stereoselective synthesis of (+)-grandisine D (279) and (+)-amabiline (283).
Scheme 63: Stereoselective synthesis of (−)-epiquinamide (266) and (+)-swaisonine (291) from aldimine (SS)-126....
Scheme 64: Stereoselective synthesis of (+)-C(9a)-epi-epiquinamide (294).
Scheme 65: Stereoselective synthesis of (+)-lasubine II (298) from chiral aldimine (SS)-109.
Scheme 66: Stereoselective synthesis of (−)-epimyrtine (300a) and (−)-lasubine II (ent-302) from β-amino keton...
Scheme 67: Stereoselective synthesis of (−)-tabersonine (310), (−)-vincadifformine (311), and (−)-aspidospermi...
Scheme 68: Stereoselective synthesis of (+)-epohelmin A (258) and (+)-epohelmin B (260) from aldehyde 313 and ...
Scheme 69: Total synthesis of (+)-lysergic acid (323) from N-tert-butanesulfinamide (RS)-1.
Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years
- Asha Budakoti,
- Pradip Kumar Mondal,
- Prachi Verma and
- Jagadish Khamrai
Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77
- methyl ricinoleate (127) with various aldehydes to produce 2,3,6-trialkyl-substituted 4-chlorotetrahydropyran 128 with excellent stereocontrol in all-cis-configuration (Scheme 30) [66]. The stereochemical outcome of this cyclization was rationalized by a chair-like transition state to produce
- Alder’s chair-like transition state 227 in which the (Z)-alkene accounts for the trans-stereocontrol at the C3 position and equatorial iodide addition accounts for the cis-stereocontrol at the C4 position, as shown below in Scheme 54. The one-pot synthesis of tetrahydropyran by utilizing the Babier–Prins
Graphical Abstract
Scheme 1: General strategy for the synthesis of THPs.
Scheme 2: Developments towards the Prins cyclization.
Scheme 3: General stereochemical outcome of the Prins cyclization.
Scheme 4: Regioselectivity in the Prins cyclization.
Scheme 5: Mechanism of the oxonia-Cope reaction in the Prins cyclization.
Scheme 6: Cyclization of electron-deficient enantioenriched alcohol 27.
Scheme 7: Partial racemization through 2-oxonia-Cope allyl transfer.
Scheme 8: Partial racemization by reversible 2-oxonia-Cope rearrangement.
Scheme 9: Rychnovsky modification of the Prins cyclization.
Scheme 10: Synthesis of (−)-centrolobine and the C22–C26 unit of phorboxazole A.
Scheme 11: Axially selective Prins cyclization by Rychnovsky et al.
Scheme 12: Mechanism for the axially selectivity Prins cyclization.
Scheme 13: Mukaiyama aldol–Prins cyclization reaction.
Scheme 14: Application of the aldol–Prins reaction.
Scheme 15: Hart and Bennet's acid-promoted Prins cyclization.
Scheme 16: Tetrahydropyran core of polycarvernoside A as well as (−)-clavoslide A and D.
Scheme 17: Scheidt and co-workers’ route to tetrahydropyran-4-one.
Scheme 18: Mechanism for the Lewis acid-catalyzed synthesis of tetrahydropyran-4-one.
Scheme 19: Hoveyda and co-workers’ strategy for 2,6-disubstituted 4-methylenetetrahydropyran.
Scheme 20: Funk and Cossey’s ene-carbamates strategy.
Scheme 21: Yadav and Kumar’s cyclopropane strategy for THP synthesis.
Scheme 22: 2-Arylcylopropylmethanolin in centrolobine synthesis.
Scheme 23: Yadav and co-workers’ strategy for the synthesis of THP.
Scheme 24: Yadav and co-workers’ Prins–Ritter reaction sequence for 4-amidotetrahydropyran.
Scheme 25: Yadav and co-workers’ strategy to prelactones B, C, and V.
Scheme 26: Yadav and co-workers’ strategy for the synthesis of (±)-centrolobine.
Scheme 27: Loh and co-workers’ strategy for the synthesis of zampanolide and dactylolide.
Scheme 28: Loh and Chan’s strategy for THP synthesis.
Scheme 29: Prins cyclization of cyclohexanecarboxaldehyde.
Scheme 30: Prins cyclization of methyl ricinoleate (127) and benzaldehyde (88).
Scheme 31: AlCl3-catalyzed cyclization of homoallylic alcohol 129 and aldehyde 130.
Scheme 32: Martín and co-workers’ stereoselective approach for the synthesis of highly substituted tetrahydrop...
Scheme 33: Ene-IMSC strategy by Marko and Leroy for the synthesis of tetrahydropyran.
Scheme 34: Marko and Leroy’s strategy for the synthesis of tetrahydropyrans 146.
Scheme 35: Sakurai dimerization/macrolactonization reaction for the synthesis of cyanolide A.
Scheme 36: Hoye and Hu’s synthesis of (−)-dactyloide by intramolecular Sakurai cyclization.
Scheme 37: Minehan and co-workers’ strategy for the synthesis of THPs 157.
Scheme 38: Yu and co-workers’ allylic transfer strategy for the construction of tetrahydropyran 161.
Scheme 39: Reactivity enhancement in intramolecular Prins cyclization.
Scheme 40: Floreancig and co-workers’ Prins cyclization strategy to (+)-dactyloide.
Scheme 41: Panek and Huang’s DHP synthesis from crotylsilanes: a general strategy.
Scheme 42: Panek and Huang’s DHP synthesis from syn-crotylsilanes.
Scheme 43: Panek and Huang’s DHP synthesis from anti-crotylsilanes.
Scheme 44: Roush and co-workers’ [4 + 2]-annulation strategy for DHP synthesis [82].
Scheme 45: TMSOTf-promoted annulation reaction.
Scheme 46: Dobb and co-workers’ synthesis of DHP.
Scheme 47: BiBr3-promoted tandem silyl-Prins reaction by Hinkle et al.
Scheme 48: Substrate scope of Hinkle and co-workers’ strategy.
Scheme 49: Cho and co-workers’ strategy for 2,6 disubstituted 3,4-dimethylene-THP.
Scheme 50: Furman and co-workers’ THP synthesis from propargylsilane.
Scheme 51: THP synthesis from silyl enol ethers.
Scheme 52: Rychnovsky and co-workers’ strategy for THP synthesis from hydroxy-substituted silyl enol ethers.
Scheme 53: Li and co-workers’ germinal bissilyl Prins cyclization strategy to (−)-exiguolide.
Scheme 54: Xu and co-workers’ hydroiodination strategy for THP.
Scheme 55: Wang and co-workers’ strategy for tetrahydropyran synthesis.
Scheme 56: FeCl3-catalyzed synthesis of DHP from alkynylsilane alcohol.
Scheme 57: Martín, Padrón, and co-workers’ proposed mechanism of alkynylsilane Prins cyclization for the synth...
Scheme 58: Marko and co-workers’ synthesis of 2,6-anti-configured tetrahydropyran.
Scheme 59: Loh and co-workers’ strategy for 2,6-syn-tetrahydropyrans.
Scheme 60: Loh and co-workers’ strategy for anti-THP synthesis.
Scheme 61: Cha and co-workers’ strategy for trans-2,6-tetrahydropyran.
Scheme 62: Mechanism proposed by Cha et al.
Scheme 63: TiCl4-mediated cyclization to trans-THP.
Scheme 64: Feng and co-workers’ FeCl3-catalyzed Prins cyclization strategy to 4-hydroxy-substituted THP.
Scheme 65: Selectivity profile of the Prins cyclization under participation of an iron ligand.
Scheme 66: Sequential reactions involving Prins cyclization.
Scheme 67: Banerjee and co-workers’ strategy of Prins cyclization from cyclopropane carbaldehydes and propargy...
Scheme 68: Mullen and Gagné's (R)-[(tolBINAP)Pt(NC6F5)2][SbF6]2-catalyzed asymmetric Prins cyclization strateg...
Scheme 69: Yu and co-workers’ DDQ-catalyzed asymmetric Prins cyclization strategy to trisubstituted THPs.
Scheme 70: Lalli and Weghe’s chiral-Brønsted-acid- and achiral-Lewis-acid-promoted asymmetric Prins cyclizatio...
Scheme 71: List and co-workers’ iIDP Brønsted acid-promoted asymmetric Prins cyclization strategy.
Scheme 72: Zhou and co-workers’ strategy for chiral phosphoric acid (CPA)-catalyzed cascade Prins cyclization.
Scheme 73: List and co-workers’ approach for asymmetric Prins cyclization using chiral imidodiphosphoric acid ...
Synthetic reactions driven by electron-donor–acceptor (EDA) complexes
- Zhonglie Yang,
- Yutong Liu,
- Kun Cao,
- Xiaobin Zhang,
- Hezhong Jiang and
- Jiahong Li
Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67
- protocol reveals a high functional-group tolerance that permits the transformation into boronic esters of natural alcohol products with high stereocontrol. The construction of C–N bonds The development of efficient methods to construct C–N bonds is an essential scheme in organic synthesis due to its
Graphical Abstract
Scheme 1: The electron transfer process in EDA complexes.
Scheme 2: Synthesis of benzo[b]phosphorus oxide 3 initiated by an EDA complex.
Scheme 3: Mechanism of the synthesis of quinoxaline derivative 7.
Scheme 4: Synthesis of imidazole derivative 10 initiated by an EDA complex.
Scheme 5: Synthesis of sulfamoylation product 12 initiated by an EDA complex.
Scheme 6: Mechanism of the synthesis of sulfamoylation product 12.
Scheme 7: Synthesis of indole derivative 22 initiated by an EDA complex.
Scheme 8: Synthesis of perfluoroalkylated pyrimidines 26 initiated by an EDA complex.
Scheme 9: Synthesis of phenanthridine derivative 29 initiated by an EDA complex.
Scheme 10: Synthesis of cis-tetrahydroquinoline derivative 32 initiated by an EDA complex.
Scheme 11: Mechanism of the synthesis of cis-tetrahydroquinoline derivative 32.
Scheme 12: Synthesis of phenanthridine derivative 38 initiated by an EDA complex.
Scheme 13: Synthesis of spiropyrroline derivative 40 initiated by an EDA complex.
Scheme 14: Synthesis of benzothiazole derivative 43 initiated by an EDA complex.
Scheme 15: Synthesis of perfluoroalkyl-s-triazine derivative 45 initiated by an EDA complex.
Scheme 16: Synthesis of indoline derivative 47 initiated by an EDA complex.
Scheme 17: Mechanism of the synthesis of spirocyclic indoline derivative 47.
Scheme 18: Synthesis of cyclobutane product 50 initiated by an EDA complex.
Scheme 19: Mechanism of the synthesis of spirocyclic indoline derivative 50.
Scheme 20: Synthesis of 1,3-oxazolidine compound 59 initiated by an EDA complex.
Scheme 21: Synthesis of trifluoromethylated product 61 initiated by an EDA complex.
Scheme 22: Synthesis of indole alkylation product 64 initiated by an EDA complex.
Scheme 23: Synthesis of perfluoroalkylation product 67 initiated by an EDA complex.
Scheme 24: Synthesis of hydrotrifluoromethylated product 70 initiated by an EDA complex.
Scheme 25: Synthesis of β-trifluoromethylated alkyne product 71 initiated by an EDA complex.
Scheme 26: Mechanism of the synthesis of 2-phenylthiophene derivative 74.
Scheme 27: Synthesis of allylated product 80 initiated by an EDA complex.
Scheme 28: Synthesis of trifluoromethyl-substituted alkynyl product 84 initiated by an EDA complex.
Scheme 29: Synthesis of dearomatized fluoroalkylation product 86 initiated by an EDA complex.
Scheme 30: Mechanism of the synthesis of dearomatized fluoroalkylation product 86.
Scheme 31: Synthesis of C(sp3)–H allylation product 91 initiated by an EDA complex.
Scheme 32: Synthesis of perfluoroalkylation product 93 initiated by an EDA complex.
Scheme 33: Synthesis of spirocyclic indolene derivative 95 initiated by an EDA complex.
Scheme 34: Synthesis of perfluoroalkylation product 97 initiated by an EDA complex.
Scheme 35: Synthesis of alkylated indole derivative 100 initiated by an EDA complex.
Scheme 36: Mechanism of the synthesis of alkylated indole derivative 100.
Scheme 37: Synthesis of arylated oxidized indole derivative 108 initiated by an EDA complex.
Scheme 38: Synthesis of 4-ketoaldehyde derivative 111 initiated by an EDA complex.
Scheme 39: Mechanism of the synthesis of 4-ketoaldehyde derivative 111.
Scheme 40: Synthesis of perfluoroalkylated olefin 118 initiated by an EDA complex.
Scheme 41: Synthesis of alkylation product 121 initiated by an EDA complex.
Scheme 42: Synthesis of acylation product 123 initiated by an EDA complex.
Scheme 43: Mechanism of the synthesis of acylation product 123.
Scheme 44: Synthesis of trifluoromethylation product 126 initiated by an EDA complex.
Scheme 45: Synthesis of unnatural α-amino acid 129 initiated by an EDA complex.
Scheme 46: Synthesis of thioether derivative 132 initiated by an EDA complex.
Scheme 47: Synthesis of S-aryl dithiocarbamate product 135 initiated by an EDA complex.
Scheme 48: Mechanism of the synthesis of S-aryl dithiocarbamate product 135.
Scheme 49: Synthesis of thioether product 141 initiated by an EDA complex.
Scheme 50: Mechanism of the synthesis of borate product 144.
Scheme 51: Synthesis of boronation product 148 initiated by an EDA complex.
Scheme 52: Synthesis of boration product 151 initiated by an EDA complex.
Scheme 53: Synthesis of boronic acid ester derivative 154 initiated by an EDA complex.
Scheme 54: Synthesis of β-azide product 157 initiated by an EDA complex.
Scheme 55: Decarboxylation reaction initiated by an EDA complex.
Scheme 56: Synthesis of amidated product 162 initiated by an EDA complex.
Scheme 57: Synthesis of diethyl phenylphosphonate 165 initiated by an EDA complex.
Scheme 58: Mechanism of the synthesis of diethyl phenylphosphonate derivative 165.
Scheme 59: Synthesis of (Z)-2-iodovinyl phenyl ether 168 initiated by an EDA complex.
Scheme 60: Mechanism of the synthesis of (Z)-2-iodovinyl phenyl ether derivative 168.
Scheme 61: Dehalogenation reaction initiated by an EDA complex.
α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams
- Mikhail K. Klychnikov,
- Radek Pohl,
- Ivana Císařová and
- Ullrich Jahn
Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58
- -diastereoselectivity. Opposite absolute configurations in both components, 7 and 8, are displaying a synergistic effect for optimal stereocontrol in the radical oxygenation step with TEMPO (3). A good diastereoselectivity of the oxygenation was also observed for the formation of 9l (cf. Table 2). Assuming a preferred
Graphical Abstract
Figure 1: Selected alkaloids containing the pyrrolidone motif.
Scheme 1: A) Classical γ-lactam synthesis by atom transfer radical cyclizations; B) previously developed tand...
Figure 2: X-ray crystal structure of the major (2R,4S)-alkoxyamine hydrochloride derived from 9j. Displacemen...
Scheme 2: Formation of the α-(aminoxy)amides 9o,p.
Figure 3: X-ray crystal structure of the minor cis-diastereomers of the keto lactam 13j (left) and the hydrox...
Scheme 3: Thermal radical cyclization reactions of amides 9l–p bearing cyclic units. Conditions: a) t-BuOH, 1...
Scheme 4: Epimerization of spirolactams 12m,n.
Scheme 5: The Dess–Martin oxidation of lactams 12l–o. Conditions: a) DMP (1.3 equiv), t-BuOH (10 mol %), CH2Cl...
Scheme 6: Selected transformations of the lactams trans-12b and 12o.
Scheme 7: Diastereoselectivity for the formation of α-(aminoxy)amides 9i–k.
Scheme 8: Rationalization of the diastereoselectivity for the formation of the α-(aminoxy)amide 9l.
Scheme 9: Rationalization of the thermal radical cyclization diastereoselectivity of alkoxyamines 9a–k. (S)-C...
Scheme 10: The stereochemical course for the formation of products 12m,n by thermal radical cyclization of alk...
Scheme 11: Formation of bicycles 12o,p.
Progress in the total synthesis of inthomycins
- Bidyut Kumar Senapati
Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7
- -catalyzed hydroboration of the terminal acetylene in 127 gave (E,E)-128 in good yield and with complete stereocontrol (Scheme 18). To accomplish the key Suzuki coupling of dienylboronic ester 128, the necessary alkenyl iodides (Z)- and (E)-130 were prepared from the propargyl alcohol (14) in good yields
Graphical Abstract
Figure 1: The inthomycins A–C (1–3) and structurally closely related compounds.
Figure 2: Syntheses of inthomycins A–C (1–3).
Scheme 1: The first total synthesis of racemic inthomycin A (rac)-1 by Whiting.
Scheme 2: Moloney’s synthesis of the phenyl analogue of inthomycin C ((rac)-3).
Scheme 3: Moloney’s synthesis of phenyl analogues of inthomycins A (rac-1) and B (rac-2).
Scheme 4: The first total synthesis of inthomycin B (+)-2 by R. J. K. Taylor.
Scheme 5: R. J. K. Taylor’s total synthesis of racemic inthomycin A (rac)-1.
Scheme 6: The first total synthesis of inthomycin C ((+)-3) by R. J. K. Taylor.
Scheme 7: The first total synthesis of naturally occurring inthomycin C ((–)-3) by Ryu et al.
Scheme 8: Preparation of E,E-iododiene (+)-84 and Z,E- iododiene 85a.
Scheme 9: Hatakeyama’s total synthesis of inthomycin A (+)-1 and inthomycin B (+)-2.
Scheme 10: Hatakeyama’s total synthesis of inthomycin C ((–)-3).
Scheme 11: Maulide’s formal synthesis of racemic inthomycin C ((rac)-3).
Scheme 12: Hale’s synthesis of dienylstannane (+)-69 and enyne (+)-82b intermediates.
Scheme 13: Hale’s total synthesis of inthomycin C ((+)-3).
Scheme 14: Hale and Hatakeyama’s resynthesis of (3R)-inthomycin C (−)-3 Mosher esters.
Scheme 15: Reddy’s formal syntheses of inthomycin C (+)-3 and inthomycin C ((−)-3).
Scheme 16: Synthesis of the cross-metathesis precursors (rac)-118 and 121.
Scheme 17: Donohoe’s total synthesis of inthomycin C ((−)-3).
Scheme 18: Synthesis of dienylboronic ester (E,E)-128.
Scheme 19: Synthesis of the alkenyl iodides (Z)- and (E)-130.
Scheme 20: Burton’s total synthesis of inthomycin B ((+)-2).
Scheme 21: Burton’s total synthesis of inthomycin C ((−)-3).
Scheme 22: Burton’s total synthesis of inthomycin A ((+)-1).
Scheme 23: Synthesis of common intermediate (Z)-(+)-143a.
Scheme 24: Synthesis of (Z)-and (E)-selective fragments (+)-145a–c.
Scheme 25: Kim’s total synthesis of inthomycins A (+)-1 and B (+)-2.
Scheme 26: Completion of total synthesis of inthomycin C ((–)-3) by Kim.
All-carbon [3 + 2] cycloaddition in natural product synthesis
- Zhuo Wang and
- Junyang Liu
Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251
- enantioselective synthesis of marcfortine C (9, Scheme 4B). Another brilliant example is the development of a chiral-phosphine-catalyzed [3 + 2] annulation reported by Lu in 2019, in which the chiral phosphine catalyst confers high stereocontrol on the formation of a spiro adduct bearing two vicinal all-carbon
Graphical Abstract
Figure 1: Highly-substituted five-membered carbocycle in biologically significant natural products.
Figure 2: Natural product synthesis featuring the all-carbon [3 + 2] cycloaddition. (Quaternary carbon center...
Scheme 1: Representative natural product syntheses that feature the all-carbon [3 + 2] cyclization as the key...
Scheme 2: (A) An intramolecular trimethylenemethane diyl [3 + 2] cycloaddition with allenyl diazo compound 38...
Scheme 3: (A) Palladium-catalyzed intermolecular carboxylative TMM cycloaddition [36]. (B) The proposed mechanism....
Scheme 4: Natural product syntheses that make use of palladium-catalyzed intermolecular [3 + 2] cycloaddition...
Scheme 5: (A) Phosphine-catalyzed [3 + 2] cycloaddition [17]. (B) The proposed mechanism.
Scheme 6: Lu’s [3 + 2] cycloaddition in natural product synthesis. (A) Synthesis of longeracinphyllin A (10) [41]...
Scheme 7: (A) Phosphine-catalyzed [3 + 2] annulation of unsymmetric isoindigo 100 with allene in the preparat...
Scheme 8: (A) Rhodium-catalyzed intracmolecular [3 + 2] cycloaddition [49]. (B) The proposed catalytic cycle of t...
Scheme 9: Total synthesis of natural products reported by Yang and co-workers applying rhodium-catalyzed intr...
Scheme 10: (A) Platinum(II)-catalyzed intermolecular [3 + 2] cycloaddition of propargyl ether 139 and n-butyl ...
Scheme 11: (A) Platinum-catalyzed intramolecular [3 + 2] cycloaddition of propargylic ketal derivative 142 to ...
Scheme 12: (A) Synthesis of phyllocladanol (21) features a Lewis acid-catalyzed formal intramolecular [3 + 2] ...
Scheme 13: The recent advances of [3 + 2] annulation in natural product synthesis. (A) The preparation of melo...
