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Search for "natural product synthesis" in Full Text gives 86 result(s) in Beilstein Journal of Organic Chemistry.
A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates
- Olusesan K. Koleoso,
- Matthew Turner,
- Felix Plasser and
- Marc C. Kimber
Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165
- innovative transformations, including cycloadditions [5][6][7][8][9], intramolecular cyclizations and intermolecular addition reactions [10][11][12][13][14][15][16][17][18], as well as the use of the allenamide building block in natural product synthesis [1]. Addition reactions of allenamides, which can also
Graphical Abstract
Scheme 1: Electrophilic activation of allenamides.
Scheme 2: The planned intramolecular radical addition to allenamides generating the conjugated N-acyliminium ...
Scheme 3: Photoredox Ir-catalyzed intermolecular addition of bromide 18 and aniline 16 to allenamide 15.
Scheme 4: Reaction scope (a) allenamide; (b) arylamine nucleophile; (c) alcohol nucleophile.
Scheme 5: (a) Tentative mechanism for the photoredox-catalyzed formation of the conjugated N-acyliminium inte...
Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations
- Rafia Siddiqui and
- Rashid Ali
Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26
- for modern synthetic chemistry, and we believe that the application in natural product synthesis and meta functionalization is highly desirable. In addition to this, to provide high selectivities and to allow for the combination of dual photoredox catalysis with HAT, the discovery of more effective
Graphical Abstract
Figure 1: List of photoredox catalysts used for C–H bond functionalizations.
Figure 2: List of metal-based photoredox catalysts used in this review article.
Figure 3: Jablonski diagram.
Figure 4: Photoredox catalysis via reductive or oxidative pathways. D = donor, A = acceptor, S = substrate, P...
Figure 5: Schematic representation of the combination of photoredox catalysis and transition metal catalysis.
Scheme 1: Weinreb amide C–H olefination.
Figure 6: Mechanism for the formation of 21 from 19 using photoredox catalyst 11.
Scheme 2: C–H olefination of phenolic ethers.
Scheme 3: Decarboxylative acylation of acetanilides.
Figure 7: Mechanism for the formation of 30 from acetanilide derivatives.
Scheme 4: Synthesis of fluorenone derivatives by intramolecular deoxygenative acylation of biaryl carboxylic ...
Figure 8: Mechanism for the photoredox-catalyzed synthesis of fluorenone derivatives.
Scheme 5: Synthesis of benzothiazoles via aerobic C–H thiolation.
Figure 9: Plausible mechanism for the construction of benzothiazoles from benzothioamides.
Scheme 6: Synthesis of benzothiazoles via oxidant-free C–H thiolation.
Figure 10: Mechanism involved in the synthesis of benzothiazoles via oxidant-free C–H thiolation.
Scheme 7: Synthesis of indoles via C–H cyclization of anilides with alkynes.
Scheme 8: Preparation of 3-trifluoromethylcoumarins via C–H cyclization of arylpropiolate esters.
Figure 11: Mechanistic pathway for the synthesis of coumarin derivatives via C–H cyclization.
Scheme 9: Monobenzoyloxylation without chelation assistance.
Figure 12: Plausible mechanism for the formation of 71 from 70.
Scheme 10: Aryl-substituted arenes prepared by inorganic photoredox catalysis using 12a.
Figure 13: Proposed mechanism for C–H arylations in the presence of 12a and a Pd catalyst.
Scheme 11: Arylation of purines via dual photoredox catalysis.
Scheme 12: Arylation of substituted arenes with an organic photoredox catalyst.
Scheme 13: C–H trifluoromethylation.
Figure 14: Proposed mechanism for the trifluoromethylation of 88.
Scheme 14: Synthesis of benzo-3,4-coumarin derivatives.
Figure 15: Plausible mechanism for the synthesis of substituted coumarins.
Scheme 15: Oxidant-free oxidative phosphonylation.
Figure 16: Mechanism proposed for the phosphonylation reaction of 100.
Scheme 16: Nitration of anilines.
Figure 17: Plausible mechanism for the nitration of aniline derivatives via photoredox catalysis.
Scheme 17: Synthesis of carbazoles via intramolecular amination.
Figure 18: Proposed mechanism for the formation of carbazoles from biaryl derivatives.
Scheme 18: Synthesis of substituted phenols using QuCN.
Figure 19: Mechanism for the synthesis of phenol derivatives with photoredox catalyst 8.
Scheme 19: Synthesis of substituted phenols with DDQ (5).
Figure 20: Possible mechanism for the generation of phenols with the aid of photoredox catalyst 5.
Scheme 20: Aerobic bromination of arenes using an acridinium-based photocatalyst.
Scheme 21: Aerobic bromination of arenes with anthraquinone.
Figure 21: Proposed mechanism for the synthesis of monobrominated compounds.
Scheme 22: Chlorination of benzene derivatives with Mes-Acr-MeClO4 (2).
Figure 22: Mechanism for the synthesis of 131 from 132.
Scheme 23: Chlorination of arenes with 4CzIPN (5a).
Figure 23: Plausible mechanism for the oxidative photocatalytic monochlorination using 5a.
Scheme 24: Monofluorination using QuCN-ClO4 (8).
Scheme 25: Fluorination with fluorine-18.
Scheme 26: Aerobic amination with acridinium catalyst 3a.
Figure 24: Plausible mechanism for the aerobic amination using acridinium catalyst 3a.
Scheme 27: Aerobic aminations with semiconductor photoredox catalyst 18.
Scheme 28: Perfluoroalkylation of arenes.
Scheme 29: Synthesis of benzonitriles in the presence of 3a.
Figure 25: Plausible mechanism for the synthesis of substituted benzonitrile derivatives in the presence of 3a....
Formation of alkyne-bridged ferrocenophanes using ring-closing alkyne metathesis on 1,1’-diacetylenic ferrocenes
- Celine Bittner,
- Dirk Bockfeld and
- Matthias Tamm
Beilstein J. Org. Chem. 2019, 15, 2534–2543, doi:10.3762/bjoc.15.246
- alkyne metatheses. A selection of such complexes is shown in Figure 1. Molybdenum alkylidyne complex I with siloxide ligands (X = OSiPh3) [10][11] is widely used in natural product synthesis, predominantly through ring-closing alkyne metathesis (RCAM) [12][13][14][15][16][17][18][19][20]. The metathesis
Graphical Abstract
Figure 1: Well-defined catalysts for alkyne metathesis.
Figure 2: Examples for a ferrrocenic thiacrown ether complexing palladium (IV), and a dicationic ferrocenopha...
Scheme 1: Synthesis of substrates 1 (a n = 2; b n = 3) via esterification of 3 and following RCAM with cataly...
Figure 3: ORTEP diagram of 1a with thermal displacement parameters drawn at 50% probability; hydrogen atoms a...
Figure 4: ORTEP diagram of 1b with thermal displacement parameters drawn at 50% probability; hydrogen atoms a...
Figure 5: ORTEP diagram of 2a with thermal displacement parameters drawn at 50% probability; hydrogen atoms a...
Figure 6: ORTEP diagram of 2b (one of two molecules of the asymmetric unit) with thermal displacement paramet...
Figure 7: Cyclic voltammogram of 2a in DCM, 0.2 M n-Bu4NPF6, 1 V s−1 scan rate, referenced vs FcH/FcH +.
Scheme 2: Top: Oxidation of ferrocenophane 2a to the corresponding ferrocenium cation 4 with Ag(SbF6) in DCM ...
Figure 8: ORTEP diagram of 4 with thermal displacement drawn at 50% probability; hydrogen atoms are omitted f...
Figure 9: 1H NMR (200.1 MHz, 298 K) spectrum of top: 2a in CDCl3; bottom: 5 in THF-d8 – signals for solvate T...
Figure 10: ORTEP diagram of 5(thf) with thermal displacement drawn at 50% probability; hydrogens atoms, [SbF6]−...
An overview of the cycloaddition chemistry of fulvenes and emerging applications
- Ellen Swan,
- Kirsten Platts and
- Anton Blencowe
Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209
- synthetically interesting scaffolds have been synthesised, including products which exhibit biological activity, complex ligands in coordination chemistry, and several natural product skeletons (Table 3). Applications of fulvene cycloadditions Organic and natural product synthesis A variety of organic molecules
- al. developed a programmable enantioselective one-pot synthesis of molecules with eight stereocentres greatly improving the efficiency of natural product synthesis [83]. Each of these natural products are biologically active, hence their total synthesis will allow further characterisation of their
- fuelled advances in organic and natural product synthesis, dynamic combinatorial chemistry and materials science, including dynamers, hydrogels and charge transfer complexes. The recent advances show that potential applications for fulvene cycloaddition reactions are varied and wide in scope. We believe
Graphical Abstract
Figure 1: General structure of fulvenes, named according to the number of carbon atoms in their ring. Whilst ...
Figure 2: Generic structures of commonly referenced heteropentafulvenes, named according to the heteroatom su...
Scheme 1: Resonance structures of (a) pentafulvene and (b) heptafulvene showing neutral (1 and 2), dipolar (1a...
Scheme 2: Resonance structures of (a) pentafulvenes and (b) heptafulvenes showing the influence of EDG and EW...
Scheme 3: Reaction of 6,6-dimethylpentafulvene with singlet state oxygen to form an enol lactone via the mult...
Scheme 4: Photosensitized oxygenation of 8-cyanoheptafulvene with singlet state oxygen to afford 1,4-epidioxi...
Figure 3: A representation of HOMO–LUMO orbitals of pentafulvene and the influence of EWG and EDG substituent...
Scheme 5: Reactions of (a) 6,6-dimethylpentafulvene participating as 2π and 4π components in cycloadditions w...
Scheme 6: Proposed mechanism for the [6 + 4] cycloaddition of tropone with dimethylfulvene via an ambimodal [...
Scheme 7: Triafulvene dimerization through the proposed 'head-to-tail' mechanism. The dipolar transition stat...
Scheme 8: Dimerization of pentafulvenes via a Diels–Alder cycloaddition pathway whereby one fulvene acts as a...
Scheme 9: Dimerization of pentafulvenes via frustrated Lewis pair chemistry as reported by Mömming et al. [116].
Scheme 10: Simplified reaction scheme for the formation of kempane from an extended-chain pentafulvene [127].
Scheme 11: The enantioselective (>99% ee), asymmetric, catalytic, intramolecular [6 + 2] cycloaddition of fulv...
Scheme 12: Intramolecular [8 + 6] cycloaddition of the heptafulvene-pentafulvene derivative [22,27].
Scheme 13: Reaction scheme for (a) [2 + 2] cycloaddition of 1,2-diphenylmethylenecyclopropene and 1-diethylami...
Scheme 14: Diels–Alder cycloaddition of pentafulvenes derivatives participating as dienes with (i) maleimide d...
Scheme 15: Generic schemes showing pentafulvenes participating as dienophiles in Diels–Alder cycloadditions wi...
Scheme 16: Reaction of 8,8-dicyanoheptafulvene and styrene derivatives to afford [8 + 2] and [4 + 2] cycloaddu...
Scheme 17: Reaction of 6-aminofulvene and maleic anhydride, showing observed [6 + 2] cycloaddition; the [4 + 2...
Scheme 18: Schemes for Diels–Alder cycloadditions in dynamic combinatorial chemistry reported by Boul et al. R...
Scheme 19: Polymerisation and dynamer formation via Diels–Alder cycloaddition between fulvene groups in polyet...
Scheme 20: Preparation of hydrogels via Diels–Alder cycloaddition with fulvene-conjugated dextran and dichloro...
Scheme 21: Ring-opening metathesis polymerisation of norbornene derivatives derived from fulvenes and maleimid...
Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides
- Madhu Babu Tatina,
- Xia Mengxin,
- Rao Peilin and
- Zaher M. A. Judeh
Beilstein J. Org. Chem. 2019, 15, 1275–1280, doi:10.3762/bjoc.15.125
- blocks especially for natural product synthesis [36][37][38][39][40]. Therefore, we used the perfluorophenyl boronic acid catalyst in the reaction between 2,3,4,6-tetra-O-acetyl-D-glucal (1a) and benzyl alcohol, n-butyl alcohol, cyclohexyl alcohol and p-toluenethiol (Figure 2). Gratifyingly, the reaction
Graphical Abstract
Figure 1: Perfluorophenylboronic acid-catalyzed reaction between 3,4,6-tri-O-acetyl-D-glucal 1a and O-, C-, S...
Figure 2: Perfluorophenylboronic acid-catalyzed reaction between 2,3,4,6-tetra-O-acetyl-D-glucal 4a and O- an...
Figure 3: Perfluorophenylboronic-acid-catalyzed reaction between 3,4-di-O-acetyl-L-rhamnal (6a) and O- and S-...
Figure 4: Plausible perfluorophenylboronic acid-catalyzed activation of glycal 1a.
A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction
- Yue Zhong,
- Wen-Yu Wu,
- Shao-Peng Yu,
- Tian-Yuan Fan,
- Hai-Tao Yu,
- Nian-Guang Li,
- Zhi-Hao Shi,
- Yu-Ping Tang and
- Jin-Ao Duan
Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26
- reactivity, shorter reaction times, and higher yields of the target compounds. Meanwhile, these flexible approaches to the phenanthrene derivatives would be expected to provide significant references to material chemistry, pharmaceutical agents and natural product synthesis. Experimental General remarks All
Graphical Abstract
Figure 1: Representative natural products containing a phenanthrene moiety.
Scheme 1: Different methods for the synthesis of phenanthrene derivatives.
Scheme 2: Substrate scope with various aryl iodides. Reaction conditions: 1 (0.3 mmol, 1.0 equiv), 2a (0.36 m...
Scheme 3: Scope of the reaction in terms of ortho-bromobenzoyl chlorides. Reaction conditions: 1a (0.3 mmol, ...
Scheme 4: Gram scale synthesis of z-6.
Scheme 5: Proposed mechanism for the formation of phenanthrene derivatives.
Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step
- Pierre-Antoine Nocquet,
- Aurélie Macé,
- Frédéric Legros,
- Jacques Lebreton,
- Gilles Dujardin,
- Sylvain Collet,
- Arnaud Martel,
- Bertrand Carboni and
- François Carreaux
Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274
- glycal scaffolds are versatile building blocks with multiple applications in the field of natural product synthesis [6], the development of new asymmetric synthetic sequences with stereochemical diversity is still of high interest. Different approaches have been reported for the asymmetric synthesis of
Graphical Abstract
Figure 1: N,N-Dimethyl-L-vancosamine as substructure of kidamycin and pluramycin.
Figure 2: Glycals as relevant scaffolds for constructing aryl C-glycosidic linkage.
Figure 3: Strategy including a ring-closing metathesis of vinyl ethers as key step for the preparation of sev...
Scheme 1: Evans aldol reaction for the preparation of diastereomeric compounds 13a and 13b.
Scheme 2: Alternative preparation of 13b based on a diastereoselective allylboration.
Scheme 3: O-Vinylation-ring-closing metathesis sequence for access to 3-amino glycals.
Scheme 4: Synthesis of key intermediate 23 for the C-3 unbranched amino glycals preparation.
Scheme 5: Access to diastereoisomeric compounds 3 and 4 from 23.
The mechanochemical synthesis of quinazolin-4(3H)-ones by controlling the reactivity of IBX
- Md Toufique Alam,
- Saikat Maiti and
- Prasenjit Mal
Beilstein J. Org. Chem. 2018, 14, 2396–2403, doi:10.3762/bjoc.14.216
- highlights the advancement of quinazolin-4(3H)-ones synthesis chemistry and may find application in the context of mechanochemical reactions towards natural product synthesis and pharmaceutical chemistry. Experimental General methods. Ball-milling experiments were carried out open to atmosphere and at room
Graphical Abstract
Figure 1: a) Explosion was observed when an arylamine was mixed with aldehydes in the presence of IBX. b) Ben...
Figure 2: Comparison of the current work with the existing literature reports.
Figure 3: Synthesis of quinazolin-4(3H)-one derivatives from the reaction of 1 with liquid aldehydes. aYields...
Figure 4: Synthesis of quinazolin-4(3H)-one derivatives from reaction of 1 and solid aldehydes. aYields with ...
Figure 5: Crystal structure of 3a (CCDC No. 1823611).
Figure 6: Plausible mechanism for the quinazolin-4(3H)-ones synthesis using IBX.
Scheme 1: Large scale synthesis of 3a.
Bi-mediated allylation of aldehydes in [bmim][Br]: a mechanistic investigation
- Mrunesh Koli,
- Sucheta Chatterjee,
- Subrata Chattopadhyay and
- Dibakar Goswami
Beilstein J. Org. Chem. 2018, 14, 2198–2203, doi:10.3762/bjoc.14.193
- ]; ionic liquid; Introduction The metal-mediated Barbier-type allylation of aldehydes has drawn considerable attention, because the resultant homoallylic alcohols are versatile intermediates for natural product synthesis [1][2][3][4][5][6][7]. The reaction, carried out in organic solvents, water, mixed
Graphical Abstract
Scheme 1: Bi-mediated allylation of aldehydes.
Figure 1: Partial 1H NMR spectra (recorded at two temperatures) of the reaction mixture of allyl bromide and ...
Figure 2: Structures of all the possible allylbismuth species.
Scheme 2: Probable reaction mechanism.
Synthesis of spirocyclic scaffolds using hypervalent iodine reagents
- Fateh V. Singh,
- Priyanka B. Kole,
- Saeesh R. Mangaonkar and
- Samata E. Shetgaonkar
Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152
- stereoselective synthesis. Additionally, the applications of these reagents in natural product synthesis are also covered. Keywords: hypervalent iodine reagents; iodoarenes; natural products; oxidative cyclization; spirocyclic compounds; Review 1. Introduction The chemistry of spirocyclic compounds is a well
- ). Furthermore, the absolute configuration of 88 was assigned by its single crystal X-ray analysis. 3.3. Application of spirolactams in natural product synthesis In 2001, Ciufolini and co-workers [103] employed PIDA (15) as an electrophile during the synthesis of naturally occurring tricyclic azaspirane
- of ortho-spirocarbocyclic compounds which is broadly found to originate in most of bioactive natural products [111][112]. 4.3. Application of spirocarbocyclic compounds in natural product synthesis In 2003, Kita and co-workers [113][114] employed a iodine(III) reagent during the total synthesis of
Graphical Abstract
Figure 1: The structures of biologically active natural and synthetic products having spirocyclic moiety.
Scheme 1: Iodine(III)-mediated spirocyclization of substituted phenols 7 and 11 to 10 and 13, respectively.
Scheme 2: PIDA-mediated spirolactonization of N-protected tyrosine 14 to spirolactone 16.
Figure 2: The structures of polymer-supported iodine(III) reagents 17a and 17b.
Scheme 3: Spirolactonization of substrates 14 to spirolactones 16 using polymer-supported reagents 17a and 17b...
Scheme 4: PIDA-mediated spirolactonization of 1-(p-hydroxyaryl)cyclobutanols 18 to spirolactones 19.
Scheme 5: Iodine(III)-mediated spirocyclization of aryl alkynes 24 to spirolactones 26 by the reaction with b...
Scheme 6: Bridged iodine(III)-mediated spirocyclization of phenols 27 to spirodienones 29.
Scheme 7: Iodine(III)-mediated spirocyclization of arnottin I (30) to its spirocyclic analogue arnottin II (32...
Scheme 8: Iodine(III)-catalyzed spirolactonization of p-substituted phenols 27 to spirolactones 29 using iodo...
Scheme 9: Iodine(III)-catalyzed oxylactonization of ketocarboxylic acid 34 to spirolactone 36 using iodobenze...
Scheme 10: Iodine(III)-mediated asymmetric oxidative spirocyclization of naphthyl acids 37 to naphthyl spirola...
Scheme 11: Oxidative cyclization of L-tyrosine 14 to spirocyclic lactone 16 using PIDA (15).
Scheme 12: Oxidative cyclization of oxazoline derivatives 41 to spirolactams 42 using PIDA (15).
Scheme 13: Oxidative cyclization of oxazoline 43 to spirolactam 44 using PIDA 15 as oxidant.
Scheme 14: PIFA-mediated spirocyclization of amides 46 to N-spirolactams 47 using PIFA (31) as an electrophile....
Scheme 15: Synthesis of spirolactam 49 from phenolic enamide 48 using PIDA (15).
Scheme 16: Iodine(III)-mediated spirocyclization of alkyl hydroxamates 50 to spirolactams 51 using stoichiomet...
Scheme 17: PIFA-mediated cyclization of substrate 52 to spirocyclic product 54.
Scheme 18: Synthesis of spiro β-lactams 56 by oxidative coupling reaction of p-substituted phenols 55 using PI...
Scheme 19: Iodine(III)-mediated spirocyclization of para-substituted amide 58 to spirolactam 59 by the reactio...
Scheme 20: Iodine(III)-mediated synthesis of spirolactams 61 from anilide derivatives 60.
Scheme 21: PIFA-mediated oxidative cyclization of anilide 60 to bis-spirobisoxindole 61.
Scheme 22: PIDA-mediated spirocyclization of phenylacetamides 65 to spirocyclic lactams 66.
Scheme 23: Oxidative dearomatization of arylamines 67 with PIFA (31) to give dieniminium salts 68.
Scheme 24: PIFA-mediated oxidative spirocarbocyclization of 4-methoxybenzamide 69 with diphenylacetylene (70) ...
Scheme 25: Synthesis of spiroxyindole 75 using I2O5/TBHP oxidative system.
Scheme 26: Iodine(III)-catalyzed spirolactonization of functionalized amides 76 to spirolactones 77 using iodo...
Scheme 27: Intramolecular cyclization of alkenes 78 to spirolactams 80 using Pd(II) 79 and PIDA (15) as the ox...
Scheme 28: Iodine(III)-catalyzed spiroaminocyclization of amides 76 to spirolactam 77 using bis(iodoarene) 81 ...
Scheme 29: Iodine(III)-catalyzed spirolactonization of N-phenyl benzamides 82 to spirolactams 83 using iodoben...
Scheme 30: Iodine(III)-mediated asymmetric oxidative spirocyclization of phenols 84 to spirolactams 86 using c...
Scheme 31: Iodine(III)-catalyzed asymmetric oxidative spirocyclization of N-aryl naphthamides 87 to spirocycli...
Scheme 32: Cyclization of p-substituted phenolic compound 89 to spirolactam 90 using PIDA (15) in TFE.
Scheme 33: Iodine(III)-mediated synthesis of spirocyclic compound 93 from substrates 92 using PIDA (15) as an ...
Scheme 34: Iodine(III)-mediated spirocyclization of p-substituted phenol 48 to spirocyclic compound 49 using P...
Scheme 35: Bridged iodine(III)-mediated spirocyclization of O-silylated phenolic compound 96 in the synthesis ...
Scheme 36: PIFA-mediated approach for the spirocyclization of ortho-substituted phenols 98 to aza-spirocarbocy...
Scheme 37: Oxidative cyclization of para-substituted phenols 102 to spirocarbocyclic compounds 104 using Koser...
Scheme 38: Iodine(III)-mediated spirocyclization of aryl alkynes 105 to spirocarbocyclic compound 106 by the r...
Scheme 39: Iodine(III)-mediated spirocarbocyclization of ortho-substituted phenols 107 to spirocarbocyclic com...
Scheme 40: PIFA-mediated oxidative cyclization of substrates 110 to spirocarbocyclic compounds 111.
Scheme 41: Iodine(III)-mediated cyclization of substrate 113 to spirocyclic compound 114.
Scheme 42: Iodine(III)-mediated spirocyclization of phenolic substrate 116 to the spirocarbocyclic natural pro...
Scheme 43: Iodine(III)-catalyzed spirocyclization of phenols 117 to spirocarbocyclic products 119 using iodoar...
Scheme 44: PIFA-mediated spirocyclization of 110 to spirocyclic compound 111 using PIFA (31) as electrophile.
Scheme 45: PIDA-mediated spirocyclization of phenolic sulfonamide 122 to spiroketones 123.
Scheme 46: Iodine(III)-mediated oxidative spirocyclization of 2-naphthol derivatives 124 to spiropyrrolidines ...
Scheme 47: PIDA-mediated oxidative spirocyclization of m-substituted phenols 126 to tricyclic spiroketals 127.
Figure 3: The structures of chiral organoiodine(III) catalysts 129a and 129b.
Scheme 48: Iodine(III)-catalyzed oxidative spirocyclization of substituted phenols 128 to spirocyclic ketals 1...
Scheme 49: Oxidative spirocyclization of para-substituted phenol 131 to spirodienone 133 using polymer support...
Scheme 50: Oxidative cyclization of bis-hydroxynaphthyl ether 135 to spiroketal 136 using PIDA (15) as an elec...
Scheme 51: Oxidative spirocyclization of phenolic compound 139 to spirodienone 140 using polymer-supported PID...
Scheme 52: PIFA-mediated oxidative cyclization of catechol derived substrate 142 to spirocyclic product 143.
Scheme 53: Oxidative spirocyclization of p-substituted phenolic substrate 145 to aculeatin A (146a) and aculea...
Scheme 54: Oxidative spirocyclization of p-substituted phenolic substrate 147 to aculeatin A (146a) and aculea...
Scheme 55: Oxidative spirocyclization of p-substituted phenolic substrate 148 to aculeatin D (149) using elect...
Scheme 56: Cyclization of phenolic substrate 131 to spirocyclic product 133 using polymer-supported PIFA 150.
Scheme 57: Iodine(III)-mediated oxidative intermolecular spirocyclization of 7-methoxy-α-naphthol (152) to spi...
Scheme 58: Oxidative cyclization of phenols 155 to spiro-ketals 156 using electrophilic species PIDA (15).
Scheme 59: Iodine(III)-catalyzed oxidative spirocyclization of ortho-substituted phenols 158 to spirocyclic ke...
Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst
- Kimihiro Komeyama,
- Shunsuke Sakiyama,
- Kento Iwashita,
- Itaru Osaka and
- Ken Takaki
Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118
- ; Introduction Carbon–carbon bond formation is the fundamental and central transformation of synthetic organic chemistry. The elaboration and extension of a carbon framework via a series of carbon–carbon bond-forming reactions are extremely important for medicinal chemistry and agrochemical and natural product
- synthesis. In these bond formations, organometallics play an essential role because they possess various reactivities depending on the central metal ions that they own. For example, carbon has strong nucleophilicity when bonded to metals with low electronegativity, as demonstrated in the reaction of
Graphical Abstract
Scheme 1: Nucleophilic and π-electrophilic characters of organometallics depending on the central metals.
Scheme 2: Ni/Cr or Co/Cr-catalyzed NHK reaction.
Scheme 3: Functionalization of alkynes via carbocobaltation.
Scheme 4: Cyclization/borylation of alkynyl iodoarenes using the Co/Cr catalyst.
Scheme 5: Three-component coupling of aryl iodides, arenes, and aldehydes using Co/Cr catalyst (this work).
Scheme 6: Screening of aldehydes in the Co/Cr-catalyzed three-component coupling reaction. All yields are det...
Scheme 7: Screening of aryl iodides in the Co/Cr-catalyzed three-component coupling reaction. All yields are ...
Scheme 8: Screening of allenes in the Co/Cr-catalyzed three-component coupling reaction. All yields are deter...
Scheme 9: Reversed diastereoselectivity using allenyl ethers 5 and 6. a4-chlorobenzaldehyde was used instead ...
Scheme 10: Stoichiometric reaction of phenylchromium(II or III) reagents (reaction 1) and the three-component ...
Scheme 11: The origin of the diastereoselectivity in the present three-component coupling.
Scheme 12: Plausible reaction mechanism of the three-component coupling.
Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes
- Zhensheng Zhao and
- Graham K. Murphy
Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67
- materials [7][8]. And as there is an abundance of chlorine-containing natural products, the synthesis of chlorinated functional groups, such as allyl- and vinyl chlorides, can represent challenging obstacles that practitioners of natural product synthesis must surmount [9][10][11][12]. More commonly, allyl
Graphical Abstract
Scheme 1: Reactions of substituted allenes with HVI reagents.
Scheme 2: Chlorination of p-tolylallene (2a) with (dichloroiodo)benzene (1a).
Scheme 3: Chlorination of various aryl-substituted allenes. General conditions: Allene 2a (0.2 mmol, 1 equiv)...
Scheme 4: Chlorination of various α-substituted phenylallene derivatives. General conditions: Allene 2a (0.2 ...
Scheme 5: Chlorination of methoxy-substituted α-methyl phenylallenes. General conditions: Allene 2a (0.2 mmol...
Scheme 6: Control reactions: (a) chlorination of deuterated biphenylallene [D2]-2b; (b) reaction with TEMPO.
Figure 1: Proposed reaction mechanism.
An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation
- Carolina S. García,
- Paula M. Uberman and
- Sandra E. Martín
Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166
- interested in investigating the synthetic applicability of this catalyst in a natural product synthesis. For this purpose, the reaction between aryl bromide 1d and 4-acetoxystyrene (2d) was studied to obtain (E)-pterostilbene (19, Scheme 1). Several derivatives of polyphenolic stilbenes as (E)-pterostilbene
Graphical Abstract
Scheme 1: Synthesis of (E)-pterostilbene (19) catalyzed by PVP-Pd NPs.
Figure 1: Reuse experiments of PdNPs in the coupling reaction between 4-bromoacetophenone (1a) and styrene (2a...
The chemistry and biology of mycolactones
- Matthias Gehringer and
- Karl-Heinz Altmann
Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159
- toxin. III. Total synthesis of mycolactones The fascinating biology and the challenging structural features of mycolactones have attracted significant interest from research groups worldwide with a focus on natural product synthesis. In this chapter the synthetic work on mycolactones that has been
Graphical Abstract
Figure 1: Initial proposal for the core macrolactone structure (left) and the established complete structure ...
Figure 2: Mycolactone congeners and their origins.
Figure 3: Misassigned mycolactone E structure according to Small et al. [50] (11) and the correct structure (6) f...
Figure 4: Schematic illustration of Kishi’s improved mycolactone TLC detection method exploiting derivatizati...
Figure 5: Fluorescent probes derived from natural mycolactone A/B (1a,b) or its synthetic 8-desmethyl analogs...
Figure 6: Tool compounds used by Pluschke and co-workers for elucidating the molecular targets of mycolactone...
Figure 7: Synthetic strategies towards the extended mycolactone core. A) General strategies. B) Kishi’s appro...
Scheme 1: Kishi’s 1st generation approach towards the extended core structure of mycolactones. Reagents and c...
Scheme 2: Kishi’s 2nd generation approach towards the extended core structure of mycolactones. Reagents and c...
Scheme 3: Kishi’s 3rd generation approach towards the extended core structure of mycolactones. Reagents and c...
Scheme 4: Negishi’s synthesis of the extended core structure of mycolactones. Reagents and conditions: a) (i) ...
Scheme 5: Burkart’s (incomplete) 1st generation approach towards the extended core structure of mycolactones....
Scheme 6: Burkart’s (incomplete) 1st, 2nd and 3rd generation approach towards the extended mycolactone core s...
Scheme 7: Altmann’s synthesis of alkyl iodide 91. Reagents and conditions: a) (i) PMB-trichloroacetimidate, T...
Scheme 8: Final steps of Altmann’s synthesis of the extended core structure of mycolactones. Reagents and con...
Scheme 9: Basic principles of the Aggarwal lithiation–borylation homologation process [185,186].
Scheme 10: Aggarwal’s synthesis of the C1–C11 fragment of the mycolactone core. Reagents and conditions: a) Cl...
Scheme 11: Aggarwal’s synthesis of the linear C1–C20 fragment of the mycolactone core. Reagents and conditions...
Figure 8: Synthetic strategies towards the mycolactone A/B lower side chain.
Scheme 12: Gurjar and Cherian’s synthesis of the C1’–C8’ fragment of the mycolactone A/B pentaenoate side chai...
Scheme 13: Gurjar and Cherian’s synthesis of the benzyl-protected mycolactone A/B pentaenoate side chain. Reag...
Scheme 14: Kishi’s synthesis of model compounds for elucidating the stereochemistry of the C7’–C16’ fragment o...
Scheme 15: Kishi’s synthesis of the mycolactone A/B pentaenoate side chain. (a) (i) NaH, (EtO)2P(O)CH2CO2Et, T...
Scheme 16: Feringa and Minnaard's incomplete synthesis of mycolactone A/B pentaenoate side chain. Reagents and...
Scheme 17: Altmann’s approach towards the mycolactone A/B pentaenoate side chain. Reagents and conditions: a) ...
Scheme 18: Negishi’s access to the C1’–C7’ fragment of mycolactone A. Reagents and conditions: a) (i) n-BuLi, ...
Scheme 19: Negishi’s approach to the C1’–C7’ fragment of mycolactone B. Reagents and conditions: a) (i) DIBAL-...
Scheme 20: Negishi’s synthesis of the C8’–C16’ fragment of mycolactone A/B. Reagents and conditions: a) 142, BF...
Scheme 21: Negishi’s assembly of the mycolactone A and B pentaenoate side chains. Reagents and conditions: a) ...
Scheme 22: Blanchard’s approach to the mycolactone A/B pentaenoate side chain. a) (i) Ph3P=C(Me)COOEt, CH2Cl2,...
Scheme 23: Kishi’s approach to the mycolactone C pentaenoate side chain exemplified for the 13’R,15’S-isomer 1...
Scheme 24: Altmann’s (unpublished) synthesis of the mycolactone C pentaenoate side chain. Reagents and conditi...
Scheme 25: Blanchard’s synthesis of the mycolactone C pentaenoate side chain. Reagents and conditions: a) (i) ...
Scheme 26: Kishi’s synthesis of the tetraenoate side chain of mycolactone F exemplified by enantiomer 165. Rea...
Scheme 27: Kishi’s synthesis of the mycolactone E tetraenoate side chain. Reagents and conditions: a) (i) CH2=...
Scheme 28: Wang and Dai’s synthesis of the mycolactone E tetraenoate side chain. Reagents and conditions: a) (...
Scheme 29: Kishi’s synthesis of the dithiane-protected tetraenoate side chain of the minor oxo-metabolite of m...
Scheme 30: Kishi’s synthesis of the mycolactone S1 and S2 pentaenoate side chains. Reagents and conditions: a)...
Scheme 31: Kishi’s 1st generation and Altmann’s total synthesis of mycolactone A/B (1a,b) and Negishi’s select...
Scheme 32: Kishi’s 2nd generation total synthesis of mycolactone A/B (1a,b). Reagents and conditions: a) 2,4,6...
Scheme 33: Blanchard’s synthesis of the 8-desmethylmycolactone core. Reagents and conditions: a) (i) TsCl, TEA...
Scheme 34: Altmann’s (partially unpublished) synthesis of the C20-hydroxylated mycolactone core. Reagents and ...
Scheme 35: Altmann’s and Blanchard’s approaches towards the 11-isopropyl-8-desmethylmycolactone core. Reagents...
Scheme 36: Blanchard’s synthesis of the saturated variant of the C11-isopropyl-8-desmethylmycolactone core. Re...
Scheme 37: Structure elucidation of photo-mycolactones generated from tetraenoate 224.
Scheme 38: Kishi’s synthesis of the linear precursor of the photo-mycolactone B1 lower side chain. Reagents an...
Scheme 39: Kishi’s synthesis of the photo-mycolactone B1 lower side chain. Reagents and conditions: a) LiTMP, ...
Scheme 40: Kishi’s synthesis of a stabilized lower mycolactone side chain. Reagents and conditions: a) (i) TBD...
Scheme 41: Blanchard’s variation of the C12’,C13’,C15’ stereocluster. Reagents and conditions: a) (i) DIBAL-H,...
Scheme 42: Blanchard’s synthesis of aromatic mycolactone polyenoate side chain analogs. Reagents and condition...
Scheme 43: Small’s partial synthesis of a BODIPY-labeled mycolactone derivative and Demangel’s partial synthes...
Scheme 44: Blanchard’s synthesis of the BODIPY-labeled 8-desmethylmycolactones. Reagents and conditions: a) (i...
Scheme 45: Altmann’s synthesis of biotinylated mycolactones. Reagents and conditions: a) (i) CDI, THF, rt, 2 d...
Figure 9: Kishi’s elongated n-butyl carbamoyl mycolactone A/B analog.
Biomimetic molecular design tools that learn, evolve, and adapt
- David A Winkler
Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125
- ]. Intensive experimental effort has been applied to the deliberate reengineering of biosynthetic pathways for natural product synthesis which, when combined with directed evolution, can generate libraries of potentially bioactive organic molecules with significant diversity and high chemical complexity [4
Graphical Abstract
Figure 1: Hypothesized evolution of ‘life’ and ‘intelligence’.
Figure 2: Structure of maitotoxin, one of the most complex natural products ever tackled by total synthesis. ...
Figure 3: Hypothesis-driven closed-loop learning rationale for Adam and Eve. Hypothesis-driven experimentatio...
Figure 4: Traditional backpropagation neural network machine learning algorithm.
Figure 5: Comparison of architectures of shallow (non-deep) and deep neural networks. Adapted with permission...
Figure 6: Tray of Josiah Wedgwood’s jasper trials from 1773 (copyright Wedgwood Museum; all rights reserved)....
Figure 7: A high-throughput-materials synthesis and characterization facility RAMP, (Rapid Automated Material...
Figure 8: An interactive procedure to design and 3D print bespoke reaction ware to optimization yield and pur...
Figure 9: (Top) Photograph of a small-molecule synthesizer comprised of three modules for deprotection, coupl...
Figure 10: An example of a composition-based descriptor vector that could be used to model or evolve materials...
Figure 11: Example of a simple elitism (copy unchanged), crossover, and point mutation operations acting on th...
Figure 12: A simple example of a two-dimensional fitness functions. The lines represent different evolutionary...
Figure 13: Robotic synthesis and testing of populations of pathogen-resistant polymers evolved by a combinatio...
Figure 14: Net deliverable energy as a function of porous material void fraction at 77 K cycling between 100 a...
Strategies toward protecting group-free glycosylation through selective activation of the anomeric center
- A. Michael Downey and
- Michal Hocek
Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123
- subject of much debate (Scheme 4B) [21]. The utility of these enzymes is very clear and even extends beyond glycobiology. They are applicable to natural product synthesis as the aglycone of a natural product glycoside can be forged to the saccharide component using either a natural or engineered GT [22
Graphical Abstract
Scheme 1: Solution-state conformations of D-glucose.
Scheme 2: Enzymatic synthesis of oligosaccharides.
Scheme 3: Enzymatic synthesis of a phosphorylated glycoprotein containing a mannose-6-phosphate (M6P)-termina...
Scheme 4: A) Selected GTs-mediated syntheses of oligosaccharides and other biologically active glycosides. B)...
Scheme 5: Enzymatic synthesis of nucleosides.
Scheme 6: Fischer glycosylation strategies.
Scheme 7: The basis of remote activation (adapted from [37]).
Scheme 8: Classic remote activation employing a MOP donor to access α-anomeric alcohols, carboxylates, and ph...
Figure 1: Synthesis of monoprotected glycosides from a (3-bromo-2-pyridyloxy) β-D-glycopyranosyl donor under ...
Scheme 9: Plausible mechanism for the synthesis of α-galactosides. TBDPS = tert-butyldiphenylsilyl.
Scheme 10: Synthesis of the 6-O-monoprotected galactopyranoside donor for remote activation.
Scheme 11: UDP-galactopyranose mutase-catalyzed isomerization of UDP-Galp to UDP-Galf.
Scheme 12: Synthesis of the 1-thioimidoyl galactofuranosyl donor.
Scheme 13: Glycosylation of MeOH using a self-activating donor in the absence of an external activator. a) Syn...
Scheme 14: The classical Lewis acid-catalyzed glycosylation.
Figure 2: Unprotected glycosyl donors used for the Lewis acid-catalyzed protecting group-free glycosylation r...
Scheme 15: Four-step synthesis of the phenyl β-galactothiopyranosyl donor.
Scheme 16: Protecting-group-free C3′-regioselective glycosylation of sucrose with α–F Glc.
Scheme 17: Synthesis of the α-fluoroglucosyl donor.
Figure 3: Protecting-group-free glycosyl donors and acceptors used in the Au(III)-catalyzed glycosylation.
Scheme 18: Synthesis of the mannosyl donor used in the study [62].
Scheme 19: The Pd-catalyzed stereoretentive glycosylation of arenes using anomeric stannane donors.
Scheme 20: Preparation of the protecting-group-free α and β-stannanes from advanced intermediates for stereoch...
Figure 4: Selective anomeric activating agents providing donors for direct activation of the anomeric carbon.
Scheme 21: One-step access to sugar oxazolines or 1,6-anhydrosugars.
Scheme 22: Enzymatic synthesis of a chitoheptaose using a mutant chitinase.
Scheme 23: One-pot access to glycosyl azides [73], dithiocarbamates [74], and aryl thiols using DMC activation and sub...
Scheme 24: Plausible reaction mechanism.
Scheme 25: Protecting-group-free synthesis of anomeric thiols from unprotected 2-deoxy-2-N-acetyl sugars.
Scheme 26: Protein conjugation of TTL221-PentK with a hyaluronan hexasaccharide thiol.
Scheme 27: Proposed mechanism.
Scheme 28: Direct two-step one-pot access to glycoconjugates through the in situ formation of the glycosyl azi...
Scheme 29: DMC as a phosphate-activating moiety for the synthesis of diphosphates. aβ-1,4-galactose transferas...
Figure 5: Triazinylmorpholinium salts as selective anomeric activating agents.
Scheme 30: One-step synthesis of DBT glycosides from unprotected sugars in aqueous medium.
Scheme 31: Postulated mechanism for the stereoselective formation of α-glycosides.
Scheme 32: DMT-donor synthesis used for metal-catalyzed glycosylation of simple alcohols.
Figure 6: Protecting group-free synthesis of glycosyl sulfonohydrazides (GSH).
Figure 7: The use of GSHs to access 1-O-phosphoryl and alkyl glycosides. A) Glycosylation of aliphatic alcoho...
Scheme 33: A) Proposed mechanism of glycosylation. B) Proposed mechanism for stereoselective azidation of the ...
Scheme 34: Mounting GlcNAc onto a sepharose solid support through a GSH donor.
Scheme 35: Lawesson’s reagent for the formation of 1,2-trans glycosides.
Scheme 36: Protecting-group-free protein conjugation via an in situ-formed thiol glycoside [98].
Scheme 37: pH-Specific glycosylation to functionalize SAMs on gold.
Figure 8: Protecting-group-free availability of phenolic glycosides under Mitsunobu conditions. DEAD = diethy...
Scheme 38: Accessing hydroxyazobenzenes under Mitsunobu conditions for the study of photoswitchable labels. DE...
Scheme 39: Stereoselective protecting-group-free glycosylation of D-glucose to provide the β-glucosyl benzoic ...
Figure 9: Direct synthesis of pyranosyl nucleosides from unactivated and unprotected ribose using optimized M...
Figure 10: Direct synthesis of furanosyl nucleosides from 5-O-monoprotected ribose in a one-pot glycosylation–...
Figure 11: Synthesis of ribofuranosides using a monoprotected ribosyl donor via an anhydrose intermediate.
Figure 12: C5′-modified nucleosides available under our conditions.
Scheme 40: Plausible reaction mechanism for the formation of the anhydrose.
Figure 13: Direct glycosylation of several aliphatic alcohols using catalytic Ti(Ot-Bu)4 in the presence of D-...
Figure 14: Access to glycosides using catalytic PPh3 and CBr4.
Figure 15: Access to ribofuranosyl glycosides as the major product under catalytic conditions. aLiOCl4 (2.0 eq...
Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds
- M. Fernanda N. N. Carvalho,
- Rudolf Herrmann and
- Gabriele Wagner
Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122
- example for such a “chiral pool” starting material is camphor. Both its substituents and its bicyclic skeleton can easily be modified and adapted to the purpose at hand, e.g., natural product synthesis [5]. The Wagner–Meerwein and Nametkin-type rearrangements are the most common reaction patterns [6] and
Graphical Abstract
Scheme 1: Synthesis of 3-oxo-camphorsulfonylimine (3) [13,15] and its bis-alkynyl derivatives 4 from camphor-10-sulf...
Scheme 2: Reactions of bis-alkynyl camphor derivative 4a with TiCl4 and with Br2, respectively.
Scheme 3: Reactions of bis-alkynylcamphor derivatives 4a–e with catalytic amounts of PtCl2(PhCN)2.
Scheme 4: Attempted selective synthesis of 3-alkynyl derivatives via sulfonylimine reduction of oxoimide 3.
Scheme 5: Selective synthesis of 2-alkynyl derivatives by protection of the 3-oxo group as an acetal.
Scheme 6: Selective synthesis of 2-alkynyl derivatives by protection of the 3-oxo group as an imine.
Scheme 7: Synthesis of the bis-alkynyl derivatives bearing different alkyne substituents and their platinum-c...
Scheme 8: Proposed mechanism of the platinum-catalysed cycloisomerisation.
A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring
- John Andraos
Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236
- scaffold, and in pharmaceuticals that typically contain one of several kinds of nitrogen-containing heterocyclic rings. Synthetic organic chemists engaged both in methodology development for the discovery of new transformations and in natural product synthesis to new complex target molecules are now
Graphical Abstract
Figure 1: Possible two-component couplings for various monocyclic rings frequently encountered in organic mol...
Figure 2: Possible three-component couplings for various monocyclic rings frequently encountered in organic m...
Figure 3: Possible four-component couplings for various monocyclic rings frequently encountered in organic mo...
Figure 4: Permutations of two-component coupling patterns for synthesizing the cyclohexanone ring. Synthesis ...
Figure 5: Permutations of two-component coupling patterns for synthesizing the cyclohexanone ring overlayed w...
Scheme 1: Conjectured syntheses of cyclohexanone via [5 + 1] strategies.
Scheme 2: Conjectured syntheses of cyclohexanone via [4 + 2] strategies.
Scheme 3: Conjectured syntheses of cyclohexanone via [3 + 3] strategies.
Figure 6: Permutations of three-component coupling patterns for synthesizing the cyclohexanone ring. Synthesi...
Figure 7: Permutations of three-component coupling patterns for synthesizing the pyrazole ring via [2 + 2 + 1...
Scheme 4: Literature method for constructing the pyrazole ring via the A4 [2 + 2 + 1] strategy.
Scheme 5: Literature methods for constructing the pyrazole ring via the A5 [2 + 2 + 1] strategy.
Scheme 6: Literature methods for constructing the pyrazole ring via the A1 [2 + 2 + 1] strategy.
Scheme 7: Literature methods for constructing the pyrazole ring via the B4 [3 + 1 + 1] strategy.
Figure 8: Intrinsic green performance of documented pyrazole syntheses according to [2 + 2 + 1] and [3 + 1 + ...
Scheme 8: Conjectured reactions for constructing the pyrazole ring via the A2 and A3 [2 + 2 + 1] strategies.
Scheme 9: Conjectured reactions for constructing the pyrazole ring via the B1, B2, B3, and B4 [3 + 1 + 1] str...
Figure 9: Permutations of three-component coupling patterns for synthesizing the Biginelli ring adduct. Synth...
Scheme 10: Reported syntheses of the Biginelli adduct via the traditional [3 + 2 + 1] mapping strategy.
Scheme 11: Reported syntheses of the Biginelli adduct via new [3 + 2 + 1] mapping strategies.
Scheme 12: Reported syntheses of the Biginelli adduct via a new [2 + 2 + 1 + 1] mapping strategy.
Scheme 13: Conjectured syntheses of the Biginelli adduct via new [2 + 2 + 2] mapping strategies.
Scheme 14: Conjectured syntheses of the Biginelli adduct via new [3 + 2 + 1] mapping strategies.
Figure 10: Intrinsic green performance of documented Biginelli adduct syntheses according to [3 + 2 + 1] three...
Figure 11: Intrinsic green performance of newly conjectured Biginelli adduct syntheses according to [4 + 1 + 1...
Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis
- Darcy J. Atkinson,
- Briar J. Naysmith,
- Daniel P. Furkert and
- Margaret A. Brimble
Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226
- -isomer exhibited 80% lower bacteriostatic activity against Mycobacterium smegmatis ATCC 607 compared to the parent natural product. Synthesis of Mannopeptimycin aglycone by Doi et al.: In 2014, the total synthesis of the mannopeptimycin aglycone (77) was reported by Doi et al. [33]. The aglycone was
Graphical Abstract
Figure 1: Structures of the enduracididine family of amino acids (1–6).
Figure 2: Enduracidin A (7) and B (8).
Figure 3: Minosaminomycin (9) and related antibiotic kasugamycin (10).
Figure 4: Enduracididine-containing compound 11 identified in a cytotoxic extract of Leptoclinides dubius [32].
Figure 5: Mannopeptimycins α–ε (12–16).
Figure 6: Regions of the mannopeptimycin structure investigated in structure–activity relationship investigat...
Figure 7: Teixobactin (17).
Scheme 1: Proposed biosynthesis of L-enduracididine (1) and L-β-hydroxyenduracididine (5).
Scheme 2: Synthesis of enduracididine (1) by Shiba et al.
Scheme 3: Synthesis of protected enduracididine diastereomers 31 and 32.
Scheme 4: Synthesis of the C-2 azido diastereomers 36 and 37.
Scheme 5: Synthesis of 2-azido-β-hydroxyenduracididine derivatives 38 and 39.
Scheme 6: Synthesis of protected β-hydroxyenduracididine derivatives 40 and 41.
Scheme 7: Synthesis of C-2 diastereomeric amino acids 46 and 47.
Scheme 8: Synthesis of protected β-hydroxyenduracididines 51 and 52.
Scheme 9: General transformation of alkenes to cyclic sulfonamide 54 via aziridine intermediate 53.
Scheme 10: Synthesis of (±)-enduracididine (1) and (±)-allo-enduracididine (3).
Scheme 11: Synthesis of L-allo-enduracididine (3).
Scheme 12: Synthesis of protected L-allo-enduracididine 63.
Scheme 13: Synthesis of β-hydroxyenduracididine derivative 69.
Scheme 14: Synthesis of minosaminomycin (9).
Scheme 15: Retrosynthetic analysis of mannopeptimycin aglycone (77).
Scheme 16: Synthesis of protected amino acids 87 and 88.
Scheme 17: Synthesis of mannopeptimycin aglycone (77).
Scheme 18: Synthesis of N-mannosylation model guanidine 92 and attempted synthesis of benzyl protected mannosy...
Scheme 19: Synthesis of benzyl protected mannosyl D-β-hydroxyenduracididine 97.
Scheme 20: Synthesis of L-β-hydroxyenduracididine 98.
Scheme 21: Total synthesis of mannopeptimycin α (12) and β (13).
Scheme 22: Synthesis of protected L-allo-enduracididine 102.
Scheme 23: The solid phase synthesis of teixobactin (17).
Scheme 24: Retrosynthesis of the macrocyclic core 109 of teixobactin (17).
Scheme 25: Synthesis of macrocycle 117.
The direct oxidative diene cyclization and related reactions in natural product synthesis
- Juliane Adrian,
- Leona J. Gross and
- Christian B. W. Stark
Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200
- stereochemical aspects, this review article provides a summary on applications in natural product synthesis. Moreover, current limitations and future directions in this area of chemistry are discussed. Keywords: asymmetric synthesis; natural products; oxidation catalysis; tetrahydrofurans; total synthesis
- ; Introduction Scope of this article After a concise introduction on the history and mechanistic aspects of the title reaction, the primary aim of the present review article is to summarize all relevant applications in natural product synthesis. The main text of this article is ordered by compound classes, so
- transformations do not have the same broad substrate spectrum as has been demonstrated for 1,5-diene precursors and there are no applications to natural product synthesis thus far. A particularly fruitful extension of the direct 1,5-diene oxidation methodology (and due to mechanistic similarities also within the
Graphical Abstract
Scheme 1: Putative structures of geraniol 1a (R = H) or 1b (R = H) (in 1924), their expected dihydroxylation ...
Scheme 2: Correlation between the substrate double bond geometry and relative stereochemistry of the correspo...
Scheme 3: Mechanisms and classification for the metal-mediated oxidative cyclizations to form 2,5-disubstitut...
Scheme 4: Synthesis of (+)-anhydro-D-glucitol and (+)-D-chitaric acid using an OsO4-mediated oxidative cycliz...
Scheme 5: Total synthesis of neodysiherbaine A via a Ru(VIII)- and an Os(VI)-catalyzed oxidative cyclization,...
Scheme 6: Formal synthesis of ionomycin by Kocienski and co-workers.
Scheme 7: Total synthesis of amphidinolide F by Fürstner and co-workers.
Scheme 8: Brown`s and Donohoe`s oxidative cyclization approach to cis-solamin A.
Scheme 9: Total synthesis of cis-solamin A using a Ru(VIII)-catalyzed oxidative cyclization and enzymatic des...
Scheme 10: Donohoe´s double oxidative cyclization approach to cis-sylvaticin.
Scheme 11: Permanganate-mediated approach to cis-sylvaticin by Brown and co-workers.
Scheme 12: Total synthesis of membranacin using a KMnO4-mediated oxidative cyclization.
Scheme 13: Total synthesis of membrarollin and its analogue 21,22-diepi-membrarollin.
Scheme 14: Total synthesis of rollidecin C and D using a late stage Re(VII)-catalyzed oxidative polycyclizatio...
Scheme 15: Co(II)-catalyzed oxidative cyclization in the total synthesis of asimilobin and gigantetrocin A.
Scheme 16: Mn(VII)-catalyzed oxidative cyclization of a 1,5-diene in the synthesis of trans-(+)-linalool oxide....
Scheme 17: Re(VII)-catalyzed oxidative cyclization in the total synthesis of teurilene.
Scheme 18: Total synthesis of (+)-eurylene via Re(VII)- and Cr(VI)-mediated oxidative cyclizations.
Scheme 19: Synthesis of cis- and trans-THF Rings of eurylene via Mn(VII)-mediated oxidative cyclizations.
Scheme 20: Cr(VI)-catalyzed oxidative cyclization in the total synthesis of venustatriol by Corey et al.
Scheme 21: Ru(VIII)-catalyzed oxidative cyclization of a 1,5-diene in the synthesis and evaluation of its ster...
Scheme 22: Ru(VII)-catalyzed oxidative cyclization of a 5,6-dihydroxy alkene in the synthesis of the core stru...
Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes
- Lucie Brulíková,
- Aidan Harrison,
- Marvin J. Miller and
- Jan Hlaváč
Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184
- organic synthesis [15][16][17][18][19][20][21][22][23][24], applications of nitroso hetero-Diels–Alder reactions for the synthesis of azasugars [10], and the utilization of nitroso hetero-Diels–Alder reactions in natural product synthesis [9][25] and the synthesis of bioactive molecules [26]. However
Graphical Abstract
Scheme 1: Nitroso hetero-Diels–Alder reaction.
Scheme 2: The hetero-Diels–Alder reaction between thebaine (4) and an acylnitroso dienophile 5.
Figure 1: Examples of nitroso dienophiles frequently used in hetero-Diels–Alder reaction studies.
Scheme 3: Synthesis of arylnitroso species by substitution of a trifluoroborate group [36].
Scheme 4: Synthesis of arylnitroso compounds by amine oxidation.
Scheme 5: Synthesis of arylnitroso compounds by hydroxylamine oxidation.
Scheme 6: Synthesis of chloronitroso compounds by the treatment of a nitronate anion with oxalyl chloride.
Scheme 7: Non-oxidative routes to acylnitroso species.
Figure 2: RB3LYP/6-31G* computed energies (in kcal·mol−1) and bond lengths for exo and endo-transition states...
Scheme 8: Hetero-Diels–Alder cycloadditions of diene 28 and nitroso dienophiles 29.
Figure 3: Relative reactivity (ΔE#) and regioselectivity (Δ) for hetero-Diels–Alder of 28 and nitroso dienoph...
Scheme 9: Reaction of chiral 1-phosphono-1,3-butadiene 31 with nitroso dienophiles 32.
Scheme 10: Hetero-Diels–Alder reactions of hydroxamic acids 35 with various dienes 37.
Scheme 11: General regioselectivity of the nitroso hetero-Diels–Alder reaction observed with unsymmetrical die...
Scheme 12: Effect of the nitroso species on the regioselectivity for weakly directing 2-substituted dienes.
Scheme 13: Regioselectivity of 1,4-disubstituted dienes 51.
Scheme 14: Nitroso hetero-Diels–Alder reaction between Boc-nitroso compound 54 and dienes 55.
Scheme 15: Nitroso hetero-Diels–Alder reaction between Wightman reagent 58 and dienes 59.
Scheme 16: Regioselective reaction of 3-dienyl-2-azetidinones 62 with nitrosobenzene (47).
Scheme 17: The regioselective reaction of 1,3-butadienes 65 with various nitroso heterodienophiles 66.
Scheme 18: Catalysis of the nitroso hetero-Diels–Alder reaction by vanadium in the presence of the oxidant CHP...
Figure 4: 1,2-Oxazines synthesized in solution with moderate to high regioselectivity, showing the favored re...
Figure 5: 1,2-Oxazines synthesized in the solid phase with moderate to high regioselectivity, showing the fav...
Scheme 19: Regioselectivity of solution-phase nitroso hetero-Diels–Alder reaction with acyl and aryl nitroso d...
Scheme 20: Favored regioisomeric outcome for the solution and solid-phase reactions, giving hetero-Diels–Alder...
Figure 6: Favored regioisomers and regioisomeric ratios for 1,2-oxazines synthesized in solid phase (91, 93, ...
Scheme 21: Regiocontrol of the reaction between 3-dienyl-2-azetidinones and nitrosobenzene due to change in a ...
Scheme 22: Regiocontrol of the reaction between diene 111 and 2-methyl-6-nitrosopyridine (112) due to metal co...
Scheme 23: Asymmetric hetero-Diels–Alder reactions reported by Vasella [56].
Scheme 24: Asymmetric hetero-Diels–Alder reaction of cyclohexa-1,3-diene (120) with acylnitroso dienophile 119....
Scheme 25: Asymmetric induction with L-proline derivatives 124–126.
Scheme 26: Asymmetric cycloaddition of the acylnitroso compound 136 to diene 135.
Scheme 27: Asymmetric induction with arylmenthol-based nitroso dienophiles 142.
Scheme 28: Cycloaddition of silyloxycyclohexadiene 145 to the acylnitroso dienophile derived from (+)-camphors...
Scheme 29: Asymmetric reaction of O-isopropylidene-protected cis-cyclohexa-3,5-diene-1,2-diol 147 with mannofu...
Scheme 30: Synthesis of synthon 152 from 2-methoxyphenol 150 and chiral auxiliary 151.
Scheme 31: Asymmetric nitroso hetero-Diels–Alder reaction with Wightman chloronitroso reagent 58.
Scheme 32: Asymmetric 1,2-oxazine synthesis using chiral cyclic diene 157 and the application of this reaction...
Scheme 33: Asymmetric 1,2-oxazine synthesis using a chiral diene reported by Jones et al. [75]. aRegioisomeric rat...
Scheme 34: The nitroso hetero-Diels–Alder reaction of acyclic oxazolidine-substituted diene 170 and chiral 1-s...
Scheme 35: The nitroso hetero-Diels–Alder reaction of acyclic lactam-substituted diene 176 with various acylni...
Scheme 36: The hetero-Diels–Alder reaction of acylnitroso dienophile.
Scheme 37: The hetero-Diels–Alder reaction of arylnitroso dienophiles using Lewis acids.
Scheme 38: Asymmetric hetero-Diels–Alder reactions of chiral alkyl N-dienylpyroglutamates.
Scheme 39: Catalytic asymmetric arylnitroso reaction between mono-substituted 1,3-cyclohexadiene 196 and disub...
Figure 7: Plausible chelate intermediate complexes formed during the hetero-Diels–Alder reaction to give 1,2-...
Scheme 40: Catalytic asymmetric nitroso hetero-Diels–Alder between cyclic dienes and 2-nitrosopyridine.
Scheme 41: The reason for the increased enantioselectivity of stereoisomer 212 compared with stereoisomer 213.
Scheme 42: The copper-catalyzed nitroso hetero-Diels–Alder reaction of 6-methyl-2-nitrosopyridine (199) with p...
Scheme 43: Asymmetric nitroso hetero-Diels–Alder reaction of nitrosoarenes with dienylcarbamates catalyzed by ...
Scheme 44: The enantioselective hetero-Diels–Alder reaction between nitrosobenzene and (E)-2,4-pentadien-1-ol (...
Scheme 45: Asymmetric nitroso hetero-Diels–Alder reaction using tartaric acid ester chelation of the diene and...
Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides
- Franziska Hemmerling and
- Frank Hahn
Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148
- cyclisation modes triggers the interest on the responsible enzymes. Due to the relevance of heterocycles, understanding the enzymology of heterocycle formation is also an important milestone on the way to using the enzymes as chemoenzymatic tools in natural product synthesis and medicinal chemistry [6][7
Graphical Abstract
Scheme 1: Schematic description of the cyclisation reaction catalysed by TE domains. In most cases, the nucle...
Scheme 2: Mechanisms for the formation of oxygen heterocycles. The degree of substitution can differ from tha...
Scheme 3: Pyran-ring formation in pederin (24) biosynthesis. Incubation of recombinant PedPS7 with substrate ...
Scheme 4: The domain AmbDH3 from ambruticin biosynthesis catalyses the dehydration of 25 and subsequent cycli...
Scheme 5: SalBIII catalyses dehydration of 29 and subsequent cyclisation to tetrahydropyran 30 [18].
Figure 1: All pyranonaphtoquinones contain either the naphtha[2,3-c]pyran-5,10-dione (32) or the regioisomeri...
Scheme 6: Pyran-ring formation in actinorhodin (34) biosynthesis. DNPA: 4-dihydro-9-hydroxy-1-methyl-10-oxo-3H...
Scheme 7: Pyran formation in granaticin (36) biosynthesis. DNPA: 4-dihydro-9-hydroxy-1-methyl-10-oxo-3H-napht...
Scheme 8: Pyran formation in alnumycin (37) biosynthesis. Adapted from [21].
Scheme 9: Biosynthesis of pseudomonic acid A (61). The pyran ring is initially formed in 57 after dehydrogena...
Scheme 10: Epoxidation–cyclisation leads to the formation of the tetrahydropyran ring in the western part of t...
Scheme 11: a) Nonactin (70) is formed from heterodimers of (−)(+)-dimeric nonactic acid and (+)(−)-dimeric non...
Figure 2: Pamamycins (73) are macrodiolide antibiotics containing three tetrahydrofuran moieties, which are a...
Scheme 12: A PS domain homolog in oocydin A (76) biosynthesis is proposed to catalyse furan formation via an o...
Scheme 13: Mechanism of oxidation–furan cyclisation by AurH, which converts (+)-deoxyaureothin (77) into (+)-a...
Scheme 14: Leupyrrin A2 (80) and the proposed biosynthesis of its furylidene moiety [69,70].
Scheme 15: Asperfuranone (93) biosynthesis, adapted from [75].
Figure 3: The four major aflatoxins produced by Aspergilli are the types B1, B2, G1 and G2 (94–97). In the di...
Scheme 16: Overview on aflatoxin B1 (94) biosynthesis. HOMST = 11-hydroxy-O-methylsterigmatocystin [78,79,82-106].
Scheme 17: A zipper mechanism leads to the formation of oxygen heterocycles in monensin biosynthesis [109-111].
Scheme 18: Formation of the 2,6-dioxabicyclo[3.2.1]octane (DBO) ring system in aurovertin B (118) biosynthesis ...
Figure 4: Structures of the epoxide-containing polyketides epothilone A (119) and oleandomycin (120) [123-125].
Scheme 19: Structures of phoslactomycin B (121) (a) and jerangolid A (122) (b). The heterocycle-forming steps ...
Scheme 20: a) Structures of rhizoxin (130) and cycloheximide (131). Model for the formation of δ-lactones (b) ...
Scheme 21: EncM catalyses a dual oxidation sequence and following processing of the highly reactive intermedia...
Figure 5: Mesomeric structures of tetronates [138,139].
Figure 6: Structures of tetronates for which gene clusters have been sequenced. The tetronate moiety is shown...
Scheme 22: Conserved steps for formation and processing in several 3-acyl-tetronate biosynthetic pathways were...
Scheme 23: In versipelostatin A (153) biosynthesis, VstJ is a candidate enzyme for catalysing the [4 + 2] cycl...
Scheme 24: a) Structures of some thiotetronate antibiotics. b) Biosynthesis of thiolactomycin (165) as propose...
Scheme 25: Aureusidine synthase (AS) catalyses phenolic oxidation and conjugate addition of chalcones leading ...
Scheme 26: a) Oxidative cyclisation is a key step in the biosynthesis of spirobenzofuranes 189, 192 and 193. b...
Scheme 27: A bicyclisation mechanism forms a β-lactone and a pyrrolidinone and removes the precursor from the ...
Scheme 28: Spontaneous cyclisation leads to off-loading of ebelactone A (201) from the PKS machinery [163].
Scheme 29: Mechanisms for the formation of nitrogen heterocycles.
Scheme 30: Biosynthesis of highly substituted α-pyridinones. a) Feeding experiments confirmed the polyketide o...
Scheme 31: Acridone synthase (ACS) catalyses the formation of 1,3-dihydroxy-N-methylacridone (224) by condensa...
Scheme 32: A Dieckmann condensation leads to the formation of a 3-acyl-4-hydroxypyridin-2-one 227 and removes ...
Scheme 33: a) Biosynthesis of the pyridinone tenellin (234). b) A radical mechanism was proposed for the ring-...
Scheme 34: a) Oxazole-containing PKS–NRPS-derived natural products oxazolomycin (244) and conglobatin (245). b...
Scheme 35: Structure of tetramic acids 251 (a) and major tautomers of 3-acyltetramic acids 252a–d (b). Adapted...
Scheme 36: Equisetin biosynthesis. R*: terminal reductive domain. Adapted from [202].
Scheme 37: a) Polyketides for which a similar biosynthetic logic was suggested. b) Pseurotin A (256) biosynthe...
Figure 7: Representative examples of PTMs with varying ring sizes and oxidation patterns [205,206].
Scheme 38: Ikarugamycin biosynthesis. Adapted from [209-211].
Scheme 39: Tetramate formation in pyrroindomycin aglycone (279) biosynthesis [213-215].
Scheme 40: Dieckmann cyclases catalyse tetramate or 2-pyridone formation in the biosynthesis of, for example, ...
Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp2 C–H and sp3 C–H bonds
- Nivesh Kumar,
- Santanu Ghosh,
- Subhajit Bhunia and
- Alakesh Bisai
Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111
- (±)-25a–h in excellent yields (Scheme 9 and Scheme 10). Later, we envisioned that the oxidative coupling products having allyl, methallyl, dimethylallyl esters after Trost–Tsuji decarboxylative allylations could serve as an interesting platform for complex natural product synthesis after further synthetic
Graphical Abstract
Scheme 1: Synthesis of 2-oxindoles via oxidative processes.
Figure 1: Substrates scope of one-pot ‘transition-metal-free’ IDC. The syntheses of compounds 4a–s according ...
Figure 2: Further substrates scope of one-pot ‘transition metal-free’ IDC. Conditions A: KOt-Bu, iodine; cond...
Figure 3: Substrates scope of ‘transition-metal-free’ IDC using KOt-Bu/I2. Reproduced from [46].
Figure 4: C-Alkylation of anilides using KOt-Bu.
Figure 5: Substrates scope of ‘transition-metal-free’ IDC of C-alkylated anilides using DBU/I2.
Scheme 2: Oxidative coupling of C-arylated anilides (±)-11a–d. The synthesis of 12b as per method A has been ...
Scheme 3: Synthesis of spirocyclic product through IDC The synthesis of 14 as per method A has been reproduce...
Scheme 4: Dimerization of β-N-aryl-amidoesters 3a and b. Reproduced from [46].
Scheme 5: Synthesis of dimeric 2-oxindoles utilizing IDC. The syntheses of 19a and b have been reproduced fro...
Scheme 6: Plausible mechanism of ‘transition-metal-free’ IDC The mechanistic consideration in Scheme 6 has been repro...
Scheme 7: Intramolecular-dehydrogenative-coupling (IDC) of 3a and 5a. Reproduced from [46].
Scheme 8: IDC of 3a and 5a using different oxidants. Reproduced from [46].
Scheme 9: Synthesis of 3-substituted-2-oxindoles from benzyl esters.
Scheme 10: 3-Substituted-2-oxindoles from p-methoxybenzyl esters.
Scheme 11: Synthetic elaboration using Tsuji–Trost reactions. Reproduced from [46].
Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization
- Barry M. Trost,
- Michael C. Ryan and
- Meera Rao
Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110
- molecular architectures hold a particular interest to the chemical community, especially in the fields of natural product synthesis and drug design, researchers have made a significant effort to discover asymmetric variations of enyne cycloisomerization reactions [11][12]. Researchers have used a variety of
Graphical Abstract
Scheme 1: Divergent behavior of the palladium and ruthenium-catalyzed Alder–ene reaction.
Scheme 2: Some asymmetric enyne cycloisomerization reactions.
Figure 1: (a) Mechanism for the redox biscycloisomerization reaction. (b) Ruthenium catalyst containing a tet...
Scheme 3: Synthesis of p-anisyl catalyst 1.
Figure 2: Failed sulfinate ester syntheses.
Scheme 4: Using norephedrine-based oxathiazolidine-2-oxide 7 for chiral sulfoxide synthesis.
Scheme 5: (a) General synthetic sequence to access enyne bicycloisomerization substrates (b) Synthesis of 2-c...
Figure 3: Failed bicycloisomerization substrates. Reactions performed at 40 °C for 16 hours with 3 mol % of c...
Scheme 6: Deprotection of [3.1.0] bicycles and X-ray crystal structure of 76.
Scheme 7: ProPhenol-catalyzed addition of zinc acetylide to acetaldehyde for the synthesis of a chiral 1,6-en...
Figure 4: Diastereomeric metal complexes formed after alcohol coordination.
Scheme 8: Curtin–Hammitt scenario of redox bicycloisomerization in acetone.
The synthesis of functionalized bridged polycycles via C–H bond insertion
- Jiun-Le Shih,
- Po-An Chen and
- Jeremy A. May
Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97
- via C–H bond insertion by carbenes and nitrenes. Applications to natural product synthesis, a description of the essential elements in substrate-controlled reactions, and mechanistic details of transformations are presented. Overall, these transformations allow the construction of important ring
Graphical Abstract
Figure 1: Bridged polycyclic natural products.
Figure 2: Strategic limitations.
Scheme 1: Bridged rings from N–H bond insertions.
Scheme 2: The synthesis of deoxystemodin.
Scheme 3: A model system for ingenol.
Scheme 4: Formal synthesis of platensimycin.
Scheme 5: The formal synthesis of gerryine.
Scheme 6: Copper-catalyzed bridged-ring synthesis.
Scheme 7: Factors influencing insertion selectivity.
Scheme 8: Bridged-lactam formation.
Scheme 9: The total synthesis of (+)-codeine.
Scheme 10: A model system for irroratin.
Scheme 11: The utility of 1,6-insertion.
Scheme 12: Piperidine functionalization.
Scheme 13: Wilkinson’s catalyst for C–H bond insertion.
Scheme 14: Bridgehead insertion and the total synthesis of albene and santalene.
Scheme 15: The total synthesis of neopupukean-10-one.
Scheme 16: An approach to phomoidride B.
Scheme 17: Carbene cascade for fused bicycles.
Scheme 18: Cascade formation of bridged rings.
Scheme 19: Conformational effects.
Scheme 20: Hydrazone cascade reaction.
Scheme 21: Mechanistic studies.
Scheme 22: Gold carbene formation from alkynes.
Scheme 23: Au-catalyzed bridged-bicycle formation.
Scheme 24: Gold carbene/alkyne cascade.
Scheme 25: Gold carbene/alkyne cascade with C–H bond insertion.
Scheme 26: Platinum cascades.
Scheme 27: Tungsten cascade.
