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Search for "alkenes" in Full Text gives 558 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues
- Rashmi Singh,
- Tomas Horsten,
- Rashmi Prakash,
- Swapan Dey and
- Wim Dehaen
Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79
- polycyclic derivatives was designed. The procedures towards such polycyclic building blocks include C–H-arylation strategies. In the classical Meerwein reaction, aryldiazonium salts are used as the reagents to couple aryl groups to electron-poor alkenes, and this process is assumed to proceed via a free
Graphical Abstract
Figure 1: Biologically relevant 2-oxydibenzofuran-containing structures 1–6.
Figure 2: Representative bioactive structures containing benzofuro-fused pyridine analogues 7–9.
Scheme 1: Strategy for metal-free access to benzofuropyridine 13.
Scheme 2: Electrophilic aromatic substitution of 6-hydroxybenzofuro[2,3-b]pyridine (13).
Scheme 3: Synthesis of isomeric oxazole-fused derivatives.
Scheme 4: Fused derivatives from 16.
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
- alcohols having unactivated and unsubstituted alkenes, whereas the substituent adjacent to the hydroxy group in the homoallylic alcohol controls the oxonia-Cope rearrangement (see 273a–c). The alkyl substituent favored the exclusive formation of crossed THP derivatives, whereas 2-oxonia-Cope rearrangement
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 ...
Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions
- Dat Phuc Tran,
- Yuki Sato,
- Yuki Yamamoto,
- Shin-ichi Kawaguchi,
- Shintaro Kodama,
- Akihiro Nomoto and
- Akiya Ogawa
Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72
- reactivities. The method using V-40 as an initiator is successfully investigated for the regio- and stereoselective phosphinylphosphination of terminal alkynes giving the corresponding trans-isomers of 1-diphenylphosphinyl-2-diphenylthiophosphinyl-1-alkenes in good yields. The protocol can be applied to a wide
- using a radical initiator such as 1,1'-azobis(cyclohexane-1-carbonitrile) (V-40) (Scheme 1a) [45] or upon photoirradiation (Scheme 1b) [38] yields vic-bis(diphenylphosphino)alkenes in good yields. Unfortunately, this photoinduced reaction of Ph2PPPh2 was not applicable to alkenes [42]. To change the
- reactivity of the P–P bond, therefore, when the combination of pentavalent phosphorus and trivalent phosphorus was examined, it was found that the desired radical addition of Ph2P(X)PPh2 (X = O, S) to alkenes successfully occurred [42][43] (Scheme 1c and 1d). However, in the case of Ph2P(O)PPh2, its
Graphical Abstract
Scheme 1: Radical addition of Ph2PPPh2 and Ph2P(X)PPh2 to unsaturated C–C bonds.
Scheme 2: The addition of Ph2P(O)PPh2 (1) to 1-octyne (2a).
Scheme 3: Phosphinylphosphination of various terminal alkynes 2 with 1. aIsolated yields. V-40 = 1,1’-azobis(...
Scheme 4: Attempted radical addition to internal alkynes and insight into the addition to 2n.
Scheme 5: A plausible reaction pathway for the radical addition of Ph2P(O)PPh2 to terminal alkynes.
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
- unactivated olefins and alkynes. This approach employed 68 and Togni reagent 69 (electron acceptor) as substrates, NMM as electron donor, and pyrrolidin-2-one as solvent to give hydrotrifluoromethylated product 70 at room temperature (Scheme 24). CF3 was added to a variety of terminal alkenes, leading to
- triethylamine as additive at 20 °C and under 405 nm irradiation (Scheme 40). A standard residence time of 5 min was required for the full conversion via the EDA complex that formed by alkene and perfluoroalkyl iodide in flow, while longer residence times were requisite for less reactive alkenes. Moreover, the
- that could react with olefin 120 with an electron-withdrawing group to give alkylation product 121 under irradiation with light (Scheme 41). The reaction is compatible with various substrates, including alkenes, secondary alkylpyridinium ions, benzylic pyridinium ions, and primary alkylpyridinium ions
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.
Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles
- Ramazan Koçak and
- Arif Daştan
Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61
- electron-demand Diels–Alder cycloaddition reactions of alkenes with tetrazines are commonly used for the synthesis of dihydropyridazines and pyridazines [50][51][52][53][54]. In our previous study, we made a discovery that would form the basis of a new class of dyestuffs with skeletons unlike those of
Graphical Abstract
Figure 1: Structures of dibenzosuberenone 1 and pyridazine and pyrrole derivatives.
Figure 2: Structures of s-tetrazines 2a–l.
Scheme 1: Inverse electron-demand Diels–Alder reactions of dibenzosuberenone (1) with tetrazines 2a–l.
Scheme 2: Inverse electron-demand Diels–Alder reactions between dibenzosuberenone 1 and tetrazines 2ka and 2lb...
Scheme 3: Proposed reaction mechanism for the formation of dibenzosuberenone derivatives 3 and 4.
Scheme 4: Proposed mechanism for the formation of 5l.
Scheme 5: Oxidation of dihydropyridazines 3a–f. All reactions were carried in CH2Cl2 at room temperature (4e:...
Scheme 6: Synthesis of pyrrole 10a. a1.34 mmol 4a, Zinc (for 10aa: 6.68 mmol, for 10ab: 13.36 mmol), 10 mL gl...
Scheme 7: Synthesis of pyrrole 10b. a1.21 mmol 4b, 12.10 mmol Zinc, 118 °C, 2 h. b1.13 mmol 10ba, 1.69 mmol K...
Scheme 8: Synthesis of p-quinone methides 13–16. a1.77 mmol 11, 1.77 mmol 2, 5 mL toluene, 80 °C (13a: overni...
Scheme 9: Proposed mechanism for the formation of 13.
Figure 3: UV–vis spectra of 3c–f and 3k in CH3CN at rt (c = 5 μM).
Figure 4: Fluorescence spectra of 3c–f and 3k in CH3CN at rt (c = 5 μM).
Figure 5: Ambient (top) and fluorescence (bottom, under 365 nm UV light) images of 3c–f and 3k in CH3CN.
Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes
- Xiaojuan Li,
- Qiang Zhang,
- Weigang Zhang,
- Jinzhu Ma,
- Yi Wang and
- Yi Pan
Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49
- , Nanjing 210023, China School of pharmacy, Wannan Medical College, Wuhu, 241002, China 10.3762/bjoc.17.49 Abstract The difunctionalization of alkenes involving a trifluoromethylthio group (SCF3) for the conversion of versatile and readily available olefins into structurally more complex molecules has been
- successfully studied. However, the disproportionate dithiolation of alkenes is unknown. Herein, a transition-metal-free protocol is presented for the vicinal trifluoromethylthio–thiolation of unactivated alkenes via a radical process under mild conditions with a broad substrate scope and excellent tolerance
- . Keywords: alkenes; difunctionalization; metal-free; photoredox; trifluoromethylthiolation; Introduction The incorporation of fluorine atoms into drug molecules will significantly enhance the physical, chemical, and biological properties of the pharmaceuticals [1][2][3][4][5][6]. Modifying drug candidates
Graphical Abstract
Scheme 1: Origin of the reaction design.
Scheme 2: Substrate scope of disulfides.
Scheme 3: Substrate scope of unactivated alkenes.
Scheme 4: Control experiments.
Scheme 5: Proposed mechanism.
A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles
- Lucía Rossi-Fernández,
- Viviana Dorn and
- Gabriel Radivoy
Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46
- materials and it could be recovered and reused maintaining its unaltered high activity. Keywords: alkenes; cobalt nanoparticles; epoxides; oxidation; TBHP; Introduction Olefin oxidation reactions are key synthetic transformations in the production of oxygenated chemicals of high interest for both academic
- heterogeneous [33][34][35][36][37] Co-based catalysts have been applied to the epoxidation of alkenes, however, most of the reported methods lead to unsatisfactory yield, low selectivity, or limited substrate scope. Suib et al. [38] reported on the synthesis of mesoporous Co3O4 for the catalytic epoxidation of
- a variety of alkenes as an interesting heterogeneous system. This cobalt oxide mesoporous nanomaterial showed good activity and selectivity to the epoxide product and could be recovered and reused, but the multistep (not straightforward) synthesis of the catalyst and the use of DMF as the solvent
Graphical Abstract
Figure 1: TEM micrograph and size distribution graphic for CoNPs@MgO catalyst (scale bar = 20 nm).
Scheme 1: Plausible mechanistic pathway for olefin epoxidation catalyzed by CoNPs/MgO in the presence of t-Bu...
Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride
- Beatrice Lansbergen,
- Catherine S. Meister and
- Michael C. McLeod
Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36
- trichloride; dichloroalkenes; Friedel–Crafts alkylation; rearrangement; trifluoroalkanes; Introduction 1,1-Dichloro-1-alkenes are valuable synthetic intermediates and have been employed in Pd-mediated cross couplings of one or both chlorine atoms [1][2][3][4][5][6][7], carbonylation reactions [8], and C–H
- bond alkynylations of heteroarenes [9]. The 1,1-dichloro-1-alkenyl moiety is found in a number of pyrethroid insecticides including permethrin and marine natural products such as caracolamide A [10] (Figure 1). 1,1-Dichloro-1-alkenes 2 are commonly prepared from the corresponding aldehydes 1 in one
- dichloroalkenes [18][19][20]. The preparation of 1,1-dichloro-1-alkenes from hydrazones [21] and from 2,2,2-trichloroethyl carbonates [22] has also been reported. Internal difluoroalkanes have been used to generate chloroalkene products using AlEt2Cl [23][24]. In this article we describe the AlCl3-mediated
Graphical Abstract
Figure 1: Examples of biologically active 1,1-dichloro-1-alkenes.
Figure 2: a) Common methods for the preparation of 1,1-dichloro-1-alkenes from aldehydes. b) This work: a two...
Scheme 1: The initial attempt for the conversion of 1,1,1-trifluoroalkanone 5a to 1,1-dichloroalkenone 6a.
Scheme 2: Substrate scope for the reaction of 1,1,1 trifluoroalkanones with AlCl3. aPurification (normal or r...
Scheme 3: Proposed mechanism for the formation of dichloroalkene 6 from trifluoroalkanone 5.
Scheme 4: Formation of bicyclic ketones 9 and 10 from 1,1,1-trifluoroalkanone 5b using 7 equivalents of AlCl3....
Scheme 5: Conversion of 1,1,1-trifluoroalkanone 5n to acid chloride 13 with AlCl3, and possible mechanism.
Scheme 6: Conversion of 1,1,1-trifluoroalkane 16 to bicycle 17 upon treatment with AlCl3, and possible mechan...
Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives
- Alexander Leslie,
- Thomas S. Moody,
- Megan Smyth,
- Scott Wharry and
- Marcus Baumann
Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33
- utilizing electron-poor alkenes as the reaction partners that would undergo aza-Michael addition reactions on the Cbz-carbamates (Scheme 4). Driven by the desire to develop readily scalable routes towards the target products 8, continuous flow processing was again exploited. In a first approach the use of
Graphical Abstract
Scheme 1: The continuous flow set-up used.
Figure 1: Scope of Cbz-carbamate products obtained via flow process (*tRes = 60 min, **T = 80 °C; isolated yi...
Scheme 2: Side reaction during formation of product 3m.
Scheme 3: Flow set-up for the CALB-mediated impurity tagging approach.
Scheme 4: Strategies towards accessing β-amino acid derivatives 8.
Scheme 5: Complementary flow approaches towards the β-amino acid derivatives 8.
Scheme 6: Batch hydrolysis of the ester group in the presence of the carbamate.
CF3-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry
- Anthony J. Fernandes,
- Armen Panossian,
- Bastien Michelet,
- Agnès Martin-Mingot,
- Frédéric R. Leroux and
- Sébastien Thibaudeau
Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32
- (hetero)arenes [104][105] and alkenes [106] under Lewis acid activation but also with electron-rich arenes under thermal activation [107][108][109]. CF3-substituted hemiacetal 168 can react with amines to furnish the corresponding hemiaminal ethers, which can be further activated by a Lewis acid to
Graphical Abstract
Figure 1: Stabilizing interaction in the CF3CH2+ carbenium ion (top) and structure of the first observable fl...
Scheme 1: Isodesmic equations accounting for the destabilizing effect of the CF3 group. ΔE in kcal⋅mol−1, cal...
Scheme 2: Stabilizing effect of fluorine atoms by resonance electron donation in carbenium ions (δ in ppm).
Scheme 3: Direct in situ NMR observation of α-(trifluoromethyl)carbenium ion or protonated alcohols. Δδ = δ19...
Scheme 4: Reported 13C NMR chemical shifts for the α-(trifluoromethyl)carbenium ion 10c (δ in ppm).
Scheme 5: Direct NMR observation of α-(trifluoromethyl)carbenium ions in situ (δ in ppm).
Scheme 6: Illustration of the ion pair solvolysis mechanism for sulfonate 13f. YOH = solvent.
Figure 2: Solvolysis rate for 13a–i and 17.
Figure 3: Structures of allyl triflates 18 and 19 and allyl brosylate 20. Bs = p-BrC6H4SO2.
Figure 4: Structure of tosylate derivatives 21.
Figure 5: a) Structure of triflate derivatives 22. b) Stereochemistry outcomes of the reaction starting from (...
Scheme 7: Solvolysis reaction of naphthalene and anthracenyl derivatives 26 and 29.
Figure 6: Structure of bisarylated derivatives 34.
Figure 7: Structure of bisarylated derivatives 36.
Scheme 8: Reactivity of 9c in the presence of a Brønsted acid.
Scheme 9: Cationic electrocyclization of 38a–c under strongly acidic conditions.
Scheme 10: Brønsted acid-catalyzed synthesis of indenes 42 and indanes 43.
Scheme 11: Reactivity of sulfurane 44 in triflic acid.
Scheme 12: Solvolysis of triflate 45f in alcoholic solvents.
Scheme 13: Synthesis of labeled 18O-52.
Scheme 14: Reactivity of sulfurane 53 in triflic acid.
Figure 8: Structure of tosylates 56 and 21f.
Scheme 15: Resonance forms in benzylic carbenium ions.
Figure 9: Structure of pyrrole derivatives 58 and 59.
Scheme 16: Resonance structure 60↔60’.
Scheme 17: Ga(OTf)3-catalyzed synthesis of 3,3’- and 3,6’-bis(indolyl)methane from trifluoromethylated 3-indol...
Scheme 18: Proposed reaction mechanism.
Scheme 19: Metal-free 1,2-phosphorylation of 3-indolylmethanols.
Scheme 20: Superacid-mediated arylation of thiophene derivatives.
Scheme 21: In situ mechanistic NMR investigations.
Scheme 22: Proposed mechanisms for the prenyltransferase-catalyzed condensation.
Scheme 23: Influence of a CF3 group on the allylic SN1- and SN2-mechanism-based reactions.
Scheme 24: Influence of the CF3 group on the condensation reaction.
Scheme 25: Solvolysis of 90 in TFE.
Scheme 26: Solvolysis of allyl triflates 94 and 97 and isomerization attempt of 96.
Scheme 27: Proposed mechanism for the formation of 95.
Scheme 28: Formation of α-(trifluoromethyl)allylcarbenium ion 100 in a superacid.
Scheme 29: Lewis acid activation of CF3-substituted allylic alcohols.
Scheme 30: Bimetallic-cluster-stabilized α-(trifluoromethyl)carbenium ions.
Scheme 31: Reactivity of cluster-stabilized α-(trifluoromethyl)carbenium ions.
Scheme 32: α-(Trifluoromethyl)propargylium ion 122↔122’ generated from silyl ether 120 in a superacid.
Scheme 33: Formation of α-(trifluoromethyl)propargylium ions from CF3-substituted propargyl alcohols.
Scheme 34: Direct NMR observation of the protonation of some trifluoromethyl ketones in situ and the correspon...
Scheme 35: Selected resonance forms in protonated fluoroketone derivatives.
Scheme 36: Acid-catalyzed Friedel–Crafts reactions of trifluoromethyl ketones 143a,b and 147a–c.
Scheme 37: Enantioselective hydroarylation of CF3-substituted ketones.
Scheme 38: Acid-catalyzed arylation of ketones 152a–c.
Scheme 39: Reactivity of 156 in a superacid.
Scheme 40: Reactivity of α-CF3-substituted heteroaromatic ketones and alcohols as well as 1,3-diketones.
Scheme 41: Reactivity of 168 with benzene in the presence of a Lewis or Brønsted acid.
Scheme 42: Acid-catalyzed three-component asymmetric reaction.
Scheme 43: Anodic oxidation of amines 178a–c and proposed mechanism.
Scheme 44: Reactivity of 179b in the presence of a strong Lewis acid.
Scheme 45: Trifluoromethylated derivatives as precursors of trifluoromethylated iminium ions.
Scheme 46: Mannich reaction with trifluoromethylated hemiaminal 189.
Scheme 47: Suitable nucleophiles reacting with 192 after Lewis acid activation.
Scheme 48: Strecker reaction involving the trifluoromethylated iminium ion 187.
Scheme 49: Reactivity of 199 toward nucleophiles.
Scheme 50: Reactivity of 204a with benzene in the presence of a Lewis acid.
Scheme 51: Reactivity of α-(trifluoromethyl)-α-chloro sulfides in the presence of strong Lewis acids.
Scheme 52: Anodic oxidation of sulfides 213a–h and Pummerer rearrangement.
Scheme 53: Mechanism for the electrochemical oxidation of the sulfide 213a.
Scheme 54: Reactivity of (trifluoromethyl)diazomethane (217a) in HSO3F.
Figure 10: a) Structure of diazoalkanes 217a–c and b) rate-limiting steps of their decomposition.
Scheme 55: Deamination reaction of racemic 221 and enantioenriched (S)-221.
Scheme 56: Deamination reaction of labeled 221-d2. Elimination products were formed in this reaction, the yiel...
Scheme 57: Deamination reaction of 225-d2. Elimination products were also formed in this reaction in undetermi...
Scheme 58: Formation of 229 from 228 via 1,2-H-shift.
Scheme 59: Deamination reaction of 230. Elimination products were formed in this reaction, the yield of which ...
Scheme 60: Deamination of several diazonium ions. Elimination products were formed in these reactions, the yie...
Scheme 61: Solvolysis reaction mechanism of alkyl tosylates.
Scheme 62: Solvolysis outcome for the tosylates 248 and 249 in HSO3FSbF5.
Figure 11: Solvolysis rate of 248, 249, 252, and 253 in 91% H2SO4.
Scheme 63: Illustration of the reaction pathways. TsCl, pyridine, −5 °C (A); 98% H2SO4, 30 °C (B); 98% H2SO4, ...
Scheme 64: Proposed solvolysis mechanism for the aliphatic tosylate 248.
Scheme 65: Solvolysis of the derivatives 259 and 260.
Scheme 66: Solvolysis of triflate 261. SOH = solvent.
Scheme 67: Intramolecular Friedel–Crafts alkylations upon the solvolysis of triflates 264 and 267.
Scheme 68: α-CF3-enhanced γ-silyl elimination of cyclobutyltosylates 270a,b.
Scheme 69: γ-Silyl elimination in the synthesis of a large variety of CF3-substituted cyclopropanes. Pf = pent...
Scheme 70: Synthetic pathways to 281. aNMR yields.
Scheme 71: The cyclopropyl-substituted homoallylcyclobutylcarbenium ion manifold.
Scheme 72: Reactivity of CF3-substituted cyclopropylcarbinyl derivatives 287a–c. LG = leaving group.
Scheme 73: Reactivity of CF3-substituted cyclopropylcarbinyl derivatives 291a–c.
Scheme 74: Superacid-promoted dimerization or TFP.
Scheme 75: Reactivity of TFP in a superacid.
Scheme 76: gem-Difluorination of α-fluoroalkyl styrenes via the formation of a “hidden” α-RF-substituted carbe...
Scheme 77: Solvolysis of CF3-substituted pentyne 307.
Scheme 78: Photochemical rearrangement of 313.
Figure 12: Structure of 2-norbornylcarbenium ion 318 and argued model for the stabilization of this cation.
Figure 13: Structures and solvolysis rate (TFE, 25 °C) of the sulfonates 319–321. Mos = p-MeOC6H4SO2.
Scheme 79: Mechanism for the solvolysis of 323. SOH = solvent.
Scheme 80: Products formed by the hydrolysis of 328.
Scheme 81: Proposed carbenium ion intermediates in an equilibrium during the solvolysis of tosylates 328, 333,...
The preparation and properties of 1,1-difluorocyclopropane derivatives
- Kymbat S. Adekenova,
- Peter B. Wyatt and
- Sergazy M. Adekenov
Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25
- . The carbene-based methods typically give the highest yields when alkenes with electron-donating substituents are used. There are few examples in which the cyclopropanation by carbene methods of electron-deficient alkenes containing substituents with a large −M effect (for example, CO2R, COR, CN, SO2R
- halodifluoromethanes and alkenes (Scheme 2). The elimination of hydrogen halide from the halodifluoromethane under basic conditions (metal alkoxide or alkyllithium) generated difluorocarbene [14][15]. The low yields of the product have been attributed to the facile addition of the strong bases to difluorocarbene. The
- yields were best in the reactions with electron-rich alkenes and when a low concentration of the base was used to minimize the destruction of difluorocarbene. The use of oxirane or epichlorohydrin as hydrogen halide scavengers avoided the need for a stoichiometric amount of the strong base [16][17]. The
Graphical Abstract
Scheme 1: Synthesis of 1,1-difluoro-2,3-dimethylcyclopropane (2).
Scheme 2: Cyclopropanation via dehydrohalogenation of chlorodifluoromethane.
Scheme 3: Difluorocyclopropanation of methylstyrene 7 using dibromodifluoromethane and zinc.
Scheme 4: Synthesis of difluorocyclopropanes from the reaction of dibromodifluoromethane and triphenylphosphi...
Scheme 5: Generation of difluorocarbene in a catalytic two-phase system and its addition to tetramethylethyle...
Scheme 6: The reaction of methylstyrene 7 with chlorodifluoromethane (11) in the presence of a tetraarylarson...
Scheme 7: Pyrolysis of sodium chlorodifluoroacetate (12) in refluxing diglyme in the presence of alkene 13.
Scheme 8: Synthesis of boron-substituted gem-difluorocyclopropanes 16.
Scheme 9: Addition of sodium bromodifluoroacetate (17) to alkenes.
Scheme 10: Addition of sodium bromodifluoroacetate (17) to silyloxy-substituted cyclopropanes 20.
Scheme 11: Synthesis of difluorinated nucleosides.
Scheme 12: Addition of butyl acrylate (26) to difluorocarbene generated from TFDA (25).
Scheme 13: Addition of difluorocarbene to propargyl esters 27 and conversion of the difluorocyclopropenes 28 t...
Scheme 14: The generation of difluorocyclopropanes using MDFA 30.
Scheme 15: gem-Difluorocyclopropanation of styrene (32) using difluorocarbene generated from TMSCF3 (31) under...
Scheme 16: Synthesis of a gem-difluorocyclopropane derivative using HFPO (41) as a source of difluorocarbene.
Scheme 17: Cyclopropanation of (Z)-2-butene in the presence of difluorodiazirine (44).
Scheme 18: The cyclopropanation of 1-octene (46) using Seyferth's reagent (45) as a source of difluorocarbene.
Scheme 19: Alternative approaches for the difluorocarbene synthesis from trimethyl(trifluoromethyl)tin (48).
Scheme 20: Difluorocyclopropanation of cyclohexene (49).
Scheme 21: Synthesis of difluorocyclopropane derivative 53 using bis(trifluoromethyl)cadmium (51) as the diflu...
Scheme 22: Addition of difluorocarbene generated from tris(trifluoromethyl)bismuth (54).
Scheme 23: Addition of a stable (trifluoromethyl)zinc reagent to styrenes.
Scheme 24: The preparation of 2,2-difluorocyclopropanecarboxylic acids of type 58.
Scheme 25: Difluorocyclopropanation via Michael cyclization.
Scheme 26: Difluorocyclopropanation using N-acylimidazolidinone 60.
Scheme 27: Difluorocyclopropanation through the cyclization of phenylacetonitrile (61) and 1,2-dibromo-1,1-dif...
Scheme 28: gem-Difluoroolefins 64 for the synthesis of functionalized cyclopropanes 65.
Scheme 29: Preparation of aminocyclopropanes 70.
Scheme 30: Synthesis of fluorinated methylenecyclopropane 74 via selenoxide elimination.
Scheme 31: Reductive dehalogenation of (1R,3R)-75.
Scheme 32: Synthesis of chiral monoacetates by lipase catalysis.
Scheme 33: Transformation of (±)-trans-81 using Rhodococcus sp. AJ270.
Scheme 34: Transformation of (±)-trans-83 using Rhodococcus sp. AJ270.
Scheme 35: Hydrogenation of difluorocyclopropenes through enantioselective hydrocupration.
Scheme 36: Enantioselective transfer hydrogenation of difluorocyclopropenes with a Ru-based catalyst.
Scheme 37: The thermal transformation of trans-1,2-dichloro-3,3-difluorocyclopropane (84).
Scheme 38: cis–trans-Epimerization of 1,1-difluoro-2,3-dimethylcyclopropane.
Scheme 39: 2,2-Difluorotrimethylene diradical intermediate.
Scheme 40: Ring opening of stereoisomers 88 and 89.
Scheme 41: [1,3]-Rearrangement of alkenylcyclopropanes 90–92.
Scheme 42: Thermolytic rearrangement of 2,2-difluoro-1-vinylcyclopropane (90).
Scheme 43: Thermal rearrangement for ethyl 3-(2,2-difluoro)-3-phenylcyclopropyl)acrylates 93 and 95.
Scheme 44: Possible pathways of the ring opening of 1,1-difluoro-2-vinylcyclopropane.
Scheme 45: Equilibrium between 1,1-difluoro-2-methylenecyclopropane (96) and (difluoromethylene)cyclopropane 97...
Scheme 46: Ring opening of substituted 1,1-difluoro-2,2-dimethyl-3-methylenecyclopropane 98.
Scheme 47: 1,1-Difluorospiropentane rearrangement.
Scheme 48: Acetolysis of (2,2-difluorocyclopropyl)methyl tosylate (104) and (1,1-difluoro-2-methylcyclopropyl)...
Scheme 49: Ring opening of gem-difluorocyclopropyl ketones 106 and 108 by thiolate nucleophiles.
Scheme 50: Hydrolysis of gem-difluorocyclopropyl acetals 110.
Scheme 51: Ring-opening reaction of 2,2-difluorocyclopropyl ketones 113 in the presence of ionic liquid as a s...
Scheme 52: Ring opening of gem-difluorocyclopropyl ketones 113a by MgI2-initiated reaction with diarylimines 1...
Scheme 53: Ring-opening reaction of gem-difluorocyclopropylstannanes 117.
Scheme 54: Preparation of 1-fluorovinyl vinyl ketone 123 and the synthesis of 2-fluorocyclopentenone 124. TBAT...
Scheme 55: Iodine atom-transfer ring opening of 1,1-difluoro-2-(1-iodoalkyl)cyclopropanes 125a–c.
Scheme 56: Ring opening of bromomethyl gem-difluorocyclopropanes 130 and formation of gem-difluoromethylene-co...
Scheme 57: Ring-opening aerobic oxidation reaction of gem-difluorocyclopropanes 132.
Scheme 58: Dibrominative ring-opening functionalization of gem-difluorocyclopropanes 134.
Scheme 59: The selective formation of (E,E)- and (E,Z)-fluorodienals 136 and 137 from difluorocyclopropyl acet...
Scheme 60: Proposed mechanism for the reaction of difluoro(methylene)cyclopropane 139 with Br2.
Scheme 61: Thermal rearrangement of F2MCP 139 and iodine by CuI catalysis.
Scheme 62: Synthesis of 2-fluoropyrroles 142.
Scheme 63: Ring opening of gem-difluorocyclopropyl ketones 143 mediated by BX3.
Scheme 64: Lewis acid-promoted ring-opening reaction of 2,2-difluorocyclopropanecarbonyl chloride (148).
Scheme 65: Ring-opening reaction of the gem-difluorocyclopropyl ketone 106 by methanolic KOH.
Scheme 66: Hydrogenolysis of 1,1-difluoro-3-methyl-2-phenylcyclopropane (151).
Scheme 67: Synthesis of monofluoroalkenes 157.
Scheme 68: The stereoselective Ag-catalyzed defluorinative ring-opening diarylation of 1-trimethylsiloxy-2,2-d...
Scheme 69: Synthesis of 2-fluorinated allylic compounds 162.
Scheme 70: Pd-catalyzed cross-coupling reactions of gem-difluorinated cyclopropanes 161.
Scheme 71: The (Z)-selective Pd-catalyzed ring-opening sulfonylation of 2-(2,2-difluorocyclopropyl)naphthalene...
Figure 1: Structures of zosuquidar hydrochloride and PF-06700841.
Scheme 72: Synthesis of methylene-gem-difluorocyclopropane analogs of nucleosides.
Figure 2: Anthracene-difluorocyclopropane hybrid derivatives.
Figure 3: Further examples of difluorcyclopropanes in modern drug discovery.
Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions
- Jean C. Kazmierczak,
- Roberta Cargnelutti,
- Thiago Barcellos,
- Claudio C. Silveira and
- Ricardo F. Schumacher
Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24
- sulfides by the acetamidosulfenylation of alkenes [12], among others [13][14][15]. Sulfur-containing compounds are important intermediates in organic synthesis, being able to act as an electrophile or nucleophile in many organic transformations [16][17][18]. Still, many of them are pharmacologically active
Graphical Abstract
Figure 1: Drugs and agrochemicals containing the α-thiocarbonyl core as a structural motif.
Scheme 1: Methods for the synthesis of α-thiocarbonyl compounds by C–C bond cleavage of 1,3-dicarbonyl compou...
Scheme 2: Formation of the enol 6 from acetylacetone (5).
Scheme 3: Formation of thio-substituted keto–enol tautomers 7 and 8.
Scheme 4: Proposed mechanism for the synthesis of 3.
Scheme 5: A tentative pathway for the synthesis of 4.
Progress in the total synthesis of inthomycins
- Bidyut Kumar Senapati
Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7
- iii) an asymmetric Mukaiyama–Kiyooka aldol reaction (Scheme 16 and Scheme 17) [8]. The total synthesis was initiated with the preparation of two alkenes precursors (rac)-118 and 121. The tiglic aldehyde 115 was converted into silyl enol ether 116 followed by treatment with acetal 117 using a
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.
Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine
- Dimas J. P. Lima,
- Antonio E. G. Santana,
- Michael A. Birkett and
- Ricardo S. Porto
Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4
- acid in toluene. After 5 minutes, 1.2 equiv of tributyltin fluoride was added to intermediate A, and at the end of the process, 63a and 63b were obtained after chromatographic purification with 81% yield for 63a and 74% yield for 63b. Finally, the alkenes were oxidized in the presence of osmium
Graphical Abstract
Figure 1: Homotropane (azabicyclononane) systems.
Figure 2: Alkaloids (−)-adaline (1), (+)-euphococcinine (2) and (+)-N-methyleuphococcinine (3).
Scheme 1: Synthetic strategies before 1995.
Scheme 2: Synthesis (±)-adaline (1) and (±)-euphococcinine (2). Reagents and conditions: i) 1. dihydropyran, ...
Scheme 3: Synthesis (+)-euphococcinine (2). Reagents and conditions: i) H2O2, SeO2 (cat), acetone, rt, 88%; i...
Scheme 4: Synthesis (+)-euphococcinine (2). Reagents and conditions: i) 2,4-bis(4-phenoxyphenyl)-1,3-dithia-2...
Scheme 5: Synthesis of (±)-euphococcinine precursor (±)-42. Reagents and conditions: i) Bu3SnH, AIBN, toluene...
Scheme 6: Synthesis of (−)-adaline (1). Reagents and conditions: i) LiH2NBH3, THF, 40 °C, 88%; ii) TPAP, NMO,...
Scheme 7: Synthesis of (−)-adaline (1) and (−)-euphococcinine (2). Reagents and conditions: i) 1. BuLi, t-BuO...
Scheme 8: Synthesis of (−)-adaline (1). Reagents and conditions: i) Ref. [52]; ii) Et3N, TBDMSOTf, CH2Cl2, 0 °C t...
Scheme 9: Synthesis of (+)-euphococcinine (2). Reagents and conditions: i) 1. Cp2ZrCl2,AlMe3, CH2Cl2; 2. p-me...
Scheme 10: Synthesis of (−)-adaline 1. Reagents and conditions: i) 1. CuBr.DMS, Et2O/DMS, -42 ºC; 2. 1-heptyne...
Scheme 11: Synthesis of (−)-euphococcinine (2) and (−)-adaline (1). Reagents and conditions: i) 102, KHMDS, Et2...
Scheme 12: Synthesis of N-methyleuphococcinine 3. Reagents and conditions: i) 108 (1.5 equiv), 3,5-di-F-C6H3B(...
Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes
- Yajing Zhang,
- Qingshan Tian,
- Guozhu Zhang and
- Dayong Zhang
Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258
- . Among the strategies for constructing diverse alkenes containing two-heteroatom bonds, such as disulfonylation [14][15][16], heterohalogenation [17][18][19][20], bis(trifluoromethyl)thiolation [21], and phosphorylation [22], the direct heterodifunctionalization of alkynes using three-component reactions
- others concerning the silver-catalyzed phosphonofluorination of alkenes [24][25][26], we herein present a general silver-catalyzed regio- and stereoselective phosphonofluorination of alkynes using Selectfluor® and phosphonates as reactants (Scheme 1). This new silver-catalyzed approach to fluorinated
Graphical Abstract
Scheme 1: Metal-catalyzed difunctionalization of unsaturated carbon–carbon bonds.
Scheme 2: Substrate scope for the synthesis of the β-fluorovinylphosphonates 2 using diethyl phosphite. React...
Scheme 3: Substrate scope for the synthesis of the β-fluorovinylphosphonates 3 using dimethyl phosphite. Reac...
Scheme 4: Radical-trapping experiments.
Scheme 5: Proposed mechanism for the silver-catalyzed phosphonofluorination of alkynes.
Scheme 6: Attempted use of a suspected phosphonofluorination intermediate to synthesize a β-fluorovinylphosph...
Amine–borane complex-initiated SF5Cl radical addition on alkenes and alkynes
- Audrey Gilbert,
- Pauline Langowski,
- Marine Delgado,
- Laurent Chabaud,
- Mathieu Pucheault and
- Jean-François Paquin
Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256
- , France 10.3762/bjoc.16.256 Abstract The SF5Cl radical addition on unsaturated compounds was performed using an air-stable amine–borane complex as the radical initiator. This method showed to be complementary to the classic Et3B-mediated SF5Cl addition on alkenes and alkynes. A total of seven alkene and
- addition of SF5Cl on alkenes and alkynes (Scheme 1) [29][30]. This strategy represented a tremendous step forward in the pentafluorosulfanyl aliphatic chemistry, since it addressed the drawbacks that were previously reported with the use of SF5Cl as a reagent. It allows the SF5Cl addition to occur in the
- recently, it has been shown that some of these common amine–borane complexes can also be used as radical initiators for atom transfer radical addition of alkyl halides to alkenes [48]. They were also used in the free-radical polymerization of alkene-containing monomers such as methyl methacrylate or
Graphical Abstract
Scheme 1: Dolbier’s protocol for the SF5Cl radical addition on alkenes.
Scheme 2: Proposed mechanism for the amine–borane complex-initiated radical addition of SF5Cl on alkenes.
Figure 1: Structures and acronyms of the amine-borane complexes investigated.
Scheme 3: Scope of the Et3B and the DICAB-initiated SF5Cl additions on alkenes. Unless noted otherwise, isola...
Scheme 4: Scope of the Et3B and the DICAB-initiated SF5Cl additions on alkynes. Unless noted otherwise, isola...
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
- mechanism. (C) The completion of total synthesis of kopsanone (19). (A) Synthesis of phyllocladanol (21) features a Lewis acid-catalyzed formal intramolecular [3 + 2] cross-cycloaddition of cyclopropane 1,1-diesters with alkenes [68]. (B) (5,6-Dihydro-1,4-dithiin-2-yl)methanol 151 used as a versatile allyl
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...
3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia
- Florian Mann,
- Daiane Szczerbowski,
- Lisa de Silva,
- Melanie McClure,
- Marianne Elias and
- Stefan Schulz
Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228
- esters, minor amounts of alkanes and alkenes were present, as well as fatty acids. The latter occurred in varying amounts in the samples, maybe depending on variation in quality of the individual sample (see Tables S3 and S4, Supporting Information File 1). Acids are also present in other tissues of the
Graphical Abstract
Figure 1: Extended hairs (arrow) of the androconia of a male Ithomia salapia aquinia (Photo: Melanie McClure)....
Scheme 1: Pyrrolizidine alkaloid lycopsamine (1) and the putative pheromone compounds methyl hydroxydanaidoat...
Scheme 2: Biosynthetic formation of hedycaryol (7) and α-elemol (8).
Figure 2: Total ion current chromatogram of androconial extracts of male butterflies of the two subspecies I....
Figure 3: Proposed mass spectrometric formation of characteristic ions in prenyl and isoprenyl esters. Format...
Figure 4: Mass spectra and fragmentation of A: isoprenyl (3-methyl-3-butenyl) 9-octadenoate (9) and B: prenyl...
Figure 5: Mass spectra and fragmentation of A: isoprenyl 3-acetoxyoctadecanoate (11); B: isoprenyl (Z)-3-acet...
Scheme 3: Synthesis of isoprenyl 3-acetoxyoctadecanoate (11). a) IBX, EtOAc, 60 °C, 3.15 h, 99%; b) SnCl2, CH2...
Scheme 4: a) 48% HBraq, toluene, 24 h, 110 °C, 79%; b) IBX, EtOAc, 60 °C, 3.15 h, 90%; c) C5H11PPh3Br, LDA, T...
Figure 6: Separation of the enantiomers of methyl (Z)-3-hydroxy-13-octadecenoate (25) on a β-6-TBDMS hydrodex...
Scheme 5: Proposed biosynthetic pathway of fatty acids leading to the observed regioisomers of the isoprenyl ...
Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation
- Alexander P. Molchanov,
- Mariia M. Efremova,
- Mariya A. Kryukova and
- Mikhail A. Kuznetsov
Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218
- ]. A wide range of pharmaceuticals, agrochemicals, and other biologically active compounds are prepared using different types of (3 + n) cycloadditions, mainly with alkenes and alkynes [3][4][5][6][7]. For example, N,N'-cyclic azomethine imines are precursors of biologically active bicyclic
Graphical Abstract
Scheme 1: The two types of azomethine imines (AMI).
Scheme 2: Reaction of 1,5-diazabicyclo[3.1.0]hexanes 1a–d with diarylpropenones 2a–l.
Figure 1: Single-crystal X-ray structure of compound 3e.
Figure 2: Single-crystal X-ray structure of compound 3g.
Scheme 3: Control experiments.
Scheme 4: Mechanistic hypothesis for cycloaddition and cycloreversion reactions of diazabicyclohexane 1a with...
Scheme 5: Experiments on the trapping of azomethine imine, generated from pyrazolopyrazole 3g.
Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity
- Yuvixza Lizarme-Salas,
- Alexandra Daryl Ariawan,
- Ranjala Ratnayake,
- Hendrik Luesch,
- Angela Finch and
- Luke Hunter
Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216
- for E-alkenes in medicinal chemistry. Keywords: Alzheimer's disease; bioisostere; conformational analysis; gauche effect; stereoselective synthesis; Introduction Piperine (1, Figure 1) is a well-known natural product that is derived from peppercorns [1][2][3]. Many biological studies of 1 have been
- -workers have recently described a method for the one-step, diastereoselective 1,2-difluorination of alkenes, mediated by a hypervalent iodine catalyst [24]. The substrate scope of the Jacobsen method has certain constraints but their original report did include some examples of α,β-unsaturated amides, and
- motif is sometimes but not always an effective surrogate for E-alkenes suggests that this bioisosteric switch could be exploited more widely in medicinal chemistry as a means of increasing the selectivity of a lead compound towards its desired target. The natural product piperine (1) is the inspiration
Graphical Abstract
Figure 1: The natural product piperine (1) is the inspiration for this work; the crystal structure is shown [14]....
Scheme 1: The attempted synthesis of 6 (a diastereoisomer of 2) via a one-step 1,2-difluorination reaction [24]. ...
Scheme 2: The attempted synthesis of 2 via a stepwise fluorination approach (ether series). THF = tetrahydrof...
Scheme 3: Synthesis of compound 2 via a stepwise fluorination approach (ester series). DIC = diisopropylcarbo...
Figure 2: Conformational analysis of 2 by DFT and NMR. The numbering scheme for NMR spins is given on structu...
Figure 3: Analog 2 has greater stability to UV light than does piperine (1).
Figure 4: Biological activity of piperine (1) and derivative 2. (a) Inihbition of AChE by 1 (IC50 >1000 μM) a...
Synthesis of novel fluorinated building blocks via halofluorination and related reactions
- Attila Márió Remete,
- Tamás T. Novák,
- Melinda Nonn,
- Matti Haukka,
- Ferenc Fülöp and
- Loránd Kiss
Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208
- (bridgehead alkenes are only stable in large ring systems), elimination was attempted only with (rac)-2a,b, (rac)-5a, (rac)-6b, (rac)-8a,b, and (rac)-11a,b. DBU in THF under reflux was insufficient to promote the elimination of the halofluorinated diesters (rac)-2a,b, (rac)-5a, and (rac)-6b. In contrast, the
Graphical Abstract
Scheme 1: Proposed outcome of the halofluorination of (rac)-1. Only the main conformers of (rac)-1 and (rac)-...
Scheme 2: Halofluorination reactions of the trans-diester (rac)-1.
Scheme 3: Probable outcomes of the halofluorination of 4. Both conformers of the compounds 4, (rac)-T2a,b, an...
Scheme 4: Halofluorination reactions of the cis-diester 4. Important NOESY interactions are indicated by two-...
Scheme 5: Halofluorination reactions of the cis-tetrahydrophthalic imide derivative 7.
Scheme 6: Synthesis and halofluorination of the trans-imide (rac)-10.
Figure 1: Crystal structure of (rac)-11b.
Scheme 7: Synthesis of the cyclic carbamide (rac)-13.
Scheme 8: Halofluorination reactions of the γ-lactam (rac)-14. Relevant NOESY interactions are indicated by t...
Figure 2: Crystal structure of the product (rac)-15a.
Figure 3: Crystal structure of the product (rac)-15b.
Scheme 9: Reactions of the diester 16 with NBS or NIS in the presence or absence of Deoxo-Fluor®.
Scheme 10: Formation of the halolactons (rac)-17a,b. The initial attack of the halogen cation occurs at the st...
Scheme 11: Unsuccessful halofluorination of the bicyclic diester 18.
Scheme 12: Halofluorination reactions of the rigid tricyclic imine 19. The relevant NOESY interactions are mar...
Scheme 13: Mechanism of the halofluorination reactions of the substrate 19. X = Br (compounds a), I (compounds...
Scheme 14: Synthesis and halofluorination of the imide 24.
Scheme 15: Cyclizations of halofluorinated diesters with potassium tert-butoxide. Relevant NOESY interactions ...
Scheme 16: Mechanism of the reaction of the cyclopropanation of the compounds (rac)-2a,b and (rac)-5a with t-B...
Scheme 17: Presumed mechanism of the reaction of the compound (rac)-6b with t-BuOK.
Scheme 18: Cyclizations of halofluorinated tetrahydrophthalimides with DBU. Relevant NOESY interactions are ma...
Scheme 19: Mechanism for the formation of (rac)-28 from (rac)-11a,b. Although the formation of the compound (r...
Scheme 20: Fluoroselenations of the cyclohexenedicarboxylates (rac)-1 and 4.
Scheme 21: PhSe+-induced lactonization of the diester 16. Relevant NOESY interactions are marked with two-head...
Scheme 22: Oxidation of the fluoroselenide (rac)-30 under acidic and basic conditions.
Scheme 23: Oxidation of the fluoroselenide mixture (rac)-31 under acidic and basic conditions.
Recent developments in enantioselective photocatalysis
- Callum Prentice,
- James Morrisson,
- Andrew D. Smith and
- Eli Zysman-Colman
Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197
- (hydrogen atom transfer) catalysis to allow the use of alkenes as the alkylating agent either in an intermolecular process using aldehydes 10 and alkenes 11 or intramolecularly using aldehydes 12 (Scheme 2) [27]. The proposed mechanism again proceeds via the formation of an enamine intermediate 13 that then
- could proceed catalytically and with a broad scope using amine catalyst 86 with enones 87 and alkenes 88 without the need for an external photocatalyst (Scheme 11b) [49]. The mechanism proposed by Alemán begins with the condensation of 86 with 87 to generate iminium ion 89, which has a suitably low
- carboxylic acids 155 with alkenes 156. A low yielding benzylation reaction was required for determination of enantioselectivities and a large excess of alkene was required for the reaction. The reaction is proposed to proceed via hydrogen-bonded complex 157, that lowers the triplet energy of the carboxylic
Graphical Abstract
Scheme 1: Amine/photoredox-catalysed α-alkylation of aldehydes with alkyl bromides bearing electron-withdrawi...
Scheme 2: Amine/HAT/photoredox-catalysed α-functionalisation of aldehydes using alkenes.
Scheme 3: Amine/cobalt/photoredox-catalysed α-functionalisation of ketones and THIQs.
Scheme 4: Amine/photoredox-catalysed α-functionalisation of aldehydes or ketones with imines. (a) Using keton...
Scheme 5: Bifunctional amine/photoredox-catalysed enantioselective α-functionalisation of aldehydes.
Scheme 6: Bifunctional amine/photoredox-catalysed α-functionalisation of aldehydes using amine catalysts via ...
Scheme 7: Amine/photoredox-catalysed RCA of iminium ion intermediates. (a) Synthesis of quaternary stereocent...
Scheme 8: Bifunctional amine/photoredox-catalysed RCA of enones in a radical chain reaction initiated by an i...
Scheme 9: Bifunctional amine/photoredox-catalysed RCA reactions of iminium ions with different radical precur...
Scheme 10: Bifunctional amine/photoredox-catalysed radical cascade reactions between enones and alkenes with a...
Scheme 11: Amine/photocatalysed photocycloadditions of iminium ion intermediates. (a) External photocatalyst u...
Scheme 12: Amine/photoredox-catalysed addition of acrolein (94) to iminium ions.
Scheme 13: Dual NHC/photoredox-catalysed acylation of THIQs.
Scheme 14: NHC/photocatalysed spirocyclisation via photoisomerisation of an extended Breslow intermediate.
Scheme 15: CPA/photoredox-catalysed aza-pinacol cyclisation.
Scheme 16: CPA/photoredox-catalysed Minisci-type reaction between azaarenes and α-amino radicals.
Scheme 17: CPA/photoredox-catalysed radical additions to azaarenes. (a) α-Amino radical or ketyl radical addit...
Scheme 18: CPA/photoredox-catalysed reduction of azaarene-derived substrates. (a) Reduction of ketones. (b) Ex...
Scheme 19: CPA/photoredox-catalysed radical coupling reactions of α-amino radicals with α-carbonyl radicals. (...
Scheme 20: CPA/photoredox-catalysed Povarov reaction.
Scheme 21: CPA/photoredox-catalysed reactions with imines. (a) Decarboxylative imine generation followed by Po...
Scheme 22: Bifunctional CPA/photocatalysed [2 + 2] photocycloadditions.
Scheme 23: PTC/photocatalysed oxygenation of 1-indanone-derived β-keto esters.
Scheme 24: PTC/photoredox-catalysed perfluoroalkylation of 1-indanone-derived β-keto esters via a radical chai...
Scheme 25: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloadditions of quinolon...
Scheme 26: Bifunctional hydrogen bonding/photocatalysed intramolecular RCA cyclisation of a quinolone.
Scheme 27: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloadditions of quinolon...
Scheme 28: Bifunctional hydrogen bonding/photocatalysed [2 + 2] photocycloaddition reactions. (a) First use of...
Scheme 29: Bifunctional hydrogen bonding/photocatalysed deracemisation of allenes.
Scheme 30: Bifunctional hydrogen bonding/photocatalysed deracemisation reactions. (a) Deracemisation of sulfox...
Scheme 31: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloaddition of coumarins....
Scheme 32: Bifunctional hydrogen bonding/photocatalysed [2 + 2] photocycloadditions of quinolones. (a) Intramo...
Scheme 33: Hydrogen bonding/photocatalysed formal arylation of benzofuranones.
Scheme 34: Hydrogen bonding/photoredox-catalysed dehalogenative protonation of α,α-chlorofluoro ketones.
Scheme 35: Hydrogen bonding/photoredox-catalysed reductions. (a) Reduction of 1,2-diketones. (b) Reduction of ...
Scheme 36: Hydrogen bonding/HAT/photocatalysed deracemisation of cyclic ureas.
Scheme 37: Hydrogen bonding/HAT/photoredox-catalysed synthesis of cyclic sulfonamides.
Scheme 38: Hydrogen bonding/photoredox-catalysed reaction between imines and indoles.
Scheme 39: Chiral cation/photoredox-catalysed radical coupling of two α-amino radicals.
Scheme 40: Chiral phosphate/photoredox-catalysed hydroetherfication of alkenols.
Scheme 41: Chiral phosphate/photoredox-catalysed synthesis of pyrroloindolines.
Scheme 42: Chiral anion/photoredox-catalysed radical cation Diels–Alder reaction.
Scheme 43: Lewis acid/photoredox-catalysed cycloadditions of carbonyls. (a) Formal [2 + 2] cycloaddition of en...
Scheme 44: Lewis acid/photoredox-catalysed RCA reaction using a scandium Lewis acid between α-amino radicals a...
Scheme 45: Lewis acid/photoredox-catalysed RCA reaction using a copper Lewis acid between α-amino radicals and...
Scheme 46: Lewis acid/photoredox-catalysed synthesis of 1,2-amino alcohols from aldehydes and nitrones using a...
Scheme 47: Lewis acid/photocatalysed [2 + 2] photocycloadditions of enones and alkenes.
Scheme 48: Meggers’s chiral-at-metal catalysts.
Scheme 49: Lewis acid/photoredox-catalysed α-functionalisation of ketones with alkyl bromides bearing electron...
Scheme 50: Bifunctional Lewis acid/photoredox-catalysed radical coupling reaction using α-chloroketones and α-...
Scheme 51: Lewis acid/photocatalysed RCA of enones. (a) Using aldehydes as acyl radical precursors. (b) Other ...
Scheme 52: Bifunctional Lewis acid/photocatalysis for a photocycloaddition of enones.
Scheme 53: Lewis acid/photoredox-catalysed RCA reactions of enones using DHPs as radical precursors.
Scheme 54: Lewis acid/photoredox-catalysed functionalisation of β-ketoesters. (a) Hydroxylation reaction catal...
Scheme 55: Bifunctional copper-photocatalysed alkylation of imines.
Scheme 56: Copper/photocatalysed alkylation of imines. (a) Bifunctional copper catalysis using α-silyl amines....
Scheme 57: Bifunctional Lewis acid/photocatalysed intramolecular [2 + 2] photocycloaddition.
Scheme 58: Bifunctional Lewis acid/photocatalysed [2 + 2] photocycloadditions (a) Intramolecular cycloaddition...
Scheme 59: Bifunctional Lewis acid/photocatalysed rearrangement of 2,4-dieneones.
Scheme 60: Lewis acid/photocatalysed [2 + 2] cycloadditions of cinnamate esters and styrenes.
Scheme 61: Nickel/photoredox-catalysed arylation of α-amino acids using aryl bromides.
Scheme 62: Nickel/photoredox catalysis. (a) Desymmetrisation of cyclic meso-anhydrides using benzyl trifluorob...
Scheme 63: Nickel/photoredox catalysis for the acyl-carbamoylation of alkenes with aldehydes using TBADT as a ...
Scheme 64: Bifunctional copper/photoredox-catalysed C–N coupling between α-chloro amides and carbazoles or ind...
Scheme 65: Bifunctional copper/photoredox-catalysed difunctionalisation of alkenes with alkynes and alkyl or a...
Scheme 66: Copper/photoredox-catalysed decarboxylative cyanation of benzyl phthalimide esters.
Scheme 67: Copper/photoredox-catalysed cyanation reactions using TMSCN. (a) Propargylic cyanation (b) Ring ope...
Scheme 68: Palladium/photoredox-catalysed allylic alkylation reactions. (a) Using alkyl DHPs as radical precur...
Scheme 69: Manganese/photoredox-catalysed epoxidation of terminal alkenes.
Scheme 70: Chromium/photoredox-catalysed allylation of aldehydes.
Scheme 71: Enzyme/photoredox-catalysed dehalogenation of halolactones.
Scheme 72: Enzyme/photoredox-catalysed dehalogenative cyclisation.
Scheme 73: Enzyme/photoredox-catalysed reduction of cyclic imines.
Scheme 74: Enzyme/photocatalysed enantioselective reduction of electron-deficient alkenes as mixtures of (E)/(Z...
Scheme 75: Enzyme/photoredox catalysis. (a) Deacetoxylation of cyclic ketones. (b) Reduction of heteroaromatic...
Scheme 76: Enzyme/photoredox-catalysed synthesis of indole-3-ones from 2-arylindoles.
Scheme 77: Enzyme/HAT/photoredox catalysis for the DKR of primary amines.
Scheme 78: Bifunctional enzyme/photoredox-catalysed benzylic C–H hydroxylation of trifluoromethylated arenes.
Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners
- Shakeel Alvi and
- Rashid Ali
Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186
- been noticed from the literature that the construction of these types of sterically hindered tetrasubstituted alkenes is really difficult through McMurry coupling reaction or by other means (Scheme 14). 2.2 Functionalization at benzene ring(s) bay positions In another event, the Sakuria group has also
Graphical Abstract
Figure 1: Representation of corannulene (1) and sumanene (2), the subunits of fullerene (C60).
Scheme 1: Mehta’s unsuccessful effort for the synthesis of sumanene scaffold 2.
Scheme 2: First synthesis of sumanene 2 by Sakurai et al. from norbornadiene 10.
Scheme 3: Synthesis of trimethylsumanene 28 from easily accessible norbornadiene (10).
Scheme 4: Generation of anions 29–31 and the preparation of tris(trimethylsilyl)sumanene 32.
Scheme 5: Synthesis of tri- and hexa-substituted sumanene derivatives.
Scheme 6: Synthesis of bowl-shaped π-extended sumanene derivatives 37a–f.
Scheme 7: Synthesis of monooxasumanene 38, trioxosumanene 40 along with imination of them.
Scheme 8: Synthesis of trimethylsumanenetrione 46 and exo-functionalized products 45a,b.
Scheme 9: Synthesis of bisumanenylidene 47 and sumanene dimer 48 from 2.
Scheme 10: The mono-substitution of 2 to generate diverse mono-sumanene derivatives 49a–d.
Scheme 11: Synthesis of sumanene building block 53 useful for further extension.
Scheme 12: Synthesis of hexafluorosumanene derivative 55 by Sakurai and co-workers.
Scheme 13: Preparation of sumanene-based carbene 60 and its reaction with cyclohexane.
Scheme 14: Barton–Kellogg reaction for the synthesis of sterically hindered alkenes.
Scheme 15: Synthesis of hydroxysumanene 68 by employing Baeyer–Villiger oxidation.
Scheme 16: Synthesis of sumanene derivatives having functionality at an internal carbon.
Scheme 17: Mechanism for nucleophilic substitution reaction at the internal carbon.
Scheme 18: Synthesis of diverse monosubstituted sumanene derivatives.
Scheme 19: Synthesis of di- and trisubstituted sumanene derivatives from sumanene (2).
Scheme 20: Preparation of monochlorosumanene 88 and hydrogenation of sumanene (2).
Scheme 21: The dimer 90 and bissumanenyl 92 achieved from halosumannes.
Scheme 22: Pyrenylsumanene 93 involving the Suzuki-coupling as a key transformation.
Scheme 23: Synthesis of various hexaarylsumanene derivatives using the Suzuki-coupling reaction.
Scheme 24: Synthesis of hexasubstituted sumanene derivatives 96 and 97.
Scheme 25: Synthesis of thioalkylsumanenes via an aromatic nucleophilic substitution reaction.
Scheme 26: Synthesis of tris(ethoxycarbonylethenyl)sumanene derivative 108.
Scheme 27: Synthesis of ferrocenyl-based sumanene derivatives.
Scheme 28: Synthesis of sumanenylferrocene architectures 118 and 119 via Negishi coupling.
Scheme 29: Diosmylation and the synthesis of phenylboronate ester 121 of sumanene.
Scheme 30: Synthesis of the iron-complex of sumanene.
Scheme 31: Synthesis of tri- and mononuclear sumanenyl zirconocene complexes.
Scheme 32: Synthesis of [CpRu(η6-sumanene)]PF6.
Scheme 33: Preparation of sumanene-based porous coordination networks 127 (spherical tetramer units) and 128 (...
Scheme 34: Synthesis of sumanenylhafnocene complexes 129 and 130.
Scheme 35: Synthesis of 134 and 135 along with PdII coordination complex 136.
Scheme 36: Synthesis of alkali metals sumanene complex K7(C21H102−)2(C21H93−)·8THF (137) containing di- and tr...
Scheme 37: The encapsulation of a Cs+ ion between two sumanenyl anions.
Scheme 38: Synthesis of monothiasumanene 140 and dithiasumanene 141 from 139.
Scheme 39: Synthesis of trithiasumanene 151 by Otsubo and his co-workers.
Scheme 40: Synthesis of trithiasumanene derivatives 155 and 156.
Scheme 41: Synthetic route towards hexathiolated trithiasumanenes 158.
Scheme 42: Synthesis of triselenasumanene 160 by Shao and teammates.
Scheme 43: Synthesis of tritellurasumanene derivatives from triphenylene skeletons.
Scheme 44: Synthesis of pyrazine-fused sumanene architectures through condensation reaction.
Scheme 45: Treatment of the trichalcogenasumanenes with diverse oxidative reagents.
Scheme 46: Ring-opening reaction with H2O2 and oxone of heterasumanenes 178 and 179.
Scheme 47: Synthesis of polycyclic compounds from sumanene derivatives.
Scheme 48: Synthesis of diimide-based heterocycles reported by Shao’s and co-workers.
Scheme 49: Synthesis of pristine trichalcogenasumanenes, 151, 205, and 206.
Scheme 50: Synthesis of trichalcogenasumanenes via hexaiodotriphenylene precursor 208.
Scheme 51: Synthesis of trisilasumanenes 214 and 215.
Scheme 52: Synthesis of trisilasumanene derivatives 218 and 219.
Scheme 53: Synthesis of novel trigermasumanene derivative 223.
Scheme 54: An attempt towards the synthesis of tristannasumanene derivative 228.
Scheme 55: Synthesis of triphosphasumanene trisulfide 232 from commercially available 229.
Scheme 56: The doping of sumanene derivatives with chalcogens (S, Se, Te) and phosphorus.
Scheme 57: Synthesis of heterasumanene containing three different heteroatoms.
Scheme 58: Synthesis of trichalcogenasumanene derivatives 240 and 179.
Scheme 59: Preparation of trichalcogenasumanenes 245 and 248.
Scheme 60: Design and synthesis of trichalcogenasumanene derivatives 252 and 178.
Scheme 61: Synthesis of spirosumanenes 264–269 and non-spiroheterasumanenes 258–263.
Scheme 62: Synthesis of sumanene-type hetero polycyclic compounds.
Scheme 63: Synthesis of triazasumanenes 288 and its sulfone congener 287.
Scheme 64: Synthesis of C3-symmetric chiral triaryltriazasumanenes via cross-coupling reaction.
Scheme 65: Synthesis of mononaphthosumanene 293 using Suzuki coupling as a key step.
Scheme 66: Synthesis of di- and trinaphthosumanene derivatives 302–304.
Scheme 67: Synthesis of hemifullerene skeletons by Hirao’s group.
Scheme 68: Design and construction of C70 fragment from a C60 sumanene fragment.
Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis
- Shahboz Yakubov and
- Joshua P. Barham
Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183
- does not require the introduction of other functional groups. Although many methods have been developed for fluorination reactions [3][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], including the addition of electrophilic fluorine to alkenes [1][28][32], the fluorination
Graphical Abstract
Figure 1: Fluorine-containing drugs.
Figure 2: Fluorinated agrochemicals.
Scheme 1: Selectivity of fluorination reactions.
Scheme 2: Different mechanisms of photocatalytic activation. Sub = substrate.
Figure 3: Jablonski diagram showing visible-light-induced energy transfer pathways: a) absorption, b) IC, c) ...
Figure 4: Schematic illustration of TTET.
Figure 5: Organic triplet PSCats.
Figure 6: Additional organic triplet PSCats.
Figure 7: A) Further organic triplet PSCats and B) transition metal triplet PSCats.
Figure 8: Different fluorination reagents grouped by generation.
Scheme 3: Synthesis of Selectfluor®.
Scheme 4: General mechanism of PS TTET C(sp3)–H fluorination.
Scheme 5: Selective benzylic mono- and difluorination using 9-fluorenone and xanthone PSCats, respectively.
Scheme 6: Chen’s photosensitized monofluorination: reaction scope.
Scheme 7: Chen’s photosensitized benzylic difluorination reaction scope.
Scheme 8: Photosensitized monofluorination of ethylbenzene on a gram scale.
Scheme 9: Substrate scope of Tan’s AQN-photosensitized C(sp3)–H fluorination.
Scheme 10: AQN-photosensitized C–H fluorination reaction on a gram scale.
Scheme 11: Reaction mechanism of the AQN-assisted fluorination.
Figure 9: 3D structures of the singlet ground and triplet excited states of Selectfluor®.
Scheme 12: Associated transitions for the activation of acetophenone by violet light.
Scheme 13: Ethylbenzene C–H fluorination with various PSCats and conditions.
Scheme 14: Effect of different PSCats on the C(sp3)–H fluorination of cyclohexane (39).
Scheme 15: Reaction scope of Chen’s acetophenone-photosensitized C(sp3)–H fluorination reaction.
Figure 10: a) Site-selectivity of Chen’s acetophenone-photosensitized C–H fluorination reaction [201]. b) Site-sele...
Scheme 16: Formation of the AQN–Selectfluor® exciplex Int1.
Scheme 17: Generation of the C3 2° pentane radical and the Selectfluor® N-radical cation from the exciplex.
Scheme 18: Hydrogen atom abstraction by the Selectfluor® N-radical cation from pentane to give the C3 2° penta...
Scheme 19: Fluorine atom transfer from Selectfluor® to the C3 2° pentane radical to yield 3-fluoropentane and ...
Scheme 20: Barrierless fluorine atom transfer from Int1 to the C3 2° pentane radical to yield 3-fluoropentane,...
Scheme 21: Ketone-directed C(sp3)–H fluorination.
Scheme 22: Ketone-directed fluorination through a 5- and a 6-membered transition state, respectively.
Scheme 23: Effect of different PSCats on the photosensitized C(sp3)–H fluorination of 47.
Scheme 24: Substrate scope of benzil-photoassisted C(sp3)–H fluorinations.
Scheme 25: A) Benzil-photoassisted enone-directed C(sp3)–H fluorination. B) Classification of the reaction mod...
Scheme 26: A) Xanthone-photoassisted ketal-directed C(sp3)–H fluorination. B) Substrate scope. C) C–H fluorina...
Scheme 27: Rationale for the selective HAT at the C2 C–H bond of galactose acetonide.
Scheme 28: Photosensitized C(sp3)–H benzylic fluorination of a peptide using different PSCats.
Scheme 29: Peptide scope of 5-benzosuberenone-photoassisted C(sp3)–H fluorinations.
Scheme 30: Continuous flow PS TTET monofluorination of 72.
Scheme 31: Photosensitized C–H fluorination of N-butylphthalimide as a PSX.
Scheme 32: Substrate scope and limitations of the PSX C(sp3)–H monofluorination.
Scheme 33: Substrate crossover monofluorination experiment.
Scheme 34: PS TTET mechanism proposed by Hamashima and co-workers.
Scheme 35: Photosensitized TFM of 78 to afford α-trifluoromethylated ketone 80.
Scheme 36: Substrate scope for photosensitized styrene TFM to give α-trifluoromethylated ketones.
Scheme 37: Control reactions for photosensitized TFM of styrenes.
Scheme 38: Reaction mechanism for photosensitized TFM of styrenes to afford α-trifluoromethylated ketones.
Scheme 39: Reaction conditions for TFMs to yield the cis- and the trans-product, respectively.
Scheme 40: Substrate scope of trifluoromethylated (E)-styrenes.
Scheme 41: Strategies toward trifluoromethylated (Z)-styrenes.
Scheme 42: Substrate scope of trifluoromethylated (Z)-styrenes.
Scheme 43: Reaction mechanism for photosensitized TFM of styrenes to afford E- or Z-products.
Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes
- Thomas Schneider,
- Michael Keim,
- Bianca Seitz and
- Gerhard Maas
Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173
- concerted conrotatory process [47][48] would create a strained cis,trans-dihydrobenzo[8]annulene ring system. Cyclobutenes resulting from a [2 + 2] cycloaddition of electrophilic alkynes and alkenes under moderate thermal conditions have been isolated also from the reaction of CF3-free propyniminium salts
- with cyclic enol ethers [49] and of other very electrophilic alkynes (i.e., Lewis acid-activated acetylenic esters [50], 1-(trifluoroacetyl)-3-haloacetylenes [44] and 4-chloro-2-oxobut-3-ynoic esters [51][52][53] with unactivated alkenes (including cyclohexene [51], which did not react with 1a). For
Graphical Abstract
Scheme 1: Diels–Alder reaction of propyn-1-iminium salt 1a compared with the reported [29] reaction of 4-phenyl-1...
Scheme 2: Sequential Diels–Alder/intramolecular SE(Ar) reaction of propyn-1-iminium triflates 1a,b. Condition...
Scheme 3: Diels–Alder reaction of 1a and anthracene followed by an intramolecular SE(Ar) reaction.
Figure 1: Solid-state molecular structure of 11 (ORTEP plot).
Scheme 4: Reactions of propyn-1-iminium salt 1a with styrenes.
Figure 2: Solid-state molecular structure of 12c (ORTEP plot).
Figure 3: Solid-state molecular structure of 12d (ORTEP plot). Both the R and the S enantiomer are present in...
Scheme 5: A mechanistic proposal for the reaction of alkyne 1a with styrenes.
Scheme 6: Reaction of alkyne 1a with 1,2-dihydronaphthalene.
Scheme 7: Synthesis and solid-state molecular structure (ORTEP plot) of pentafulvene 19; selected bond distan...
Scheme 8: Proposed mechanistic pathway leading to fulvene 19.
