Cyclopropanation ylide-mediated

Stabilized sulfonium ylides react with cyclopentenone to give the corresponding cyclopropane with high diastereoselectivity as a result of base- or ylide-mediated (g) equilibration of the intermediate betaine.38 When using chiral sulfonium ylides, betaine equilibration compromises enantioselectivity, because whereas one diastereomer ring closes rapidly, the other diastereomer undergoes epimerization at the ester stereocentre, ultimately leading to the opposite enantiomer of the cyclopropane. 

Nitrogen Ylide-Mediated Cyclopropanation 10.4.3.1 Development of a Catalytic Method... 

Scheme 10.27 Proposed mechanism for N-ylide-mediated catalytic cyclopropanation.

Aggarwal VK, Winn CL. Catalytic, asymmetric sulfur ylide-mediated epoxidation of carbonyl compounds scope, selectivity, and applications in synthesis. Acc. Chem. Res. 2004 37 611-620. Li A-H, Dai L-X, Aggarwal VK. Asymmetric ylide reactions epoxidation, cyclopropanation, aziridination, olefination, and rearrangement. Chem. Rev. 1997 97 2341-2372. 

The cyclopropanation of a, (3-unsaturated carbonyls can be achieved using metal-free ylides. This is an attractive strategy avoiding the use of expensive metal-based catalysts and potentially hazardous diazo compounds. Two main approaches to the asymmetric ylide-mediated cyclopropanation have been developed, both utilising enantiopure amines as catalysts. 

Riches, S. L., Saha, C., Filgueira, N. F., Grange, E., McGarrigle, E. M., Aggarwal, V. K. (2010). On the mechanism of ylide-mediated cyclopropanations evidence for a proton-transfer step and its effect on stereoselectivity. Journal of the American Chemical Society, 132,7626-7630. 

Highly enantioselective ylide-type covalent catalysis has been achieved with sulfides, phosphines, tertiary amines, selenides, and teUurides, and the reported reaction types include epoxidation, aziridination, cyclopropanation, and other cyclization reactions. So far, the sulfur ylide-mediated reactions are the best... 

Methylene difluorocyclopropanes are relatively rare and their rearrangement chemistry has been reviewed recently [14]. In addition, electron deficient alkenes such as sesquiterpenoid methylene lactones may be competent substrates. Two crystal structures of compounds prepared in this way were reported recently [15,16]. Other relatively recent methods use dibromodifluoromethane, a relatively inexpensive and liquid precursor. Dolbier and co-workers described a simple zinc-mediated protocol [17], while Balcerzak and Jonczyk described a useful reproducible phase transfer catalysed procedure (Eq. 6) using bromo-form and dibromodifluoromethane [18]. The only problem here appears to be in separating cyclopropane products from alkene starting material (the authors recommend titration with bromine which is not particularly amenable for small scale use). Schlosser and co-workers have also described a mild ylide-based approach using dibromodifluoromethane [19] which reacts particularly well with highly nucleophilic alkenes such as enol ethers [20], and remarkably, with alkynes [21] to afford labile difluorocyclopropenes (Eq. 7). 

The vast majority of organocatalytic reactions proceeds via covalent formation of the catalyst-substrate adduct to form an activated complex. Amine-based reactions are typical examples, in which amino acids, peptides, alkaloids and synthetic nitrogen-containing molecules are used as chiral catalysts. The main body of reactions includes reactions of the so-called generalized enamine cycle and charge accelerated reactions via the formation of iminium intermediates (see Chapters 2 and 3). Also, Morita-Baylis-Hillman reactions (see Chapter 5), carbene-mediated reactions (see Chapter 9), as well as asymmetric ylide reactions including epoxidation, cyclopropanation, and aziridination (see Chapter 10), and oxidation with the in situ generation of chiral dioxirane or oxaziridine catalysts (see Chapter 12), are typical examples. 

Dirhodium compounds have proved to be highly efficient and effective catalysts for diverse reactions, which has led to their reputation as being important players in synthetic organic chemistry. A wide range of synthetically useful transformations, such as cyclopropanation, cyclopropenation, insertion into C-H and heteroatom-H bonds, cydoadditions, ylide formation and rearrangement, and other processes are mediated by the catalytic formation of dirhodium(II) carbenes via diazocarbonyl compounds [77],... 

Scheme 7.42 Catalytic epoxide (X=0), aziridine (X=iV-Ts or iV-SES) and cyclopropane (X=CH-COY) formation mediated by chalcogen-ylides generated from diazo compounds via metal carbenes (start at upper right corner)...

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