Asymmetric ylide reactions

Asymmetric ylide reactions such as epoxidation, cyclopropanation, aziridination, [2,3]-sigmatropic rearrangement and alkenation can be carried out with chiral ylide (reagent-controlled asymmetric induction) or a chiral C=X compound (substrate-controlled asymmetric epoxidations). Non-racemic epoxides are significant intermediates in the synthesis of, for instance, pharmaceuticals and agrochemicals. 

In reagent-controlled epoxidation the asymmetric induction has its origin in a chiral ylide. The reaction of an achiral aldehyde or ketone with a chiral ylide gives optically active compounds. 

The process of epoxidation involves two steps alkylation of the ligand and isolation of the resulting salt, followed by treatment with a base in the presence of a carbonyl compound. 

The successful example of catalytic asymmetric chiral sulfonium epoxidation was reported with enantiomeric excess (43%) of trans-stilbene oxide (3.71) by the reaction of 4-chlorobenzaldehyde with benzyl bromide in acetonitrile at room temperature by using 0.5 equiv. of optically active sulfide 3.70 (with exo-OH group). Powdered KOH was used as a base. f 

Johnson et al. were the first to prepare enantiomerically pure aminosulfoxonium ylide 3.73 from 3.72, which on reaction with benzaldehyde gave (P)-styrene oxide (3.69) in 20% ee. The reaction of aminosulfoxonium ylide 3.74 with heptaldehyde gave the corresponding epoxide 3.75 with opposite enantioselectivity (39% ee, S) as expected. 

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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. 

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. 

Li A-H, Dai L-X, Aggarwal VK. Asymmetric ylide Reactions epoxidation, cyclopropanation, aziridination, olefination, and rearrangement. Chem. Rev. 1997 97(6) 2341-2372. 

Aziridination remains less well developed than epoxidation. Nevertheless, high selectivity in inline aziridination has been achieved through the use of chiral sulfi-nimines as auxiliaries. Highly successful catalytic asymmetric aziridination reactions employing either sulfur ylides or diazo esters and chiral Lewis acids have been developed, although their scope and potential applications in synthesis have yet to be established. 

Keywords Cycloprop anation Insertion Ylide reactions Asymmetric catalysis Synthesis... 

In a similar approach, Garner et al. (78) made use of silicon-based tethers between ylide and dipolarophile during their program of research into the application of azomethine ylides in the total asymmetric synthesis of complex natural products. In order to form advanced synthetic intermediates of type 248 during the asymmetric synthesis of bioxalomycins (249), an intramolecular azomethine ylide reaction from aziridine ylide precursors was deemed the best strategy (Scheme 3.84). Under photochemically induced ylide formation and subsequent cycloaddition, the desired endo-re products 250 were formed exclusively. However, due to unacceptably low synthetic yields, this approach was abandoned in favor of a longer tether (Scheme 3.85). 

Stereoselective oxonium ylide reaction, in particular the asymmetric catalysis, has been a problem of considerable challenge in this field. Since the first report by McKervey and co-workers in the asymmetric induction in metal carbene-mediated ylide formation/[2,3]-sigmatropic rearrangement in 1992, there have been efforts being directed... 

The asymmetric catalysis has not been well explored in the reaction of a metal carbene complex-generated ammonium ylide. The ammonium ylide reaction is assumed to proceed through a free ylide rather than a metal... 

Reviews have featured epoxidation, cyclopropanation, aziridination, olefination, and rearrangement reactions of asymmetric ylides 66 non-phosphorus stabilized carbanions in alkene synthesis 67 phosphorus ylides and related compounds 68 the Wittig reaction 69,70 and [2,3]-Wittig rearrangement of a-phosphonylated sulfonium and ammonium ylides.71 Reactions of carbanions with electrophilic reagents, including alkylation and Wittig-Homer olefination reactions, have been discussed with reference to Hammett per correlations.72... 

Scheme 10.12 Catalytic asymmetric ylide epoxidation as the key step in a six-step synthesis of Prelactone B (14), 10% yield, 93% ee. Reaction conditions (a) Sulfide 4 (25 mol%), Rh2(OAc)4 (1 mol%), BnEt3NCI (10 mol%), MeCN, 40 °C, 36 h.

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