Carbonyl ylides enantioselective syntheses

Sulfur ylides are a classic reagent for the conversion of carbonyl compounds to epoxides. Chiral camphor-derived sulfur ylides have been used in the enantioselective synthesis of epoxy-amides <06JA2105>. Reaction of sulfonium salt 12 with an aldehyde and base provides the epoxide 13 in generally excellent yields. While the yield of the reaction was quite good across a variety of R groups, the enantioselectivity was variable. For example benzaldehyde provides 13 (R = Ph) in 97% ee while isobutyraldehyde provides 13 (R = i-Pr) with only 10% ee. These epoxy amides could be converted to a number of epoxide-opened... 

Hashimoto and coworkers [69] have recently begun to explore the use of chiral rhodium catalysts in the intramolecular dipolar cycloadditirai reactions of indoles, and have applied their methodology to the synthesis of the Aspidosperma ring system. Thus, the cycloaddition of the cyclopropyl carbonyl ylides derived from cyclopropyl diazo-5-imido-3-ketoesters 135 upon treatment with dirhodium (11) tetrakis[Af-tetrachlorophthaloyl-(5)-ferf-leucinate] gave cycloadducts 136 along with the spiro[2.3]hexanes 137 in only moderate yields (Scheme 34). Although the reaction proceeds with exclusive endo diastereoselectivity, only moderate enantioselectivities of up to 66% enantiomeric excess (ee) could be obtained. 

Muthusamy S, Gunanathan C et al (2004) Regioselective synthesis of mono- and bis-decahy-drobenzocarbazoles via tandem reactions of a-diazo ketones. Tetrahedron 60 7885-7897 Nambu H, Hikime M et al (2009) Asymmetric approach to the pentacyclic skeleton of aspidosperma alkaloids via enantioselective intramolecular 1,3-dipolar cycloaddition of carbonyl ylides catalyzed by chiral dirhodium(II) carboxylates. Tetrahedron Lett 50 3675-3678... 

Somfai has described three-component 1,3-dipolar cycloadditions of in situ generated carbonyl ylides to aldimines induced by chiral Rh(II) carboxylate catalysts 202 [65]. The reaction of ethyl diazoacetate 164, benzaldehyde (92a), and benzylidene benzylamine (203) gave rise to the corresponding syn- -amino alcohol 206 in 62% yield and 88% dr with 24% ee. In spite of its low enantioselectivities, this process provided interesting building blocks for the synthesis of natural products and other biologically important products that are syn- -amino alcohols (Scheme 11.44). 

The sulfide-catalyzed enantioselective epoxidation reaction is the most extensively studied transformation in ylide catalysis, and two ylide generation methods (aUcylation/deprotonation and carbene transfer) have been developed. Compared with conventional methods for epoxidation via oxygen transfer to the carbon-carbon double bond, such as the Sharpless epoxidation, Jacobsen-Katsuki epoxidation, and Shi epoxidation, the yhde approach can be regarded as an alkyUdene transfer reaction to carbonyl groups (C=0), providing a different retrosynthetic analysis for the construction of epoxides. In particular, in the synthesis of vinyl epoxides, the ylide route has priority over conventional oxidation methods, since the issue of regjoselectivity in the epoxidation of dienes will not be present [32]. 

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