Practical and Highly Selective Sulfur Ylide Mediated Asymmetric Epoxidations and Aziridinations Using an Inexpensive, Readily Available Chiral Sulfide. Applications to the Synthesis of Quinine and Quinidine

Abstract

Heating one of the most abundant naturally occurring inorganic chemicals (elemental sulfur) with one of the most readily available homochiral molecules (limonene) gives a one-step synthesis of a chiral sulfide which exhibits outstanding selectivities in sulfur ylide mediated asymmetric epoxidations and aziridinations. In particular reactions of benzyl and allylic sulfonium salts with both aromatic and aliphatic aldehydes gave epoxides with perfect enantioselectivities and the highest diastereoselectivities reported to date. In addition reactions with imines gave aziridines again with the highest enantioselectivities and diastereoselectivities reported to date. The reactions are scaleable, and the sulfide can be reisolated in high yield. The epoxidation has been used as the key step in a convergent and stereoselective synthesis of each of the diastereoisomers of the cinchona alkaloids, quinine and quinidine.

The Epoxidation of Carbonyl Compounds with a Benzyne-Triggered Sulfur Ylide

“…[1][2][3][4][5] This class of intermediates has been found to have wide applications in the synthesis of epoxides, 6,7 cyclopropanes, 8 aziridines, [9][10][11] terminal alkenes, 12 and organoboron compounds. 13,14 The most common method of sulfur ylide generation consists of proton abstraction from the corresponding sulfonium salts, which are available by the direct alkylation of thioethers (Scheme 1, method A, path 1).…”

1,6-Conjugated Addition-Mediated [2+1] Annulation: Approach to Spiro[2.5]octa-4,7-dien-6-one

“…To achieve the optically active spiro [2,5]octa-4,7-dien-6-one, we employed the known chiral sulfur ylides 7 developed by Aggarwal 16 instead of 3a to operate our reaction (Scheme 3). Unfortunately, only trace 4aa could be detected.…”

A mild access to chiral syn 1,2-diaryl glycols by stereoselective ring opening of ortho substituted trans 2,3-diaryl-oxiranes using Amberlyst 15 in H2O/THF system

“…32 Thus a series of new enantioenriched 2-aryl-3-phenyloxiranes was prepared by asymmetric sulfur ylide mediated epoxidation of aldehydes, 33 using Isothiocineole as chiral precursor, which is readily available in both enantiomeric forms and has been recently shown to be highly efficient in epoxidation and aziridination reactions, with high levels of enantioselectivity. 34 Reactions of the corresponding benzyl sulfonium salt 35 with aromatic aldehydes in presence of KOH as a base, in either H 2 O/ CH 3 CN or t-BuOH/CH 3 CN solvent mixtures, worked smoothly well in all cases, furnishing good yields and very high levels of diastereoand enantioselectivity ( Table 1).…”