Asymmetric Darzens-Type Epoxidation via Chiral Ammonium Ylides

Abstract

Asymmetric Darzens-type epoxide formation of aryl aldehydes with chiral para-substituted benzylammonium ylides, prepared from brucine and corresponding benzylic chlorides and treated in situ under basic condition, was carried out to afford chiral 2,3-diaryl epoxides with moderate to good ee (84% ee). Brucine was found to be an excellent tertiary amine for a chirality transfer agent.Chiral epoxides are important functional organic molecules due to their presence in natural products, 1 their biological activity, and their serving as intermediates 2 for chiral ring-opened products to obtain amino alcohols, diols, and alcohols. To date, aside from the epoxidation of olefins, 3 chiral epoxides have been prepared by catalytic asymmetric sulfur ylide mediated epoxidation 4 and by asymmetric Darzens reaction catalyzed by phase-transfer catalysts. 5 Epoxides are easily converted to amino alcohols, diols, and alcohols (often important components of biologically active natural products) by the corresponding nucleophilic, acidic, and reductive ring-opening reactions. 6 In a previous paper, we reported the trans-selective synthesis of 2,3-diaryl epoxides by Darzens-type reaction via ammonium ylides derived from electron-poor benzylammonium chlorides. We have also reported the effectiveness of sterically demanding tertiary amines such as DABCO and quinuclidine on the formation of quaternary ammonium salts 7 (Scheme 1).With the aim of advancing and expanding this useful methodology, we studied the first example of one-pot trans-selective asymmetric epoxidation of chiral ammonium chlorides and aryl aldehydes (Scheme 2).There have been many reports on cinchonium or cinchonidium salt catalyzed asymmetric Darzens glycidic ester formation, 5 but many of the reactions proceed slowly, taking a few days for completion. Encouraged by our results, we undertook the study of the scope and limitations of the chirality transferring ability of tertiary amines on the asymmetric Darzens-type epoxidation via ammonium ylides. The epoxidations were carried out using cinchonine (1), brucine (2), and chiral quinuclidine derivatives 3-5 (Figure 1).