Asymmetric Epoxidation of α-Substituted Acroleins Catalyzed by Diphenylprolinol Silyl Ether

Abstract

Asymmetric epoxidation of α-substituted acroleins with hydrogen peroxide has been catalyzed by diphenylprolinol diphenylmethylsilyl ether to afford α-substituted-β,β-unsubstituted-α,β-epoxy aldehyde with excellent enantioselectivity and the generation of a chiral quaternary carbon center. The method was applied to a short synthesis of (R)-methyl palmoxirate.

Asymmetric Organocatalyzed Epoxidation of 2‐Oxoindoline‐3‐ylidene Acetaldehydes

“…The yield, diastereo-and enantioselectivities were determined after reduction of the epoxy aldehyde 9 a to the epoxy alcohol 10 a. Since the O-silyl prolinol 4 is known to be effective for the asymmetric epoxidation of a-substituted-a,b-unsaturated alkenes, [24] the organocatalyst 4 was tried first. The epoxy aldehyde 9 a was generated as a mixture of diastereomers in a ratio of 1:1.8; subsequent aldehyde reduction provided the epoxy alcohol 10 a in 56 % yield with moderate enantioselectivity (entry 1).…”

“…[23] In 2010, we reported the asymmetric epoxidation of a-substituted-a,b-unsaturated aldehydes by using diphenylprolinol silyl ether as the chiral catalyst. [24] This organocatalyst was developed independently by our group [25] and Jørgensen's group [26] [Scheme 1a]. Recently, we have also reported the asymmetric Michael addition of nitromethane to 2-oxoindoline-3-ylidene acetaldehydes as catalyzed by diarylprolinol silyl ether to construct all-carbon quaternary stereogenic centers with excellent enantioselectivity [Scheme 1b].…”

Applications of Chiral Three-membered Rings for Total Synthesis: A Review

“…As an application, the authors developed a short synthesis of natural products (-)-(5R,6S)-norbalasubramide and (-)-(5R,6S)-balasubramide which is depicted in Scheme 48. In 2010, Hayashi et al reported a short synthesis of (R)-methyl palmoxirate, a potent oral hypoglycemic agent, based on the first successful asymmetric epoxidation of aliphatic -substituted acroleins, that was catalyzed by diphenylprolinol silyl ether 121 and H 2 O 2 as oxidant [105]. Terminal epoxide 122, bearing a quaternary stereocenter, was obtained as key intermediate in good yield (78%) and high enantioselectivity (up to 92% ee) starting from alkene 123, as shown in Scheme 49.…”

Organocatalysts for enantioselective synthesis of fine chemicals: definitions, trends and developments

“…These organocatalytic reactions paved the way to many research teams that started to work in the same field, thus developing many different catalysts types and contributing to the growth of the application potential for organocatalysis. For the enantioselective epoxidation of α and β-branched enals, Hayashi's and Jørgensen's groups independently disclosed the remarkable potential of α,α-diaryl prolinol silyl ethers (30 and 31, Figure 8a and 8b), obtaining the desired epoxide in high enantioselectivities (up to 98% ee) and excellent yields (up to 90%) [32,33]. Furthermore, both groups investigated on the reaction mechanism, hypothesising an iminium ion covalent catalysis.…”

“…For this reason, many of such catalysts are also called bifunctional. Noteworthy examples of bifunctional non-covalent organocatalysts are the Soós thiourea (32) and diphenyl prolinol (33), depicted in Figure 10 [38]. Both of these catalysts bear H-bond donor groups and a Brønsted base functionality [39].…”