The osmium-catalyzed asymmetric dihydroxylation: a new ligand class and a process improvement

Abstract

The nonchelate enforced chiral amide enolates derived from 4-7 react with alkyl iodide and protected a-amino epoxide electrophiles to produce the HIV protease inhibitors 10 and 16-19 with high diastereoselectivity.

Synthetic Studies of Natural 10-Membered Lactones, Mueggelone, Microcarpalide, and Sch 642305, Which Have Interesting Bioactivities

“…28,29) Olefinic alcohol 21 was synthesized by Sharpless asymmetric dihydroxylation (AD) 30,31) of unsaturated ester 20 and the following introduction of a C 2 unit. On the other hand, acid 23 was derived from the known compound 22, 32,33) which was easily obtained from D-mannose.…”

“…44) They constructed the intermediate ent-18 by cross metathesis 4,19) of , -unsaturated ester 44 using 2nd-generation Grubbs catalyst 20) under ethylene, because direct methylenation of hemiacetal 43 (conversion to ent-18) was not successful, and RCM of , -unsaturated ester 44 did not proceed. 47) Hemiacetal 43 was synthesized from alcohol 41 and acid 42, whose stereocenters originated in Sharpless AD 30,31) and (S)-malic acid respectively. In their synthesis, installation of the second double bond for RCM was problematic and lowered synthetic efficiency.…”

“…In their synthesis, installation of the second double bond for RCM was problematic and lowered synthetic efficiency. Chavan's group 45) installed all four stereocenters of 18 by Sharpless AD, 30,31) while Fürstner's group 46) installed them by Sharpless AE 17) and AD 30,31) (schemes not shown). All of three groups reported that RCM of 18 (or ent-18) resulted in E/Z selectivity similar to that of Marco's group.…”

“…We also decided to introduce all four stereocenters using Sharpless AD. 30,31) Starting from the known diol 45, 52) olefinic ester 46 was prepared by Claisen rearrangement, 53,54) which was subjected to Sharpless AD. Enrichment of enantiomeric purity was achieved by recrystallization of an intermediate to give aldehyde 47 in an enantiomerically pure form.…”

“…58) They also introduced all four stereocenters using Sharpless AD. 30,31) Acetylene 53 was prepared from , -unsaturated ester 52, which was obtained from 1,4-butanediol. Stereocenters were installed by Sharpless AD, and terminal acetylene was constructed by Corey-Fuchs protocol 59) to give 53.…”