Highly Enantioselective Mukaiyama Aldol Reactions Catalyzed by a Chiral Oxazaborolidinium Ion: Total Synthesis of (−)-Inthomycin C

Abstract

A cationic oxazaborolidinium-catalyzed asymmetric Mukaiyama aldol reaction of (1-methoxy-2-methyl-propenyloxy)-trimethylsilane with various aldehydes including α,β-disubstituted acroleins has been developed in high yields and enantioselectivities. The synthetic utility of this methodology was demonstrated in the first short synthesis of naturally occurring inthomycin C in high enantiopurity.

The Impact of the Mukaiyama Aldol Reaction in Total Synthesis

“…Chiral oxazaborolidinium salts, such as 69, are also effective Lewis acids for aldehyde activation in aldol reactions with silicon enolates. [36] In the total synthesis of the antimicrobial and anticancer agent inthomycin C (70, Scheme 14) of Ryu and co-workers, the aldol reaction of the stannyl aldehyde 71 with silicon enolate 72 proceeded smoothly in the presence of catalyst 69 to give adduct 73 (92 %, 93 % ee), and retaining the sensitive dienylstannane moiety.…”

Die Bedeutung der Mukaiyama‐Aldolreaktion für die Totalsynthese

“…Chirale Oxazaborolidiniumsalze wie 69 sind ebenfalls effektive Lewis-Säuren zur Aldehydaktivierung in Aldolreaktionen mit Siliciumenolaten. [36] In der Totalsynthese des antimikrobischen krebshemmenden Wirkstoffs Inthomycin C (70) von Ryu und Mitarbeitern (Schema 14) verlief die Al-Schema 11. Synthese von Khafrefungin (Kobayashi, 2001).…”

Enantiospecific Formal Synthesis of Inthomycin C

“…Inthomycin C, a prominent member of inthomycin family of natural products has attracted the attention of many research groups and resulted in several syntheses of the target molecule in recent times . Inthomycins, originally isolated by Zeeck et al .…”

“…Here, we have summarized the highlights of events with respect to inthomycin C in Table starting from its isolation in the year 1991 to recent efforts. Although several synthesis are documented and controversies are resolved, all syntheses relied on enantioselective methods using chiral reagents including very recent syntheses . Because of interesting biological activity, structural features and occurrence of several related molecules in the nature, we decided to develop a route to synthesize target compound 1 in an enantiospecific manner.…”