Formation of Chiral Quaternary Carbon Stereocenters Using Silylene Transfer Reactions:  Enantioselective Synthesis of (+)-5-epi-Acetomycin

Abstract

Chiral quaternary carbon stereocenters can be established with high diastereoselectivity by a silylene transfer/Ireland-Claisen rearrangement. The utility of this method was demonstrated by application to a synthesis of (+)-5-epi-acetomycin. [reaction: see text]

Modular Synthesis of Axially Chiral 3,3′‐Disilyl Dicarboxylic Acids by Silalactones

“…In the reported example to synthesize silalactones, Shindo and coworkers synthesized similar five-membered silalactones by the oxidative cleavage of the siliconÀcarbon bond by treatment with iodine or N-iodosuccinimide (NIS) and demonstrated that addition of a Grignard reagent to silalactones occurs at the silicon center to give trialkylsilyl carboxylic acid (Scheme 2). [5,6] Based on this inspiring report, we initially anticipated that disilalactones (R)-3 might be formed by oxidative dehydrogenation. However, it turned out that no oxidative treatment was actually required, as hydrogen gas evolved spontaneously from this intermediate to give disilalactones.…”

Silver‐Catalyzed Silylene Transfer

“…109,113,114 By forming a silver silylenoid reactive intermediate, Woerpel and coworkers enabled involvement of divalent silylenes in pericyclic reactions involving silacarbonyl ylides 115 to afford synthetically useful products. 82,116,117 While exploring the scope of silver-catalyzed silylene transfer to olefins, Woerpel and Calad observed that the electrophilic silver silylenoid species reacted preferentially with the enolizable ester group to produce vinylsilane 129 instead of a an allyl substituent (e.g., 130h) to reaction conditions facilitated an Ireland-Claisen rearrangement after the initial electrocyclization. This process was highly diastereoselective; the reaction of ester 130h produced silalactone 135 with three contiguous stereocenters as a single isomer.…”

“…Diol 137 was generated from silalactone after reduction of the lactone moiety with lithium aluminum hydride followed by oxidation of the C--Si bond. 65 116 The reaction of ester 130j revealed that the facial selectivity of the 6p-electrocyclization could not be controlled. Exposure of (Z)-allyl ester 130k to reaction conditions produced a mixture of silalactones 142 and 143.…”

“…116 When chiral, nonracemic versions of these substrates are employed, Woerpel and Calad demonstrated that the cascade reaction efficiently transfers the chiral information. While silver salts were competent catalysts for the diastereoselective formation of silalactone 144 from 130l, on scale-up, copper(II) triflate proved to be more efficient.…”

“…7.1). 116 The major diastereomer was posited to originate from transition state TS-145, which minimizes the developing diaxial-1,3 interactions through placement of the isopropyl group in a pseudoequatorial position. Because only (E)-olefins were obtained, the origin of the minor diastereomer was attributed to the boat-like transition state TS-150.…”