Open AccessAn Effective Bifunctional Aldehyde Linchpin for Type II Anion Relay Chemistry: Development and Application to the Synthesis of a C16–C29 Fragment of Rhizopodin
Author(s) -
Bruno Melillo,
Ming Z. Chen,
Roberto Forestieri,
Amos B. Smith
Publication year - 2015
Publication title -
organic letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.94
H-Index - 239
eISSN - 1523-7060
pISSN - 1523-7052
DOI - 10.1021/acs.orglett.5b03235
Subject(s) - chemistry , bifunctional , dithiane , alkoxide , aldehyde , adduct , electrophile , stereochemistry , enantioselective synthesis , combinatorial chemistry , nucleophilic addition , organic chemistry , catalysis
The design, synthesis, and validation of a new bifunctional aldehyde linchpin for Type II anion relay chemistry have been achieved. For this linchpin, the initial nucleophilic addition proceeds under Felkin-Anh control to generate the syn-alkoxide, which undergoes a 1,4-Brook rearrangement to relay the negative charge, thus leading to the formation of a dithiane-stabilized carbanion. Subsequent trapping with an electrophile furnishes a tricomponent adduct with an embedded propionate subunit, a ubiquitous structural motif found in polyketides. The utility of this new linchpin is demonstrated with the construction of a potential C16-C29 fragment for the synthesis of rhizopodin, an actin-binding macrolide.