An Effective Bifunctional Aldehyde Linchpin for Type II Anion Relay Chemistry: Development and Application to the Synthesis of a C16-C29 Fragment of Rhizopodin.

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.