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.