Synthesis of (−)-6,7-Dideoxysqualestatin H5 by Carbonyl Ylide Cycloaddition–Rearrangement and Cross-electrophile Coupling

An asymmetric synthesis
of (−)-6,7-dideoxysqualestatin H5
is reported. Key features of the synthesis include the following:
(1) highly diastereoselective n-alkylation of a tartrate
acetonide enolate and subsequent oxidation–hydrolysis to provide
an asymmetric entry to a β-hydroxy-α-ketoester motif;
(2) facilitation of Rh­(II)-catalyzed cyclic carbonyl ylide formation–cycloaddition
by co-generation of keto and diazo functionality through ozonolysis
of an unsaturated hydrazone; and (3) stereoretentive Ni-catalyzed
Csp3–Csp2 cross-electrophile coupling
between tricarboxylate core and unsaturated side chain to complete
the natural product.