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 <i>n</i>-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 Csp<sup>3</sup>–Csp<sup>2</sup> cross-electrophile coupling between tricarboxylate core and unsaturated side chain to complete the natural product.