Design of a Nonreductive Method for Chemoselective Cleavage of Hydrazines in the Presence of Unsaturations:  Application to a Stereoconvergent Three-Component Synthesis of (−)-Methyl Palustramate

A chemoselective hydrazine (N−N) cleavage methodology that preserves the integrity of alkenes was developed based on a mild acid-promoted fragmentation of tetrasubstituted 1-(trimethylsilylmethyl)-1-benzylhydrazines. This strategy was applied to a concise asymmetric synthesis of (−)-methyl palustramate (4), which featured a convergent stereo- and regioselective sequential three-component aza[4+2]cycloaddition/allylboration/retro-sulfinyl-ene rearrangement between diene 1f, dienophile 2b, and propionaldehyde to afford cis-2-carboxy-6-hydroxyalkylpiperidine 25. The acid-promoted hydrazinolysis of 25 cleanly afforded key intermediate 31, and the latter led to target 4 in four steps after a series of functional group transformations.