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.
Touré
Barry B
BB
Department of Chemistry, Gunning-Lemieux Chemistry Centre, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada.
Hall
Dennis G
DG
D000143:Acids / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry*; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010880:Piperidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000143:Acids; D000475:Alkenes; D006834:Hydrazines; D010880:Piperidines; C494952:methyl palustramate