Hydrogen-mediated reductive coupling of conjugated alkynes with ethyl (N-Sulfinyl)iminoacetates: synthesis of unnatural alpha-amino acids via rhodium-catalyzed C-C bond forming hydrogenation.
Rhodium-catalyzed hydrogenation of 1,3-enynes 1a-8a and 1,3-diynes 9a-13a at ambient temperature and pressure in the presence of ethyl (N-tert-butanesulfinyl)iminoacetate and ethyl (N-2,4,6-triisopropylbenzenesulfinyl)iminoacetates, respectively, results in reductive coupling to afford unsaturated alpha-amino acid esters 1b-13b in good to excellent yields with exceptional levels of regio- and stereocontrol. Further hydrogenation of the diene containing alpha-amino acid esters 1b-8b using Wilkinson's catalyst at ambient temperature and pressure results in regioselective reduction to afford the beta,gamma-unsaturated alpha-amino acid esters 1c-8c in good to excellent yields. Exhaustive hydrogenation of the unsaturated side chains of the Boc- and Fmoc-protected derivatives of enyne and diyne coupling products 14b-16b occurs in excellent yield using Crabtree's catalyst at ambient temperature and pressure providing the alpha-amino acid esters 14d-16d, which possess saturated side chains. Finally, cross-metathesis of the Boc-protected reductive coupling product 14b with cis-1,4-diacetoxy-2-butene proceeds readily to afford the allylic acetate 14e. Isotopic labeling studies that involve reductive coupling of enyne 1a and diyne 9a under an atmosphere of elemental deuterium corroborate a catalytic mechanism in which oxidative coupling of the alkyne and imine residues is followed by hydrogenolytic cleavage of the resulting metallacycle. A stereochemical model accounting for the observed sense of asymmetric induction is provided. These studies represent the first use of imines as electrophilic partners in hydrogen-mediated reductive carbon-carbon bond formation.
Kong
Jong-Rock
JR
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, USA.
Cho
Chang-Woo
CW
Krische
Michael J
MJ
D000085:Acetates / Q000737:chemistry*; D000480:Alkynes / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D006859:Hydrogen / Q000737:chemistry*; D006865:Hydrogenation; D007097:Imines / Q000737:chemistry; D012238:Rhodium / Q000737:chemistry*
D000085:Acetates; D000480:Alkynes; D000596:Amino Acids; D007097:Imines; D002244:Carbon; D006859:Hydrogen; D012238:Rhodium