Highly enantioselective direct reductive coupling of conjugated alkynes and alpha-ketoesters via rhodium-catalyzed asymmetric hydrogenation.
Catalytic hydrogenation of 1,3-enynes 1a-7a in the presence of ethyl pyruvate and related activated ketones using chirally modified cationic rhodium catalysts results in reductive coupling to afford dienylated alpha-hydroxy esters 1b-7b and 3c-3f with exceptional levels of regio- and enantiocontrol. These studies represent the first highly enantioselective direct catalytic reductive couplings of alkynes to ketones. As illustrated by the conversion of 6b to 6c-6h, the diene containing the side chain of the coupling products is subject to diverse chemo- and regioselective manipulation. Reductive coupling of enyne 6a and ethyl pyruvate using elemental deuterium provides the monodeuterated product deuterio-6b, consistent with a catalytic mechanism involving alkyne-carbonyl oxidative coupling followed by hydrogenolytic cleavage of the resulting oxametallacycle, as corroborated by ESI-MS analysis.
Kong
Jong-Rock
JR
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, USA.
Ngai
Ming-Yu
MY
Krische
Michael J
MJ
D000438:Alcohols / Q000138:chemical synthesis*; D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D006865:Hydrogenation; D007659:Ketones / Q000737:chemistry*; D010084:Oxidation-Reduction; D012238:Rhodium / Q000737:chemistry; D013237:Stereoisomerism
D000438:Alcohols; D000480:Alkynes; D004952:Esters; D007659:Ketones; D012238:Rhodium