Highly Enantioselective Direct Reductive Coupling of Conjugated Alkynes and α-Ketoesters via Rhodium-Catalyzed Asymmetric Hydrogenation

• Published in: Journal of the American Chemical Society Vol. 128; no. 3; pp. 718 - 719
• Main Authors: Kong, Jong-Rock, Ngai, Ming-Yu, Krische, Michael J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 25.01.2006; Amer Chemical Soc
• Subjects: Alcohols - chemical synthesis; Alkynes - chemistry; Catalysis; Chemistry; Chemistry, Multidisciplinary; Esters - chemical synthesis; Esters - chemistry; Exact sciences and technology; Hydrogenation; Ketones - chemistry; Organic chemistry; Oxidation-Reduction; Physical Sciences; Rhodium - chemistry; Science & Technology; Stereoisomerism; ALCOHOLS; 1,6-ENYNES; ALKENYLZINC ADDITIONS; REAGENTS; C BOND FORMATION; KETO; ENONES; ALDEHYDES; CYCLOREDUCTION; CYCLIZATION; Catalytic reaction; Enantioselectivity; Catalyst selectivity; Transition metal Complexes; Complex catalyst; Experimental study; Enynic compound; Chemical coupling; Chemical reduction; Rhodium Complexes; Asymmetric reaction; Platinoid Complexes; Ketoester; Conjugated compound; Catalyst activity
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja056474l

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 α-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.