Enantioselective Reductive Coupling of 1,3-Enynes to Heterocyclic Aromatic Aldehydes and Ketones via Rhodium-Catalyzed Asymmetric Hydrogenation:  Mechanistic Insight into the Role of Brønsted Acid Additives

• Published in: Journal of the American Chemical Society Vol. 128; no. 51; pp. 16448 - 16449
• Main Authors: Komanduri, Venukrishnan, Krische, Michael J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 27.12.2006; Amer Chemical Soc
• Subjects: Acids - chemistry; Alcohols - chemical synthesis; Alcohols - chemistry; Aldehydes - chemistry; Alkynes - chemistry; Catalysis; Chemistry; Chemistry, Multidisciplinary; Exact sciences and technology; General and physical chemistry; Hydrogenation; Ketones - chemistry; Kinetics and mechanisms; Molecular Structure; Organic chemistry; Oxidation-Reduction; Physical Sciences; Reactivity and mechanisms; Rhodium - chemistry; Science & Technology; Stereoisomerism; 1,6-ENYNES; ALKENYLZINC ADDITIONS; ALLYLIC ALCOHOLS; C BOND FORMATION; CONJUGATED ALKYNES; CARBONYL-COMPOUNDS; GENERATION; CYCLIZATION; HYDROFORMYLATION; PARTNERS; Catalytic reaction; Enantioselectivity; Transition metal; Aldehyde; Ketone; Hydrogenation; Enynic compound; Chemical reduction; Brönsted acid; Rhodium; Asymmetric synthesis; Reaction mechanism; Aromatic compound; Platinoid; Heterocyclic compound
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0673027

Hydrogenation of 1,3-enynes 1a−e in the presence of heterocyclic aromatic aldehydes and ketones using chirally modified cationic rhodium precatalysts results in reductive coupling to afford dienylated α-hydroxy heteroarenes 2−23 with exceptional levels of regio- and enantiocontrol. Coupling of enyne 1a to 2-pyridinecarboxaldehyde using an achiral rhodium catalyst in the presence of a chiral Akiyama−Terada-type phosphoric acid derived from BINOL as the Brønsted acid co-catalyst provides the coupling product 2 with substantial levels of optical enrichment (82% ee). This result suggests that substrate protonation and/or formation of a strong hydrogen bond occurs in advance of the stereogenic C−C bond forming event. Further, the high levels of asymmetric induction demonstrate that interaction of the aldehyde with the Brønsted acid activates the system toward C−C coupling. Reductive coupling of enyne 1a and 2-pyridinecarboxaldehyde under an atmosphere of elemental deuterium provides the monodeuterated product deuterio- 2, consistent with a catalytic mechanism involving alkyne−carbonyl oxidative coupling followed by hydrogenolytic cleavage of the resulting oxametallacycle. The diene side chain of the coupling products is subject to diverse selective transformations, as demonstrated by the conversion of coupling products 2 and 8 to compounds 24−26 and 27−29, respectively.