American Chemical Society
ja0673027_si_002.pdf (4.9 MB)

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

Download (4.9 MB)
journal contribution
posted on 2006-12-27, 00:00 authored by Venukrishnan Komanduri, Michael J. Krische
Hydrogenation of 1,3-enynes 1ae 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 223 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 2426 and 2729, respectively.