Enantioselective Conjugate Addition of Boronic Acids to α,β-Unsaturated 2-Acyl Imidazoles Catalyzed by Chiral Diols

Abstract

Herein, we report the enantioselective conjugate addition of organic boronic acids to α,β-unsaturated 2-acyl imidazoles using (R)-3,3′-I 2 -BINOL as the catalyst. The catalytic system shows high efficiency and tolerance to alkenylboronic acids and heteroarylboronic acids. The corresponding Michael addition products were obtained in moderate to excellent yields and with moderate to excellent enantioselectivities (up to 97% ee). A gram-scale reaction was also conducted, and the desired product was obtained in high yield with no erosion in enantioselectivity. Finally, the synthetic utility of the methodology was demonstrated by transforming the 2-acyl imidazole moiety to the corresponding aldehyde, carboxylic acid, ester, and amide derivatives.

Regio- and enantioselective synthesis of acyclic quaternary carbons via organocatalytic addition of organoborates to (Z)-Enediketones

“…The minor diastereomer of 5h was produced along with the quaternary product in 17% yield as an inseparable 2:1 mixture. An initial regioselectivity hypothesis was that the relative locations of the phenyl and aliphatic ketones have a directing effect on the addition, where C–C bond formation is more strongly favored at the β-carbon of an aryl ketone than that of an alkyl ketone 43 – 53 . Based on work by Goodman and Pellegrinet 44 , we believed that the phenyl ketone directed an intramolecular 5-exo-trig 1,4-addition that reinforced the favored quaternary carbon formation.…”

“…2B ) 35 – 42 . A newer class of easily synthesized BINOL–derived enantioselective 1,4–addition organocatalysts have proven to be useful, recyclable, and functional group tolerant in many transformations 43 – 53 ; however, these reactions have only produced chiral tertiary carbon centers to date. In fact, β,β–disubstituted enones were investigated for quaternary carbon formation but completely lacked reactivity 54 .…”

Highly Enantioselective Chiral Diol-Catalyzed Conjugate Addition of Boronic Acids to α,β-Unsaturated Trifluoromethyl Ketones

“…9 Organocatalyzed enantioselective conjugate addition of organic boron compounds to α,β-unsaturated carbonyl compounds have been reported by several groups, 10 such as May's group (Scheme 1c), 11 Chong's group (Scheme 1d), 12 Sugiura's group, 13 Mao's group, 14 and our group. 15 Herein, we report a chiral diol-catalyzed asymmetric conjugate addition of organic boronic acids to α,β-unsaturated 1,1,1-trifluoromethyl ketones (Scheme 1e). To the best of our knowledge, this is the first report on the organocatalyzed synthesis of CF 3 carbonyl compounds in excellent enantioselectivity by the enantioselective conjugate addition of alkenylboronic acids to α,β-unsaturated trifluoromethyl ketones.…”