Organocatalyzed Enantioselective Conjugate Addition of Boronic Acids to β,γ-Unsaturated α-Ketoesters

Abstract

We report herein the (R)-3,3′-Br2-BINOL-catalyzed enantioselective conjugate addition of organic boronic acids to β,γ-unsaturated α-ketoesters to generate the corresponding Michael addition products in moderate to high yields and with moderate to excellent enantioselectivities (up to 99% ee). This catalytic system features characteristics of mild reaction conditions, high efficiency, and tolerance to alkenylboronic acids and heteroarylboronic acids.

Further developments of β,γ-unsaturated α-ketoesters as versatile synthons in asymmetric catalysis

“…Recently, a series of enantioenriched γ -allyl (aryl)- α -ketoesters was well synthetized by Chai and Chang et al. via ( R )-3,3′-Br 2 -BINOL-catalyzed enantioselective Michael addition of organic boronic acids to β,γ -unsaturated α -ketoesters (not shown) ( Zhao et al., 2021 ).…”

Chiral dihydroxytetraphenylene-catalyzed enantioselective conjugate addition of boronic acids to β-enaminones

“…6 Organocatalyzed enantioselective conjugate additions of alkenyl and alkynyl boronic acids and trifluoroborate salts to enones have been reported by several groups, 7 such as those of Chong, 8 May, 9 Sugiura 10 and ours. 11 β-Amino α,β-unsaturated carbonyl compounds are useful synthetic building blocks widely applied in various organic transformations. 12 Several studies involving the asymmetric conjugate addition of nucleophiles to β-amino α,β-unsaturated carbonyl compounds have been conducted.…”

“…Tetraphenylenes with a distinct saddle-shaped framework have been widely studied by Wong and co-workers, 17,18 and substituted C 2 -symmetric chiral 1,16-dihydroxytetraphenylene (DHTP) showed an unique and outstanding performance in different asymmetric transformations. 11 a ,18 c – f Based on our previous work on the chiral diol-catalyzed conjugate addition of organic boronic acids to α,β-unsaturated carbonyls, 11 we hypothesized that a chiral diol-catalyzed enantioselective conjugate addition of organic boronic acids to β-enaminone could be accomplished with excellent enantioselectivity to deliver chiral and highly functionalized β-alkenyl-β-amino carbonyl scaffolds. In this context, we disclose the enantioselective conjugate addition of organic boronic acids to β-enaminones catalyzed by chiral substituted DHTPs (Scheme 1c).…”