Origins of the enantio- and N/O selectivity in the primary-amine-catalyzed hydroxyamination of 1,3-dicarbonyl compounds with in-situ-formed nitrosocarbonyl compounds: a theoretical study.

Abstract

Chemoselective control over N/O selectivity is an intriguing issue in nitroso chemistry. Recently, we reported an unprecedented asymmetric α-amination reaction of β-ketocarbonyl compounds that proceeded through the catalytic coupling of enamine carbonyl groups with in-situ-generated carbonyl nitroso moieties. This process was facilitated by a simple chiral primary and tertiary diamine that was derived from tert-leucine. This reaction featured high chemoselectivity and excellent enantioselectivity for a broad range of substrates. Herein, a computational study was performed to elucidate the origins of the enantioselectivity and N/O regioselectivity. We found that a bidentate hydrogen-bonding interaction between the tertiary N(+)-H and nitrosocarbonyl groups accounted for the high N selectivity, whilst the enantioselectivity was determined by Si-facial attack on the (E)- and (Z)-enamines in a Curtin-Hammett-type manner. The bidentate hydrogen-bonding interaction with the nitrosocarbonyl moieties reinforced the facial selectivity in this process.