On the Origin of Rh-Catalyzed Selective Ring-Opening Amidation of Substituted Cyclopropanols to Access β 2 -Amino Ketones.

β 2 -Amino carbonyls, an α-substituted β-amino scaffold, hold a prominent place in the development of new pharmaceuticals and peptidomimetics. Herein, we report a highly efficient Rh-catalyzed ring-opening amidation of substituted cyclopropanols, which turned out to serve as a linchpin for the selective synthesis of β 2 -amino ketones to outcompete the formation of β 3 -isomers. Instead of the generally accepted rationale to consider steric factors for the β 2 -selectivity, orbital interaction was elucidated to play a more critical role in the amidative ring-opening of cyclopropanols to generate the key Rh-C intermediate. Subsequent inner-sphere acylnitrene transfer was achieved in excellent efficiency (TON > 5000) by using readily accessible dioxazolones as the amino source to afford β 2 -amino ketones with broad applicability.