Determination of the Absolute Configuration of 2′-Amino-3′-methylacetophenone Based on the Modified Mosher and Microcrystal Electron Diffraction Methods

Abstract

This study investigated the application of Corey–Bakshi–Shibata (CBS) catalysts to asymmetric reduction of 2′-aminoacetophenone derivatives and determined their absolute configuration using the modified Mosher and microcrystal electron diffraction methods. The results reveal that stereoselective CBS reduction is effective on 2′-amino-3′-methylacetophenone, yielding secondary alcohol, and that the reaction proceeds stereoselectively, even on the gram scale. Moreover, (R)-(–)-secondary alcohol configuration was obtained using an (S)-Me-CBS catalyst, and the stereoselectivity of the reduction followed a previously proposed reaction mechanism for acetophenone derivatives. Thus, this study demonstrated that secondary alcohol could be obtained with the expected stereoselectivity, although requiring a slightly higher amount of the CBS catalyst. The study findings suggest that the amino group of aniline may affect the progress of CBS reduction but does not significantly affect the transition state.