Direct Conversion of Primary Alcohols to 1,2-Amino Alcohols: Enantioselective Iridium-Catalyzed Carbonyl Reductive Coupling of Phthalimido-Allene via Hydrogen Auto-Transfer

Abstract

The first catalytic enantioselective carbonyl (α-amino)allylations are described. Phthalimido-allene <b>1</b> and primary alcohols <b>2a</b>-<b>2z</b>, <b>2a'</b>-<b>2c'</b> engage in hydrogen auto-transfer-mediated carbonyl reductive coupling by way of (α-amino)allyliridium-aldehyde pairs to form vicinal amino alcohols <b>3a</b>-<b>3z</b>, <b>3a'</b>-<b>3c'</b> with high levels of regio-, <i>anti</i>-diastereo-, and enantioselectivity. Reaction progress kinetic analysis and isotopic labeling studies corroborate a catalytic cycle involving turnover-limiting alcohol dehydrogenation followed by rapid allene hydrometalation.