Intermolecular Selective 1,2-Aminohydroxylation of 1,3-Dienes Enabled by Palladium/Copper/Oxygen Cooperation.

β-Amino alcohols are important structural motifs that are widely present in pharmaceutical molecules and natural products with significant biological activities, making the development of synthetic methodologies for their preparation a long-standing research focus. Among current synthetic approaches, 1,2-aminohydroxylation of alkenes offers a direct route to β-amino alcohols. In particular, metal-catalyzed 1,2-aminohydroxylation of alkenes represents an efficient methodology. However, existing methods are restricted to intramolecular reactions or rely on either directing groups or active reagents (preoxidized nitrogen sources or special oxidants). Therefore, the development of a more general catalytic system that does not require intramolecular reactions, directing groups, or active reagents has remained highly desirable. Herein, we report an intermolecular selective 1,2-aminohydroxylation of 2,3-disubstituted 1,3-dienes enabled by palladium/copper/oxygen cooperation, using a simple nitrogen source. Notably, for 2,3-dialkyl-1,3-dienes bearing different alkyl groups, this aminohydroxylation enables alkyl recognition, favoring the less-hindered double bond with moderate to good chemoselectivity. This methodology provides a direct and powerful route to the synthesis of β-amino alcohols.