α‐Quaternary Mannich Bases through Copper‐Catalyzed Amination‐Induced 1,2‐Rearrangement of Allylic Alcohols

Abstract

A novel copper-catalyzed amination-induced 1,2-rearrangement reaction of allylic alcohols has been developed under simple and mild conditions. The commercially available N-fluorobenzenesulfonimide (NFSI) is employed as an amination reagent. In this transformation, not only alkyl, but also aryl substituents can efficiently undergo 1,2-carbon atom migration, thereby providing an efficient and powerful route to prepare a wide range of α-quaternary Mannich bases. The reaction features a broad substrate scope, operational simplicity, and excellent practicality.

Recent development and applications of semipinacol rearrangement reactions

“…Besides N-centered electrophiles, an N-radical induced rearrangement has been reported wherein N-uorobenzenesulfonimide (NFSI) was used as the radical source under the catalysis of Cu(I). 30 Additionally, with the assistance of photoredox-catalysis, the phosphinylation/semipinacol rearrangement could be realized either with a diaryl(alkyl)phosphine oxide 31 or oxime phosphonate substrate. 32 Chalcogen, specically sulfur and selenium, related electrophiles and radicals are also viable species in promoting the rearrangement reactions of allylic alcohols.…”

Copper-catalysed radical reactions of alkenes, alkynes and cyclopropanes with N–F reagents

“…A different method for the aminative 1,2-difunctionalisation of alkenes catalysed by copper complexes was reported by Zhang's group (Scheme 8). 18 They employed NFSI to generate nitrogen-centred radicals which then undergo addition across the double bond of an allylic alcohol. The resulting carboncentred radical then experiences a 1,2-rearrangement, providing access to -quaternary Mannich bases bearing an all-carbon quaternary centre.…”

Recent Advances in the Synthesis of β‐Functionalized Ketones by Radical‐Mediated 1,2‐Rearrangement of Allylic Alcohols

“…[24] The protocol provides as imple and efficient approach to access aw ide range of a-q uaternary Mannich bases 125 in moderate to good yields under mild conditions. [24] The protocol provides as imple and efficient approach to access aw ide range of a-q uaternary Mannich bases 125 in moderate to good yields under mild conditions.…”

“…β‐Amino ketones (Mannich bases) are an important class of privileged structural motifs in synthetic chemistry and medicinal chemistry . In light of the importance of this class of compound, we recently reported a novel approach to prepare Mannich bases 40 with concomitant formation of α‐quaternary carbon by a copper‐catalyzed amination‐induced 1,2‐rearrangement reaction of allylic alcohols 39 under simple and mild conditions (Scheme a) . The reaction uses commercially available N ‐fluorobenzenesulfonimide (NFSI) as an amination reagent and CuCl as precatalyst.…”