A Mechanistic Analysis of the Palladium‐Catalyzed Formation of Branched Allylic Amines Reveals the Origin of the Regio‐ and Enantioselectivity through a Unique Inner‐Sphere Pathway. Issue 41 (9th September 2019)

• Record Type: Journal Article
• Authors: Hu, Lingfei; Cai, Aijie; Wu, Zhenzhen; Kleij, Arjan W.; Huang, Genping
• Is Part Of: Angewandte Chemie international edition. Volume 58:Issue 41(2019)
• Page Start: 14694
• Page End: 14702
• Publication Date: 2019-09-09
• Subjects: allylic substitution -- DFT calculations -- enantioselectivity -- inner-sphere pathway -- palladium; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201907375
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A recently reported palladium‐catalyzed allylic substitution of vinyl‐substituted cyclic carbonates (VCCs) with aryl amines represents a rare example of a regio‐ and enantioselective synthesis of α, α‐disubstituted allylic N ‐aryl amines. However, the underlying reasons for this unusual selectivity profile remain elusive. In the present work, density functional theory (DFT) calculations in combination with mechanistic control experiments were performed to elucidate in detail this allylic amination manifold and the origin of the regio‐ and enantioselectivity. The combined data show that after oxidative addition of the VCC to Pd 0, the nucleophilic attack via an originally proposed outer‐sphere pathway gives, however, the opposite regioisomer compared to the experimental results. Instead, nucleophilic attack of the amine reagent via a unique type of chelation‐assisted, inner‐sphere pathway accounts for the experimentally observed "branched" regioselectivity and high enantio‐control. Abstract : A unique chelation‐assisted, inner‐sphere pathway for the Pd‐catalyzed allylic amination of vinyl cyclic carbonates with aryl amines was revealed by DFT calculations and various experiments. A chelation effect enabled through a η 2 ‐coordination of the N‐aryl group to the Pd centre was identified as a key interaction with profound implication for the selectivity parameters.