Chiral Brønsted Acid Catalyzed Enantioselective Phosphonylation of Allylamine via Oxidative Dehydrogenation Coupling

Abstract

A new strategy for the synthesis of chiral α-amino phosphonates by enantioselective C-H phosphonylation of allylamine with phosphite in the presence of a chiral Brønsted acid catalyst has been developed. This protocol successfully integrates direct C-H oxidation with asymmetric phosphonylation and exhibits high enantioselectivity.

Recent Advances in C(sp3)—H Phosphorylation Based on Secondary Phosphine Oxides and Phosphite Esters

“…Particularly, the group of Yang [53] developed a chiral Brønsted acid-catalyzed enantioselective C(sp 3 ) -H phosphorylation of allylamines, providing chiral α-amino phosphonates in up to 92% ee (Scheme 10). In this reaction, an allylimine intermediate is generated via the oxidation of allylamine by Ag 2 CO 3 .…”

Recent Advances in the Enantioselective Oxidative α-C–H Functionalization of Amines

“…Recently, our group reported a chiral Brønsted acid-catalyzed enantioselective phosphonylation of allylamines through oxidative dehydrogenation coupling (Scheme 28). 30 This method benefits from easily accessible starting material, a simple catalytic system and offers easy and efficient access to bioactive chiral α-amino phosphonates with high enantioselectivities (up to 92% ee). The N-aryl protecting group was crucial to reactivity and enantioselectivity and could be removed to afford the corresponding α-amino phosphonate without any loss in enantioselectivity.…”

Asymmetric Access of γ-Amino Acids and γ-Amino Phosphonic Acid Derivatives via Copper-Catalyzed Enantioselective and Regioselective Hydroamination

“…In general, chiral α-aminophosphine oxides and phosphonates are prepared by the Lewis acid and metal catalyzed nucleophilic addition reaction of H-P(O)R 2 with imines. [37][38][39][40][41][42][43][44][45][46] Very recently, Huang and Wang reported an elegant enantioselective reductive phosphonylation of secondary amides for the synthesis of enantioenriched chiral α-aminophosphonates by combining iridium with chiral thiourea catalysis. 47 The most amino phosphonic acid derivatives, most of the methodologies were still limited to the usage of chiral auxiliaries and α-amino acids, which were greatly suffered from poor diversity, expensive chiral amino acid substrates and multi-step process.…”