A Revised Mechanism for the Kinugasa Reaction

Abstract

Detailed kinetic analysis for the Cu(I)-catalyzed Kinugasa reaction forming β-lactams has revealed an anomalous overall zero-order reaction profile, due to opposing positive and negative orders in nitrone and alkyne, respectively. Furthermore, the reaction displays a second-order dependence on the catalyst, confirming the critical involvement of a postulated bis-Cu complex. Finally, reaction progress analysis of multiple byproducts has allowed a new mechanism, involving a common ketene intermediate to be delineated. Our results demonstrate that β-lactam synthesis through the Kinugasa reaction proceeds via a cascade involving (3 + 2) cycloaddition, (3 + 2) cycloreversion, and finally (2 + 2) cycloaddition. Our new mechanistic understanding has resulted in optimized reaction conditions to dramatically improve the yield of the target β-lactams and provides the first consistent mechanistic model to account for the formation of all common byproducts of the Kinugasa reaction.

Visual kinetic analysis

“…VTNA has already been used successfully by academic and industrial research groups in metal-catalysed [25][26][27][28][29][30][31][32][33][34][35][36][37][38] and organocatalytic reactions. [39][40][41][42][43]…”

Efficient one-pot green synthesis of tetrakis(acetonitrile)copper(i) complex in aqueous media

“…used in research laboratories and industrial processes as catalysts in cycloaddition 3,4 and Ullmann 5 reactions, intramolecular aromatic annulations, 6,7 oxidation of primary alcohols 8 and many other popular reactions of organic synthesis. [9][10][11][12][13] At the same time they serve as important precursors for the synthesis of overwhelming majority of mononuclear [14][15][16] and homo- 17 and hetero-polynuclear 18,19 copper(I) complexes, which also have numerous practical applications, [20][21][22] one of which is large-scale production of emitting materials for OLED fabrication. 23 Total number of references related to these compounds as reagents/reactants exceeds 3100 (over 100 of them during 2018 year), including the papers in journals of highest rank.…”

Reactions of HDDA Benzynes with C,N‐Diarylimines (ArCH=NAr')

“…Polyyne substrates 8 , 19a , and 19b were synthesized according to reported methods. N ‐Benzylideneaniline ( 2a ) was prepared according to a reported procedure …”