Enantioselective Synthesis of alpha,beta-Unsaturated Aryl Lactams by Heck-Matsuda and Heck-Mizoroki Arylations of Enelactams

Author(s)

Braga, Ingredy Bastos ; Angnes, Ricardo Almir ; de Lucca Junior, Emilio Carlos ; Carmo Braga, Ataualpa Albert ; Duarte Correia, Carlos Roque

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY; v. 2022, n. 39, p. 7-pg., 2022-07-20.

Abstract

The chiral aryl lactam nucleus is a common motif present in many bioactive natural products and the development of effective enantioselective methodologies for its preparation is of great interest. In this work, we report the synthesis of several enantioenriched aryl lactams in good yields and enantiomeric ratios using a combined strategy employing arenediazonium salts bearing electron-withdrawing substituents, aryl iodides with electron-donating substituents, and chiral N,N-ligands. The chiral alpha,beta-unsaturated aryl lactams were obtained in yields of up to 78 % and enantiomeric ratios up to 95 : 5. Furthermore, this work demonstrates the use of chiral N,N-ligands as a viable alternative to the phosphine-based ligands in the enantioselective Heck-Mizoroki reactions using aryl iodides. The origins of the enantioselectivity and the full catalytic cycle for the Heck-Matsuda arylation of the enelactams were investigated through DFT calculations. (AU)

• FAPESP's process: 14/25770-6 - New frontiers in cross-coupling reactions promoted by palladium: combining enantioselective catalysis, C-H activations, new materials and in flux reactions aiming at high efficiency and sustainability in synthetic processes
• Grantee: Carlos Roque Duarte Correia
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/02052-4 - Computational mechanistic studies of transition metal catalyzed functionalizations of alkenes: nonintuitive enantioselectivity induction modes applied on contiguos stereocenter formation and difunctionalizations.
• Grantee: Ricardo Almir Angnes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/01491-3 - Theoretical study of cross-coupling reactions: homogeneous and heterogeneous catalysis
• Grantee: Ataualpa Albert Carmo Braga
• Support Opportunities: Regular Research Grants