Work

Palladium-catalyzed cascade of aza-Wacker and Povarov reactions of aryl amines and 1,6-dienes for hexahydro-cyclopenta[b]quinoline framework

Year: 2024

Type: article

Abstract: Palladium catalyzed tandem reaction represents a one-pot synthetic approach to efficiently synthesize complex functionalized molecules while reducing synthetic steps, aligning with the principles of green chemistry. However, achieving a direct cascade of the aza-Wacker and Povarov reactions in one-pot synthesis presents a challenge due to substrate compatibility issues between the two reactions. In this work, we describe an aza-Wacker/Povarov reaction employing a highly electrophilic palladium catalyst, which effectively converts anilines and 1,6-dienes into hexahydro-cyclopenta[b]quinolines. The optimized conditions yield up to 79%, with a diastereoselectivity > 20:1. Substrate range testing reveals compatibility with various sensitive functional groups, and successful late-stage modifications are performed on several natural products and drug molecules, demonstrating the versatility and practicality of the method. Additionally, a preliminary investigation into the reaction mechanism suggests an aza-Wacker process followed by a Povarov process. Achieving a direct cascade of the aza-Wacker and Povarov reactions in one-pot synthesis presents a challenge due to substrate compatibility issues between the two reactions. Here, the authors report an aza-Wacker/Povarov reaction of anilines with 1,6-dienes to obtain the hexahydro-cyclopenta[b]quinolines.

Source: Nature Communications

DOI: 10.1038/s41467-024-51173-4

Authors: Jiahao Wu, Xiangwen Tan, Wanqing Wu, Huanfeng Jiang

Institution: South China University of Technology

Language: English

Topic: Catalytic Cross-Coupling Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $6,790

Funder: National Natural Science Foundation of China