Dirhodium-Palladium Dual-Catalyzed [1 + 1 + 3] Annulation to Heterocycles Using Primary Amines or H2O as the Heteroatom Sources

Jie Xu; Gaoyin Wang; Kuiling Ding; Xiaoming Wang

doi:10.1021/jacs.4c15161

Dirhodium-Palladium Dual-Catalyzed [1 + 1 + 3] Annulation to Heterocycles Using Primary Amines or H₂O as the Heteroatom Sources

J Am Chem Soc. 2025 Jan 7. doi: 10.1021/jacs.4c15161. Online ahead of print.

Authors

Jie Xu^{1

2}, Gaoyin Wang², Kuiling Ding^{1

2

3}, Xiaoming Wang^{2

4

5}

Affiliations

¹ Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China.
² State Key Laboratory of Organometallic Chemistry and Shanghai Hongkong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
³ Frontier Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
⁴ School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou 310024, China.
⁵ School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China.

PMID: 39772613
DOI: 10.1021/jacs.4c15161

Abstract

The ever-increasing demand in chemical biology and medicinal research requires the development of new synthetic methods for the rapid construction of libraries of heterocycles from simple raw materials. In this context, the utilization of primary amines or H₂O as the simple N- or O-sources in the assembly of a heterocyclic ring skeleton is highly desirable from the viewpoint of atom- and step-economy. Herein, we describe a highly efficient three-component reaction of diazo, allylic diacetates, and commercially available anilines (or H₂O) to access structurally diverse pyrrolidine and tetrahydrofuran derivatives. This formal [1 + 1 + 3] annulation reaction features high efficiency, good yields, and broad functional group compatibility, making it a versatile and robust platform for the (formal) synthesis of several important bioactive molecules. Mechanistic studies suggested that the dirhodium-palladium bimetallic relay catalysis should play a key role in the successive steps of the current reaction, including sequential carbene insertion into the X-H bond and double allylic substitutions, thus allowing for building up molecular complexity from these simple raw materials.