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Chemo‐, Diastereo‐, and Enantioselective (3+2) Cycloadditons of Bicyclobutanes with Enals Enabled by Synergistic Palladium and Organocatalysis

Year: 2025

Type: article

Abstract: Comprehensive Summary Despite significant progress in catalytic asymmetric (3+ X ) cycloadditions of bicyclobutanes (BCBs) for constructing pharmaceutically valuable bicyclo[ n .1.1]alkanes, current strategies are limited to using a single catalyst for the separate activation of BCBs or the " X " components. Herein, we report a new strategy that synergistically combines achiral Pd‐catalysis for BCB activation with chiral iminium activation of α,β‐unsaturated aldehydes, thereby overcoming existing limitations. These limitations include issues of chemo‐, diastereo‐, and enantioselectivity in the (3+2) cycloadditions of BCBs with enals for the synthesis of multisubstituted all‐carbon bicyclo[2.1.1]hexanes (BCHs). Despite these challenges, up to 99% ee , >20 : 1 d.r., and 88% yield have been achieved. Moreover, the protocol demonstrates a wide range of substrates, high tolerance to various functional groups, scalable synthesis and versatile product functionalization, highlighting its practical value in constructing complex chiral BCH structures. Additionally, synergizing transition‐metal catalysis and organocatalysis activation principles broadens the mechanistic and synthetic scope of the asymmetric cycloadditions of BCBs.

Source: Chinese Journal of Chemistry

DOI: 10.1002/cjoc.70355

Authors: Feng Wu, Quanxin Peng, Yu‐Jie Li, Yuanjiu Xiao, Jian‐Jun Feng

Institution: Hunan University

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Natural Science Foundation of China, Hunan University, Fundamental Research Funds for the Central Universities

Award: G1447870626