Work

Chiral Phosphoric Acid-Catalyzed Enantioselective Higher-Order Cycloadditions: Temperature-Dependent Periselectivity

Year: 2025

Type: article

Abstract: Higher-order cycloadditions (HOCs) are powerful tools for constructing complex cyclic structures, but their synthetic utility is often limited by poor periselectivity and challenges in achieving high diastereo- and enantioselectivity. Herein, we report a chiral phosphoric acid-catalyzed reaction between tropones and trifluoroacetamido-1,3-dienes that proceeds efficiently at room temperature, delivering bicyclo[4.4.1]undecatrienones in high yields with excellent peri-, diastereo-, and enantioselectivities. Without isolation, these (6 + 4) cycloadducts undergo a regioselective Cope rearrangement at 100 °C, yielding bicyclo[3.2.2]nonadienones─products of formal (4 + 2) cycloaddition. Remarkably, 7-alkyl-substituted analogues undergo a distinct transformation at 150 °C, producing tetracyclic products featuring a unique decahydro-1,5-methanoazulene motif. The presence of multiple functional groups in these adducts provides versatile synthetic handles for the further derivatization of these structurally intricate bridged polycyclic molecules.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.5c01808

Authors: Xin-Qi Zhu, Qian Wang, Matthew D. Wodrich, Jieping Zhu

Institutions: Yunnan Normal University, École Polytechnique Fédérale de Lausanne

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: École Polytechnique Fédérale de Lausanne, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Xiamen University

Award: Ynimines and Isocyanides: From Methodology Development to Natural Product Synthesis