Redox reorganization: aluminium promoted 1,5-hydride shifts allow the controlled synthesis of multisubstituted cyclohexenes

Journal article

An efficient synthesis of cyclohexenes has been achieved from easily accessible tetrahydropyrans via a tandem 1,5-hydride shift–aldol condensation. We discovered that readily available aluminium reagents, e.g. Al2O3 or Al(OtBu)3 are essential for this process, promoting the 1,5-hydride shift with complete regio- and enantiospecificity (in stark contrast to results obtained under basic conditions). The mild conditions, coupled with multiple methods available to access the tetrahydropyran starting materials makes this a versatile method with exceptional functional group tolerance. A wide range of cyclohexenes (>40 examples) have been prepared, many in enantiopure form, showing our ability to selectively install a substituent at each position around the newly forged cyclohexene ring. Experimental and computational studies revealed that aluminium serves a dual role in facilitating the hydride shift, activating both the alkoxide nucleophile and the electrophilic carbonyl group.

Authors: Smith, LB; Armstrong, RJ; Hou, J; Smith, E; Sze, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Angewandte Chemie International Edition
• Volume: 62
• Issue: 36
• Article number: e202307424
• Publication date: 2023-09-04
• Acceptance date: 2023-06-26
• DOI: 10.1002/anie.202307424
• EISSN: 1521-3773
• ISSN: 1433-7851
• Language: English
• Keywords: ring formation; cyclohexene; 5-hydride shift; FFR; aluminium; selective; 1