Redox Reorganization: Aluminium Promoted 1,5-Hydride Shifts Allow the Controlled Synthesis of Multisubstituted Cyclohexenes.

ABSTRACT: 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. Al₂ O₃ or Al(O^t Bu)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.

SUBMITTER: Smith LB 

PROVIDER: S-EPMC10953022 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature