Asymmetric Hydrogenation of Naphthalenes with Molybdenum Catalysts: Ligand Design Improves Chemoselectivity

Abstract

The asymmetric hydrogenation of substituted naphthalenes with a series of highly enantioenriched oxazoline imino(pyridine) (OIP) molybdenum cyclooctadiene precatalysts is described. The chemoselectivity of the hydrogenation for the formation of tetralin versus decalin products was systematically explored as a function of the aniline substituents on the molybdenum precatalysts. Examples with 2,6-disubstitution with methyl, ethyl, or iso-propyl substituents were the most active but produced near equimolar mixtures of tetralins and decalins, both with high enantiomeric excesses. Introduction of anilines with either 2-tert-butyl or 2,5-di-tert-butyl substituents increased the selectivity for decalin formation albeit with reduced overall hydrogenation activity. In all cases with 2,6-disubtituted naphthalenes, high enantiomeric excesses are observed. Mechanistic studies demonstrated that [(OIP)Mo] catalysts are inactive for tetralin hydrogenation and analysis of the catalytic reactions by NMR spectroscopy, in combination with independent synthesis, identified (OIP)Mo(η⁶-naphthalene) complexes as the catalyst resting states. Assaying product selectivity as a function of catalyst loading established that increasing the amount of molybdenum precatalyst increased the selectivity for decalin formation. Substrate concentration studies were also conducted and support a pathway whereby tetralin formation arises from displacement of the arene from the coordination sphere of the molybdenum by incoming substrate. These studies establish general design principals for [(OIP)Mo] arene hydrogenation catalysts where larger 2,6-aniline substituents increase activity, likely by promoting η⁶ to η⁴ haptotropic rearrangement from the arene resting state, while single tert-butyl substitution promotes more selective hydrogenation to decalin products.