Diastereo- and Enantioselective Construction of Stereochemical Arrays Exploiting Non-Classical Hydrogen Bonding in
Matthew Li1, Stephan Scheeff1, Jiahua Chen2
1Department of Chemistry and the State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P.R. China.
Abstract:
We report a copper-catalyzed reductive aldol addition to aldehydes and ketones, with pinacolborane as stoichiometric reductant, that results in the generation of stereodefined syn-aldol products. Cyclic, acyclic, fused and spirocyclic aldols bearing contiguous stereocenters are obtained with excellent yields and diastereoselectivities. Moreover, enantioselective reactions could be carried out with cycloalkenones to deliver aldols bearing three contiguous stereocenters and with up to 98 % ee. Computations reveal that the enolborate intermediate undergoes the syn-aldol reaction via a twist-boat transition state that is stabilized by non-classical hydrogen bonding interactions.
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