Diastereo- and Enantioselective CuH-Catalyzed Hydroamination of Strained Trisubstituted Alkenes

Amine-substituted cyclobutanes and cyclopropanes are
important
substructures in biologically active compounds. Moreover, many of
the cycloalkane units bear multiple substituents and stereocenters.
Therefore, synthetic methods that produce polysubstituted aminocyclobutanes
and aminocyclopropanes in a highly diastereo- and enantioselective
manner are of importance. Herein, we describe the diastereo- and enantioselective
synthesis of various types of polysubstituted aminocyclobutanes and
aminocyclopropanes through CuH-catalyzed hydroamination of 1-substituted
cyclobutenes and cyclopropenes. These strained trisubstituted alkenes
exhibit much higher reactivity compared to their unstrained analogues
in the initial hydrocupration step of the reaction. Moreover, an interesting
reversal of regioselectivity was observed in the hydroamination of
1-aryl-substituted cyclobutenes compared to the cyclopropene analogues.
The origins of the enhanced reactivity of strained trisubstituted
alkenes as well as the differences in the regio- and enantioselectivity
between reactions with cyclobutenes and cyclopropenes were investigated
computationally.