Organocatalytic Transannular Approach to Stereodefined Bicyclo[3.1.0]hexanes

A diastereodivergent
approach to highly substituted bicyclo[3.1.0]­hexanes
has been developed through a transannular alkylation reaction that
builds up the bicyclic core employing asymmetric organocatalysis as
the tool for the installation of all stereocenters. On one hand, a
Michael/Michael cascade process between enals and 4-alkenyl sulfamidate
imines under the iminium/enamine activation manifold provides an oxathiazole-2,2-dioxide-fused
cyclohexane adduct that, after isolation, is subsequently engaged
in a transannular alkylation/hydrolysis through enamine activation
by the use of a primary amine. On the other hand, the corresponding
C-2 epimers are directly obtained from the same starting materials
in a single operation through a cascade Michael/Michael/transannular
alkylation/hydrolysis sequence through sequential iminium/enamine/enamine
combination of aminocatalytic activation manifolds.