Stereodefined Cyclopentanes by Hydroarylation–Ring Opening

The hydroarylation of 2-azabicyclo[2.2.1]hept-5-en-3-one followed by nucleophilic ring opening was employed as an operationally simple route to stereodefined trisubstituted cyclopentane analogs. This synthetic sequence was successfully executed using a variety of nucleophiles including hydroxide, alkoxide, hydride, Grignard reagents, and amines. This methodology facilitated the preparation of a constrained version of dipeptidyl peptidase 4 inhibitor sitagliptin.