Diastereoselective Alkylations of Chiral Tetrazolo[1,5‑a]azepines via Heterobenzylic Anion Intermediates

The alkylations of chiral seven-membered rings fused to tetrazoles are highly diastereoselective. The diastereoselectivity depended on the placement and the size of the substituent on the ring and on the electrophile. Subsequent alkylations occurred with high stereoselectivity, allowing for the construction of quaternary stereocenters. Computational studies revealed that torsional effects are responsible for the observed diastereoselectivities. Substituted products can be reduced to the corresponding secondary amines, thus providing an approach for synthesizing diastereomerically enriched azepanes.