Chemoselectivity Control in the Reactions of 1,2-Cyclic Sulfamidates with Amines

Although 1,2‐cyclic sulfamidates derived from α‐methylisoserine undergo nucleophilic displacement at the quaternary center, to the best of our knowledge their behavior with amines as nucleophiles has never been explored. We have found that a broad range of amines can be used, demonstrating the scope of the reaction, and that excellent control of the chemoselectivity can be achieved. Application of this methodology for the synthesis of a chiral α,β‐diamino acid and an important piperazinone heterocycle is also presented. Additionally, we have found that DMF and DMSO behave not only as polar aprotic solvents but also as O‐nucleophilic reagents, allowing the incorporation of an oxygen atom at a quaternary center of the electrophile, with inversion of configuration. Chemoselectivity control: The reactions of amines with a 1,2‐cyclic sulf amidate provide an elegant example of chemoselectivity control. Three types of reaction have been observed, namely, N‐deprotection, ester–carboxamide exchange, and nucleophilic substitution (see scheme), with both the solvent and amine affecting the outcome. The nucleophilic substitution offers a route to a new α,β‐diamino acid and a chiral piperazinone derivative, which is a restricted scaffold suitable for use in peptide chemistry.