Amino-Protecting Groups Subject to Deblocking under Conditions of Nucleophilic Addition to a Michael Acceptor. Structure−Reactivity Studies and Use of the 2-(<i>tert-</i>Butylsulfonyl)-2-propenyloxycarbonyl (Bspoc) Group

Abstract

A new type of amino-protecting group is described in which a Michael acceptor is incorporated into the protectant so that treatment with a nucleophile will trigger deblocking. Comparison of various Michael acceptors showed that for several key electron-withdrawing groups, the order of reactivity was C 6 H 5 SO 2 > Me 3 CSO 2 > COOEt > C 6 H 5 SO > C 6 H 4 NO 2 - p . The reactivity of the nucleophile (e.g., primary and secondary aliphatic amines) followed an order related to both intrinsic basicity and steric effects. β-Substituents in the Michael acceptor caused significant retardation of the deblocking process. The Bspoc function was chosen for initial elaboration into a practical system for use in peptide synthesis. Bspoc amino acid chlorides were used as coupling agents and silica-tethered secondary amines as deblocking agents. With the latter, deblocking occurs cleanly and no byproducts remain in the organic solvent in which the deblocking is executed.