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

• Published in: Journal of organic chemistry Vol. 64; no. 12; pp. 4315 - 4323
• Main Authors: Carpino, Louis A, Philbin, Michael
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 11.06.1999; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; 9-FLUORENYLMETHYLOXYCARBONYL; COUPLING REAGENTS; PHASE PEPTIDE-SYNTHESIS; FMOC; SULFONE; ACID FLUORIDES; FAMILY
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo982141d

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 C6H5SO2 > Me3CSO2 > COOEt > C6H5SO > C6H4NO2-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.