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
La. Carpino et M. Philbin, 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, J ORG CHEM, 64(12), 1999, pp. 4315-4323
A new type of amino-protecting group is described in which a Michael accept
or is incorporated into the protectant so that treatment with a nucleophile
will trigger deblocking. Comparison of various Michael accepters showed th
at for several key electron-withdrawing groups, the order of reactivity was
C6H5SO2 > Me3CSO2 > COOEt > CsH5SO > C(6)H(4)NO(2-)p. The reactivity of th
e nucleophile. (e.g., primary and secondary aliphatic amines) followed an o
rder related to both intrinsic basicity and steric effects. beta-Substituen
ts in the Michael acceptor caused significant retardation of the deblocking
process. The Bspoc function was chosen for initial elaboration into a prac
tical 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.