Combinatorial Chemistry for Ligand Development in Catalysis: Synthesis and Catalysis Screening of Peptidosulfonamide Tweezers on the Solid Phase.
On the basis of a pyrrolidine tweezer 1, a library of peptidosulfonamide tweezers (15a-e, 16a-e) was synthesized on the solid phase. This library was screened in a simultaneous substrate screening procedure for the ability to enantioselectively catalyze the Ti(O-i-Pr)(4)-mediated addition of diethylzinc to aldehydes. One of the best solid-phase tweezer catalyst (i.e., 16d, giving an ee of 32% in solid-phase catalysis) was resynthesized in solution (compounds 20 and 21). The now homogeneous solution-phase catalysis showed even better enantioselectivity (i.e., up to 66%).
Brouwer
AJ
Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, NL-3508 TB Utrecht,The Netherlands.
van Der Linden HJ
Liskamp
RM