Combinatorial chemistry for ligand development in catalysis: Synthesis andcatalysis screening of peptidosulfonamide tweezers on the solid phase

On the basis of a pyrrolidine tweezer 1, a library of peptidosulfonamide tw eezers (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 diethyl zinc to aldehydes. One of the best solid-phase tweezer catalyst (i.e., led, giving an ee of 32% in solid-phase catalysis) was resynthesized in solutio n (compounds 20 and 21). The now homogeneous solution-phase catalysis showe d even better enantioselectivity (i.e., up to 66%).