A NEW SET OF STRUCTURALLY RELATED ENANTIOPURE POLYPYRAZOLYL LIGANDS OF VARYING ROTATIONAL SYMMETRY - SYNTHESIS, METAL COMPLEXATION, AND COMPARISON OF ASYMMETRIC INDUCTION

A new family of enantiomerically pure pyrazoles with a variety of subs titutions on a key stereogenic center was synthesized from (R)-(+)-pul egone by a straightforward, large-scale route involving initial constr uction of the pyrazole ring via formylation/dehydration with hydrazine followed by ozonolysis to yield a readily functionalized ketone(5). A lkylation of 5 with a variety of Grignard reagents, dehydration, hydro genation, and recrystallization afforded the set of new chiral pyrazol es (7a-c). Cis and/or trans diastereomers of one of these pyrazoles ha ving a phenyl substituent (7a) were elaborated into enantiopure, multi dentate C-1-symmetric bis(pyrazolyl)diphenylborate (T1[cis-Ph(2)Bp(pm) ]), Ct-symmetric bis(pyrazolyl)methane (cis-and trans-X-pm), and C-3-s ymmetric tris(pyrazolyl)phosphine oxide (cis-and trans-OPpm) and tris( pyrazolyl)hydroborate (K[trans-Tp(pm)]) ligands. Interestingly, epimer ization of the benzylic stereogenic center occurred during the synthes is of K[trans-Tp(pm)], as determined by comparison of 2D NMR spectral and X-ray crystal structural data for the starting cis-pyrazole (cis-7 a) and the copper complex (trans-Tp(pm))Cu(CH3CN). Comparison of the a bilities of copper complexes of the various [Ph(2)Bp(pm)], X-pm, OPpm, and Tp(pm) ligands to catalyze the cyclopropanation of styrene by eth yldiazoacetate revealed significantly enhanced enantioselectivity for the Tp(pm) case. This result represents the first example of a high de gree of enantiocontrol in a catalytic reaction of any complex of a Tp ligand and provides experimental support for the possible efficacy of higher order rotational symmetry in metal-mediated stereoselective rea ctions.