A new set of structurally related enantiopure polypyrazolyl ligands of varying rotational symmetry: Synthesis, metal complexation, and comparison of asymmetric induction

Michael C. Keyes, Bradley M. Chamberlain, Scott A. Caltagirone, Jason A. Halfen, William B Tolman

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Abstract

A new family of enantiomerically pure pyrazoles with a variety of substitutions on a key stereogenic center was synthesized from (R)-(+)-pulegone by a straightforward, large-scale route involving initial construction of the pyrazole ring via formylation/dehydration with hydrazine followed by ozonolysis to yield a readily functionalized ketone (5). Alkylation of 5 with a variety of Grignard reagents, dehydration, hydrogenation, and recrystallization afforded the set of new chiral pyrazoles (7a-c). Cis and/or trans diastereomers of one of these pyrazoles having a phenyl substituent (7a) were elaborated into enantiopure, multidentate Ci-symmetric bis(pyrazolyl)diphenylborate (Tl[cis-Ph2Bppm]), C2-symmetric bis-(pyrazolyl)methane (cis- and trans-Xpm), and C3-symmetric tris(pyrazolyl)phosphine oxide (cis- and trans-OPpm) and tris(pyrazolyl)hydroborate (K[trans-Tppm]) ligands. Interestingly, epimerization of the benzylic stereogenic center occurred during the synthesis of K[trans-Tppm], as determined by comparison of 2D NMR spectral and X-ray crystal structural data for the starting cis-pyrazole (cis-7a) and the copper complex (trans-Tppm)Cu(CH3CN). Comparison of the abilities of copper complexes of the various [Ph2Bppm]-, Xpm, OPpm, and Tppm ligands to catalyze the cyclopropanation of styrene by ethyldiazoacetate revealed significantly enhanced enantioselectivity for the Tppm case. This result represents the first example of a high degree 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 reactions.

Original languageEnglish (US)
Pages (from-to)1984-1992
Number of pages9
JournalOrganometallics
Volume17
Issue number10
DOIs
StatePublished - May 11 1998

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