N-(4-[2.2]paracyclophanyl)-2 '-hydroxyacetophenone imine: An effective paracyclophane Schiff-base ligand for use in catalytic asymmetric cyclopropanation reactions

Douglas S. Masterson, University of Southern Mississippi
Caitlyne Shirley, University of Southern Mississippi


The synthesis of planar chiral N-(4-[2.2]paracyclophanyl)-2'-hydroxyacetophenone imine (5) and its use as a ligand for the copper(II) catalyzed cyclopropanation of styrene and stilbene derivatives using diazoesters is presented. Catalyst loadings of 0.1 mol% gave conversions of >80% (turnover numbers approaching 1000) for styrene and its derivatives. When enantiomerically enriched (R)-5 was used to form the catalyst for cyclopropanation of styrene using ethyldiazoacetate, the cyclopropane products were obtained in a trans/cis ratio of 1.9-1 and 75.8% and 60.5% ee (corrected), respectively. The use of t-butyldiazoacetate resulted in an increased trans/cis ratio of 4.6-1 and 88.2% and 77.9% ee, respectively. Enantioselectivities of up to 95% ee were observed. These are among the highest enantioselectivities observed for asymmetric reactions using catalysts where chirality is solely derived from the paracyclophanyl moiety. When compared to its non-methylated analog, the simple presence of a methyl group on the carbon of the imine moiety in 5 resulted in an average increase in enantioselectivity of ca. 60% ee for a variety of substrates. The origin of this dramatic improvement in selectivity is discussed. (c) 2012 Elsevier B.V. All rights reserved.