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

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.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (106 K)Download as PowerPoint slideHighlights► New salen-type planar chiral ligand derived from [2.2]paracyclophane. ► Highly effective for Cu(II)-catalyzed asymmetric cyclopropanation reactions. ► 0.1 mol% catalyst gives turnover numbers approaching 1000. ► Enantiomeric excesses (ee) for cyclopropane products up to 95% ee. ► Small structural modification leads to an average increase in ee of 60%.