Investigation of the Effects of the Structure and Chelate Size of Bis-oxazoline Ligands in the Asymmetric Copper-Catalyzed Cyclopropanation of Olefins: Design of a New Class of Ligands.

A set of novel, C(2)-symmetric bis-oxazoline ligands has been synthesized by mounting two oxazoline rings onto an optically active 1,3-dioxolane backbone. This design allows for the control of both orientation as well as the proximity of the oxazolinyl R-groups around the reactive site. As a result of the twist imparted by the 1,3-dioxolane ring, the stereogenic oxazolinyl substituents can be brought either toward or away from the complexed metal in a controllable fashion. Starting from L-amino alcohols and either L- or D-tartaric acid, two sets of ligands (6b-e and 7a,b) were synthesized and evaluated in the copper-catalyzed cyclopropanation of olefins. The comparison of benzyl and isopropyl derivatives of these ligands with previously reported five- and six-membered bis-oxazolines clearly indicates the beneficiary effect of the larger chelate size and the chiral tether of the tartrate-derived ligand. The effect of the different oxazolinyl groups along with the different substituents on the dioxolane tethers was also investigated. The influence of the alkyl group of the diazoacetate was studied, and the diazoacetate derived from (-)-8-phenylmenthol was found to be superior to (-)-menthyl diazoacetate. The cyclopropanation of vinyl acetate, a relatively unexplored substrate for this reaction, furnished cyclopropanol derivatives in good optical purity.