Creation of a quaternary centre by copper mediated SN2’ substitution with PhMgBr

In our studies of the formation of quaternary stereogenic centres, we have worked on the addition of arylcoppermagnesium reagents to geranyl chloride. Based on the work published by Bäckvall(1), the primary focus was optimisation of SN2’-substitution versus SN2-substitution. By examination of different copper salts, it was found that SN2’-selectivity increased in the following order; CuCl <CuOTf <CuBr <CuI  CuCN and that preformation of a stoichiometric arylcopper species is necessary for a high SN2’ selectivity. Examination of the leaving group on the geranyl species revealed that Cl > Br > OAc, and in accordance with the observations by Bäckvall’s group1 it was found the addition of geranyl chloride over a long period (10.5h) gives a higher selectivity. Interesting solvent effects were seen; as CH2Cl2 and THF were equally good, but that the results obtained in THF were very temperature-sensitive, with an optimum at 20C, whereas results in CH2Cl2 were consistently high (67-68%) with temperatures ranging from -50 to 20C. In spite of our efforts the maximum selectivity achieved was 68%, therefore work still lies ahead. 1) Bäckvall, J. E.; Persson, E. S. M.; Bombrun, A. J. Org. Chem. 1994, 59, 4126 - 4130.