Asymmetric Copper-Catalyzed Carbomagnesiation of Cyclopropenes

In the last few years, we have been interested in the selective ring-opening of cyclopropanes for the preparation of quaternary carbon stereocenter in acyclic systems.¹ However, for this approach to be reliable and efficient, one needs to have an easy access to the preparation of diastereo- and enantiomerically enriched polysubstituted cyclopropanes from a common and easily accessible precursor. In this context and in continuation of our previous effort on the preparation of diastereo and enantiomerically enriched polysubstituted cyclopropanes,² we demonstrate herein a highly enantio- and diastereoselective Cu-catalyzed carbomagnesiation reaction of unfunctionalized cyclopropenes with a great variety of alkyl Grignard reagents. The flexibility and easily availability of both partners (cyclopropenes and Grignard reagents) provide a novel, mild and convenient approach to a variety of polysubstituted cyclopropanes. The carbometalated species generated in situ readily undergo C-C and C-X bond forming reactions with various electrophiles with retention of configuration.

Reference:

[1] For our recent works on the C-C bond cleavage of cyclopropanes, see: a) S. Simaan, I. Marek, J. Am. Chem. Soc. 2010, 132, 4066; b) P.-O. Delaye, D. Didier, I. Marek, Angew. Chem. Int. Ed. 2013, 52, 5333; c) A. Masarwa, D. Didier, T. Zabrodski, M. Schinkel, L. Ackermann, I. Marek, Nature 2014, 505, 199; d) A. Vasseur, L. Perrin, O. Eisenstein, I. Marek, Chem. Sci. 2015, 6, 2770; e) A. Masarwa, D. Gerbig, L. O., A. Loewenstein, H. P. Reisenauer, P. Lesot, P. R. Schreiner, I. Marek, Angew. Chem. Int. Ed. 2015, 54, 13106; f) M. Simaan, P.-O. Delaye, M. Shi, I. Marek, Angew. Chem. Int. Ed. 2015, 54, 12345; g) S. R. Roy, D. Didier, A. Kleiner, I. Marek, Chem. Sci. 2016, 7, 5989; h) F.-G. Zhang, G. Eppe, I. Marek, Angew. Chem. Int. Ed. 2016, 55, 714.

[2] D. S. Müller, I. Marek, J. Am. Chem. Soc. 2015, 137, 15414. For previous works on the asymmetric carbozincation of cyclopropens by other groups, see: b) M. Nakamura, A. Hirai, E. Nakamura, J. Am. Chem. Soc. 2000, 122, 978; c) K. Krämer, P. Leong, M. Lautens, Org. Lett. 2011, 13, 819.