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Enantioselective intermolecular C-H functionalization of primary benzylic C-H bonds using ((Aryl)(diazo)methyl)phosphonates
Naeem, Y., Matsuo, B. T., & Davies, H. M. L. (2023). Enantioselective intermolecular C-H functionalization of primary benzylic C-H bonds using ((Aryl)(diazo)methyl)phosphonates. ACS Catalysis, 14(1), 124-130. https://doi.org/10.1021/acscatal.3c04661
Catalyst-controlled C-H functionalization using donor/acceptor carbenes has been shown to be an efficient process capable of high levels of site control and stereocontrol. This study demonstrated that the scope of the donor/acceptor carbene C-H functionalization can be extended to systems where the acceptor group is a phosphonate. When using the optimized dirhodium catalyst, Rh-2(S-di-(4-Br)TPPTTL)(4), ((aryl)(diazo)methyl)phosphonates undergo highly enantioselective (84-99% ee) and site-selective (>30:1 r.r.) benzylic C-H functionalization. The phosphonate group is much more sterically demanding than the previously studied carboxylate ester group, leading to much higher selectivity for a primary site versus more sterically crowded positions. The effectiveness of this methodology has been demonstrated by the late-stage primary C-H functionalization of estrone, adapalene, (S)-naproxen, clofibrate, and gemfibrozil derivatives.