Highly enantioselective rhodium-catalyzed cross-coupling of boronic acids and racemic allyl halides

Mechanistic Investigation of Rh(I)-Catalyzed Asymmetric Suzuki-Miyaura Coupling with Racemic Allyl Halides

“…We performed the reactions on a 7.0 mmol scale as a relatively large amount of product is required for quantitative 13 C NMR spectroscopy and the reaction must be stopped at low conversion to ensure the product is enriched in the faster reacting isotope. However, using optimized conditions at this scale at 60 °C, the reaction was much faster than anticipated; when the reaction was quenched after 2 min, the conversion was already 60%.…”

“…For the quantitative 13 C spectroscopy, we took C5 as the reference carbon. Although 13 C KIE are intrinsically small (ranging from 0.98-1.10), 43 after running these experiments in triplicate we observed appreciable KIE at positions C1, C3 and C7 (Fig. 4a).…”

“…However, this transformation is currently limited to electrophiles that, after cleavage of the carbon-halogen bond, are achiral about the allyl unit. 13,14 In order to further understand the limitations and potential of Rh-catalysed asymmetric additions and of catalytic processes involving racemic substrates, we set out to design a series of experimental and computational experiments to reveal the mechanisms involved in this transformation.…”

“…To gain more understanding we sought to determine natural abundance 12 C/ 13 C ratios using the method developed by Singleton. 32,33 This approach has been employed with great success to measure competitive intermolecular 13 C kinetic isotope effects (KIE) in mechanistic studies of catalytic reactions. [34][35][36][37][38][39][40][41][42] This commonly relies on running the reaction to high conversion, and examining the 12 C/ 13 C ratio in recovered starting material.…”

“…20 It is also plausible that the two enantiomers of 6 could undergo conversion at different rates, confounding analysis of KIE by examining the starting material. We therefore chose to determine 12 C/ 13 C ratios generated in product 8 when the reaction is quenched at low conversion and quantify the depletion of 13 C by quantitative 13 C NMR spectroscopy.…”