Temperature Dual Enantioselective Control in a Rhodium-Catalyzed Michael-Type Friedel-Crafts Reaction: A Mechanistic Explanation

By changing the temperature from 283 to 233 K, the S (99% ee) or R (96% ee) enantiomer of the Friedel-Crafts (FC) adduct of the reaction between N-methyl-2-methylindole and trans-beta-nitrostyrene can be obtained by using (S-Rh,R-C)-[(eta(5)-C5Me5)Rh{(R)-Prophos}(H2O)][SbF6](2) as the catalyst precursor. This catalytic system presents two other uncommon features: 1) The ee changes with reaction time showing trends that depend on the reaction temperature and 2) an increase in the catalyst loading results in a decrease in the ee of the S enantiomer. Detection and characterization of the intermediate metal-nitroalkene and metal-aci-nitro complexes, the free aci-nitro compound, and the FC adduct-complex, together with solution NMR measurements, theoretical calculations, and kinetic studies have allowed us to propose two plausible alternative catalytic cycles. On the basis of these cycles, all the above-mentioned observations can be rationalized. In particular, the reversibility of one of the cycles together with the kinetic resolution of the intermediate aci-nitro complexes account for the high ee values achieved in both antipodes. On the other hand, the results of kinetic measurements explain the unusual effect of the increment in catalyst loading.