Catalytic Enantioselective Alkylation of Indoles with trans-4-Methylthio-β-Nitrostyrene.

Isabel Méndez,Ricardo Rodríguez,Daniel Carmona,Carlos Ferrer,Pilar García-Orduña,Fernando J Lahoz

doi:10.1021/acsomega.0c03485

Isabel Méndez, Ricardo Rodríguez + Show 4 more

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https://doi.org/10.1021/acsomega.0c03485

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Abstract

The reaction of the rhodium aqua-complex (SRh,RC)-[Cp*Rh{(R)-Prophos} (OH2)][SbF6]2 [Cp* = C5Me5, Prophos = propane-1,2-diyl-bis(diphenylphosphane)] (1) with trans-4-methylthio-β-nitrostyrene (MTNS) gives two linkage isomers (SRh,RC)-[Cp*Rh{(R)-Prophos}(κ1O-MTNS)]2+ (3-O) and (SRh,RC)-[Cp*Rh{(R)-Prophos}(κ1S-MTNS)]2+ (3-S) in which the nitrostyrene binds the metal through one of the oxygen atoms of the nitro group or through the sulfur atom, respectively. Both isomers are in equilibrium in dichloromethane solution, the equilibrium constant being affected by the temperature in such a way that when the temperature increases, the relative concentration of the oxygen-bonded isomer 3-O increases. The homologue aqua-complex of iridium, (SIr,RC)-[Cp*Ir{(R)-Prophos}(OH2)][SbF6]2 (2), also reacts with MTNS; but only the sulfur-coordinated isomer (SIr,RC)-[Cp*Ir{(R)-Prophos}(κ1S-MTNS)]2+ (4-S) is detected in the solution by NMR spectroscopy. The crystal structures of 3-S and 4-S have been elucidated by X-ray diffractometric methods. Complexes 1 and 2 catalyze the Friedel–Crafts reaction of indole, N-methylindole, 2-methylindole, or N-methyl-2-methylindole with MTNS. Up to 93% ee has been achieved for N-methyl-2-methylindole. With this indole, the ee increases as conversion increases, ee at 263 K is lower than that obtained at 298 K, and the sign of the chirality of the major enantiomer changes at temperatures below 263 K. Detection and characterization of the catalytic intermediates metal-aci-nitro and the free aci-nitro compound as well as detection of the Friedel–Crafts (FC)-adduct complex involved in the catalysis allowed us to propose a plausible double cycle that accounts for the catalytic observations.

Highlights

Chiral catalysts based on transition metals are among the most efficient and versatile for the preparation of enantioenriched compounds.1 Metallic catalysts activate organic substrates by coordination and chiral induction takes place when the reaction occurs within the asymmetric environment generated around the metal by enantiopure ligands.2In particular, transition-metal complexes efficiently catalyze asymmetric Friedel−Crafts (FC) reactions,3 and several metallic systems have been successfully applied to the alkylation of indoles with nitroalkenes
It should be taken into account that intermediates detected under catalytic conditions may not be responsible for the catalysis, the study of the metallic intermediates involved in catalytic processes is one of the most powerful tools available for the chemists to get a deep insight into the reaction mechanisms
We have recently reported on the application of the chiral half-sandwich rhodium and iridium complexes (SM,RC)-[Cp*M{(R)-Prophos}(OH2)][SbF6]2 [Prophos = propane-1,2-diyl-bis(diphenylphosphano); M = Rh (1), Ir (2)] (Scheme 1)12 as catalyst precursors for the Michael-type Friedel−Crafts reaction between indoles and trans-β-nitrostyrenes

Summary

Introduction

Chiral catalysts based on transition metals are among the most efficient and versatile for the preparation of enantioenriched compounds. Metallic catalysts activate organic substrates by coordination and chiral induction takes place when the reaction occurs within the asymmetric environment generated around the metal by enantiopure ligands.2In particular, transition-metal complexes efficiently catalyze asymmetric Friedel−Crafts (FC) reactions, and several metallic systems have been successfully applied to the alkylation of indoles with nitroalkenes. Chiral catalysts based on transition metals are among the most efficient and versatile for the preparation of enantioenriched compounds.. Metallic catalysts activate organic substrates by coordination and chiral induction takes place when the reaction occurs within the asymmetric environment generated around the metal by enantiopure ligands.. Transition-metal complexes efficiently catalyze asymmetric Friedel−Crafts (FC) reactions, and several metallic systems have been successfully applied to the alkylation of indoles with nitroalkenes. Metal-containing hydrogen bond donors catalyze the FC reaction between nitroalkenes and indoles through second coordination sphere mechanisms, in some instances, enantioselectively.. It should be taken into account that intermediates detected under catalytic conditions may not be responsible for the catalysis, the study of the metallic intermediates involved in catalytic processes is one of the most powerful tools available for the chemists to get a deep insight into the reaction mechanisms

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