Stereoselective synthesis of cationic heterobidentate C(NHC)/SR rhodium(I) complexes using stereodirecting N,N-dialkylamino groups

The synthesis of two different types of chiral C/S ligands based upon N-(N,N-dialkylamino)-substituted N-heterocyclic carbenes and thioether functionalities, along with their neutral [RhCl(CNH)(COD)] and cationic [Rh(I)(NHC/S)(COD)]+ complexes, has been accomplished. (S)-2-[(Phenylthio)methyl]pyrrolidine, carrying the thioether moiety, and (2S,5S)-2,5-diphenylpyrrolidine, combined with a thioether functionalized side chain, were studied as potential stereodirecting groups. Only the latter provided high selectivity in the formation of the neutral complex, leading to a single atropoisomer (de >98%) of the newly formed, configurationally stable C(NHC)–Rh bond. The synthesis of the corresponding cationic [Rh(I)(NHC/S)(COD)]+ complexes, however, resulted in the formation of single (Ra,SS) and (Sa,SS) diastereomers, respectively, of the four possible complexes in each case [combinations of the (Ra/Sa) C(NHC)–Rh axis and the (Ss/Rs) stereogenic S center formed upon coordination]. For the proline derivative, the resolution of the mixture of (Ra/Sa)-[RhCl(CNH)(COD)] neutral complexes proceeds via dynamic kinetic resolution through coordinatively unsaturated Rh(I) intermediates formed after halide abstraction. The absolute configurations of both types of cationic complexes were unequivocally assigned on the basis of X-ray diffraction analysis.

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(S)-2-(Phenylthiomethyl)pyrrolidin-1-amineC11H16N2SEe = 100%[α]D20=-95.2 (c 1.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-N-[2-(2-Phenylthiomethylpyrrolidin-1-ylimino)ethyl]formamideC14H19N3OSEe = 100%[α]D20=-73.8 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-1-{2-[(Phenylthio)methyl]pyrrolidin-1-yl}-1H-imidazoleC14H17N3SEe = 100%[α]D20=-37.0 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S)-1-{2-[(Phenylthio)methyl]pyrrolidin-1-yl}-1H-imidazoleC14H17N3SEe = 100%[α]D20=-25.0 (c 0.3, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(2S,Ra,SS)-1-Isopropyl-3-{2-[(phenylthio)methyl]pyrrolidin-1-yl}-imidazol-2-ilydene (1,5-cyclooctadiene)rhodium(I) hexafluoroantimonateC25H35F6N3RhSSbEe = 100%[α]D20=+50.0 (c 0.1, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,Ra,SS)

1-[(R)-2-(Cyclohexylthio)-3-methylbutyl]-3-[(2S,5S)-2,5-diphenylpyrrolidin-1-yl]-imidazol-2-ylidene (1,5-cyclooctadiene)rhodium(I) bromideC38H51BrN3RhSEe = 100%[α]D20=-160.0 (c 0.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,2′S,5S)

(Sa,SS)-{1-[(R)-2-(Cyclohexylthio)-3-methylbutyl]-3-[(2S,5S)-2,5-diphenylpyrrolidin-1-yl]-imidazol-2-ylidene}(1,5-cyclooctadiene)rhodium(I) hexafluorophosphateC38H51F6N3PRhSEe = 100%[α]D20=-61.6 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (Sa,SS, 2R,2′S,5S)