Chiral α-alkylation/arylation in 1-phenyl-2-(1-pyrrolidinyl)-1-propanol through Grignard reactions

Complete asymmetric induction has been achieved during Grignard alkylations/arylations resulting in (1S,2R)- and (1R,2R)-1-phenyl-1-alkyl/aryl-2-(1-pyrrolidinyl)-1-propanols which are isolated as hydrochlorides.

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erythro-(1S,2R)-(−)-1-Phenyl-1-methyl-2-(1-pyrrolidinyl)-1-propanol hydrochlorideC14H22NOClEe = 100%[α]D25=-12.5 (c 1.0, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

erythro-(1S,2R)-(−)-1-Phenyl-1-ethyl-2-(1-pyrrolidinyl)-1-propanol hydrochlorideC15H24NOClEe = 100%[α]D25=-18.4 (c 1.0, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

erythro-(1S,2R)-(−)-1-Phenyl-1-(2-propyl)-2-(1-pyrrolidinyl)-1-propanol hydrochlorideC16H26NOClEe = 100%[α]D25=-6.6 (c 1.0, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

erythro-(1S,2R)-(−)-1-Phenyl-1-butyl-2-(1-pyrrolidinyl)-1-propanol hydrochlorideC17H28NOClEe = 100%[α]D25=-9.1 (c 1.0, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

erythro-(1S,2R)-(−)-1-Phenyl-1-(2-methylpropyl)-2-(1-pyrrolidinyl)-1-propanol hydrochlorideC17H28NOClEe = 100%[α]D25=-6.9 (c 1.0, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

erythro-(1S,2R)-(−)-1-Phenyl-1-benzyl-2-(1-pyrrolidinyl)-1-propanol hydrochlorideC20H26NOClEe = 100%[α]D25=-71.8 (c 1.0, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

erythro-(1S,2R)-(+)-1-Phenyl-1-phenethyl-2-(1-pyrrolidinyl)-1-propanol hydrochlorideC21H28NOClEe = 100%[α]D25=+29.2 (c 1.0, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

erythro-(1R,2R)-(−)-1-Phenyl-1-(3-methoxyphenyl)-2-(1-pyrrolidinyl)-1-propanol hydrochlorideC20H26NO2ClEe = 100%[α]D25=-58.4 (c 1.0, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R)

erythro-(1R,2R)-(+)-1-Phenyl-1-(1-naphthyl)-2-(1-pyrrolidinyl)-1-propanol hydrochlorideC23H26NOClEe = 100%[α]D25=+135.3 (c 1.0, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R)