An optimised synthetic approach to a chiral derivatising agent and the utilisation of a dimerisation reaction in the synthesis of a novel C2-symmetric diphosphine ligand

We report an optimised synthetic approach to the chiral derivatising agent (5R)-methyl-1-(chloromethyl)-2-pyrrolidinone. In addition, the observation of an unwanted dimerisation product is turned to our advantage by providing a method for the synthesis of a new class of C2-symmetric chiral diphosphine.

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Ethyl-(2S)-5-oxopyrrolidineC7H11NO3Ee = 100%[α]D22 = −6.8 (c 0.03, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S)

[(2S)-5-Oxopyrrolidin-2-yl]methyl-4-methylbenzenesulfonate 4C12H15NO4SEe = 100%[α]D22 = −6.5 (c 0.013, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S)

(5R)-5-Methylpyrrolidin-2-one 5C5H9NOEe = 100%[α]D22 = +15.8 (c 0.023, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (5R)

(5R)-Methyl-1-(chloromethyl)-2-pyrrolidinoneC6H10NOClEe = 100%[α]D22 = +106.9 (c 0.021, CHCl3)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (5R)

(5R)-5-Methyl-1-{[(2R)-2-methyl-5-oxopyrrolidin-1-yl]methylpyrrolidin-2-oneC11H18N2O2Ee = 100%[α]D22 = +207.7 (c 0.48, CHCl3)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (5R,2R)

l-(+)-1,1′-Methylenebis[5-oxo-2-pyrrolidinecarboxylic acid]C11H14N2O6Ee = 100%[α]D22 = +104.0(c 0.022, H2O)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S,2′S)

l-(+)-1,1′-Methylenebis[5-oxo-2-pyrrolidinecarboxylic acid ethyl ester]C15H22N2O6Ee = 100%[α]D22 = +52.7 (c 0.0204, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S,2′S)

l-(+)-1,1′-Methylenebis[5-hydroxymethyl-2-pyrrolidinone]C11H18N2O4Ee = 100%[α]D22 = +91.3 (c 0.0145, H2O)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S,2′S)

l-(+)-1,1′-Methylenebis[toluene-4-sulfonic acid (S)-5-oxo-pyrrolidin-2-ylmethyl ester]C25H30N2O4S2Ee = 100%[α]D22 = +52.6 (c 0.0204, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S,2′S)

Methylenebis[5-diphenylphosphino-2-pyrrolidinone]C35H36N2O2P2Ee = 100%[α]D22 = +83.6 (c 0.031, EtOH)Source of chirality: enantiomerically pure starting materialAbsolute configuration: (2S,2′S)