Convenient synthesis of an enantiomerically pure bicyclic proline and its N-oxyl derivatives

An enantiomerically pure bicyclic proline derivative was prepared by cis-selective allylation and diastereospecific intramolecular alkylation starting from d-pipecolinic acid. In addition, enantiomerically pure azabicyclo N-oxyls derived from the bicyclic proline worked well as catalysts for the enantioselective electrooxidation of racemic sec-alcohols to afford optically active sec-alcohols in moderate enantiomeric purity.

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Methyl N-methoxycarbonyl-(6S)-allyl-d-pipecolinateC12H19NO4[α]D20=+106.6 (c 1.0, CHCl3)Absolute configuration: (6S)Source of chirality: d-pipecolinic acid

Methyl N-methoxycarbonyl-(6S)-(2-hydroxyethyl)-d-pipecolinateC11H19NO5[α]D20=+50.2 (c 1.0, CHCl3)Absolute configuration: (6S)Source of chirality: d-pipecolinic acid

Methyl N-methoxycarbonyl-(6S)-[2-(p-tolunesulfonyloxy)ethyl]-d-pipecolinateC18H25NO7S[α]D20=+61.5 (c 1.0, CHCl3)Absolute configuration: (6S)Source of chirality: d-pipecolinic acid

Methyl (1R)-N-methoxycarbonyl-8-azabicyclo[3.2.1]octane-1-carboxylateC11H17NO4Ee = >99%[α]D23=+25.0 (c 1.0, CHCl3)Absolute configuration: (1S)Source of chirality: d-pipecolinic acid

(1R)-N-Methoxycarbonyl-8-azabicyclo[3.2.1]octane-1-carboxylic acidC10H15NO4Ee = >99%[α]D29=+21.6 (c 1.0, CHCl3)Absolute configuration: (1S)Source of chirality: d-pipecolinic acid

Methyl N-[(1R)-N-methoxycarbonyl-8-azabicyclo[3.2.1]octane-1-carbonyl]dimethylglycyl-dimethylglycinateC19H31N3O6[α]D25=+25.6 (c 0.5, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

Methyl (1R)-8-azabicyclo[3.2.1]octane-1-carboxylateC9H15NO2Ee = >99%[α]D28=+14.3 (c 0.7, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

Methyl (1R)-8-azabicyclo[3.2.1]octane-1-carboxylate-N-oxylC9H13NO3Ee = >99%[α]D29=-13.9 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

(1R)-N-Methoxycarbonyl-1-hydroxylmethyl-8-azabicyclo[3.2.1]octaneC10H17NO3Ee = >99%[α]D26=-21.3 (c 0.9, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

(1R)-N-Methoxycarbonyl-1-benzoyloxymethyl-8-azabicyclo[3.2.1]octaneC17H21NO4Ee = >99%[α]D25=+51.3 (c 1.2, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

(1R)-Benzoyloxymethyl-8-azabicyclo[3.2.1]octaneC15H19NO2Ee = >99%[α]D25=+1.4 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

(1R)-Benzoyloxymethyl-8-azabicyclo[3.2.1]octane-N-oxylC15H18NO3Ee = >99%[α]D24=+48.8 (c 1.0, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

(1R)-N-Methoxycarbonyl-1-N-phenylcarbamoyl-8-azabicyclo[3.2.1]octaneC16H20N2O3Ee = >99%[α]D18=+71.6 (c 1.0, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

(1R)-N-Methoxycarbonyl-1-N-benzylcarbamoyl-8-azabicyclo[3.2.1]octaneC17H22N2O3Ee = >99%[α]D25=+70.8 (c 1.0, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

Methyl N-[(1R)-N-Methoxycarbonyl-8-azabicyclo[3.2.1]octane-1-carbonyl]-l-phenylglycinateC19H24N2O5Ee = >99%[α]D25=+53.0 (c 0.9, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

Methyl N-[(1R)-N-Methoxycarbonyl-8-azabicyclo[3.2.1]octane-1-carbonyl]-d-phenylglycinateC19H24N2O5Ee = >99%[α]D25=+74.7 (c 0.9, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

(1R)-N-Phenylcarbamoyl-8-azabicyclo[3.2.1]octaneC14H18N2OEe = >99%[α]D27=+74.6 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

(1R)-N-Benzylcarbamoyl-8-azabicyclo[3.2.1]octaneC15H20N2OEe = >99%[α]D28=+28.2 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

Methyl N-[(1R)-8-azabicyclo[3.2.1]octane-1-carbonyl]-l-phenylglycinateC17H22N2O3Ee = >99%[α]D24=+0.8 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

Methyl N-[(1R)-8-azabicyclo[3.2.1]octane-1-carbonyl]-d-phenylglycinateC17H22N2O3Ee = >99%[α]D25=+1.4 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

(1R)-N-Phenylcarbamoyl-8-azabicyclo[3.2.1]octane-N-oxylC14H17N2O2Ee = >99%[α]D29=+72.1 (c 0.9, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

(1R)-N-Benzylcarbamoyl-8-azabicyclo[3.2.1]octane-N-oxylC15H19N2O2Ee = >99%[α]D29=+18.7 (c 0.6, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

Methyl N-[(1R)-8-azabicyclo[3.2.1]octane-1-carbonyl]-l-phenylglycinate-N-oxylC17H21N2O4Ee = 99%[α]D25=+86.1 (c 0.8, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid

Methyl N-[(1R)-8-azabicyclo[3.2.1]octane-1-carbonyl]-d-phenylglycinate-N-oxylC17H21N2O4Ee = >99%[α]D25=+119.7 (c 1.3, CHCl3)Absolute configuration: (1R)Source of chirality: d-pipecolinic acid