An efficient, asymmetric synthesis of pipecolic acid and 2-alkyl pipecolic acids

Both (R)- and (S)-pipecolic acids and their 2-alkyl derivatives have been synthesized via diastereoselective alkylations of (R)-5-phenylmorpholin-2-one 5.

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(R)-Pipecolic acidC6H11NO2Ee >95%[α]D25=+25.8 (c 1.0, water)Source of chirality: diastereoselective synthesisAbsolute configuration: R

(S)-2-Methyl-2-piperidinecarboxylic acidC7H13NO2Ee >95%[α]D25=-3.7 (c 1.0, water)Source of chirality: diastereoselective synthesisAbsolute configuration: S

(S)-2-Ethyl-2-piperidinecarboxylic acidC8H15NO2Ee >95%[α]D25=-11.9 (c 1.0, water)Source of chirality: diastereoselective synthesisAbsolute configuration: S

(S)-2-Propyl-2-piperidinecarboxylic acidC9H17NO2Ee >95%[α]D25=-22.3 (c 1.0, water)Source of chirality: diastereoselective synthesis Absolute configuration: S

(R)-2-Benzyl-2-piperidinecarboxylic acidC13H17NO2Ee >95%[α]D25=-2.8 (c 1.0, water)Source of chirality: diastereoselective synthesisAbsolute configuration: R