An efficient synthesis of (R)- and (S)-2-(aminomethyl)piperidine dihydrochloride

The synthesis of the dihydrochloride salts of (R)-1 and (S)-1 2-(aminomethyl)piperidine is reported starting from either (S) or (R) lysine, respectively. A key step in the synthetic protocol involves the in situ formation of aziridinium 8, which then undergoes an intramolecular ring opening with concomitant piperidinium ring formation, in a stereoselective manner. The route offers a practical synthesis of (R)-1 and (S)-1, and it should make them more accessible for exploration in asymmetric catalysis or as building blocks in pharmaceutical research.

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(R)-2-(Aminomethyl)piperidine dihydrochlorideC6H16Cl2N2[α]D20=+2.3 (c 1.4, MeOH)Source of chirality: (S)-l-lysine·HClAbsolute configuration: (R)

(S)-benzyl 2,6-bis(dibenzylamino)hexanoateC41H44N2O2[α]D20=-46.9 (c 1.6, CHCl3)Source of chirality: (S)-l-lysine·HClAbsolute configuration: (S)

(S)-2,6-Bis(dibenzylamino)hexan-1-olC34H40N2O[α]D20=+49.5 (c 0.8, CHCl3)Source of chirality: (S)-l-lysine·HClAbsolute configuration: (S)

(R)-1,1-Dibenzyl-2-((dibenzylamino)methyl)piperidinum chlorideC34H39ClN2[α]D20=-73.5 (c 1.1, CHCl3)Source of chirality: (S)-l-lysine·HClAbsolute configuration: (R)