Chemoenzymatic synthesis of chiral 4-(N,N-dimethylamino)pyridine derivatives

Chiral 4-(N,N-dimethylamino)pyridine derivatives have been prepared through a chemoenzymatic synthesis where the enzymatic kinetic resolution of a family of 4-chloro-2-(1-hydroxyalkyl)pyridines is the key step for the formation of potentially important chiral catalysts. Pseudomonas cepacia lipase (PSL) showed excellent enantioselectivity in the acylation of the (R)-enantiomers (E > 200) using vinyl acetate as acylating agent and THF as solvent, obtaining products and substrates enantiomerically pure and with excellent yields.

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(R)-(+)-2-(1-Hydroxyethyl)pyridineC7H9NOEe 99% (HPLC, Chiralcel OB-H)[α]D20=+18.4 (c 1.0, EtOH)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: R

(R)-(+)-2-(1-Hydroxypropyl)pyridineC8H11NOEe 99%[α]D20=+11.7 (c 1.1, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: R

(R)-(+)-2-(1-Hydroxybutyl)pyridineC9H13NOEe 99%[α]D20=+29.8 (c 0.5, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: R

(R)-(+)-2-(1-Hydroxypentyl)pyridineC10H15NOEe 99%[α]D20=+20.7 (c 1.5, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: R

(S)-(−)-4-Chloro-2-(1-hydroxyethyl)pyridineC7H8NOClEe 99% (HPLC, Chiralcel OB-H)[α]D20=-36.1 (c 2, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: S

(S)-(−)-4-Chloro-2-(1-hydroxypropyl)pyridineC8H10NOClEe 99% (HPLC, Chiralcel OB-H)[α]D20=-29.4 (c 2, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: S

(S)-(−)-4-Chloro-2-(1-hydroxybutyl)pyridineC9H12NOClEe 99% (HPLC, Chiralcel OB-H)[α]D20=-41.7(c 2, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: S

(S)-(−)-4-Chloro-2-(1-hydroxypentyl)pyridineC10H14NOClEe 99% (HPLC, Chiralcel OB-H)[α]D20=-45.8 (c 2, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: S

(S)-(−)-4-(N,N-Dimethylamino)-2-(1-hydroxyethyl)pyridineC9H14N2OEe 99% (HPLC, Chiralcel OD)[α]D20=-31.5 (c 1, EtOH)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: S

(R)-(+)-4-(N,N-Dimethylamino)-2-(1-hydroxyethyl)pyridineC9H14N2OEe 99% (HPLC, Chiralcel OD)[α]D20=+34.1 (c 1, EtOH)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: R

(S)-(−)-4-(N,N-Dimethylamino)-2-(1-hydroxypropyl)pyridineC10H16N2OEe 99%[α]D20=-19.9 (c 1, EtOH)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: S

(S)-(−)-4-(N,N-Dimethylamino)-2-(1-hydroxybutyl)pyridineC11H18N2OEe 99%[α]D20=-26.7 (c 1, EtOH)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: S

(S)-(−)-4-(N,N-Dimethylamino)-2-(1-hydroxypentyl)pyridineC12H20N2OEe 99%[α]D20=-21.8 (c 1, EtOH)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: S

(R)-(+)-1-[4-(N,N-Dimethylamino)-2-pyridinyl]ethyl acetateC11H16N2O2Ee 99% (HPLC, Chiralcel OD)[α]D20=+36.6 (c 0.8, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: R

(R)-(+)-1-(4-Chloro-2-pyridinyl)ethyl acetateC9H10NO2ClEe 99% (HPLC, Chiralcel OD)[α]D20=+90.6 (c 2, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: R

(R)-(+)-1-(4-Chloro-2-pyridinyl)propyl acetateC10H12NO2ClEe 99% (HPLC, Chiralcel OB-H)[α]D20=+82.5 (c 2, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: R

(R)-(+)-1-(4-Chloro-2-pyridinyl)butyl acetateC11H14NO2ClEe 99% (HPLC, Chiralcel OB-H)[α]D20=+74.9 (c 2, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: R

(R)-(+)-1-(4-Chloro-2-pyridinyl)pentyl acetateC12H16NO2ClEe 99% (HPLC, Chiralcel OD)[α]D20=+70.8 (c 2, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: R