Synthesis of enantiomerically pure γ-azidoalcohols by lipase-catalyzed transesterification

An enantioselective synthesis of chiral γ-azidoalcohols via lipase-catalyzed resolution is described. The efficiency of various lipases and the effect of different solvents have been studied. Pseudomonas cepacia immobilized on diatomaceous earth (PS-D) in n-hexane catalyzed the transesterification process in an efficient manner providing γ-azidoalcohols in high enantiomeric excess.

Figure optionsDownload as PowerPoint slide

(S)-3-Azido-1-phenylpropan-1-olC9H11N3OEe = 99% (by chiral HPLC)[α]D30=-33.5 (c 6.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(R)-3-Azido-1-phenylpropyl acetateC11H13N3O2Ee = 92% (by chiral HPLC)[α]D30=+56.4 (c 3.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(S)-3-Azido-1-p-tolylpropan-1-olC10H13N3O2Ee >99% (by chiral HPLC)[α]D30=-26.9 (c 0.5, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(R)-3-Azido-1-p-tolylpropyl acetateC12H15N3O2Ee = 94% (by chiral HPLC)[α]D30=+62.1 (c 0.6, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(S)-3-Azido-1-(4-chlorophenyl)propan-1-olC9H10ClN3OEe = 99% (by chiral HPLC)[α]D30=-20.3 (c 0.7, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(R)-3-Azido-1-(4-chlorophenyl)propyl acetateC11H12ClN3O2Ee = 93% (by chiral HPLC)[α]D30=+55.4 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(S)-3-Azido-1-(4-bromophenyl)propan-1-olC9H10BrN3OEe = 99% (by chiral HPLC)[α]D30=-23.1 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(R)-3-Azido-1-(4-bromophenyl)propyl acetateC11H12BrN3O2Ee = 99% (by chiral HPLC)[α]D30=+40.8 (c 1.2, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(S)-3-Azido-1-(4-methoxyphenyl)propan-1-olC10H13N3O2Ee >99% (by chiral HPLC)[α]D30=-18.4 (c 0.6, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(R)-3-Azido-1-(4-methoxyphenyl)propyl acetateC12H15N3O3Ee = 96% (by chiral HPLC)[α]D30=+77.4 (c 1.0, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)

(S)-3-Azido-1-(thiophen-2-yl)propan-1-olC7H9N3OSEe = 96% (by chiral HPLC)[α]D30=-17.8 (c 1.7, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3S)

(R)-3-Azido-1-(thiophen-2-yl)propyl acetateC9H11N3O2SEe = 76%(by chiral HPLC)[α]D30=+67.3 (c 1.1, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (3R)