Enzymatic resolution of five membered heterocyclic bromohydrins

The lipase catalyzed resolution of trans-3,4-tetrahydrofuran and pyrrolidine bromohydrins by acylation or hydrolysis of their acylated derivatives has been studied. For both heterocycles, the best enantioselectivity was obtained using Candida antarctica lipase B as the catalyst in the hydrolytic processes. The enantiomerically pure bromohydrins are useful intermediates for the preparation of 3,4-fuctionalized cis-heterocycles.

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(3R,4R)-3-Bromo-4-hydroxytetrahydrofuranC4H7BrO2ee = 99%[α]D20=-27.6 (c 0.08, CH2Cl2)Source of chirality: lipase-catalyzed hydrolysisAbsolute configuration: (3R,4R)

(3S,4S)-3-Bromo-4-(2-phenylacetoxy)tetrahydrofuranC12H13BrO3ee = 99%[α]D20=+73.1 (c 0.1, CH2Cl2).Source of chirality: lipase-catalyzed hydrolysisAbsolute configuration: (3S,4S)

(3R,4R)-3-Azido-4-(2-phenylacetoxy)tetrahydrofuranC12H13N3O3ee = 99%[α]D20=+1.4 (c 0.08, CH2Cl2).Source of chirality: lipase-catalyzed hydrolysisAbsolute configuration: (3R,4R)

(3R,4R)-1-Benzyloxycarbonyl-3-bromo-4-hydroxypyrrolidineC12H14BrNO3ee = 99 %[α]D20=-5.0 (c 0.1, CHCl3).Source of chirality: lipase-catalyzed hydrolysisAbsolute configuration: (3R,4R)

(3S,4S)-1-Benzyloxycarbonyl-3-bromo-4-(2-methoxyacetyl)pyrrolidineC15H18BrNO5ee = 99%[α]D20=-10.0 (c 0.05, CHCl3).Source of chirality: lipase-catalyzed hydrolysisAbsolute configuration: (3S,4S)

(3S,4R)-1-Benzyloxycarbonyl-3-azido-4-(tbutyldimethylsilyloxy)pyrrolidineC18H28N4O3Siee = 99%[α]D20=+35.0 (c 0.1, CHCl3).Source of chirality: lipase-catalyzed hydrolysisAbsolute configuration: (3S,4R)