Halohydrin resolution

The reversibility of halohydrin dehalogenase-catalyzed reactions has been used for the regioselective epoxide-opening with nonnatural nucleophiles (an example is given in Scheme 10.34) [133]. The stereoselectivity of the enzyme results in the resolution of the racemic substrate. At the same time, the regioselectivity imposed by the active site geometry yields the anti-Markovnikov product. [128]... 

Majeric Elenkov, M., Tang, L., Hauer, B. and Janssen, D.B., Sequential kinetic resolution catalyzed by halohydrin dehalogenase. Org. Lett., 2006, 8, 4227. 

Enantiomerically enriched epoxides have also been generated using (1) in the Darzens reaction of a-chloro ketones with aldehydes, as well as through ring closure of racemic halohydrins. The extent of enantioselectivity for both reactions is similar (optical purity 6-8% 1), suggesting a moderate degree of kinetic resolution occurring in each case. 

Kinetic Resolution of Racemic Secondary Alcohols. Racemic cyclic and acyclic secondary alcohols and p-halohydrins are kinetically resolved in good chemical yields with modest-to-excellent enantioselectivity (eqs 2 and 3). 

Finally, mention may be made of those articles in which this method is utilized in the synthesis of optically active oxiranes for example, the simple synthesis of monosubstituted (S)-oxiranes and the asymmetric cyclization of some chlorohydrins catalyzed by optically active cobalt (salen)-type complexes, or in the enantiomeric selection of racemic oxiranes via halohydrins and /3-hydroxy sulfides. A useful three-step synthesis has been worked out from (S)-amino acids to (R)-alkyloxiranes as well as enantiomer resolution for chiral oxiranes by complexation gas chromatography. ... 

N. Kasai, T. Suzuki, Production of Chiral C3 and C4 Units via Microbial Resolution of 2,3-Dichloro-l-propanol, 3-Chloro-l,2-propanediol and Related Halohydrins, in H. U. Blaser, E. Schmidt (Eds.), Asymmetric Catalysis on Industrial Scale,Wiley-VCH,Weinheim, 2004,... 

An altemative synthesis of fosfomycin has been effected by the halohydrin route. 9 Thus, treatment of ( ) (Z)-l-propenylphosphonic acid in aqueous solution with sodium hypochlorite gave t/zreo-l-chloro-2-hydroxypropylphosphonic acid (85%). Resolution is accomplished by means of (-)-a-phenylethylamine to yield (-i-)-chlorohydrin (80%), which is converted with 10 M aqueous NaOH into fosfomycin (85-90%). ... 

Practical applications of biocatalysis for the manufacture of chiral alcohols such as (R)-l,3-butanediol by stereospecific oxidoreduction Production of chiral C3 and C4 units via microbial resolution of 2,3-dichloro-l-propanol, 3-chloro-1,2-propanediol and related halohydrins... 

Production of Chiral C3 and C4 Units via Microbial Resolution of 2,3-Dichloro-l-propanol, 3-Chloro-l,2-propanediol and Related Halohydrins... 

Scheme 2.237 Kinetic resolution of halohydrins using halohydrin dehalogenase...

A generally applicable method for the preparation of optically active epoxides makes use of a lipase-catalyzed resolution of halohydrins bearing the halogen in the terminal position (Scheme 3.10). Pseudomonas sp. lipase-catalyzed acylation of racemic halohydrins affords a readily separable mixture of (f )-halohydrin and the corresponding (5)-ester in good to excellent optical purities [193, 194]. Treatment of the latter with base leads to the formation of epoxides with no loss of optical purity. A semiquantitative comparison of the reaction rate obtained with different acyl donors using substrates of this type revealed that they were in the order ethyl... 

Dehydro- halogenation Halohydrin Epoxide Synthesis of epoxides resolution of halohydrins and epoxides Halohydrin dehalogenase... 

Epoxides can be produced by elimination of HCl from vidnal-halohydrins by halohydrin dehalogenase enzymes. These enzymes can be used for the resolution of racemic halohydrins to chiral halohydrins that can be converted easily to chiral epoxides, an important building block for synthesis of variety of compounds (Figure 1.14). 

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