Oxirane enantioselective transformations

Enantioselective transformations of several cyclopropane or oxirane-containing nitriles were studied using nitrile-transforming enzymes [78]. Microbial Rhodococcus sp. whole cells containing a nitrile hydratase/amidase system hydrolyzed a number... 

R. erythropolis (previously R. rhodochrous) AJ270, which has been utilized in many enantioselective transformations of nitriles such as cyclopropane, oxirane, and aziridine analogs [10, 12], was recently proved to catalyze the enantioselective hydrolysis of azetidine-2-carbonitriles [13] and P-lactam carbonitriles also [14] (Figure 11.2). Carboxylic acids and carboxamides were also obtained with significant enantiomeric excesses from 3-hydroxy-4-aryloxybutanenitriles and 3-hydroxy-3-arylpropanenitriles (Figure 11.3) using R. rhodochrous ATCC BAA-870 [15], which is more elaborately discussed in Chapter 14. 

Enantioselective synthesis and transformations of oxirane and aziridine derivatives 99PAC423. 

In addition, several research groups have also developed enantioselective syntheses [130] and enzymatic processes [131] for this class of drugs. A 1-aryloxy-3-chloropropan-2-ol can for example be esterified enantioselectively with vinyl acetate in presence of a Pseudomonas-lipase. The unreacted, enantiomerical-ly-enriched (l )-chlorohydrins are then transformed with potassium t-butoxide to the corresponding oxiranes, which are without isolation reacted further to the target compound. In case of penbutolol, the enantiomericaUy pure (S)-beta-blocker is obtained by recrystallisation of its hydrochloride salt... 

Disubstituted aliphatic oxiranes have been reported to be hydrolyzed by EHs from fungi [131], yeast, and bacteria. The most interesting results were observed with yeast and bacterial EHs. As far as kinetic resolution is concerned, it was shown by Weijers [116] that R. glutinis catalyzed the enantioselective hydrolysis of cis-2,3- and trans-2,3-epoxypentane, resulting in residual (2R)-epoxides with yields that approached the theoretical maximum of 50%. More interestingly, biocatalytic transformations of racemic 2,3-disubstituted oxiranes to vicinal diols with high ees at... 

Aziridine-2-phosphonates spiro-fused with 2-oxindole (790) have been prepared by a straightforward Horner-Wadsworth-Emmons reaction of ethyl 7V- [(4-nitrophenyl)sulfonyl]oxy -carbamate (791) and 3-(phosphoryl-methylene)oxindoles (792) in the presence of calcium oxide. Oxindoles (792) were also transformed into novel oxirane-2-phosphonates (793), as oxygen analogues of (790), by reaction with H202/Na0H (Scheme 201). " Cinchonine-based thiourea (797) catalysed asymmetric Michael addition of simple p-oxo-alkyl phosphonates (794) to nitro olefins (795), which afforded valuable a-substituted p-oxo phosphonates (796) in satisfactory yields with good to excellent enantioselectivities (up to 98% ee) (Scheme 202). ... 

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