Enantioselective Hydrolysis of P-Amino Nitriles

Surprisingly, acyclic vinylogous amino nitrile ( )-6a, prepared by the Aza-Baylis-HUlman reaction, only reacted to the corresponding a-methylene-P-amirio amide [34], In agreement with this, the related oxo-analog was recently reported to give the amide as well upon incubation with Rhodococcus sp. AJ270 cells [35]. 

Incubation with whole cells of Rhodococcus sp. R 312 yielded (i.e. 50%) the amide trons-8b in 98% e.e. quantitatively, with not even traces of the acid, leaving the ds-nitrile untouched [34]. 

AcycUc amino nitriles ( )-5a and ( )-7a reacted sluggishly and no clear trend in the formation of a preferred product was observed, thus their results have been omitted. N-Carbobenzoxylated pyrrolidine-3-carbonitrile, a precursor for P-proline, was the fastest reacting five-membered compound. The substrate was entirely consumed within a few minutes yielding P-proline in low enantiomeric purity 

Similar to diastereoselectivities, the enantioselectivities also strongly correlate with the relative stereochemistry of the 1,2-substituents and with the ring size of amino nitriles ( )-la-( )-4a trans-cyclopentane carbonitriles gave the amides in excellent enantiopurity, whereas trans-cyclohexane carbonitriles resulted in the 

the trans-aminocydohexanecarboxyhc acid 3c was prepared by all three microorganisms in very high e.e. (87-99%), whereas the intermediate amides were formed in moderate e.e. In contrast, five-membered trans-amide lb was obtained in very high enantiopurity, but not so its acid [34]. The high enantiomeric purity of the remaining trons-nitriles la and 3a is remarkable in view of the extent of conversion (38 and 24%, respectively).This can be attributed to the reportedly high enantioselectivity of the nitrile hydratase from R. erythropolis A4 for the transformation of ( )-la to lb at the least [40]. 

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