1.1- Dinitriles methyl groups

Attempts to prepare cinnoline-3,4-dicarboxylic acid (94) from 3,4-dimethylcinnoline apparently foundered on the relative inertness of the 3-methyl group the hitherto unknown diacid was eventually formed by acid hydrolysis of the dinitrile (93), itself prepared as shown in Scheme 53. ... 

Nitriles and dinitriles are also valuable intermediates, and their preparation by phosphite deoxygenation of furoxans (Section V,D,3) opens further routes via these compounds. It has been suggested512 that methyl groups may be modified, by alkylation, condensation, etc., before deoxygenation ... 

Dinitriles 97 on treatment with bases gave iminopyrrolizines 98a or aminopyrrolizines 98b.67,68 Imine 98a (R = piperidyl) formed a salt (99) with methyl iodide or with Meerwein s salt. Substitution of the dimethylamino group to give derivatives 100 is easily achieved67 (see Section III). 

Desymmetrization of Prochiral Dinitriles. Prochiral a,a-disubstituted malono-nitriles can be hydrolyzed in an asymmetric manner by the aid of Rhodococcus rhodochrous [678] (Scheme 2.106). In accordance with the above-mentioned trend, the dinitrile was nonselectively hydrolyzed by the nitrile hydratase in the cells to give the dicarboxamide. In a second consecutive step, the latter was subsequently transformed by the amidase with high selectivity for the pro-(/ ) amide group to yield the (/ )-amide-acid in 96% e.e. and 92% yield. This pathway was confirmed by the fact that identical results were obtained when the dicarboxamide was used as substrate. The nonracemic amide-acid product thus obtained serves as a starting material for the synthesis of nonnatural a-methyl-a-amino acids [679]. 

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