Synthesis of Chiral Nitriles

Two primary alkyl groups are readily introduced in this way, whereas introduction of more-hindered groups, such as isobutyl or cyclopentyl, is more sluggish and requires reflux in THF for an extended period. As the protonolysis of the boron intermediate in these cases is slow, a mixed solvent, tert-butylalcohol-THF (1 4), is used to liberate the desired product (Chart 10.2). 

The introduction of two different alkyl groups is achieved by the successive alkylation of dichloroacetonitriles and without isolating the intermediate. The typical results are shown in Chart 10.2 [2]. 

The chiral E-R -9-BBN alkylates the chloroacetonitrile to afford in good yields the corresponding chiral nitriles. Sodium ferf-butoxide in THF is best suited for the a-alkylation of chloroacetonitrile (Eq. 10.4) [4]. 

Organoborane R3B or B-R-9-BBN Chloronitrile CI2CHCN or RCH(C1)CN Reaction conditions Temp Time ( O (h) Product Yield (%) 

B-Cyclohexyl sec-Butylchloro Reflux 24 2-Cyclohexyl-3-methyl- pentanonitrile 61 

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Hernandez, R., Leon, E.I., Moreno, P., and Suarez, E, Radical fragmentation of P-hydroxy azides. Synthesis of chiral nitriles,/. Org. Chem., 62, 8974, 1997. 

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