Cyclohexylcarbonitriles: diastereoselective arylations with TMPZnCl·LiCl.


Deprotonating substituted cyclohexanecarbonitriles with TMPZnCl·LiCl affords zincated nitriles that diastereoselectively couple with aryl bromides in the presence of catalytic Pd(OAc)(2) and S-Phos. Steric and electronic effects influence the diastereoselectivity; 4-t-butyl-, 4-TBSO-, and 2-Me-cyclohexanecarbonitriles exert virtually complete diastereocontrol whereas modest diastereoselectivity is observed with 4-i-Pr-, 4-Me-, and 3-Me-cyclohexanecarbonitriles. The unusual diastereoselectivity trends should prove useful for synthesizing substituted cyclohexanecarbonitrile-containing pharmaceuticals.

DOI: 10.1021/jo301127n

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@article{Mycka2012CyclohexylcarbonitrilesDA, title={Cyclohexylcarbonitriles: diastereoselective arylations with TMPZnCl·LiCl.}, author={Robert J Mycka and St{\'e}phanie Duez and Sebastian Bernhardt and Johannes Heppekausen and Paul Knochel and Fraser F Fleming}, journal={The Journal of organic chemistry}, year={2012}, volume={77 17}, pages={7671-6} }