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.
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282-1530, USA.
Robert J
RJ
Mycka
Stéphanie
S
Duez
Sebastian
S
Bernhardt
Johannes
J
Heppekausen
Paul
P
Knochel
Fraser F
FF
Fleming
D003510:Cyclohexanes / Q000737:chemistry*; D006842:Hydrocarbons, Brominated / Q000737:chemistry*; D018021:Lithium Chloride / Q000737:chemistry*; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry*
D003510:Cyclohexanes; D006842:Hydrocarbons, Brominated; D009570:Nitriles; D009942:Organometallic Compounds; D018021:Lithium Chloride; D015032:Zinc