Sequential addition of i-PrMgCl and BuLi to sp3 hybridized iodoalcohols triggers a facile iodine-metal exchange. Intercepting the resulting cyclic Grignard reagents with a slight excess of an electrophile leads to a diverse range of substituted alcohols. The iodine-magnesium exchange strategy is effective with 3-carbon iodoalcohols bearing alkyl substitutents on the carbinol or adjacent carbons and with the chain-extended homolog 4-iodobutan-1-ol.

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.

No abstract

Quaternary centers are efficiently installed in chelation-controlled alkylations of acyclic hydroxynitriles. Intriguingly, the stereoselectivity is determined by the nature of the electrophile and the structure of the Grignard used for the deprotonation. The alkylation strategy addresses the long-standing difficulty of performing diastereoselective alkylations with conformationally mobile, acyclic nitriles.

This is a detailed account on preliminary published studies.