Cyclic Nitriles: Stereodivergent Addition−Alkylation−Cyclization to <i>cis-</i> and <i>trans-</i>Abietanes

Diverse cyclic hydroxy nitriles are readily synthesized through sequential 1,2−1,4-Grignard addition−methylations to 3-oxo-1-cyclohexene-1-carbonitrile. Acid-catalyzed intramolecular cyclizations of the cyclic hydroxy nitriles reveal fundamental stereoselectivity trends in Friedel−Crafts cyclizations to cis- and trans-abietanes. In contrast to previous assumptions, comparative cationic cyclizations with electron-rich and electron-poor aromatic nucleophiles exhibit similar preferences for cyclization to cis-abietanes. Optimizing the cyclizations for trans-abietanes has identified ZrCl4 as an exceptional Lewis acid which, for cyclizations of iminolactones, favors trans-abietanes as the only observable diastereomer. The sequential oxonitrile addition−Friedel−Crafts cyclization strategy provides a rapid, stereodivergent synthesis of cis- or trans-abietanes, demonstrates the dramatic influence of ZrCl4 in promoting cationic cyclizations, and in contrast to previous assumptions suggests that the cyclization stereoselectivity is not correlated with the electronic nature of the aromatic nucleus.