Cyclic nitriles: stereodivergent addition-alkylation-cyclization to cis- and trans-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 ZrCl 4 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 ZrCl 4 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.
Fleming
Fraser F
FF
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282-1530, USA. flemingf@duq.edu
Wei
Guoqing
G
Steward
Omar W
OW
D045784:Abietanes / Q000138:chemical synthesis* / Q000737:chemistry; D000478:Alkylation; D003500:Cyclization; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D013237:Stereoisomerism
D045784:Abietanes; D009570:Nitriles; D009942:Organometallic Compounds