Omega-halonitriles: domino cyclizations to oxa- and carbocyclic nitriles.
t-BuOK-induced deprotonation of omega-haloalkylnitriles generates remarkably stable potassiated nitriles. In situ deprotonation and alkylation of omega-chloroalkylnitriles with aldehyde electrophiles trigger sequential nucleophilic-electrophilic alkylations generating substituted tetrahydrofuranyl and tetrahydropyranyl nitriles. Redirecting the cyclization manifold with 5-iodopentanenitrile and a ketone causes a complementary electrophilic-nucleophilic cyclization to the corresponding carbonitrile. Collectively these cyclizations provide rapid assembly of five- and six-membered oxa- and carbocyclic nitriles demonstrating the utility of omega-halonitriles in domino alkylations.
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282-1530, USA. flemingf@duq.edu
Fraser F
FF
Fleming
Venugopal
V
Gudipati
Omar W
OW
Steward
D000478:Alkylation; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D003500:Cyclization; D006846:Hydrocarbons, Halogenated / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009570:Nitriles / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D011188:Potassium / Q000737:chemistry; D013237:Stereoisomerism
D006846:Hydrocarbons, Halogenated; D007202:Indicators and Reagents; D009570:Nitriles; D011188:Potassium