title: Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis.
abstract: An electrophilic cyanation of aryl Grignard or lithium reagents, generated in situ from the corresponding aryl bromides or iodides, by a transnitrilation with dimethylmalononitrile (DMMN) was developed. DMMN is a commercially available, bench-stable solid. The transnitrilation with DMMN avoids the use of toxic reagents and transition metals and occurs under mild reaction conditions, even for extremely sterically hindered substrates. The transnitrilation of aryllithium species generated by directed ortho-lithiation enabled a net C-H cyanation. The intermediacy of a Thorpe-type imine adduct in the reaction was supported by isolation of the corresponding ketone from the quenched reaction. Computational studies supported the energetic favorability of retro-Thorpe fragmentation of the imine adduct.
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Reeves
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Malapit
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Frederic G
authors.initials: FG
authors.lastname: Buono
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Kanwar P
authors.initials: KP
authors.lastname: Sidhu
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Maurice A
authors.initials: MA
authors.lastname: Marsini
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: C Avery
authors.initials: CA
authors.lastname: Sader
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fandrick
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Busacca
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Senanayake
mesh_terms: D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D007202:Indicators and Reagents / Q000737:chemistry; D008094:Lithium / Q000737:chemistry*; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*
chemical_list: D007202:Indicators and Reagents; D009570:Nitriles; D009942:Organometallic Compounds; C000607394:dimethylmalononitrile; D008094:Lithium