Ruthenium-Catalyzed Oxidative Coupling of Primary Amines with Internal Alkynes through C-H Bond Activation: Scope and Mechanistic Studies.
The oxidative coupling of primary amines with internal alkynes catalyzed by Ru complexes is presented as a general atom-economy methodology with a broad scope of applications in the synthesis of N-heterocycles. Reactions proceed through regioselective C-H bond activation in 15 minutes under microwave irradiation or in 24 hours with conventional heating. The synthesis of 2,3,5-substituted pyridines, benzo[h]isoquinolines, benzo[g]isoquinolines, 8,9-dihydro-benzo[de]quinoline, 5,6,7,8-tetrahydroisoquinolines, pyrido[3,4g]isoquinolines, and pyrido[4,3g]isoquinolines is achievable depending on the starting primary amine used. DFT calculations on a benzylamine substrate support a reaction mechanism that consists of acetate-assisted C-H bond activation, migratory-insertion, and C-N bond formation steps that involve 28-30 kcal mol(-1) . The computational study is extended to additional substrates, namely, 1-naphthylmethyl-, 2-methylallyl-, and 2-thiophenemethylamines.
Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, Fac. de Ciencias, Edificio D, Pedro Cerbuna 12, 50009 Zaragoza (Spain), Fax: (+34) 976761187.
Sara
S
Ruiz
Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, Fac. de Ciencias, Edificio D, Pedro Cerbuna 12, 50009 Zaragoza (Spain), Fax: (+34) 976761187.
Pedro
P
Villuendas
Departament de Química, Edifici Cn, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallés, Barcelona (Spain), Fax: (+34) 935812920.
Manuel A
MA
Ortuño
Departament de Química, Edifici Cn, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallés, Barcelona (Spain), Fax: (+34) 935812920. agusti@klingon.uab.es.
Agustí
A
Lledós
Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, Fac. de Ciencias, Edificio D, Pedro Cerbuna 12, 50009 Zaragoza (Spain), Fax: (+34) 976761187. esteban@unizar.es.
Esteban P
EP
Urriolabeitia
CH activation; amines; density functional calculations; nitrogen heterocycles; ruthenium