title: Metal-Free Synthesis of C-4 Substituted Pyridine Derivatives Using Pyridine-boryl Radicals via a Radical Addition/Coupling Mechanism: A Combined Computational and Experimental Study.
abstract: Density functional theory investigations revealed that the pyridine-boryl radical generated in situ using 4-cyanopyridine and bis(pinacolato)diboron could be used as a bifunctional "reagent", which serves as not only a pyridine precursor but also a boryl radical. With the unique reactivity of such radicals, 4-substituted pyridine derivatives could be synthesized using α,β-unsaturated ketones and 4-cyanopyridine via a novel radical addition/C-C coupling mechanism. Several controlled experiments were conducted to provide supportive evidence for the proposed mechanism. In addition to enones, the scope could be extended to a wide range of boryl radical acceptors, including various aldehydes and ketones, aryl imines and alkynones. Lastly, this transformation was applied in the late-stage modification of a complicated pharmaceutical molecule.
authors.affiliation: Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.|College of Chemistry and Chemical engineering, Yan'an University , Yan'an 716000, P. R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.affiliation: Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Liuzhou
authors.initials: L
authors.lastname: Gao
authors.affiliation: Institute of Chemistry and Biomedical Sciences, Jiangsu Key Laboratory of Advanced Organic Material, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210023, P. R. China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Chemistry and Biomedical Sciences, Jiangsu Key Laboratory of Advanced Organic Material, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210023, P. R. China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Huang
authors.affiliation: Institute of Chemistry and Biomedical Sciences, Jiangsu Key Laboratory of Advanced Organic Material, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210023, P. R. China.|State Key Laboratory of Elemento-organic Chemistry, Nankai University , Nankai P. R. China.
authors.forename: Xu
authors.identifier: 0000-0001-6218-611X
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, P. R. China.
authors.forename: Shuhua
authors.identifier: 0000-0001-6756-057X
authors.initials: S
authors.lastname: Li