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.

Trifluoromethanesulfonic Anhydride as a Low‐Cost and Versatile Trifluoromethylation Reagent

“…On the basis of the above results and other reports, [10a,14, 18] ar eaction mechanism was proposed (Scheme 4 [21] would give radical species B [22] and [Ru(bpy) 3 ] 3+ .T his SET process was confirmed by fluorescence-quenching experiments (see the Supporting Information). Radical B would then release the electrophilic CF 3 radical.…”

The Phosphinoboration of N‐Heterocycles

“…However, a particularly insightful and perceptive suggestion by one of the reviewers of this manuscript highlighted the possibility that phosphinoboration may well occur via of a radical‐based process and a survey of the literature revealed several recent pertinent papers. For example, pyridine boryl radicals generated by a Lewis base‐assisted homolytic cleavage of the B−B σ‐bond in diborane are involved in the reduction of azo compounds to hydrazines, the catalytic borylation of aryl halides, the metal‐free synthesis of 4‐substituted pyridines via a novel radical addition/C−C coupling sequence and the borylative/cyclisation of 1,6‐enynes . Thus, this study will provide a platform to undertake a more comprehensive investigation into the phosphinoboration reaction and, to this end, further studies are currently underway to establish the viability of Ib as a key intermediate in the solvent dependent 1,2‐ and 1,4‐phosphinoboration and future computational investigations will focus on exploring the possibility of a radical based process involving base initiated homolytic cleavage of the P−B bond to generate an active pyridine boryl radical.…”

The Effect of Weblog Media Toward Writing Ability of the First Grade Students

“…One of variety of media technologies in teaching writing is weblog (Ardi, 2012). According to As'ad (2010) cited by (Fahreza, 2017) weblog is a combination from Web and Log, or now more popular is called a blog or blogging. The term blog means the writing activities in an internet application where the outcome of these writings can be accessed by anyone who has an internet connection and the owner of his/her own blog.…”