Unusual Approach to 3-Aryl-2-aminopyridines through a Radical Mechanism: Synthesis and Theoretical Rationale from Quantum Mechanical Calculations

Abstract

Tris(trimethylsilyl)silane and azobis(cyclohexanenitrile) promoted the easy intramolecular arylation of aryl bromopyridine carbamates through a radical [1,6] ipso substitution process. These substrates showed a preference for this type of reaction over the alternative [1,7] addition. The results were rationalized by making use of quantum mechanical calculations and computer graphics.

Thirty Years of (TMS)3SiH: A Milestone in Radical-Based Synthetic Chemistry

“…A catalytic version under photoredox conditions was also devised using a tertiary amine as the terminal reductant, but the scope was slightly reduced as compared to the TTMSS method. Biaryls may finally be prepared from carbamates such as 345 , relying on an unusual 1,6- ipso substitution process, shown to be more favorable than the alternative 1,7-addition reaction . Treatment of pyridine carbamate 345 in the presence of TTMSS and ACCN thus led to the corresponding biaryl 346 with modest to good yields, after 1,6- ipso substitution process, decarboxylation of the corresponding carbamoyloxyl radical, and final reduction of the aminyl radical with TTMSS.…”

Reaction mechanisms: radical and radical ion reactions

“…Calculations revealed remarkable orbital interactions in this reaction with the single electron of the aryl radical in its low lying SOMO interacting with the HOMO-1 orbital of the second aryl moiety, whereas the electrons in the HOMO orbital participate in the p cloud of the pyridine system and are not directly involved in the bond-forming process. 44 Miyata et al developed a radical-chain procedure for the direct generation of benzyl radicals from toluenes using triethylborane as initiator, which could be trapped through addition to electron deficient alkenes 69 (Scheme 15). 45 The yields for this 2.2.2 Oxidative processes.…”