5579-85-1Relevant articles and documents
Predictable site-selective functionalization: Promoter group assistedpara-halogenation ofN-substituted(hetero)aromatics under metal-free condition
Gupta, Shiv Shankar,Manisha,Kumar, Rakesh,Dhiman, Ankit Kumar,Sharma, Upendra
, p. 9675 - 9687 (2021/12/01)
Herein, regioselectivepara-C-H halogenation ofN-pyrimidyl (hetero)aromatics through SEAr (electrophilic aromatic substitution) type reaction is disclosed. SEAr type reaction has been utilized for the C5-bromination of indolines (para-selective) withN-bromosuccinimide under metal and additive-free conditions in good to excellent yields. The developed methodology is also applicable for iodination and challenging chlorination. The pyrimidyl group is identified as a reactivity tuner that also controls the regioselectivity. The present method is also applicable for selective halogenation of aniline, pyridine, indole, oxindole, pyrazole, tetrahydroquinoline, isoquinoline, and carbazole. DFT studies such as Fukui nucleophilicity and natural charge maps also support the observedp-selectivity. Post-functionalization of the title compound into the corresponding arylated, olefinated, and dihalogenated products is achieved in a one-pot, two-step fashion. Late-stage C-H bromination was also executed on drug/natural molecules (harmine, etoricoxib, clonidine, and chlorzoxazone) to demonstrate the applicability of the developed protocol.