Three Sequential C–N Bond Formations: tert-Butyl Nitrite as a N1 Synthon in a Three Component Reaction Leading to Imidazo[1,2-a]quinolines and Imidazo[2,1-a]isoquinolines

Abstract

tert-Butyl nitrite serves the dual role of an oxidant as well as a N1 synthon in a multicomponent reaction involving quinolines, isoquinolines, and styrenes. Herein, two sp C-H functionalizations of styrenes and one sp C-H functionalization of quinolines and isoquinolines lead to the formation of fused quinolines and isoquinolines via three sequential C-N bond formations.

tert‐Butyl Nitrite Mediated Nitro‐Nitratosation of Internal Alkenes

“…prop-2-ene-1,1,3triyltriaryl system gave exclusively a mono nitro product where the nitro group is at the benzylic position (α-carbon) (Scheme 1f ). Surprisingly, compared to all other previous results [5][6][7] this is an unusual attacking position for the nitro group as it always prefers to attack at the -position (Scheme 1a-d). [11] Styrenes react with TBN in an oxygen atmosphere to givenitro alcohols and their nitrate derivatives, where the exclusive attack of the NO 2 group is at the terminal carbon of the styrene (Scheme 1c).…”

“…Under a similar condition α, -unsaturated carboxylic acids and cyclic internal alkene afforded nitroalkenes. [11] During the formation of isoxazoline, [4,5] imidazo [1,2-a]quinolines, [6] and 1,2,4-oxadiazole-5(4H)-ones [7] from styrenes and TBN, the in situ generated NO 2 radical attacks at the -carbon while the NO radical attacks at the α-carbon even though both the radicals coexist in the medium. From the computational calculation, it was found that the attack of NO 2 radical at the terminal carbon that is at the -carbon is stabilised by around 6 kcal/mole less than the attack by NO radical at the same site.…”

tert‐Butyl Nitrite (TBN), a Multitasking Reagent in Organic Synthesis

“…Most of the intermediates were detected by HRMS analysis. The present methodology was successfully applied for the synthesis of 4‐((2‐phenylimidazo[2,1‐ a ]isoquinolin‐3‐yl)methyl)morpholine hydrochloride that possesses a significant range of biological activities (Scheme ) …”

“…Initially,T BN oxidizes alkenyl oxime (129) The nitrile group is au biquitous functional group in synthetic organic chemistrya nd can be easily used form any functional group conversions. Wang and co-workers reported the synthesis of aromatic nitriles( 132)v ia ap alladium-catalyzed ammoxidation of methyl arenes (131) using tert-butyl nitrite (TBN) and N-hydroxyphthalimide (NHPI) where TBN simultaneously acts both as the nitrogen source as well as an oxidant (Scheme 97). [126] In 2016, Song and co-workers reported the synthesis of aryl nitrilesf rom aryl acetylenes.…”

“…The present methodology was successfully applied for the synthesis of 4-((2-phenylimidazo[2,1-a]isoquinolin-3-yl)methyl)morpholine hydrochloridet hat possesses as ignificant range of biological activities (Scheme 101). [131] Initially,aradical intermediate Subsequently,a ni minium carbocation (F)i sg enerated via base-mediated dehydration followed by two sequential singleelectron transfer in the presenceo fC uI and DTBP.F inally,t he base abstracts ap rotonf rom intermediate (F)g iving the anticipated product (138)( Scheme 102).…”