Synthesis of thieno[2,3-h]-/[3,2-h]quinolines and thieno[2,3-f] quinolines by Brønsted acid mediated cycloisomerisation

Abstract

Several thieno[2,3-h]-/[3,2-h]- and [2,3-f]quinolines have been synthesised from 2,3-dihalogenated pyridines or -quinolines by site-selective Pd catalysed cross-coupling reactions and Brønsted acid mediated cycloisomerisations as the final key step.

Synthesis and Properties of Diphenylbenzo[j]naphtho[2,1,8‐def][2,7]phenanthrolines

“…[4] In recent years, we and others investigated the combination of Suzuki-Miyaura and Sonogashira cross-coupling reactions with acid mediated cycloisomerizations for the synthesis of heterocyclic systems, including N-doped PAHs. [27][28][29][30][31][32][33][34][35][36][37][38][39] The Povarov reaction represents an [4 + 2] aza-Diels-Alder cycloaddition with inverse electron demand which results in formation of quinolines. [40][41] The classical approach encompasses a reaction between an aldehyde, aniline, and an alkene or alkyne to give tetrahydro-or dihydroquinolines, respectively.…”

Synthesis of Nitrogen Heterocycles by a C–C Cross-Coupling/Cycloisomerization Strategy

“…The Suzuki–Miyaura reaction of 2,3-dibromopyridine ( 29 ) with 3-thienylboronic acid afforded 2-(3-thienyl)-3-bromopyridine ( 30 ) in 91% yield and with excellent regioselectivity (Scheme 9 ). 11…”

“…The Suzuki–Miyaura reaction of 29 with 2-thienylboronic acid gave 2-(2-thienyl)-3-bromopyridine ( 33 ) in 77% yield (Scheme 10 ). 11 Subsequent Sonogashira reaction with phenylacetylene afforded 2-(2-thienyl)-3-alkynylpyridine 34 in moderate yield. Treatment of the latter with MSA gave rise to formation of thieno[3,2- h ]quinoline 35 in moderate yield.…”

“…The Suzuki–Miyaura reaction of 29 with 3-benzothienylboronic acid afforded product 36 in excellent yield (Scheme 11 ). 11…”

“…The Sonogashira reaction of 29 with various alkynes gave 2-alkynyl-3-bromopyridines 39a – j in moderate to excellent yields (Scheme 12 ). 11 Subsequent Suzuki–Miyaura reaction with 3-thienylboronic acid afforded 3-(3-thienyl)-2-alkynylpyridines 40a – j in moderate to excellent yields. Treatment of the latter with MSA gave rise to formation of thieno[2,3- f ]quinolines 41a – h in good to excellent yields.…”