Furan Ring Opening – Pyridine Ring Closure: An Efficient Approach towards 6H‐Isochromeno[4,3‐b]pyridin‐6‐ones from Readily Available Furans and Phthalaldehydic Acid Methyl Esters

Abstract

An efficient iodine‐catalyzed three‐component Mannich‐type reaction of various 2‐alkylfurans, methyl 2‐formylbenzoates and carbamates under mild reaction conditions was realized. Synthetic utility of the resulting N‐Boc‐1‐[2‐(carbomethoxy)aryl]furfurylamines was demonstrated by their facile two‐step transformation into 2‐methyl‐6H‐isochromeno[4,3‐b]pyridin‐6‐ones, which are employed in high‐performance cyclometalated OLEDs.

Cycloamination strategies for renewable N-heterocycles

“…For example, Shpuntov et al showed that a three-component Mannich-type reaction of 2-alkylfuran, methyl 2-formylbenzoate, and carbamate in the presence of iodine at 0°C for 2 h affords N-Boc-1-[2-(carbomethoxy)aryl]furfurylamines in moderate yields (51-89%), and further application of a two-step reaction process of oxidative furan-ring cleavage and N-Boc deprotection catalyzed by meta-chloroperoxybenzoic acid and HCl, respectively, gives 6H-isochromeno-[4,3-b]pyridin-6-ones in moderate yields (61-68%). 285 The coupling of chitin-derived 3-acetamido-5-acetylfuran 140 with ketones 141 catalyzed by HCl provides dihydrodifuropyridines (up to 64% yield) after reaction at 70°C for 16 h (Scheme 35). 286 The ketone 141 initially reacts with 140 to form difurylmethane 142, followed by sequential acid-mediated acetamide hydrolysis, tautomerism, and intramolecular cyclisation, eventually giving dihydrodifuropyridine 143 after removal of ammonia (Scheme 35), as proposed by those authors.…”

Transformation of 3-(Furan-2-yl)-1,3-di(het)arylpropan-1-ones to Prop-2-en-1-ones via Oxidative Furan Dearomatization/2-Ene-1,4,7-triones Cyclization

“…Based on our experience on the use of furans dearomatization in the synthesis of various heterocycles [ 26 , 27 , 28 , 29 , 30 , 31 ], we assumed that the removal of EWG may lead to a switch of reactivity pattern via the crucial decrease of the enol A ′ form contribution. As a result, the oxidation of oxoalkyl furans, which lack α-EWG-functionality, may lead to different products.…”

Application of Continuous Flow-Flash Chemistry to Scale-up Synthesis of 5-Cyano-2-formylbenzoic Acid

“…Phthalaldehydic acid 1 derivatives have been used widely as key intermediates for various heterocyclic compounds of biological importance, such as isoindolin-1-one, 2 dihydroisoindolo[2,1a]quinolin-11-one, 3 benzo [c]thiophen-1(3H)-one, 4 phthalazin-1(2H)-one, 5 6H-isochromeno [4,3-b]pyridin-6-one, 6 and 2-benzofuran-1(3H)-one 7 derivatives. Among them 5-cyano-2formylbenzoic acid or the cyclic 6-cyano-3-hydroxy-2-benzofuran-1(3H)-one (1) derivatives 2e−g,3a,b have been reported to be employed as key intermediates for synthesis of the 3-cyanodihydroisoindolo[2,1-a] quinolin-11-one derivative (2) 3 as an inhibitor of tyrosyl-DNA phosphodiesterase I (Tdp1) and topoisomerase I (Top1), and they would also be potential key intermediates for various biologically active compounds bearing an isoindolin-1-one pharmacophore substituted at the C( 6) position with a cyano group (3) 8a and (4) 8d or a 1,2,4-oxaziazol-3-yl group (5) 9a and ( 6) 9c (Figure 1).…”