A catalyst-controlled selective synthesis of pyridines and pyrroles

Abstract

We have developed a dual reaction manifold that enables the selective synthesis of both pyridines and pyrroles from the common substrates α-diazo oxime ethers.

Expedient synthesis of heterocycles and methyl sulfonyl compounds via C-X BONDS (X = O, N, S) construction

“…In chapter 3, we have described two methodologies to synthesize multi-substituted pyridines from rhodium-catalyzed nitrene reaction and DBU-mediated ring opening of 2-allyl-2H-azirines. α-Diazo-β-keto oxime ethers underwent cascade rearrangement to yield 2-vinyl-2H-azirines as key intermediates, which further underwent ring-opening in the presence of Rh(II) catalyst to achieve amination of sp 3 C-H bond of allylic carbon. This reaction tolerated a variety of functional groups and provided a new access to multi-substituted pyridines.…”

“…Furans and their derivatives take an important role in the class of oxygenated heterocycles due to their prevalence in many pharmaceuticals, natural products, and functional materials. 1 2-Aminofurans serve as important organic intermediates that could undergo facile transformations to various synthetic targets including pyrroles, 2 cyclohexenones, 3 aniline derivatives, 4 and maleic anhydrides. 5 Despite the valuable utility of 2-aminofurans, promising synthetic methods for them are rather limited because of their instability.…”

“…Further screening of the reaction temperature and solvents revealed that the reaction proceeded most efficiently in dichloroethane at 60 ºC (Table 1-2, entries 7-10). As we envisaged that 2-amino-2,3-dihydrofurans 26aa is the key intermediate of the reaction, our attention then turned to screen the oxidation conditions leading to 2-aminofurans (Table 1- 3). The result revealed that the treatment of cycloadduct 26aa…”

“…2-Aminofurans are important organic intermediates that have been applied to synthesis of pyrroles, cyclohexenones, aniline derivatives, and maleic anhydrides. [2][3][4][5] For instance, Padwa reported that a Diels-Alder reaction of 2-aminofuran derivatives 12 with activated dienophiles 13 as the key step in the synthesis of substituted anilines 15 (Scheme 1.2). 22…”

Preliminaries

“…via palladium-catalyzed oxidative directed C(sp 3 )-H bond activation 6 ; a samarium(III)-catalyzed synthesis of 1,2,4-trisubstituted imidazoles from 2-acetylene-sec-amines and nitriles 7 ; a metal-free synthesis of 3-aroylindoles from tertiary o-(arylethynyl)anilines using Bu 4 NI as catalyst and t-BuOOH as oxidant via geminal C(sp 3 )-H bond activation 8 ; an N-alkylative ring closure of β-amino-α-diazo-esters to 1,2,3-triazoline-4-carboxylic acid esters, and Au-catalyzed conversion of propargyl-derivatives to pyrroles 9 ; the conversion of α-diazo-γ,δ-ethylene-β-ketoalkoximes to either pyridine-3-carboxylic acid esters under rhodium catalysis or pyrrole-3-carboxylic acid esters (cf. 81, 494) under nickel catalysis 10 ; a palladium-catalyzed double carbonylation of o-dibromides to give N-substituted phthalimides, including application to the syntheis of the controversial drug, thalidomide 11 ; a triphenylphosphinecatalyzed synthesis of N-tosyl-4(1H)-quinolone-3-carbonyl compounds from o-(tosylamino)thiolic acid aryl esters and electron-deficient acetylene derivatives 12 ; a regioselective rhodium-catalyzed route to 3-alkyl-substituted isoquinolines from aryl O-pivaloyloximes and 1,3-dienes under mild, redoxneutral conditions 13 ; an organocatalyzed oxidative annelation of arylhydroxamic acid esters with acetylene derivatives to afford N-alkoxyisocarbostyrils using simple reagents, such as iodobenzene and peroxyacetic acid 14 ; and an unprecedented oxidative rearrangement of 2,2′-diamino-1,1′-binaphthyls [BINAMS] to U-shaped azaacenes via C-C bond cleavage and nitrogen migration 15 . In O-heterocyclic synthesis, a new approach to cyclic ethers has emerged involving intramolecular reaction of carbanions with tert-butyl peroxides, which may be extended to a one-step synthesis of oxaspirocycles from cyclic ketones and peroxyiodides 16 , while an enantioselective palladium-catalyzed 6-endo-trig ring closure of 1-(o-acetoxyaryl)cinnamyl acetates affords chiral 2-aryl-3-chromenes 17 .…”