Synthesis of 2,3-disubstituted benzofurans on solid-support

A library of 2,3-disubstituted benzofuran scaffold was developed by using intramolecular Wittig olefination and Friedel-Crafts acylation.     

Synthesis of 2,3-disubstituted benzofurans by platinum-olefin-catalyzed carboalkoxylation of o-alkynylphenyl acetals

The PtCl2-catalyzed cyclization reaction of o-alkynylphenyl acetals 1 in the presence of 1,5-cyclooctadiene produces 3-(alpha-alkoxyalkyl)benzofurans 2 in good to high yields. For example, the reaction of acetaldehyde ethyl 2-(1-octynyl)phenyl acetal (1a), acetaldehyde ethyl 2-(cyclohexylethynyl)phenyl acetal (1c), and acetaldehyde ethyl 2-(phenylethynyl)phenyl acetal (1f) in the presence of 2 mol % of platinum(II) chloride and 8 mol % of 1,5-cyclooctadiene in toluene at 30 degrees C gave the corresponding 2,3-disubstituted benzofurans 2a, 2c, and 2f in 91, 94, and 88% yields, respectively.     

High-yield syntheses of 2,3-disubstituted furans and thiophenes

The course of lithiation of furan- and thiophene-2-carboxylic acids is critically dependent on the identity of the lithium base allowing high-yielding syntheses of 2,3- and 2,5-disubstituted thiophenes: the proposed use of a trimethylsilyl blocking group to control metallation in the furan acid provides a useful route to 2,3-disubstituted furans.     

Efficient syntheses of 2,3-disubstituted natural quinazolinones via iridium catalysis

Natural products sclerotigenin, pegamine, deoxyvasicinone, mackinazolinone, and rutaecarpine were synthesized. Core quinazolinone structures were constructed via Ir catalysis.     

Facile synthesis of 2,3-disubstituted benzofurans via DBU-promoted intramolecular annulation of ortho oxyether aroylformates

A facile synthesis of 2,3-disubstituted benzofurans from ortho oxyether aroylformates has been developed. Under the mediation of DBU, the intramolecular annulation of ortho oxyether aroylformates proceeds smoothly to provide the corresponding 2,3-disubstituted benzofurans in moderate to good yields under mild conditions. Furthermore, a one-pot two-step synthesis of 2,3-disubstituted benzofurans has also been demonstrated from readily available ortho hydroxy aroylformates.     

Formation of 2,3-disubstituted benzofurans in the reaction of dichlorocarbene with a 2-alkylthiomethylbenzofuran

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 129–130, January, 1990.     

Palladium-assisted organic reactions: VIII. Simple syntheses of 2,3-disubstituted phthalimidines

Electron-poor alkenes such as alkyl acrylates have been found to insert into the aromatic carbon—palladium bond in orthobromobenzamides under the conditions of the Heck reaction. For primary and secondary benzamides a further palladium-catalysed reaction occurs to yield 3-substituted, or 2,3-disubstituted phthalimidines.     

CuI-catalyzed domino process to 2,3-disubstituted benzofurans from 1-bromo-2-iodobenzenes and beta-keto esters

CuI-catalyzed coupling of 1-bromo-2-iodobenzenes with beta-keto esters in THF at 100 degrees C leads to 2,3-disubstituted benzofurans. This domino transformation involves an intermolecular C-C bond formation and a subsequent intramolecular C-O bond formation process. Benzofurans with different substituents at the 5- and 6-position are accessible by employing the corresponding 1-bromo-2-iodobenzenes.     

Novel routes to 1-aryl-1,4-dihydro-3(2H)-isoquinolinones and 2-substituted or 2,3-disubstituted benzofurans by intramolecular cyclizations

N-(α-Benzotriazolylalkyl)arylacetamides, readily available from an arylacetamide, an aldehyde and benzotriazole, undergo intramolecular cyclization under acidic conditions to give 1-aryl-1,4-dihydro-3(2H)-isoquinolinones in good to excellent yields. Similarly, 2-(benzotriazol-1-yl)-2-(o-hydroxyphenyl)ethanols, obtained by lithiation of 2-(benzotriazol-1-ylmethyl)phenols followed by quenching with aldehydes or ketones, eliminate a molecule of water and a molecule of benzotriazole yielding 2-substituted and 2,3-disubstituted benzofurans.     

Facile syntheses of substituted 2,3-dihydrofurans and benzofurans by palladium-catalyzed reactions of propargylic carbonates with nucleophiles

Substituted 2,3-dihydrofurans and benzofurans are synthesized by the palladium-catalyzed reaction of 5-methoxycarbonyloxy-3-pentyn-1-ols and 1-(2-hydroxyphenyl)-3-methoxycarbonyloxy-1-propyne with nucleophiles, respectively. Various substituted propargylic carbonates and nucleophiles are efficiently transformed to their corresponding products. Additionally, a reaction using substrates containing a nucleophilic phenoxy group within the same molecule also produces the corresponding dihydrofuran.     

Chiral pyridin-3-ones and pyridines: syntheses of enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones, 2,3-disubstituted 4-iodopyridines, and enantiopure 2,3-disubstituted 4-pyridinemethanols

The development of an innovative method to access enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones starting from D-glucal via the aza-Achmatowicz transformation has been described. These highly functionalized pyridin-3-ones have been utilized for the synthesis of contiguously substituted pyridines through a rapid and efficient Et(3)N/Ac(2)O promoted cyclo-elimination, aromatization cascade, allowing the facile assembly of important pyridine-based building blocks like 2-substituted 3-acetoxy-4-iodopyridines and enantiopure 2-substituted 3-acetoxy-4-pyridinemethanols possessing benzylic stereogenic centers, whose synthesis otherwise would be tedious. The utilization of commercially available sugars as starting materials, mild reaction conditions, catalytic transfer hydrogen (CTH) of α-furfuryl azide derivatives, transfer of chiral aryl/alkyl methanols from enulosides to pyridin-3-ones and pyridines, high yields, and short reaction times are key features of this method. The utility of the method has been further exemplified by demonstrating the usage of the 2-substituted 3-acetoxy-4-iodopyridine for the construction of biologically significant molecules like 2,7-disubstituted furo[2,3-c]pyridines and 7,7'-disubstituted 2,2'-bifuro[2,3-c]pyridines.     

Palladium-catalyzed cyclization reactions of propargylic carbonates with nucleophiles: a methodology for the syntheses of substituted 2,3-dihydrofurans and benzofurans

Phenoxy-substituted 2,3-dihydrofurans were synthesized by the palladium-catalyzed reaction of 5-methoxycarbonyloxy-3-pentyn-1-ol with phenols. The propargylic carbonate containing a nucleophilic phenoxy group also reacted in the presence of palladium to produce the product. The reaction of 1-(2-hydroxyphenyl)-3-methoxycarbonyloxy-1-propyne with 2-methyl-1,3-cyclohexanedione or 2-methyl-1,3-cycohexanedione yielded the substituted benzofurans. The propargylic compound having a acetoxy group as a leaving group exhibited similar reactivity.     

Palladium-catalyzed beta-allylation of 2,3-disubstituted indoles

Given the prevalence of the indole nucleus in biologically active compounds, the direct C3-functionalization of 2,3-disubstituted indoles represents an important problem. Described is a general, high-yielding method for the palladium-catalyzed beta-allylation of carba- and heterocycle fused indoles, including complex natural product substrates.     

Stereochemistry of 2,3-disubstituted 1,3,2-dioxaborinanes

According to¹H NMR spectroscopic data, molecules of 2,4-disubstituted 1,3,2-dioxaborinanes exist in the preferred sofa conformation with equatorial alkyl groups at C₍₄₎. This conclusion has been confirmed by calculation of the optimal geometry of the ring of the cyclic boron esters by the MM2 molecular mechanics method. A. V. Bogatskii Physicochemical Institute, Ukraine National Academy of Sciences, Odessa 270080. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1574–1578, November, 1997.     

Novel synthesis of 2-aryl and 2,3-disubstituted indoles by modified double elimination protocol

[reaction: see text] Syntheses of 2-aryl and 2,3-substituted indoles were realized by modified double elimination protocol. Under basic conditions, vinyl sulfones derived from the reaction of 2-aminobenzyl sulfone with benzaldehydes underwent cyclization and alkylation followed by elimination of sulfinic acid to afford 2,3-substituted indoles.     

Microwave assisted syntheses of 2,5-disubstituted 1,3,4-oxadiazoles

2,5-Disubstituted 1,3,4-oxadiazoles have been synthesized by oxidation of 1-aroyl-2-arylidene hydrazines with potassium permanganate on the surface of a solid mineral support as well as in mixtures of acetone and water under microwave irradiation.     

Aryl radical-induced cyclization routes to furo[2,3-b]benzofurans. Abbreviated formal syntheses of aflatoxins B1 and B2

Radical-induced cyclization of butenolide ethers 3a-c affords furobenzofurans 4a-c; deprotection of 4c gives 4d, thus concluding formal total syntheses of aflatoxins B₁ (5) and B₂ (6).     

Novel syntheses of 2,3-dihydro-5H-1,4-benzoxathiepins and 1,2,3,5-tetrahydro-4,1-benzothiazepines

2,3-Dihydro-5H-1,4-benzoxathiepins were prepared by intramolecular Friedel-Crafts reactions of ethyl α-[2-(aryloxy)ethylthio]-α-chloroacetates or by acid-catalyzed cyclizations of ethyl α-[2-(aryloxy)ethylsulfinyl]-acetate. 1,2,3,5-Tetrahydro-4,1-benzothiazepines were similarly prepared.     

A new synthesis of 2,3-disubstituted indoles

A novel synthesis of 2,3-disubstituted indoles starting from N-alkyl-N-propvnyl anilines is described. The reactions employed are analogous to the thermal rearrangement of aryl propynyl sulfoxides.