Tetrasubstituted olefin synthesis via Pd-catalyzed addition of arylboronic acids to internal alkynes using O2 as an oxidant

The Pd(II)-catalyzed reaction of arylboronic acids and internal alkynes provides a convenient route to a wide variety of tetrasubstituted olefins. The reaction is conducted in DMSO using molecular O2 as an oxidant in the absence of any base. The reaction involves the cis addition of two aryl groups from the arylboronic acid to opposite ends of the triple bond of the internal alkyne. The synthesis tolerates a wide variety of functional groups, including alcohol, aldehyde, ester, TMS, and acetal groups. Electron-rich dialkylacetylenes, such as 4-octyne, provide highly substituted 1,3-dienes in moderate yields. The very mild O2/DMSO conditions also afford good to excellent yields of biaryls by the homocoupling of arylboronic acids.     

Synthesis of tetrasubstituted olefins by Pd-catalyzed addition of arylboronic acids to internal alkynes

[Reaction: see text] Tetrasubstituted olefins are readily prepared by the Pd-catalyzed cis addition of two aryl groups from an arylboronic acid to opposite ends of the triple bond of internal alkynes. The synthesis proceeds under very mild reaction conditions and tolerates a wide variety of functional groups, including alcohol, aldehyde, ester, TMS, and acetal groups.     

Sonogashira reaction of aryl halides with propiolaldehyde diethyl acetal catalyzed by a tetraphosphine/palladium complex

All-cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyzes the Sonogashira reaction of propiolaldehyde diethyl acetal with a variety of aryl bromides and chlorides. A minor electronic effect of the substituents of the aryl bromide was observed. Similar reaction rates were observed in the presence of activated aryl bromides such as 4-trifluoromethylbromobenzene and deactivated aryl bromides such as bromoanisole. Turnover numbers up to 95,000 can be obtained for this reaction. Even aryl chlorides and heteroarylbromides or chlorides have been successfully alkynylated with this catalyst. Moreover, a wide variety of substituents on the aryl halide such as fluoro, trifluoromethyl, acetyl, benzoyl, formyl, nitro, dimethylamino or nitrile are tolerated.     

Samarium(II)-mediated spirocyclization by intramolecular aryl radical addition onto an aromatic ring

Samarium(II)-mediated spirocyclization by intramolecular addition of aryl radicals onto an aromatic ring was achieved by the reaction of N-(2-iodophenyl)-N-alkylbenzamides with SmI2 in the presence of HMPA, yielding spirocyclic indolin-2-one derivatives. The ether congeners afford spirocyclic benzofuran derivatives in moderate yields by aryl radical addition onto a benzene ring without having an electron-withdrawing group. The reaction with other aryl groups such as naphthalene and indole rings is also described.     

Brønsted acid catalyzed formal insertion of isocyanides into a C-O bond of acetals

The Br?nsted acid catalyzed formal insertion of an isocyanide into a C-O bond of an acetal is described. A diverse array of acyclic and cyclic acetals can be applied to the catalytic insertion to form alpha-alkoxy imidates. Functional groups, such as nitro, cyano, halogen, ester, and alkoxy groups, are tolerant to the reaction conditions employed. The course of the reaction is highly dependent on the structure of the isocyanide. The use of an electron-deficient aryl isocyanide, such as 2c and 2d, is required to selectively obtain the monoinsertion product. When aryl isocyanides containing alkyl substituents, such as 2a and 2b, are employed, two molecules of the isocyanide are incorporated, and the double-insertion product is obtained. The reaction of tert-octyl isocyanide also induces a double incorporation, but the subsequent acid-mediated fragmentation leads to the 2-alkoxy imidoyl cyanide. The monoinsertion products, alpha-alkoxy imidates, can readily be hydrolyzed to alpha-alkoxy esters, realizing the formal carbonylation of an acetal.     

Phosphorylated Aminoacetal in the Synthesis of New Acyclic,Cyclic, and Heterocyclic Polyphenol Structures

New phosphorylated aminoacetal has been synthesized by the Kabachnik–Fields reaction; its reactivity has been studied in acid‐catalyzed condensation with linear polyphenols (2‐methylresorcinol, resorcinol, pyrogallol) and the Mannich reaction with macrocyclic polyphenol (calix[4]resorcinol). It has been determined for the first time that acid‐catalyzed reaction of phosphorus‐containing acetal with resorcinol and its derivatives in ethanol in the presence of hydrochloric acid gives new phosphorylated piperazines in addition to the compounds of diarylmethane series. Condensation of macrocyclic polyphenol (calix[4]resorcinol) with formaldehyde and N‐((dihexylphosphoryl)methyl)‐2, 2‐dimethoxyethylamine (the Mannich reaction) has resulted in novel tetrasubstituted calixarene containing aminophosphine oxide and acetal groups on the “upper rim” of molecule.     

Novel C-C bond cleavage under mild, neutral conditions: conversion of electron-deficient aryl alkyl ketones to aryl carboxylic esters

A novel, unique way to cleave the carbon-carbon bond in aryl alkyl ketones under mild, neutral conditions is described. Treatment of aryl alkyl ketones in a refluxing mixture of N,N-dimethylformamide dimethyl acetal and methanol for 16 h provided aryl carboxylic esters. The scope and limitations of the reaction are discussed. Useful yields of the reaction can be obtained with electron-deficient aryl groups, and the yields are higher when the alkyl group is larger than a methyl group. Studies toward elucidation of the reaction mechanism led to a proposed mechanism that is consistent with all the observations.     

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.     

钯催化芳基溴代物和氨基乙醛缩二乙醇的偶联反应研究

以Pd2（dba）3／XantPhos为原位生成的催化剂,研究了以芳基溴代物与氨基乙醛缩二乙醇之间的偶联反应合成N-（2,2-二乙氧基乙基）芳胺的反应,考察了催化剂前体、配体以及催化剂前体与配体的用量对该反应的影响．实验结果表明,当以2．5％Pd2（dba）3作为催化剂前体,3．75％XantPhos作为配体,吸电子取代和给电子取代的芳基溴代物均可与氨基乙醛缩二乙醇发生C—N交叉偶联反应,高选择性的得到产物N-（2,2-二乙氧基乙基）芳胺,分离收率为73％-96％．     

Lewis-acid-catalyzed rearrangement of arylvinylidenecyclopropanes: significant influence of substituents and electronic nature of aryl groups

Lewis-acid-catalyzed reactions of arylvinylidenecyclopropanes having three substituents at the corresponding cyclopropyl rings have been investigated thoroughly. The reaction products are highly dependent on the substituents at the corresponding cyclopropyl rings and the electronic nature of the aryl groups. For arylvinylidenecyclopropanes bearing two alkyl groups at the C-1 position (R1, R2, R3=aryl; R4=H; R5, R6=alkyl), naphthalene derivatives were formed in the presence of Lewis-acid Eu(OTf)3 in DCE at 40 degrees C. For arylvinylidenecyclopropanes in which R1, R2, R3=aryl and R4, R5=alkyl (syn/anti isomeric mixtures), the corresponding 6aH-benzo[c]fluorine derivatives were formed in the syn-configuration via a double intramolecular Friedel-Crafts reaction when all of the aryl groups do not have electron-withdrawing groups or the corresponding indene derivatives were obtained via an intramolecular Friedel-Crafts reaction as long as one electron-deficient aryl group was attached. For arylvinylidenecyclopropanes in which R1, R2, R3, R4=aryl and R5=alkyl or H, the corresponding indene derivatives were obtained exclusively via a sterically demanding intramolecular Friedel-Crafts reaction. Lewis-acid effects and mechanistic insights have been discussed on the basis of experimental investigations.     

A convenient synthesis of 5-acyl-6-substituted 3-cyano-2(1H)-pyridinones

2-Dimethylaminomethylidene-1,3-diketones are useful synthons for the construction of 5-acyl-6-substituted-3-cyano-2(1H)-pyridinones. The reaction of these 1,3-diketones and the anion of cyanoacetamide gave the title compounds. When the 1,3 diketone contained different alkyl or aryl groups, mixtures of regioisomers were formed. To circumvent this problem, dimethylaminomethylidene hydrazones, regioselectively prepared from dimethylhydrazino enones and dimethylformamide dimethyl acetal were reacted with cyanoacetamide anion followed by acid hydrolysis to give the title compounds.     

Direct synthesis of 3-arylpropionic acids by tetraphosphine/palladium catalysed Heck reactions of aryl halides with acrolein ethylene acetal

Through the use of [PdCl(C₃H₅)]₂/Cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of aryl bromides undergoes Heck reaction with acrolein ethylene acetal. With this acetal, the selective formation of 3-arylpropionic acids/esters was observed. The functional group tolerance on the aryl halide is remarkable; substituents such as fluoro, methyl, methoxy, acetyl, formyl, benzoyl, nitro or nitrile are tolerated. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl bromides.     

Practical and high stereoselective synthesis of 3-(arylmethylene)isoindolin-1-ones from 2-formylbenzoic acid

Practical and high stereoselective synthesis of 3-(arylmethylene)isoindolin-1-ones is reported. The synthetic method involves the preparation of dimethyl isoindolin-1-one-3-yl-phosphonates by a ‘one-pot’ three-component reaction of 2-formylbenzoic acid with 4-methoxybenzylamine or aminoacetaldehyde dimethyl acetal and dimethyl phosphite under solvent and catalyst free-conditions, followed by a Horner reaction with several aryl aldehydes.     

Equilibrating C-S bond formation by C-H and S-S bond metathesis. Rhodium-catalyzed alkylthiolation reaction of 1-alkynes with disulfides

In the presence of a catalytic amount of RhH(PPh3)4 (2 mol %) and 1,1'-bis(diphenylphosphino)ferrocene (dppf) (3 mol %), silylacetylenes reacted with dialkyl disulfides giving 1-alkylthio-2-trialkylsilylethynes in high yields. Alkanethiols liberated in this reaction did not interfere with the reaction, and the addition to silylacetylene forming 1-alkylthio-1-alkenes could be minimized under the conditions. Alkylacetylenes and arylacetylenes also reacted with disulfides when the alkyl or aryl groups were bulky. Diaryl disulfides gave arylthio derivatives under slightly modified conditions. The C-S bond-forming reaction is reversible: A reaction of a thiol and a 1-alkylthio-1-alkyne in the presence of the rhodium catalyst gave a 1-alkyne; alkylthio exchange reaction proceeded between a 1-alkylthio-1-alkyne and a disulfide. This is an equilibrating oxidative reaction of organic molecules with C-H and S-S bond metathesis forming C-S and S-H bonds.     

Preparation of polyfunctional aryl azides from aryl triazenes. A new synthesis of ellipticine, 9-methoxyellipticine, isoellipticine, and 7-carbethoxyisoellipticine

The preparation of polyfunctional aryl azides by the reaction of aryl triazenes with NaN3 in the presence of KHSO4 or BF3.OEt2/TFA (trifluoroacetic acid) has been described. A variety of functional groups (halides, esters, ketones, nitriles, aldehydes, and boronic esters) are tolerated under the Lewis acidic conditions. By using this methodology, the potent antitumor agents, ellipticine and 9-methoxyellipticine, have been synthesized. In addition, isoellipticine and a related derivative, 7-carbethoxyisoellipticine, were also prepared.     

Total synthesis and structure revision of deacetylravidomycin M

Total synthesis of the unnatural enantiomer of deacetylravidomycin M was accomplished. The key steps include, (1) aryl C-glycosidation of the azido-bearing fucosyl acetate 2 by using catalytic Sc(OTf)₃, (2) the [2+2] cycloaddition reaction of alkoxybenzyne bearing an azido sugar to ketene silyl acetal, and (3) the ring expansion reaction of alkoxybenzocyclobutenone. The synthesis revealed that the natural product is not the proposed amine, but the corresponding N-oxide.     

Suzuki-Miyaura cross-coupling reactions of aryl tellurides with potassium aryltrifluoroborate salts

[reaction: see text] Palladium(0)-catalyzed cross-coupling between potassium aryltrifluoroborate salts and aryl tellurides proceeds readily to afford the desired biaryls in good to excellent yield. The reaction seems to be unaffected by the presence of electron-withdrawing or electron-donating substituents in both the potassium aryltrifluoroborate salts and aryl tellurides partners. Biaryls containing a variety of functional groups can be prepared. A chemoselectivity study was also carried out using aryl tellurides bearing halogen atoms in the same compound. In addition, this new version of the Suzuki-Miyaura cross-coupling reaction was monitored by electrospray ionization mass spectrometry where some reaction intermediates were detected and analyzed.     

Cross-coupling reactions of (1-fluorovinyl)methydiphenylsilane(1) with aryl halides and aryl triflates

The cesium fluoride (CsF)-assisted cross-coupling reaction of (1-fluorovinyl)methyldiphenylsilane (1) with aryl halides and aryl triflates was examined. The reaction with aryl iodides smoothly proceeded to afford the corresponding (1-fluorovinyl)arenes in the presence of a catalytic amount of CuI and Pd(PPh(3))(4) in aprotic polar solvents such as DMF, DMI, DMA, and NMP in good yields. A variety of functional groups (nitro, ester, ketone, and ether) on the aromatic rings can be tolerated under these mild conditions. Aryl iodides are superior to aryl bromides as the coupling reaction partner. The cross-coupling reaction of 1 with aryl triflates instead of aryl halides was also accomplished in the presence of tetrabutylammonium iodide (n-Bu(4)NI) as the additive under similar conditions.     

α‐exomethylene lactone possessing acetal–ester linkage: Polymerization and postpolymerization modification for water‐soluble polymer

2,6‐Dimethyl‐5‐methylene‐1,3‐dioxa‐4‐one (DMDO), a cyclic acrylate possessing acetal–ester linkage, was obtained as a mixture of cis‐ and trans‐isomers (95:5) from Baylis–Hillman reaction of an aryl acrylate. The radical and anionic polymerizations of DMDO yielded the corresponding vinyl polymers without any side reactions such as cleavage of the acetal–ester linkage. The polymerization behaviors were significantly different from that of the acyclic acrylate, α‐(hydroxymethyl)acrylic acid, which was expected inactive against polymerization due to the steric hindrance around the vinylidene group by the α‐substituent. The acetal–ester linkage of the obtained polymer ( P1 ) was completely cleaved via acid hydrolysis to afford a water soluble polymer, P2 . © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 955–961     

Lactam acetals

The diethyl acetal of N-methylpiperidin-2-one has been synthesized and its reactions with compounds having active CH₂ and CH₃ groups have been studied. In the reaction of diethyl acetal of N-methylpiperidin-2-one with malonic ester, in addition to the condensation product, ethylmalonic ester is formed. The reaction of the acetal with benzoic acid leads to O-alkylation and the formation of ethyl benzoate.For communication IV, see [2].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 954–957, July, 1973.