Lewis acid-promoted reactions of zirconacyclopentadienes with isocyanates. A one-pot three-component synthesis of multiply-substituted iminocyclopentadienes from one isocyanate and two alkynes

Multiply-substituted iminocyclopentadienes were formed from Lewis acid-promoted reactions of zirconacyclopentadienes and isocyanates via a one-pot three-component coupling process; the C=O double bond of the RN=C=O moiety in the isocyanate was cleaved, and the isocyanates behaved formally as a one-carbon unit with Lewis acid-dependent and substituent-dependent reactions being realized.     

Reactions of diazo esters with electron-deficient alkenes in the presence of Lewis acids

1,3-Dipolar cycloaddition reaction of diazo esters to electron-deficient dipolarophiles to yield the corresponding 1- or 2-pyrazolines was found to be significantly accelerated with Lewis acids (Yb(OTf)₃, Sc(OTf)₃, GaCl₃, EtAlCl₂). The use of GaCl₃ as the catalyst leads to the acceleration not only of the 1,3-dipolar cycloaddition reaction, but also subsequent insertion of the CHCO₂Me electrophilic fragment of methyl diazoacetate into the N-H bond of 2-pyrazolines formed. Such Lewis acids as SnCl₄, BF₃, TiCl₄, and In(OTf)₃ are not efficient in the described processes, since they rapidly decompose starting diazo compounds.     

Lewis acid catalyzed regioselective ring opening of azetidines with alcohols and thiols

An efficient synthesis of amino ethers and amino thioethers has been achieved via the ring cleavage of N-tosylazetidines with alcohols or thiols. The reactions were studied in the presence of various Lewis acids and BF₃·OEt₂ was found to be the most efficient. The products were obtained in modest to good yields under very mild conditions in 5-15 min.     

A new and efficient method for the facile synthesis of N-acyl sulfonamides under Lewis acid catalysis

The N-acylation of sulfonamides with carboxylic acid anhydrides in the presence of Lewis acids is described. Several Lewis acids such as BF₃·Et₂O, ZnCl₂, MoCl₅, TiCl₄, B(C₆F₅)₃, Sc(OTf)₃ and I₂ were found to catalyze the reaction efficiently to furnish the N-acylated products in good yields under solvent-free conditions. The reactions of various sulfonamides were studied with different carboxylic acid anhydrides including the less reactive benzoic and pivalic anhydrides, in the presence of 3 mol % ZnCl₂ as the catalyst. Carboxylic acids were also successfully used as acylating agents via the mixed anhydride method.     

Electrophilic cyclization of 3-alkynyl-4-chalcogen-2-H-chromenes: synthesis of 3-halo-chalcogenophene[3,2-c]chromene derivatives

An efficient synthesis of 3-halo-chalcogenophene[3,2-c]chromene has been accomplished via electrophilic cyclization reaction of 3-alkynyl-4-chalcogen-2H-chromene using I₂, PhSeBr, and BuTeBr₃ as electrophilic sources. The cyclization reaction proceeded cleanly under mild reaction conditions, and 3-halochalcogen-chromenes were formed in good yields. In addition, the obtained 3-iodo-chalcogenophene-chromenes were readily transformed to more complex products using a metal-halogen exchange reaction with n-BuLi and trapping the lithium-intermediate formed with aldehyde, furnishing the desired secondary alcohol in good yield. Conversely, using the palladium catalyzed cross-coupling reactions with terminal alkynes and boronic acid, we were able to obtain the Sonogashira and Suzuki type products in good yields.     

Synthesis of highly substituted ureas and thioureas through 1,3-diaza-Claisen rearrangements

Isocyanates and isothiocyanates that are not activated by an electron withdrawing group react with azanorbornenes in benzene at reflux to afford ureas and thioureas through the corresponding 1,3-diaza-Claisen rearrangements. At higher temperatures, a triazinone byproduct is observed. Isocyanates and isothiocyanates that are activated by an electron-withdrawing group react at room temperature to give the corresponding ureas and thioureas. The reactions of the activated isocyanates and isothiocyanates are also accompanied by the formation of isoureas and isothioureas. Interestingly, while benzoyl isocyanate reacts with N-benzyl azanorbornene at room temperature to give a 2:1 mixture of urea to isourea, in benzene at reflux the only product observed is the urea. A crossover experiment rules out the possibility that the products are formed through a retro-Diels-Alder, [4+2] cycloaddition sequence instead of a 1,3-diaza-Claisen rearrangement. Competition experiments between isocyanates and isothiocyanates with limiting azanorbornene indicate that isothiocyanates react faster to give the rearrangement product. Since isocyanates are shown to be more electrophilic, these data are consistent with a fast addition step and a rate-determining rearrangement step.     

Synthesis,Structure, and In Vitro Anti-HIV Activity of New Pyrazole, 1,2,4-Thiadiazole,and 1,2,4-Triazole Derivatives

α,α′-Dichloroazo compounds 6 react with Lewis acid to furnish 1-(chloroalkyl)-1-aza-2-azoniaallene salts 4. The cations 4 react with acetylenes, isothiocyanates, isocyanates, and carbodiimides under [3+2]-cycloaddition. The cycloadducts undergo consecutive reactions, e.g., [1,2]-shifts of alkyl groups. The newly synthesized products were evaluated for their anti-HIV-1 and anti-HIV-2 activity in MT-4 cells.     

Ene reaction of Diels–Alder adducts of levoglucosenone and 1,3-dienes with acetaldehyde

Diels–Alder adducts of levoglucosenone with isoprene, butadiene and piperylene in the presence of AlCl₃ smoothly react with acetaldehyde or benzaldehyde to give products of the ene reaction, the hydroxy group of the primary intermediates participating in the formation of semiketal moiety. The yields of the reaction products depend both on the Lewis acid used (AlCl , BF ·Et O, ZnBr , SnCl or EtAlCl₂) and on the nature of the substrate.     

The reaction of fluoroxysulfate,sof-. liith aromatic compounds: catalysis by acids

The effects of the acid catalysts HF, H₂S0₄, BF₃, CF₃S0₃H, FSO₃H, and SbF₅.FS0₃H on the reactions of CsSO₄F with toluene, nitrobenzene and naphthalene in CH₃CN have been studied. The catalys general accelerate reaction and enhance yields of ring-fluorinated products. Efficacity roughly parallels H₀ of the acids, though H₂S0₄ is more effective than stronger acids for the fluorination of naphthalene. Combined room temperature yields of fluorine-substituted products are as much as 45-50% for toluene and naphthalene and up to 30% for nitrobenzene. The predominant products are o-fluorotoluene, 1- fluoronaphthalene, and m-fluoronitrobenzene. With naphthalene the isomer selectivity is considerably less than in the absence of catalyst. Low yields (10%) of monomeric oxygenated products are obtained, along with considerable oxygen- and fluorine-containing dimers and higher polymers. The results are interpreted in terms of acid-catalyzed electrophilic fluorination or oxygenation, followed by further fluorination and/or free-radical-induced oxidative coupling of the oxygenated products.     

An improved procedure for phenylselenoetherification of some Δ5-alkenols using pyridine,Ag2O,and some Lewis acids as catalysts

An improved procedure for intramolecular cyclization of some Δ⁵-alkenols, using PhSeX (X = Cl, Br) has been developed. We found that cyclization can be facilitated in the presence of pyridine, Ag₂O, and some Lewis acids as catalysts. Thus catalytic amount of additives (pyridine and Ag₂O) influences higher yields but equimolar amount achieves almost quantitative yield under extremely mild experimental conditions. In the presence of Lewis acids (ZnCl₂ and FeCl₃) high yields of cyclic ether products are obtained with catalytic amounts. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:146–149, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10227     

Quantum chemical study of the arylacyl azide complexes with Lewis acids and their Curtius rearrangement to isocyanates

The structures of donor-acceptor complexes of syn-benzoyl azide, its 2-methyl- and 2,6-dimethyl-substituted derivatives with BF₃, AlCl₃, and SbCl₅, and the corresponding transition states of the rearrangement into isocyanates were studied by the PBE/TZ2P method in the framework of the density functional theory (DFT). The complexes are formed at the oxygen and nitrogen atoms of the acyl azide group and have the composition 1: 1 or 1: 2 depending on the Lewis acid (L) structure. The complexes at the oxygen atom are more stable; the most stable complexes are formed by the reactions of acyl azides with AlCl₃. Complex formation with Lewis acids decreases the activation energy of the transformation of acyl azides into isocyanates owing to the +M effect and stabilization of the Ar-C(O-L^(1?))=N(1)-N(2)⁽¹⁺⁾≡N(3) mesomeric form. The activation energy decreases with an increase in the number of ortho-methyl substituents in benzoyl azide due to the +I effect of the phenyl group. The turn of the phenyl ring at almost 90° with respect to the CON₃ group is needed for the rearrangement to occur, and the energy necessary for this process is ～8 kcal mol^?1.     

Transformation d'oxydes d'alkyles et de polyfluoroalkyles par les acides de Lewis. Influence des radicaux alkyles.

The generation of perfluoroalkanoyl fluorides from perfluoroalkyl ethers by Lewis acids R_HOCF₂R_F → FR_H + R_FCOF depends mainly upon the nature of the alkyl R_H radical. It is necessary to use R_H groups with donor character and also electrophilic groups present on the radicals can facilitate the breaking of the R_H-O bond. As examples, ethers with Me₃SiCH₂CH₂ or CH₂=CH-CH₂ groups allowed reactions to occur readily at room temperature or below using common Lewis acids such as ZnCl₂, BF₃-Et₂O, AlCl₃.     

‘One-flask’ transformation of isocyanates and isothiocyanates to guanidines hydrochloride by using sodium bis(trimethylsilyl)amide

A ‘one-flask’ synthesis of guanidines was developed by reacting isocyanates and isothiocyanates with sodium bis(trimethylsilyl)amide followed by addition of primary or secondary amines with a catalytic amount of AlCl₃. The desired guanidines were obtained in good yields and the reaction was applicable to aliphatic and aromatic substrates. A plausible mechanism was proposed through the generation of cyanamide anion from isocyanates or isothiocyanates with sodium bis(trimethylsilyl)amide. Addition of amines and catalytic amount of AlCl₃ smoothly converted the cyanamides to the desired guanidines.     

亲电硫试剂参与的2-芳基-3-硫代-2,3-二氢喹啉-4(1H)-酮的合成研究

本文报道了以(E)-1-(2-对甲苯磺酰胺基)-3-芳基丙-2-烯-1-酮(1)为底物与N-硫代丁二酰亚胺(2)通过亲电环化反应合成2-芳基-3-硫代-2,3-二氢喹啉-4(1H)-酮类化合物。以三氟化硼乙醚为催化剂(20 mol %),1,2-二氯乙烷为溶剂,反应温度为60 _oC,可以60-92%的收率得到一系列2-芳基-3-硫代-4(1H)-喹啉酮衍生物,化合物3a-k均未见文献报道,其结构均经过₁H NMR, ₁₃C NMR以及高分辨质谱进行确定。     

Study on halolactamization-γ-hydroxylation or haloiminolactonization of 2,3-alkadienamides

The reactions of 4-mono- or 4-unsubstituted 2,3-alkadienamides with CuX₂ afforded 5-hydroxypyrrol-2(5H)-ones via the sequential lactamization and γ-hydroxylation process in aqueous THF while those of 4,4-disubstituted 2,3-alkadienamides with CuX₂ in THF afforded iminolactones in high yields. Iodoiminolactonization and iodolactamization/γ-hydroxylation were achieved by the corresponding reaction with I₂ in THF at rt. The structures of the products depend on the steric hindrance at the 4-position of the starting allenamides. Relatively electron-rich allenes afforded the corresponding products in much higher yields under milder reaction conditions implying the intramolecular electrophilic nature of the cyclization reaction.     

Does a fluorinated Lewis acid catalyst change the molecular mechanism of the decomposition process of nitroethyl carboxylates?

The molecular mechanism of the decomposition reaction of nitroethyl benzoates catalyzed by Lewis acids based on boron element—BH₃ and BF₃—was studied using density functional theory methods. These reactions take place much faster than the uncatalyzed process. However, the presence of fluorinated Lewis acids has a unique influence on the molecular mechanism. In the case of BF₃, a change from a one-step mechanism to a two-step one involving a zwitterionic intermediate is observed.     

BF3-promoted synthesis of spiroindenyl heterocycles

An easy and straightforward synthesis of spiroindenyl heterocycles by the repeated treatment of boron trifluoride etherate (BF₃-OEt₂) is reported. The overall transformation from ketones 1 to spiro-fused indenes 3 proceeds via Wittig olefination, deconjugation, Grignard addition, and intramolecular electrophilic cyclization in moderate yields. It presents a novel rearrangement reaction catalyzed by boron trifluoride etherate and broadens the scope of application.     

Recent Progress on Nazarov Cyclizations: The Use of Iron Salts as Catalysts in Ionic Liquid Solvent Systems

Nazarov cyclization is an important and versatile method for the synthesis of five‐membered carbocycles, and extensive studies have been conducted to optimize the reaction. Among recent studies, several trends are recognized. One is the combination of different reactions with Nazarov cyclization in a one‐pot reaction system which enables the preparation of unique cyclization products. The second is the use of a transition‐metal catalyst, though Lewis or Brønsted acids have generally been used for the reaction. The third is the realization of the asymmetric Nazarov cyclization. The fourth is the base‐catalyzed Nazarov cyclization. Furthermore, several useful protocols for realizing Nazarov cyclization have also been developed. The recent progress on Nazarov cyclizations is summarized in Section 2. Section 3 is our chronicle in this field. We focused on the use of iron as the catalyst in Nazarov cyclizations and ionic liquids as solvents: Nazarov cyclization of thiophene derivatives using FeCl₃ as the catalyst was accomplished and we succeeded in demonstrating the first example of an iron‐catalyzed asymmetric Nazarov reaction. We next established Nazarov cyclization of pyrrole or indole derivatives using Fe(ClO₄)₃·Al₂O₃ as the catalyst with high trans selectivities in excellent yields. Since the cyclized product was reacted with a vinyl ketone in the presence of the same iron salt, the system allowed realization of the sequential type of Nazarov/Michael reaction of pyrrole derivatives. Furthermore, we demonstrated the recyclable use of the iron catalyst and obtained the desired Nazarov/Michael reaction products in good yields for five repetitions of the reactions without any addition of the catalyst using an ionic liquid, [bmim][NTf₂], as the solvent. We expect that the iron‐catalyzed Nazarov cyclization, in particular, in an ionic liquid solvent might become a useful method to synthesize functional molecules that include cycloalkene moieties.     

Efficient synthesis of ferrocenylenones by Friedel-Crafts acylation with EtAlCl2-Me3Al

Efficient synthesis of ferrocenylenones using a Friedel-Crafts acylation reaction is described. Acryloyl, methacryloyl, crotonoyl, cinnamoyl, and β-methylcrotonoyl chlorides react with ferrocene in the presence of a Lewis acid (EtAlCl₂ or EtAlCl₂-Me₃Al) to give the corresponding ferrocenylenones (acryloyl, methacryloyl, crotonoyl, cinnamoyl, and methylcrotonoylferrocenes) in good isolated yields. Besides ferrocenylenones, chloroactylferrocene is also synthesised by this method.     

Direct oxidative cyclization of 3-arylpropionic acids using PIFA or Oxone: synthesis of 3,4-dihydrocoumarins

The direct oxidative cyclization of 3-arylpropionic acids using PIFA or Oxone is reported. In the presence of BF₃·OEt₂, the reaction of 3-arylpropionic acids with PIFA or Oxone proceeded smoothly at 30 °C to give 3,4-dihydrocoumarins in good to excellent yields.