Rhodium-catalyzed interconversion between acid fluorides and thioesters controlled using heteroatom acceptors

A rhodium complex catalyzed the equilibrium acyl transfer reaction between acid fluorides and thioesters. In the presence of fluoride or thiolate acceptors, the reaction could be shifted to either product. RhH(PPh₃)₄-dppe catalyzed the reaction of acid fluorides and diorgano disulfides in the presence of triphenylphosphine giving thioesters, which was accompanied by triphenylphosphine difluoride. The same complex catalyzed the reaction of aryl thioesters and hexafluorobenzene giving acid fluorides, which was accompanied by 1,4-di(arylthio)-2,3,5,6-tetrafluorobenzenes.     

Synthesis of acylphosphine sulfides by rhodium-catalyzed reaction of acid fluorides and diphosphine disulfides

A rhodium complex catalyzed the reaction of acid fluorides and tetraethyldiphosphine disulfide giving acylphosphine sulfides. Aromatic acid fluorides with electron donating p-groups reacted smoothly giving the products in high yields. Aliphatic acid fluorides with secondary and tertiary α-carbons were also converted to alkanoylphosphine sulfides, whereas the reaction of a substrate with an α-methylene carbon was accompanied by enol ester formation.     

Rhodium-catalyzed cleavage reaction of aryl methyl ethers with thioesters

A rhodium complex catalyzed the reaction of aryl methyl ethers and thioesters giving the corresponding aryl esters and methyl sulfides. S-(p-Chlorophenyl) p-(dimethylamino)benzothioate was used for the reaction of methyl aryl ethers with electron-withdrawing groups, and an S-(p-tolyl) derivative was used for those with electron-donating groups. Polymethoxybenzenes were converted to the esters in a regioselective manner.     

A unique catalyst effects the rapid room-temperature cross-coupling of organozinc reagents with carboxylic acid fluorides, chlorides, anhydrides, and thioesters

We have identified a catalyst capable of effecting the rapid, room-temperature cross-coupling between acid fluorides and diorganozinc reagents. The use of acid fluorides as electrophilic partners allows this reaction to tolerate epimerizable functionality as well as beta leaving groups. The same catalyst is also capable of cross-coupling acid chlorides, acyl cyanides, anhydrides, thioesters, and pyridyl esters. Noteworthy is the ability of the reaction to successfully transfer both groups from the organometalic fragment.     

Application of a novel thioesterification reaction to the synthesis of chemokine CCL27 by the modified thioester method

Aryl thioesters of peptide segments were prepared by the conventional 9-fluorenylmethoxycarbonyl (Fmoc) strategy using a novel N-alkyl cysteine (NAC)-assisted thioesterification reaction. The peptide carrying NAC at its C-terminus was prepared by the Fmoc strategy and converted to the aryl thioester by 4-mercaptophenylacetic acid (MPAA) treatment without significant side reactions. The peptide thioester was used for the efficient preparation of 95-amino acid (AA) chemokine CCL27 by an Ag(+)-free thioester method.     

Evaluation of acylphosphine oxide polymerization initiators using differential scanning calorimetry

This study examines the polymerization of dental monomers catalyzed by synthesized acylphosphine oxides in a differential scanning calorimetry (DSC) cell. This research focuses on establishing a relationship between radicals generated by the acylphosphine oxide photoinitiators and the kinetic reaction rates of methyl methacrylate (MMA) and acrylamide (ACM), a model monomer. The thermal stability of mono- and di-acylphosphine oxides was examined by DSC. Endothermic melting and exothermic polymerization reactions initiated with the two initiators were recorded. The acrylamide model system laid the ground work for the critical evaluation of the synthesized new initiators of mono (2,4,6-trimethylbenzoyl) diphenylphosphine oxide, and bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide. The bis(acyl) phosphine oxide photoinitiator was more reactive than the mono-(acyl) phosphine oxide with methyl methacrylates under laboratory conditions. In exothermic reactions, temperatures rose higher and more rapidly for bis(acyl) phosphine oxide initiated reactions than mono-(acyl) phosphine oxide initiated reactions.     

A new method for making acyl fluorides using BrF3

While many carboxylic acids could be converted directly to acyl fluorides by using BrF₃, the reaction with acyl chlorides was found to be of a more general nature and yields better results. Surprisingly, reacting t-butyl esters with bromine trifluoride also resulted in acyl fluorides in reasonable yields. The reactions were completed in a few seconds at 0 °C.     

Preparation of acyl fluorides with hydrogen fluoride-pyridine and 1,3-dicyclohexylcarbodiimide

This work presents an efficient procedure for preparing acyl fluorides by simply reacting carboxylic acid with hydrogen fluoride-pyridine and 1,3-dicyclohexylcarbodiimide (DCC) in dichloromethane. The acyl fluorides were converted in situ to the corresponding benzyl carboxylic esters by adding benzyl alcohol and triethylamine to the reaction mixture.     

Dechalcogenative allylic selenosulfide and disulfide rearrangements: complementary methods for the formation of allylic sulfides in the absence of electrophiles. Scope, limitations, and application to the functionalization of unprotected peptides in aqueous media

Primary allylic selenosulfates (seleno Bunte salts) and selenocyanates transfer the allylic selenide moiety to thiols giving primary allylic selenosulfides, which undergo rearrangement in the presence of PPh3 with the loss of selenium to give allylically rearranged allyl alkyl sulfides. This rearrangement may be conducted with prenyl-type selenosulfides to give isoprenyl alkyl sulfides. Alkyl secondary and tertiary allylic disulfides, formed by sulfide transfer from allylic heteroaryl disulfides to thiols, undergo desulfurative allylic rearrangement on treatment with PPh3 in methanolic acetonitrile at room temperature. With nerolidyl alkyl disulfides this rearrangement provides an electrophile-free method for the introduction of the farnesyl chain onto thiols. Both rearrangements are compatible with the full range of functionality found in the proteinogenic amino acids, and it is demonstrated that the desulfurative rearrangement functions in aqueous media, enabling the derivatization of unprotected peptides. It is also demonstrated that the allylic disulfide rearrangement can be induced in the absence of phosphine at room temperature by treatment with piperidine, or simply by refluxing in methanol. Under these latter conditions the reaction is also applicable to allyl aryl disulfides, providing allylically rearranged allyl aryl sulfides in good yields.     

The Aryl Sulfide Synthesis via Sulfide Transfer

Aryl sulfides are in great demands in drugs and materials sciences. To avoid using nucleophilic and noxious thiols, many efforts have been focused on exploring novel sulfide resources. Herein, a reductive Pd-catalyzed, Ni-mediated method to synthesize aryl sulfides via a sulfide transfer reaction is developed. The utility and scope of this reaction is exemplified by various aryl electrophiles and aryl sulfides. Mechanistic studies reveal two competing catalytic cycles of sulfide transfer and aryl transfer in this reaction, where the former one is favored over the later one because of the large energy barrier difference during the transmetalation. Moreover, two important chemicals are late-stage functionalized by this method, exhibiting the potential applications in drugs and materials science.     

Indium(I) iodide-promoted cleavage of diaryl diselenides and disulfides and subsequent condensation with alkyl or acyl halides. One-pot efficient synthesis of diorganyl selenides, sulfides, selenoesters, and thioesters

Diphenyl diselenides and disulfides undergo facile cleavages by indium(I) iodide and the corresponding generated selenate and thiolate anions condense in situ with alkyl or acyl halides present in the reaction mixture. Thus, a simple, efficient, and general procedure has been developed for the synthesis of unsymmetrical diorganyl selenides, sulfides (thioethers), selenoesters, and thioesters by this one-pot reaction at room temperature.     

Direct transformation of organosulfur compounds to organophosphorus compounds: rhodium-catalyzed synthesis of 1-alkynylphosphine sulfides and acylphosphine sulfides

A rhodium-catalyzed method for the synthesis of organophosphorus compounds directly from organosulfur compounds was developed. In the presence of RhH(PPh₃)₄ and depe, the reaction of 1-alkylthioalkynes with tetraethyldiphosphine disulfide gave 1-alkynylphosphine sulfides. The same complex catalyzed the reaction of thioesters giving acylphosphine sulfides.     

芳甲酸氰基芳甲酯的合成

芳甲酸氰基芳甲酯是重要的有机合成中间体,其现有合成方法采用剧毒氰化物为氰源来合成。 本研究以K₄[Fe(CN)₆]为绿色氰化试剂,芳酰氯为原料,采用一锅两步反应合成芳甲酸氰基芳甲酯。 通过改变第二步反应温度、反应时间、硼氢化钠和催化剂的用量获得最佳反应条件,以61.7%~80.3%的产率合成了10种芳甲酸氰基芳甲酯(2a~2j),产物结构通过傅里叶变换红外光谱仪(FTIR)、核磁共振波谱仪(NMR)分析确认。 根据实验结果,提出了可能的反应机理。 该法避免了对剧毒氰化剂的使用,具有产率高、操作简单、后处理方便等优点。     

Reactions of halometal alkoxides

Aryl thenyl and aryl aryl-α-thienylmethyl sulfides have been obtained by the action of oxalic acid esters on an equimolecular mixture of bromomagnesium thienyl or aryl α-thienyl carbinolates and bromomagnesium thiophenolates (or thionaphtholates). Derivatives of the sulfides, sulfoxides and sulfones, are also described.     

Design of highly active heterogeneous palladium catalysts for the activation of aryl chlorides in Heck reactions

In situ generation of highly active palladium species by intermediate dissolution of Pd from solid supported catalysts has been demonstrated to be a very successful approach for the activation of aryl chlorides in Heck reactions. The new ‘heterogeneous’ Pd catalysts act as reservoir for molecular Pd species with unsaturated coordination sphere in solution. Crucial Pd leaching and re-deposition onto the support can be controlled by optimization of reaction conditions and by the properties of the catalysts. Pd is re-deposited onto the support at the end of the reaction. The catalysts, palladium supported on activated carbon, on various metal oxides or fluorides and Pd complexes in zeolites, are easy to prepare, though the preparation conditions are crucial. The catalysts convert all aryl bromides completely within minutes (TON 100,000). Aryl chlorides (even deactivated ones) are converted with high yields, within 2-6 h. The catalysts belong to the most active ones in Heck reactions at all (including best homogeneous systems) and fulfill all relevant requirements for practical applications in laboratory and industry.     

以N-杂环卡宾为配体的金属络合物催化有机合成的反应

综述了近几年来以N-杂环卡宾为配体的金属络合物催化有机合成的反应。     

11C-Cyanation of Aryl Fluorides via Nickel and Lithium Chloride-Mediated C−F Bond Activation

Aryl fluorides are expected to be useful as radiolabeling precursors due to their chemical stability and ready availability. However, direct radiolabeling via carbon-fluorine (C−F) bond cleavage is a challenging issue due to its significant inertness. Herein, we report a two-phase radiosynthetic method for the ipso-¹¹C-cyanation of aryl fluorides to obtain [¹¹C]aryl nitriles via nickel-mediated C−F bond activation. We also established a practical protocol that avoids the use of a glovebox, except for the initial preparation of a nickel/phosphine mixture, rendering the method applicable for general PET centers. This method enabled the efficient synthesis of diverse [¹¹C]aryl nitriles from the corresponding aryl fluorides, including pharmaceutical drugs. Stoichiometric reactions and theoretical studies indicated a significant promotion effect of lithium chloride on the oxidative addition, affording an aryl(chloro)nickel(II) complex, which serves as a precursor for rapid ¹¹C-cyanation.     

Heck-type coupling vs. conjugate addition in phosphine-rhodium catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyl compounds: a systematic investigation

The competition between Heck-type coupling and conjugate addition in phosphine-rhodium catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyls has been systematically investigated in a toluene-H(2)O biphasic system. Aside from the intrinsic nature of rhodium and the enolization of carbonyls, the phosphine supporting ligand on rhodium, the ratio of aryl boronic acid to alpha,beta-unsaturated carbonyl and the pH value of the aqueous phase were found to affect the competition significantly. Highly selective rhodium-based catalyst systems have therefore been developed for both Heck-type coupling and conjugate addition by synergistically tuning the supporting ligand, the boronic acid to olefin ratio and other reaction conditions. Conjugate addition with selectivity >99% and Heck-type coupling with selectivity of up to 100%, 98% and 84% for acrylates, acrylamides and methyl vinyl ketone, respectively, could be achieved in the rhodium-catalyzed reactions of aryl boronic acids with alpha,beta-unsaturated carbonyls using the corresponding optimized rhodium-based catalyst systems.     

Rhodium-catalyzed disulfide exchange reaction

A system of RhH(PPh3)4, trifluoromethanesulfonic acid, and (p-tol)3P catalyzes the disulfide exchange reaction. Treatment of two symmetrical dialkyl disulfides with the catalyst provides an equilibrium mixture of three disulfides within 15 min in refluxing acetone. The catalyst is active after reaching the equilibrium, and addition of a disulfide to the mixture changes the ratio of the products. The use of 4 mol equiv excess of one of the disulfides provides the unsymmetrical disulfide in a yield exceeding 80%. Disulfide-containing peptides also undergo an exchange reaction. The reactions of diaryl disulfides and dialkyl disulfides are even faster, and reach equilibrium within 5 min at room temperature in the presence of the rhodium complex and 1,2-bis(diphenylphosphino)ethane (dppe). This exchange reaction is considerably affected by the substituents on the disulfides. Treatment of diphenyl disulfide, di(p-tolyl) disulfide, and bis(sec-butyl) disulfide yields phenyl p-tolyl disulfide at room temperature with unchanged bis(sec-butyl) disulfide; random disproportionation occurs at reflux. The rhodium catalysis can be used for the exchange reaction of disulfides and diselenides giving selenosulfides as well as disulfides and ditellurides giving tellurinosulfides.     

Probing the steric limits of rhodium catalyzed hydrophosphinylation. P-H addition vs. dimerization/oligomerization/polymerization

The reactivity of secondary phosphine oxides containing bulky organic fragments in hydrophosphinylation reactions has been investigated using several rhodium based catalysts. Upon heating in a focused microwave reactor, HP(O)(2-C₆H₄Me)₂ adds to prototypical terminal alkynes affording a complex mixture containing 1,2 and 1,1-addition products. Addition of a second ortho-substituent (HP(O)Mes₂) completely suppresses the hydrophosphinylation reaction for alkyl and aryl substituted alkynes. Variations in the temperature, catalyst loading, solvent, and microwave power were unable to induce an addition reaction in the case of HP(O)Mes₂. While this secondary phosphine oxide did not participate in the hydrophosphinylation reaction, it promoted the polymerization of phenylacetylene. HP(O)R₂ substrates are not commonly thought of as innocent ligands for rhodium complexes in reactions involving alkynes due to facile hydrophosphinylation. While this is certainly true for diphenylphosphine oxide, the chemistry presented herein suggests that HP(O)Mes₂ and related bulky secondary phosphine oxides have great potential as valuable ligands for rhodium catalyzed transformations involving alkynes due to their lack of reactivity towards the addition reaction.