Microwave-assisted synthesis of cyclopentanones using the relevant phosphorus ylides

A one-pot synthesis of cyclopentanone derivatives from phosphorus ylide under lab-type microwave assisted methodology was described. The phosphorus ylides were obtained via the reaction of activated acetylenic compounds, ethyl 4-chloroacetoacetate and triphenylphosphine. The structure of phosphorus ylides was assigned by 1H, 13C and 31PNMR. The phosphorus ylides as precursor were crystallized as two enantiomers (R,R) and (S,S) and one of the phosphorus ylide structures was confirmed by single X-ray crystallography.     

Sulfonium ylides

The thermal transformations of phthalimido-substituted keto-stabilized sulfonium ylides, including optically active ylides, were studied. The thermolysis of sulfonium ylides obtained from α- and β-amino acids leads to methylthio-substituted pyrrolizidine- and indolizidinediones. Racemization of optically active ylides does not occur. Sulfonium ylides with longer carbon chains do not undergo intramolecular cyclization.     

Kinetic and mechanistic study on the thermal reactivity of stabilized phosphorus ylides,part 3: [(Acetyl)(arylcarbamoyl)methylene]triphenylphosphoranes and [(alkoxycarbonyl)(arylcarbamoyl)methylene]triphenylphosphoranes and their thiocarbamoyl analogues

A series of five [(acetyl)(arylcarbabmoyl)methylene]triphenyl‐phosphoranes 1a–e and their thiocarbamoyl analogues 2a–e , [(alkoxycarbonyl)(arylcarbamoyl)methylene]triphenylphosphoranes 3a–e and their thiocarbamoyl analogues 4a–e were prepared and fully characterized. All ylides are found under conditions of flash vacuum pyrolysis to fragment giving arylisocyanate or isothiocyanate and acetyl ylides or alkoxy ylides which undergo thermal extrusion of Ph₃PO. A kinetic study shows that these reactions are unimolecular and are of first‐order nature with no significant substituent effect. The thiocarbamoyl ylides 2 react from 4.6 to 42 times faster than their carbamoyl ylides 1 , while the thiocarbamoyl ylides 4 react from 6.6 to 20.9 times faster than their carbamoyl ylides 3 . © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 39: 6–16, 2007     

Transition-Metal Free Catalytic Synthesis of Trifluoromethyl Indolines by [4+1] Cycloaddition of Trifluoromethyl Benzoxazinones with Sulfur Ylides

Stereoselective catalytic synthesis of 3-trifluoromethyl indolines through the [4+1] cycloaddition of benzoxazinones and sulfur ylides in a transition-metal-free manner was developed. In the presence of a catalytic amount of sodium hydride, aza-ortho-quinone methide intermediates were formed from trifluoromethyl benzoxazinones through decarboxylation after the first nucleophilic attack of sulfur ylides, which progressed to a second nucleophilic attack of sulfur ylides, resulting in the [4+1] cycloaddition. The key for this catalytic transformation is the dual attack of sulfur ylides on substrates. This unique transition-metal-free protocol is applicable to the synthesis of non-fluorinated vinyl-, ethynyl- or methyl-substituted indolines. The synthesis of 3-trifluoromethyl indoles was also achieved described under stoichiometric conditions.     

Synthesis of pyrrolo[3,4-c]quinolines by 1,5-electrocyclisation of non-stabilised azomethine ylides

A new route to the pyrrolo[3,4-c]quinoline ring system has been developed via the 1,5-dipolar electrocyclisation reactions of azomethine ylides derived from easily available 3-formylquinoline derivatives. The intermediacy of azomethine ylides was shown by the trapping of the proposed dipoles with N-phenylmaleimide.     

Photocatalytic Vicinal Aminopyridylation of Methyl Ketones by a Double Umpolung Strategy

A photocatalytic double umpolung strategy for the vicinal aminopyridylation of ketones was developed using pyridinium N?N ylides. The inversion of the polarity of the pyridinium N?N ylides by single‐electron oxidation successfully enables radical‐mediated 1,3‐dipolar cycloadditions with enolsilanes formed in situ from ketones, followed by homolytic cleavage of the N?N bond. Intriguingly, the nucleophilic amino and electrophilic pyridyl groups in the ylides can be installed at the nucleophilic α‐position and electrophilic carbonyl carbon, respectively, which are typically inaccessible by their innate polarity‐driven reactivity. This method accommodates a broad scope, and the utility was further demonstrated by the late‐stage functionalization of complex biorelevant molecules. Moreover, the strategy can be successfully applied to enamides.     

Synthesis of pyrrolo[3,4-c]quinolines by 1,5-electrocyclisation of non-stabilised azomethine ylides

A new route to the pyrrolo[3,4-c]quinoline ring system has been developed via the 1,5-dipolar electrocyclisation reactions of azomethine ylides derived from easily available 3-formylquinoline derivatives. The intermediacy of azomethine ylides was shown by the trapping of the proposed dipoles with N-phenylmaleimide.     

1,4-silatropy of S-alpha-silylbenzyl thioesters: a convenient route to silyl enol and dienol ethers accompanied by C-C bond formation via thiocarbonyl ylides

A novel convenient method for the generation of thiocarbonyl ylides from readily accessible starting materials and the first synthetic application of in situ generated ylides in the synthesis of silyl enol and dienol ethers, accompanied by C-C bond formation, is described. Under completely neutral conditions without any catalyst or additive, thermal reactions of S-alpha-silylbenzyl thioesters in sealed tubes at 180 degrees C provided silyl enol and dienol ethers in good to excellent yields with high stereoselectivities. This procedure consists of a multistep reaction in a one-pot process, i.e., 1,4-silatropy of S-alpha-silylbenzyl thioesters to give thiocarbonyl ylides, 1,3-electrocyclization of the ylides to give thiiranes, and the extrusion of sulfur from thiiranes to give silyl enol and dienol ethers.     

Copper‐Catalyzed Formal [4+2] Cycloaddition of Enoldiazoimides with Sulfur Ylides

Enoldiazoimides, a new subclass of enoldiazo compounds, generate enol‐substituted carbonyl ylides whose reactions with sulfur ylides enable an unprecedented formal [4+2] cycloaddition. The resulting multifunctionalized indolizidinones, which incorporate sulfur, are formed in good yields under mild reaction conditions. The uniqueness of this transformation stems from the role of the silyl‐protected enol, since the corresponding acetyldiazoimide failed to provide any cross‐products in metal‐catalyzed reactions with sulfur ylides. This copper‐catalyzed cycloaddition is initiated with the generation of enol‐substituted carbonyl ylides and sulfur ylides from enoldiazoimides and sulfonium salts, respectively, and proceeds through stepwise six‐membered ring formation, C?O and C?S bond cleavage, and silyl and acetyl group migration.     

Synthesis of Amino Acid Derived Cyclic Phosphorus Ylides

Abstract

We recently reported the thermal elimination of Ph₃PO from suitably protected aminoacyl ylides 1 as a route to acetylenic amino acid analogues 2. Pyrolysis of ylides such as 3 with a free amino group takes a different course. Ethanol is eliminated to give the c h i d cyclic ylides 4 which can be viewed as 3-triphenylphosphoranylidene tetramic acids. Specific examples prepared include 4 (R = Me, Pri), the parent compound 5 (from glycine) and the six-membered ring compound 6 (from p-alanine). Using a similar approach, bicyclic ylides such as 7 (from proline) can be prepared. In the case of the glutamate derived ylide 8, thermolysis initially gives a mixturc of 9 and 10 but these both cyclise to the bicyclic product 11 with time. The structure and reactivity of these interesting cyclic ylides are now being examined.     

Synthesis of benz[5,6]azepino[4,3-b]indoles by 1,7-electrocyclisation of azomethine ylides

A new, general route to the benz[5,6]azepino[4,3-b]indole ring system has been developed via the 1,7-dipolar electrocyclisation reactions of azomethine ylides derived from easily available 3-formyl indole derivatives. The intermediacy of azomethine ylides was shown by the trapping of the proposed α,β:γ,δ-conjugated dipole with N-phenylmaleimide.     

Computational investigations on the general reaction profile and diastereoselectivity in sulfur ylide promoted aziridination

Mechanism and diastereoselectivity of sulfur ylide promoted aziridination reactions were studied by density functional theory with inclusion of solvent effects through the continuum solvation model. The general reaction pathway was modeled for the addition of substituted sulfur ylides (Me(2)S(+)CH(-)R) to an aldimine ((E)-methyl ethylidenecarbamate, MeHC=NCO(2)Me). The nature of the substituents on the ylidic carbon atom substantially affects the reaction profile. The stabilized (R=COMe) and semistabilized (R=Ph) ylides follow a cisoid addition mode leading to trans aziridines via anti betaine intermediates. The simplest model ylide (unstabilized, R=H) underwent cisoid addition in a similar fashion. In the case of stabilized ylides product diastereoselectivity is controlled by the barriers of the elimination step leading to the 2,3-trans aziridine, whereas it is decided in the addition step in the case of semistabilized ylides. The importance of steric and electronic factors in diastereoselective addition (2 and 5) and elimination (5) transition states was established. Comparison of results obtained with the gas-phase optimized geometries and with the fully optimized solvent-phase geometries reveals that the inclusion of solvent effects does not bring about any dramatic changes in the reaction profiles for all three kinds of ylides. In particular, diastereoselectivity for both kinds of ylides was found to be nearly the same in both these approaches.     

Preparation and properties of some stable arsonium ylides

Stable crystalline arsonium ylides have been prepared by thermal decomposition of diazo compounds in the presence of triphenylarsine, and by condensation reactions of reactive methylene compounds with triphenylarsine oxide. The spectra of these ylides, and their reactions with benzaldehydes are discussed. Like other stabilised arsonium ylides they give alkenes rather than epoxides in Wittig reactions. They are generally more polar than their phosphonium analogues and also are more reactive in the Wittig reaction. With diphenylcyclopropenone some more reactive arsonium ylides form α-pyrones.     

Chemistry of P-F Ylides

Results of the research into ylides containing fluorine atoms on the phosphorus atom of the P=C group are summarized. These compounds are convenient reagents for preparing various organic and organo-phosphorus compounds hardly available by other methods. Main synthetic routes to P-fluoroylides are considered. Chemical and physical properties of the ylides are reviewed. The peculiar chemistry of these compounds is shown, that significantly differs from the chemistry of triphenylphosphonium ylides. Prospective synthetic applications of P-fluoroylides are analyzed.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 7, 2005, pp. 1076–1099.Original Russian Text Copyright © 2005 by Kolodyazhnyi.     

An efficient method to prepare sulfoxonium ylides and their reactivity studies using copper powder and Sc(III) as catalysts: Molecular and electronic structure analysis

Sulfoxonium ylides are the viable alternatives for diazo compounds as carbene precursors. Unlike diazo compounds, these are bench-stable and crystalline solids. However, the existing methods for the synthesis of sulfoxonium ylides have disadvantages related to the yields, substrate scope, and usage of expensive catalysts. Therefore, it is necessary to develop efficient and competitive protocols for the preparation of sulfoxonium ylides. In this study, we developed an economically affordable protocol for the synthesis of sulfoxonium ylides from diazo compounds using copper powder as a catalyst. This protocol leads to the efficient multigram-scale synthesis of a wide range of sulfoxonium ylides in good yields. Further, we demonstrated scandium triflate–catalyzed carbene insertion into the N−H bond from sulfoxonium ylide. A variety of anilines and sulfoxonium ylides with various functional groups reacted well and produced the corresponding α-amino esters in good yields. All the synthesized compounds were characterized using various standard spectroscopic and analytical techniques. We also used computational methods to understand the electronic structure of all the sulfoxonium ylides using geometry optimization, frequency calculation, molecular orbital and natural bond orbital analysis, and energy decomposition analysis. Our computational results revealed that the interaction between carbene and dimethyl sulfoxide is covalent in nature and stable enough to handle in the absence of any catalyst.     

Synthesis of Chiral Aziridines Through Decarboxylative Generation of Sulfur Ylides and Their Reaction with Chiral Sulfinyl Imines

Reaction of sulfur ylides with a series of aryl substituted chiral nonracemic sulfinyl imines afforded the corresponding aziridines in good yields with good stereoselectivity. The sulfur ylides were generated by the thermally induced decarboxylation of carboxymethylsulfonium betaines. A drop in the diastereomeric ratio was observed when going from electron-deficient to electron-releasing aryl substituted imines. S-Methylene aziridinations involving the decarboxylation of carboxymethylsulfonium betaine functionality complements existing technologies with the advantages of the reaction protocol, levels of conversion, and scope.     

Silver acetate-catalysed asymmetric 1,3-dipolar cycloadditions of imines and chiral acrylamides

N-Metallated azomethine ylides were generated by the reaction of arylidene glycine imines with AgOAc and triethylamine. These azomethine ylides undergo cycloaddition to chiral acrylamides with excellent diastereoselectivity. The configuration of two of the cycloadducts was confirmed by X-ray crystallography.     

The first example of the generation of azomethine ylides from a fluorocarbene: 1,3-cyclization and 1,3-dipolar cycloaddition

The reaction of Schiff bases with fluorocarbene, generated by reduction of dibromofluoromethane with active lead in the presence of Bu₄NBr under ultrasound irradiation, involves the formation of fluoro-substituted azomethine ylides which undergo cyclization into aziridines. 1,3-Cyclization of ylides, generated from N-arylimines of benzaldehyde, proceeds stereoselectively. When carrying out the reaction of Schiff bases with fluorocarbene in the presence of dimethyl maleate or dimethyl acetylenedicarboxylate, the products of dehydrofluorination of the primary adducts of the 1,3-dipolar cycloaddition of fluoro-substituted azomethine ylides to multiple bonds of dipolarophiles were obtained. In the case of the reaction of N-alkylimines of benzaldehyde the cycloaddition of ylides to dimethyl maleate completely suppressed the cyclization to aziridines.     

Enantioselective Protonation of Cyclic Carbonyl Ylides by Chiral Lewis Acid Assisted Alcohols

Chiral Lewis acid-catalyzed asymmetric alcohol addition reactions to cyclic carbonyl ylides generated from N-(α-diazocarbonyl)-2-oxazolidinones featuring a dual catalytic system are reported. Construction of a chiral quaternary heteroatom-substituted carbon center was accomplished in which the unique heterobicycles were obtained in good yields with high stereoselection. The alcohol adducts were successfully converted to optically active oxazolidine-2,4-diones by hydrolysis. Mechanistic studies by DFT calculations revealed that alcohols could be activated by Lewis acids, enabling enantioselective protonation of the carbonyl ylides.     

Preparation of Novel Polyoxo Ylides and Diylides and Their Behaviour Towards Pyrolysis and Oxidation

Abstract

We recently reported the preparation of the new trioxoylides 1 and their pyrolysis to give symmetrical diacylalkynes.¹ Reaction of acyl ylides with oxalyl chloride gkes the tetraoxo diylides 2 as shown. The corresponding reactions starting from the α-oxoacyl ylides have been used to obtain examples of tetraoxo ylides 3 and hexaoxo diylides 4.