Silylation of silyl- and germylketenes containing bulky substituents at the silicon or germanium atom

Silylation of silyl- and germylketenes with trialkylsilyl triflates was studied. Either the corresponding bis-organoelement-substituted ketenes or mixtures of these compounds with isomeric (silyloxy)silylacetylenes were formed depending on the size of the substituents at the silicon or germanium atom (both in ketenes and triflates) and on the nature of the heteroelement. The resulting (silyloxy)silylacetylenes were isomerized into the corresponding bis-silylketenes upon prolonged storage.     

Contribution to the synthesis of chiral allenic esters

A phosphorus ylide bearing a 10-phenylsulfonylisoborneol unit reacted with ketenes, generated in situ from acid chlorides and triethylamine, to give allenic compounds. The reaction with methylketene led to asymmetric induction with the selective synthesis of an allene with axial chirality corresponding to an S configuration. The structure of the chiral allene 10-phenylsulfonylisobornyl penta-2,3-dienoate was determined by X-ray crystallography. Chirooptical studies of the chiral allene derivatives were done.     

Diastereoselective [2+2]-cycloaddition reactions of unsymmetrical cyclic ketenes with imines: synthesis of modified prolines and theoretical study of the reaction mechanism

The synthesis of enantiomerically pure modified proline derivatives was achieved by using spiro beta-lactams as starting material that were prepared in turn by the [2+2]-cycloaddition of unsymmetrical cyclic ketenes with optically active imines. A theoretical study of the [2+2]-cycloaddition reaction, using density-functional methods, gave insights on the origin of the observed stereoselectivity of the Staudinger reaction. The spiro beta-lactams were transformed in the N-Boc derivatives and subjected to nucleophilic ring opening, affording the corresponding enantiomerically pure modified proline derivatives, isolated as orthogonally protected compounds.     

Chiral N-heterocyclic carbene catalyzed staudinger reaction of ketenes with imines: highly enantioselective synthesis of N-Boc beta-lactams

N-heterocyclic carbenes (NHCs) were demonstrated to be efficient catalysts for the Staudinger reaction of ketenes with N-tosyl, N-benzyloxycarbonyl, or N-tert-butoxycarbonyl imines. Chiral NHC 8b, conveniently prepared from L-pyroglutamic acid, catalyzed the reactions of arylalkylketenes with a variety of N-tert-butoxycarbonyl arylimines to give the corresponding cis-beta-lactams in good yields with good diastereoselectivities and excellent enantioselectivities (up to 99% ee). Two possible catalytic pathways, initiated by the addition of NHC to ketenes or imines, were discussed.     

Radical additions of TEMPO to ketenes: correlation of free radical and nucleophilic reactivity

[reaction: see text] Tetramethylpiperidinyloxy (TEMPO, TO*) reacts with a variety of ketenes R1R2C=C=O by rate-limiting attack on carbonyl carbon to give the 1,2-bis(adducts) R1R2C(OT)CO2T. The alpha,beta-unsaturated ketenes (E)-PhCH=CHCH=C=O (8b) and PhC=CCH=C=O (8c) give the 1,4-bis(adducts) PhCH(OT)CH=CHCO2T and PhC(OT)=C=CHCO2T. The ketenes may be generated in situ for these reactions in the presence of TEMPO by either dehydrochlorination of R1R2CHCOCl with Et3N or Wolff rearrangement. Ketenes PhCH=C=O (8a), 8b, and 8c had not previously been observed as long-lived species at room temperature, but when formed by photochemical Wolff rearrangement, these could be characterized in solution by conventional IR spectroscopy and used for kinetic studies for reaction with TEMPO using UV detection. The reactions of six ketenes with TEMPO in hydrocarbon solvents follow second-order kinetics, with a range of 2.5 x 10(5) in the rate constants, which are correlated with unit slope with the corresponding rate constants for hydration.     

Reaction of 1-arylmethylidenepyrazolidin-1-azomethine imines with aryl ketenes

A reaction of aryl ketenes with 1-arylmethylidenepyrazolidin-1-azomethine imines, generated by the diaziridine ring opening in 6-aryl-1,5-diazabicyclo[3.1.0]hexanes catalyzed with Et2O·BF3, leads to 1,2-bis(phenylacetyl)pyrazolidine, 2-arylacetyl-1-arylidenepyrazolidin-1-ium chlorides, or a representative of 1,5-diazabicyclo[3.3.0]octan-2-ones, viz., 4-(4-eth-oxyphenyl)-3,3-diphenyl-1,5-diazabicyclo[3.3.0]octan-2-one, depending on the reaction conditions and the structure of the starting compounds. A mechanism suggested earlier for the transformation of 1,5-diazabicyclo[3.1.0]hexanes in the reaction with ketenes was confirmed.     

Solvent and Substituent Effects in the Periselectivity of the Staudinger Reaction between Ketenes and alpha,beta-Unsaturated Imines. A Theoretical and Experimental Study

The outcome of the cycloaddition between activated ketenes and alpha,beta-unsaturated imines has been investigated both experimentally and theoretically. Our results indicate that activated monosubstituted ketenes yield exclusively [2 + 2] cycloadducts. Disubstituted activated ketenes yield [2 + 2] and/or [4 + 2] cycloadducts. In one case, an unexpected piperidin-2-one has been obtained, although its relative abundance with respect to the corresponding [2 + 2] or [4 + 2] cycloadducts can be minimized by the proper choice of experimental conditions. The ability of different ab initio and semiempirical methods to account for these results has been tested. The best agreement between theory and experiment is achieved at the MP2/6-31G level of theory, with solvent effects taken into account. The semiempirical hamiltonian AM1, at the RHF level, tends to overestimate the stability of the transition structures leading to six-membered cycloadducts, whereas 3 x 3CI-HE/AM1 and CASSCF(2,2)/6-31G methods tend to overestimate the stability and the biradical character of the transition structures leading to [2 + 2] cycloadducts.     

The organometallic chemistry of Ph3PCCO.: A route to metal-substituted ketenes

Ketenylidenetriphenylphosphorane, Ph₃PCCO (1), presents, at a first glance, the characteristics of both ylides and ketenes, but its behavior is that typical of ylides, undergoing electrophilic attacks on the ylidic carbon that transform 1 into a ‘true’ ketene having PPh₃ as one substituent. Here we review the synthesis, the chemical–physical properties as well as the reactivity of these compounds, with a particular emphasis on the interaction with transition metal complexes. With this compound it has always been observed that the ylidic carbon of 1 binds to coordinatively unsaturated metals, which act as electrophiles, forming η¹-ketenyl derivatives that can also be viewed as stabilized metal-substituted ketenes. Perspectives for the synthesis of other metal-substituted ketenes and developments on their study are also presented.     

Metal-Free Hydrosilylation of Ketenes with Silicon Electrophiles: Access to Fully Substituted Aldehyde-Derived Silyl Enol Ethers

Little-explored hydrosilylation of ketenes promoted by main-group catalysts is reported. The boron Lewis acid tris(pentafluorophenyl)borane accelerates the slow uncatalyzed reaction of ketenes and hydrosilanes, thereby providing a convenient access to the new class of β,β-di- and β-monoaryl-substituted aldehyde-derived silyl enol ethers. Yields are moderate to high, and Z configuration is preferred. The corresponding silyl bis-enol ethers are also available when using dihydrosilanes. The related trityl-cation-initiated hydrosilylation involving self-regeneration of silylium ions is far less effective.     

Exploring the solid-phase synthesis of 3,4-disubstituted beta-lactams: scope and limitations

This work describes a comprehensive study on the solid-phase synthesis of 3,4-disubstituted beta-lactams. In situ generated ketenes react with immobilized aldimines under mild conditions to generate libraries of beta-lactams in good to very good overall isolated yields. Different commercially available solid supports were studied, with the cost-effective Wang resin proving to be the most effective. The utility of the protocol was also demonstrated by the highly efficient asymmetric versions when homochiral ketenes or homochiral aldimines were used. A practical technique for the preparation of manual solid-phase parallel libraries of biologically interesting beta-lactam compounds, using Mukaiyama's salt as dehydrating agent, is also presented. Reactions were easily monitored by FT-IR and gel-phase 13C NMR using conventional equipment.     

Cationic 1,3‐diazadienes in annulation reactions. Synthesis of pyrimidine,thiadiazinedioxide and triazine derivatives

Triazapentadienium iodides 2 prepared from N'‐thiocarbamoylformamidines 1 are efficient intermediates in heterocyclic synthesis. They react with ketenes, sulfenes, phenyl isocyanate or isothiocyanate and dimethyl acetylenedicarboxylate affording the corresponding dihydropyrimidinones 3 , thiadiazinedioxides 5 , triazinones 6 , triazinethiones 7 and pyrimidines 9 .     

Silylation and germylation of trialkylsilyl(germyl)ethoxyacetylenes containing bulky substituents at the silicon or germanium atom

Silylation and germylation of trialkylsilyl(germyl)ethoxyacetylenes containing bulky substituents at the silicon or germanium atom were performed. In all cases, the corresponding bis-organoelement-containing ketenes were obtained as the only reaction products. No intermediate isomeric ynol ethers were detected by spectroscopy.     

Amination of pyridylketenes: experimental and computational studies of strong amide enol stabilization by the 2-pyridyl group

Laser flash photolyses of 2-, 3-, and 4-diazoacetylpyridines 8 give the corresponding pyridylketenes 7 formed by Wolff rearrangements, as observed by time-resolved infrared spectroscopy, with ketenyl absorptions at 2127, 2125, and 2128 cm(-1), respectively. Photolysis of 2-, 3-, and 4-8 in CH(3)CN containing n-BuNH(2) results in the formation of two transients in each case, as observed by time-resolved IR and UV spectroscopy. The initial transients are assigned as the ketenes 7, and this is confirmed by IR measurements of the decay of the ketenyl absorbance. The ketenes then form the amide enols 12, whose growth and decay are monitored by UV. Similar photolysis of diazoacetophenone leads to phenylketene (5), which forms the amide enol 17. For 3- and 4-pyridylketenes and for phenylketene, the ratios of rate constants for amination of the ketene and for conversion of the amide enol to the amide are 3.1, 7.7, and 22, respectively, while for the 2-isomer the same ratio is 1.8 x 10(7). The stability of the amide enol from 2-7 is attributed to a strong intramolecular hydrogen bond to the pyridyl nitrogen, and this is supported by the DFT calculated structures of the intermediates, which indicate this enol amide is stabilized by 12.8 kcal/mol relative to the corresponding amide enol from phenylketene. Calculations of the transition states indicate a 10.9 kcal/mol higher barrier for conversion of the 2-pyridyl amide enol to the amide as compared to that from phenylketene.     

Synthesis and chemistry of α-iodoperfluoroacid esters

The title compounds have been synthesized by irradiation of acetonitrile solutions of perfluoroacid esters and diesters containing tetrabutylammonium iodide. They are versatile synthetic intermediates from which ketenes, Reformatsky adducts, α,β-unsaturated esters and α-hydroesters can be prepared.     

Molecular orbital quantities of conjugated ketenes and influence of structural variations on their electronic features

MO quantities by CNDO/2 method on several valence isomeric ketenes and structurally corresponding allene molecules were calculated to evaluate the influence of structural feature on magnitude of back-donation of oxygen n-electrons in ketene, and to rationalize an unusual cycloaddition involved in diphenyl ketene.     

N-Heterocyclic carbene catalysed beta-lactam synthesis

N-Heterocyclic carbenes promote the formal [2+2] cycloaddition of ketenes with N-tosyl imines to give the corresponding beta-lactams in good to excellent isolated yields; chiral NHCs give beta-lactams in high e.e. after crystallisation.     

Asymmetric Synthesis of Bicyclic Pyrazolidinones through Alkaloid-Catalyzed [3+2]-Cycloadditions of Ketenes and Azomethine Imines

A versatile asymmetric synthesis of bicyclic pyrazolidinones through alkaloid-catalyzed formal [3+2]- and [3+2+2]-cycloadditions of ketenes with azomethine imines is described. The methodology was found to be tolerant of ketene and a variety of monosubstituted ketenes (R=alkyl, OAc). The products were formed in good to excellent yields (71–99 % for 24 examples, 39 examples in all), with good to excellent diastereoselectivity in many cases (dr 3 : 1 to 27 : 1 for 22 examples), and with excellent enantioselectivity for most examples (≥93 % ee for 34 products). In the case of most disubstituted ketenes, the reaction proceeded through a [3+2+2]-cycloaddition to form structurally interesting bicyclic pyrazolo-oxadiazepinediones with moderate diastereoselectivity (dr up to 3.7 : 1) and as racemic mixtures (3 examples). The method represents the first unambiguous example of an enantioselective reaction between ketenes and a 1,3-dipole.     

The Wolff Rearrangement of α-Diazo Carbonyl Compounds

The readily accessible α-diazo carbonyl compounds are distinguished by their high reactivity, which opens up a variety of preparative applications under modified conditions. Wolff rearrangements of these compounds, induced thermally, photochemically, or catalytically, afford ketenes. Free and complexed carbenes, 1,3-dipoles, 1,3-diradicals, and the antiaromatic oxirenes have been considered as intermediates or transition states. The present progress report attempts to integrate preparative and theoretical aspects.     

Ketene reactions with the aminoxyl radical tempo: preparative, kinetic, and theoretical studies

Tetramethylpiperidinyloxy (TEMPO, TO*) reacts with ketenes RR(1)C=C=O generated by either Wolff rearrangement or by dehydrochlorination of acyl chlorides to give products resulting from addition of one TEMPO radical to the carbonyl carbon and a second to the resulting radical. Reactions of phenylvinylketenes 4b and 4f, phenylalkynylketene 4c, and the dienylketene AcOCMe=CHCH=CHCMe=C=O (11) occur with allylic or propargylic rearrangement. Even quite reactive ketenes were generated as rather long-lived species by photochemical Wolff rearrangement in isooctane solution, characterized by IR and UV, and used for kinetic studies. The rate constants of TEMPO addition to eight different ketenes have been measured and give a qualitative correlation of log k(2)(TEMPO) = 1.10 log k(H(2)O) -3.79 with the rate constants for hydration of the same ketenes. Calculations at the B3LYP/6-311G//B3LYP/6-311G level are used to elucidate the ring opening of substituted cyclobutenones leading to vinylketenes and of 2,4-cyclohexadienone (17) forming 1,3,5-hexatrien-1-one (18).     

The Chemistry of α-Carbonyl Azo Compounds

α-Carbonyl azo compounds such as diesters of azodicarboxylic acids, diacylazo compounds, and esters of arylazocarboxylic acids are highly reactive. They add e.g. to amines, aromatic compounds, olefins, CH acids, Grignard and diazo compounds, aldehydes, ketones, and ketenes. These reactions can be used for the preparation of triazanes, hydrazones, oxa-diazoline, azomethinimine, and diazetidine derivatives, etc. α,α′-Dicarbonyl azo compounds are among the strongest dienophiles known.