Studies on the Reactions of Thiocarbonyl S‐Methanides with Hetaryl Thioketones

Dihetaryl thioketones react with thiocarbonyl ylides to give 1,3‐dithiolanes in high yields. No competitive side reactions of the thiocarbonyl ylides were observed, evidencing the ‘superdipolarophilic’ character of this less‐known group of thioketones. Depending on the type of substituents present in both the thiocarbonyl ylide and the thioketone, formal [3+2] cycloadditions occur with complete regioselectivity or with formation of a mixture of both regioisomers. Regioselective formation of the sterically more crowded 1,3‐dithiolanes is explained via a mechanism involving stabilized 1,5‐biradicals. In systems with less‐efficient radical stabilization, e.g., in the case of adamantanethione S‐methanide, substantial violation of the regioselectivity was observed as a result of steric hindrance.     

1,3‐Dipolar cycloadditions of diphenyldiazomethane to thioketones: Rate measurements disclose thiones to be superdipolarophiles

1,3‐Dipolar cycloadditions of diphenyldiazomethane to thioketones afford 2,5‐dihydro‐1,3,4‐thiadiazoles 8 , which rapidly lose N₂. The liberated thiocarbonyl ylides 10 furnish thiiranes 9 by electrocyclic ring closure. The rate constants, measured by spectrophotometry (DMF, 40°C) for 16 cycloaliphatic and aromatic thioketones and one cyclic trithiocarbonate, stretch over five powers of 10 with fluorene‐9‐thione at the top and 2,2,5,5‐tetramethylcyclopentanethione at the bottom. Electron‐releasing substituents decrease the cycloaddition rate of thiobenzophenone; thus, the ambiphilic diphenyldiazomethane reacts as nucleophilic partner with the electrophilic thioketone. The influence of substituents and ring size on the reactivity of cycloalkanethiones, which are sterically hindered by two gem‐dimethyl groups, will be discussed. Compared with electron‐deficient CC and CC bonds, thiones are superdipolarophiles. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:433–442, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20262     

New gas-phase cascade reactions of stabilized phosphorus ylides leading to ring-fused indoles and to quinolines

Gas-phase cyclization processes of stabilized phosphorus ylides bearing a suitably substituted 2-aminophenyl group lead efficiently either to 3-substituted quinolines or benzo[c]carbazole and heterocyclic-fused analogues depending on the substituents present.     

Thioformaldehyde S-methylide and thioacetone S-methylide: an ab initio MO study of structure and cycloaddition reactivity

The mechanisms of cycloaddition of thioformaldehyde S-methylide and thioacetone S-methylide, as models for an alkyl-substituted ylide, to thioformaldehyde and thioacetone, as well as to ethene as a model for a C=C double bond have been studied by ab initio calculations. Restricted and unrestricted B3LYP/6-31G* calculations were performed for the geometries of ground states, transition structures, and intermediates. Although basis sets with more polarization functions were tested, the 6-31G* basis set was applied throughout. Single-point CASPT2 calculations are reported for analysis of the unsubstituted system. The stabilities of structures with high biradical character seem to be overestimated by DFT methods in comparison to CASPT2. The general trends of the results are independent of the level of theory. Thioformaldehyde adds to thioformaldehyde S-methylide without activation energy, and the activation energies for two-step biradical pathways to 1,3-dithiolane are low. C,S biradicals are more stable than C,C biradicals. The two-step cycloaddition is not competitive with the concerted cycloaddition. Methyl substitution in the 1,3-dipole and the dipolarophile does not change the mechanistic relationships. TSs for the concerted formation of the regioisomeric cycloadducts of thioacetone Smethylide and thioacetone were located. Concerted addition remains the preferred reaction. The reactivity of the C=S double bond is high relative to that of the C=C double bond.     

The methoxycarbonylcarbene insertion into 1,3-dithiolane and 1,3-oxathiolane rings

Treatment of substituted 1,3-dithiolanes and 1,3-oxathiolanes with methyl diazoacetate in the presence of Rh₂(OAc)₄ effects ring expansion to the corresponding substituted 1,4-dithiane-2-carboxylates and 1,4-oxathiane-3-carboxylates. The sulfur ylides initially generated in these reactions undergo Stevens rearrangement in competition with both [2,3]-C-C-sigmatropic rearrangement and intramolecular fragmentation. In the case of 2-styryl-substituted 1,3-oxathiolane and 1,3-dithiolane, ring expansion on one-, three- and four-carbons subsequently takes place.     

Copper(II) tetrafluoroborate as an extremely efficient catalyst for 1,3-dithiolane/dithiane formation from carbonyl compounds under solvent-free conditions at room temperature

Copper(II) tetrafluoroborate hydrate is a new and extremely efficient catalyst for 1,3-dithiolane/dithiane formation from aromatic, heteroaromatic and aliphatic aldehydes and cyclic saturated ketones in 1-5 min under solvent-free conditions at room temperature. The reaction is compatible with other functionalities such as ether, ester, hydroxyl, halide, nitro and cyano groups and exhibits excellent chemoselectivity. α,β-Unsaturated aldehydes/ketones lead to selective formation of 1,3-dithiolanes instead of Michael addition products. For substrates bearing an aldehyde and a ketone carbonyl group, chemoselective dithiolane formation takes place with the aldehyde.     

Catalytic asymmetric oxidation of cyclic dithioacetals: highly diastereo- and enantioselective synthesis of the S-oxides by a chiral aluminum(salalen) complex

Aluminum(salalen) complex 1 [salalen = half-reduced salen, salen = N,N'-ethylenebis(salicylideneiminato)] was found to be a highly efficient catalyst for asymmetric oxidation of cyclic dithioacetals in the presence of 30% hydrogen peroxide as an oxidant. In the reaction of a series of 2-substituted 1,3-dithianes bearing alkyl, alkenyl, alkynyl, and aryl groups as the substituent, the trans-monoxides were obtained in high yields with 19:1 → >20:1 dr (diastereomeric ratio) and 98-99% ee (enamtiomeric excess). The reaction of nonsubstituted 1,3-dithiane also proceeded in a highly enantioselective manner to give the monoxide with a small formation of the trans-1,3-dioxide, an overoxidation product. Five-membered 1,3-dithiolanes and seven-membered 1,3-dithiepanes also underwent oxidation to give monoxides with high diastereo- and enantioselectivity. It was found that the equilibrium between the two chairlike conformers of dithianes has relevance to the observed diastereoselectivity in the first oxidation process, and the dioxide formation in the oxidation of 1,3-dithiane and its stereochemistry also can be explained by the conformational equilibrium of the product monoxide.     

Reactivity and selectivity in the Wittig reaction: a computational study

The salt-free Wittig reaction of non-, semi-, and stabilized ylides has been investigated on realistic systems using density functional theory (DFT) calculations, including continuum solvation. Our results provide unequivocal support for the generally accepted mechanism and are in very good agreement with experimental selectivities. This study shows that E/Z selectivity of non- and semi-stabilized ylides cannot be fully understood without considering the energy of the elimination TS. The influence of ylide stabilization and the nature of phosphorus substituents on reversibility of oxaphosphetane formation is clarified. Unexpectedly, the puckering ability of addition TSs is shown not to depend on ylide stabilization, but the geometry of the TS is decided by an interplay of 1,2; 1,3; and C-H...O interactions in the case of non- and semi-stabilized ylides, whereas a dipole-dipole interaction governs the addition TS structures for stabilized ylides. The well-known influence of ylide stabilization on selectivity of PPh(3) derivatives is explained as follows: in non- and semi-stabilized ylides reactions, cis and trans addition TSs have, respectively, puckered and planar geometries, and selectivity is governed by an interplay of 1,2 and 1,3 interactions. For stabilized ylides, the high E selectivity is due to a strong dipole-dipole interaction at the addition TS. The influence of the nature of phosphorus substituents on selectivity is also detailed, the different behavior of (MeO)(3)PCHCO(2)Me ylides being explained by their lower dipole. This novel picture of the factors determining TS structures and selectivity provides a sound basis for the design of new ylides.     

Novel Ylidic Phosphoryl Compounds from Halogenated Furan-2,5-Diones with Trivalent Phosphorus Esters: Application of this Approach to New Trisphosphonates Containing a Geminal Bisphosphonate Unit

Abstract

The reactions of trivalent phosphorus esters, including trialkyl phosphites, dialkyl phosphonites, and alkyl phosphinites, with 3-halo- and 3,4-dihalo-furan-2,5-diones has been shown to lead to the formation of novel phosphorus ylides possessing additional phosphoryl-containing groups. For the reaction of 3,4-dihalo-furan-2,5-diones with trialkyl phosphites, the products are trialkoxyphosphonium ylides containing an adjacent geminal bisphosphonate unit. These can be used to provide a convenient route to novel 2,3,3-tris(dialkoxyphosphoryl)-substituted propionate esters which can be hydrolyzed to give the corresponding novel trisphosphonic monocarboxylic acid.     

Photochemical synthesis of phosphinolines from phosphonium-iodonium ylides

We describe three different series of experiments which were undertaken to test our hypothesis that during irradiation of phosphonium-iodonium ylides (1a, 1b) an electrophilic carbene is generated. By opposing the assumed intermediate to monosubstituted alkynes, we observed in the case of electron-rich substituents at the triple bond a domination of a 1,3-dipolar cycloaddition of the intermediate with the triple bond to yield furans. In the case of electron poorer substituents, the formation of phosphinolines prevails. A second series of experiments was carried out with mixed ylides in which one phenyl ring at the triarylphosphonium group was replaced by a thienyl group. In this case, we observe only an intramolecular reaction with the thienyl ring to yield the phosphinolines 21-23. In a third test, we replaced in the mixed ylides 1a, 1b the COR group by a CN substituent. This modification leads to phosphinolines only and avoids a 1,3-dipolar cycloaddition.     

Determination of the stereochemistry of the monomethylated homologues of 1-chloro- and 1-bromo-1-methylcyclobutane by means of NMR spectroscopy

The 300 MHz ¹H NMR spectra of 1-chloro- and 1-methylcyclobutane and all monomethylated homologues are reported and analysed with regard to the ring conformations. The results indicate that halogen substituents in methylated halocyclobutanes have a greater preference for the pseudo equatorial position than do methyl groups. The ¹³C NMR spectral data are given, and substituent parameters for halogen substituents and methyl groups are calculated. Of note are the variable γ effects, especially the remarkable difference between the γ-methyl effects of the stereo-isomeric 1,3-substituted cyclobutane compounds.     

Selenophen‐2‐yl‐Substituted Thiocarbonyl Ylides – at the Borderline of Dipolar and Biradical Reactivity

The reactions of aryl (selenophen‐2‐yl) thioketones with CH₂N₂ occur with spontaneous elimination of N₂, even at low temperature (?65°), to give regioselectively sterically crowded 4,4,5,5‐tetrasubstituted 1,3‐dithiolanes and/or a novel type of twelve‐membered dithia‐diselena heterocycles as dimers of the transient thiocarbonyl S‐methanides. The ratio of these products depends on the type of substituent located at C(4) of the phenyl ring. Whereas the formation of the 1,3‐dithiolanes corresponds to a [3+2] cycloaddition of an intermediate thiocarbonyl ylide with the starting thioketone, the twelve‐memberd ring has to be formed via dimerization of the ‘thiocarbonyl ylide’ with an extended biradical structure.     

Facile synthesis of enantioenriched Cγ-tetrasubstituted α-amino acid derivatives via an asymmetric nucleophilic addition/protonation cascade

An asymmetric nucleophilic addition/protonation reaction of 3-substituted oxindoles and ethyl 2-phthalimidoacrylate has been described. This strategy can give direct access to C(γ)-tetrasubstituted α-amino acid derivatives bearing 1,3-nonadjacent stereocenters with up to 98% yield, 94:6 dr, and >99% ee. Dual activation is proposed in the transition state, and the opposite enantiomers can be obtained simply by changing cinchonidine-derived catalyst to the cinchonine analogue.     

Research on perinone compounds

11-Substituted 14H-benz[4,5]isoquinolino[2,1-a]perimidin-14-ones were synthesized, and their spectra were studied. In contrast to electron-acceptor substituents, electron-donor substituents have little effect on the shift of the absorption maxima. In the reactions of 1,8-naphthalenediamine with various 4-substituted naphthalic anhydrides, electron-donor substituents have little effect on the shift of the absorption maxima. In the reactions of 1,8-naphthalenediamine with various 4-substituted naphthalic anhydrides, electron-donor substituents lead primarily to 10-substituted naphthaloperinones, whereas electron-acceptor substituents lead primarily to 11-substituted naphthaloperinones. An assumption regarding the mechanism of the formation of 10- and 11-substituted naphthaloperinones is expressed.See [1] for communication IV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1649–1654, December, 1974.     

Regioselektive 1,3-dipolare Cycloadditionen von Thiocarbonyl-yliden mit 1,3-Thiazol-5(4H)-thionen

Regioselective 1,3-Dipolar Cycloadditions of Thiocarbonyl Ylides with 1,3-Thiazole-5(4H)-thiones The thiocarbonyl ylides 13 and 1,3-thiazol-5(4H)-thiones 1 undergo a smooth reaction to yield spirocyclic 1,3-dithiolanes 14 – 16 (Schemes 4–6). The 1,3-dipolar cycloadditions occur in a regioselective manner, but the orientation of the thiobcnzophenone-S-methylide ( 13b ) differs from that of the cycloalkane thione-S-methylides 13a and 13c . Whereas the 1,3-cycloadduct with 13b is formed in accordance with frontier-orbital considerations, the inverse orientation in the reactions with 13a and 13c most likely is the result of steric hindrance in the transition state. The thiocarbonyl ylides have been prepared in situ from the corresponding 2,5-dihydro-1,3,4-thiadiazoles 12 . The more stable aliphatic precursors 12a and 12c undergo decomposition at 50°, the unstable 12b at ?30°.     

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.     

Carbon Participation in the Solvolysis of 6-endo-Substituted 2-exo-Norbornyl Toluenesulfonates. Norbornanes part 6

The solvolysis rate constants k for the 6-endo-substituted 2-exo-norbornyl toluenesulfonates 7 have been determined. Values of logk correlate well with the respective inductive constants of the substitutents except when the latter are nucleophilic and therefore lead to endo-cyclization, or when they are n-electron donors and cause concerted fragmentation. In general 6-endo-substituted tosylates 7 react somewhat more slowly than their 6-exo-epimers. Identical or different mixtures were obtained from the C(6)-epimers 7 and 1 depending on whether the substituent was an electron donor or acceptor. It is concluded that donor substituents at C(6) enhance 1,3-bridging in the intermediate epimeric cations and lead to their rapid and complete equilibration, and that electron acceptors reduce bridging and hence their equilibration rates.     

Bu3P-CS2加合物与含不饱和键化合物的环化反应

Bu₃P-CS₂加合物与含不饱和键化合物(富电子炔类、磷酰基炔类、磷酸基烯类)以及醛进行一锅反应以较好的收率得到1,3-二硫环戊烯或1,3-二硫环戊烷衍生物.Bu₃P-CS₂加合物与偶氮化合杨和醛类进行类似反应却得到四氢噻二唑硫酮衍生物.对反应机理进行了讨论.     

Thermolysis of dimethyl <Emphasis Type="Italic">cis</Emphasis>- and <Emphasis Type="Italic">trans</Emphasis>-1 pthalimidoaziridine-2,3-dicarboxylates in the presence of dipolarophiles

Thermolysis of dimethyl esters of stereoisomeric phthalimidoaziridine-2,3-dicarboxylic acids in the presence of dimethyl fumarate, dimethyl maleate, and N-phenylmaleimide occurred stereo-specifically and stereoselectively led to the formation of derivatives of 1-phthalimidopyrrolidine, products of 1,3-dipolar additrion of intermediately arising azomethine ylides. In keeping with the rules of the conservation of orbital symmetry the thermal opening of the 2,3-disubstituted 1-phthalimidoaziridines into azomethine ylides occurred conrotatory. The relative positions of the substituents in the dipolarophiles is retained in the reaction products indicating the concerted addition mechanism.     

Synthesis of substituted disulfonyl-containing polycyclic azines with the bridgehead nitrogen atom. Effects of the structure of 3-substituted pyridinium ylides on the regioselectivity of their reactions with <Emphasis Type="Italic">E</Emphasis>-1,2-di(alkylsulfonyl)-1,2-dichloroethenes

Heating the substituted pyridinium and isoquinolinium salts with E-1,2-di(alkylsulfonyl)-1,2-dichloroethenes in either chloroform or acetone in the presence of three-fold excess of Et₃N gave high yields of substituted 1,2-di(alkylsulfonyl)indolizines and 1,2-di(alkylsulfonyl) pyrrolo[2,1-a]isoquinolines, respectively. Effects of the structure of 3-substituted pyridinium ylides on the regioselectivity of their reaction with E-1,2-di(alkylsulfonyl)-1,2-dichloroethenes were revealed. It was shown that the presence of electron-releasing and electron-withdrawing substituents in the pyridinium ylide favors the formation of 8-substituted and 6-substituted 1,2-(dialkylsulfonyl)indolizines, respectively.