1,4-Addition reaction of ethyl bromodifluoroacetate to Michael acceptors in the presence of copper powder: Improvement of the reaction using TMEDA as an additive

Reaction of ethyl bromodifluoroacetate with a variety of Michael acceptors was tremendously improved by the addition of TMEDA. Using this additive, 1,4-adducts were formed exclusively, and any 1,2-adducts or radical adducts were not obtained. THF or other low boiling solvents can be used as a solvent. This simplifies the work-up of the reaction effectively.     

Efficient approach to 3,3-bissilyl carbonyl and enol derivatives via retro-[1,4] brook rearrangement of 3-silyl allyloxysilanes

A facile and highly stereoselective retro-[1,4] Brook rearrangement of 3-silyl allyloxysilanes has been discovered. While basic hydrolysis of the formed (Z)-3,3-bissilyl lithium enolates provides 3,3-bissilyl carbonyl compounds efficiently, trapping the species with various electrophiles including alkyl halides leads to the exclusive O-substituted (Z)-3,3-bissilyl enol derivatives that can undergo a Sakurai reaction with aldehyde to produce the synthetically useful 1,2-diol diastereoselectively.     

Addition of 1,2- and 1,3-Dithiols to 2-alkoxypropenals - a New Method for the Production of Substituted Dithiacycloalkanes

The reaction of 2-alkoxypropenals with ethane-1,2-dithiols and propane-1,3-dithiols under various conditions was studied by ¹H NMR and chromato-mass spectrometry. Under kinetically controlled conditions at 20° in the absence of catalysts the addition of dithiols takes place according to the Markovnikov rule. The primary adducts are unstable and are quickly converted into the corresponding substituted 1,4-dithiacycloheptane or 1,4-dithiane. The latter in turn can be converted under the reaction conditions or at high temperature into a thiolane derivative. The reaction of 2-ethoxypropenal with a twofold excess of ethane-1,2-dithiol at 60°C in the presence of p-toluenesulfonic acid leads to 2-methyl-2,2'-bi(dithiolane)     

丁烯醛与聚乙烯醇的缩醛化反应机理

化学分析法及碳核磁共振研究表明 ,作为不饱和醛的α 丁烯醛 (巴豆醛 )与聚乙烯醇在水溶液中进行缩醛化时存在着 1,2 加成与 1,4 加成两种反应方式 .此机理不同于只有 1,2 加成方式的聚乙烯醇缩饱和醛化反应 .1,4 加成主要导致聚乙烯醇缩丁烯醛的交联 .还提出了根据化学分析结果计算聚乙烯醇缩丁烯醛的缩醛度以及这两种加成方式的分率的方法     

Effect of substituents on the homo-1,4 addition of difluorocarbene to norbornadienes

Difluorocarbene reacts with 2-methoxy and 2-carbomethoxy-7,7-dimethylnorbornadiene to give homo-1,4 adducts only. The relative rates of addition are compared with that for 7,7-dimethylnorbornadiene and are found to be 2.63, 0.045 and 1.0 respectively. Consequently, an electrophilic process is operating. Difluoro, dichloro and dibromocarbenes react with 7,7-dimethylnorbornadiene exclusively on the endo face to give 1,2 and homo-1,4 adducts in ratios of ≈0.1, 0.5 and 0.7 respectively. The homo-cheletropic reaction, compared to the competing cyclopropanation, is increasingly sensitive to the bulk of the carbene partner.     

Catalytic Direct‐type 1,4‐Addition Reactions of Alkylazaarenes

1,4‐addition reactions of alkylazaarenes catalyzed by strong Brønsted bases have been developed for the first time. The desired reactions with α,β‐unsaturated amides proceeded under mild reaction conditions to give the 1,4‐adducts in high yields. Both ortho‐ and para‐substituted azaarenes afforded the desired adducts in high yields. Regioselective reactions of di‐ or trimethylpyridine were found to be possible depending on the acidity of the α‐hydrogen atoms. Furthermore, a candidate of allosteric protein kinase modulators was synthesized in two steps. An asymmetric variant of this reaction was also found to be feasible.     

The role of entropic and electronic factors in controlling homo-1,4 addition of dihalocarbenes to norbornadiene-type molecules

The proportion of 1,2 and homo-1,4 adducts obtained from the reaction of difluoro-carbene with norbornadiene and its 7-oxa, 7-methyl, and 7,7-difluoro derivatives is reflected by the calculated energies of the frontier molecular orbitals of the dienes. It appears that the product composition is dictated by competing 1,2 electrophilic and homo-1,4 nucleophilic cheletropic reactions.     

Halosulfenylation of Conjugated Dienes with Arylsulfenamides in the Presence of Phosphorus Oxyhalides

Electrophilic sulfenylation of cyclic and open-chain conjugated dienes effected by a system arylsulfenamide-phosphorus oxyhalide was investigated. The initially formed adducts of 1,2-halosulfenylation in the course of the reaction and also at storage and chromatograqphic purification on silica gel undergo quantitative isomerization into a mixture of stereoisomeric products of 1,4-addition. The effect of halogen nature and the character of substituents in the benzene ring of arenesulfenamide on the addition rate of sulfenamides activated by phosphorus oxyhalides to open-chain and cyclic conjugated dienes and isomerization rate of the arising 1,2-adducts was examined.     

Electrophilic additions involving fluoronium ions II. The addition of fluoroxy groups to perfluoro-aromatic compounds

The addition of fluoroxy groups to perfluoroaromatic compounds results in the formation of stable adducts. Thus, for the reaction of equimolar quantities of hexafluorobenzene and trifluoromethyl hypofluorite, the main products are the 1,4-monofluoroxy and 1,2-monofluoroxy adducts, but the latter adduct is not detected in the corresponding reaction with perfluoro-t-butyl hypofluorite. Polyfluoroxy additions to perfluoroaromatic compounds occur more readily for (CF₃)₃ COF than for CF₃OF in spite of steric hindrance in the former. The other OF-containing compound which has been studied is oxygen difluoride which reacts with hexafluorobenzene to form polymeric perfluoroalicyclic ethers. In contrast to nucleophilic reactions, fluoroxy addition reactions occur more readily with hexafluorobenzene than with octafluorotoluene, a result which may be attributed to deactivation of the fluoroaromatic ring towards electrophilic addition by the trifluoromethyl group.     

Hydrogenation of simple aromatic molecules: a computational study of the mechanism

Quantum chemistry calculations have been used to study the metal-free hydrogenation reactions of a variety of simple aromatic, heteroaromatic, and related linear conjugated systems. We find that the barrier for uncatalyzed 1,4-hydrogenation is always substantially lower (by approximately 200 kJ mol-1) than that for 1,2-hydrogenation, despite similar reaction enthalpies. The presence of hydrogen fluoride as a catalyst is found to decrease the 1,2-hydrogenation barriers but, in most cases, to slightly increase the 1,4-hydrogenation barriers when a constrained geometric arrangement is employed. These qualitative observations are consistent with orbital symmetry considerations, which show that both the uncatalyzed 1,4-hydrogenation and the catalyzed 1,2-hydrogenation are formally symmetry-allowed processes. An extreme example of the catalyzed 1,2-hydrogenation of benzene is provided by the involvement of a second molecule of hydrogen, which leads to a substantial lowering of the barrier. The effect of catalysis was further investigated by applying a selection of additional catalysts to the 1,2- and 1,4-hydrogenation of benzene. A decreasing barrier with increasing catalyst acidity is generally observed for the catalytic 1,2-hydrogenation, but the situation is more complex for catalytic 1,4-hydrogenation. For the uncatalyzed 1,4-hydrogenation of aromatic systems containing one or more nitrogen heteroatoms, the barriers for [C,C], [C,N], and [N,N] hydrogenations are individually related to the reaction enthalpies by the Bell-Evans-Polanyi principle. In addition, for a given reaction enthalpy, the barriers for [C,C] hydrogenation are generally lower than those for [C,N] or [N,N] hydrogenation. Finally, we find that the distortion experienced by the reactants in forming the transition structure represents a secondary factor that influences the reaction barrier. The correlation between these quantities allows the 1,4-hydrogenation barriers to be predicted from a ground-state property.     

Dithionite adducts of pyridinium salts: regioselectivity of formation and mechanisms of decomposition

¹H and ¹³C NMR spectroscopy has been used to detect and to characterize the adducts formed, in alkaline solutions, by the attack of dithionite anion on 3-carbamoyl or 3-cyano substituted pyridinium salts. In all studied cases, only 1,4-dihydropyridine-4-sulfinates, formed by attack of dithionite oxyanion on the carbon 4 of pyridinium ring, were found. This absolute regioselectivity seems to suggest a very specific interaction between the pyridinium cation and the dithionite through the formation of a rigidly oriented ion pair, determining the position of attack. In weak alkaline solution, the adducts decompose according to two mechanisms S_Ni and S_Ni′: the S_Ni path is operative in all studied cases and preserves the 1,4-dihydro structure yielding the corresponding 1,4-dihydropyridines, whereas the S_Ni′ path involves the shift of 2,3 or 5,6 double bonds yielding 1,2- or 1,6-dihydropyridines, respectively. The formation of 1,2- or 1,6-dihydropyridines, in addition to 1,4-dihydro isomers, depends on their respective thermodynamic stabilities.     

Diazapolycyclic compounds—XIII : Reactions of diazaquinone adducts with N-bromosuccinimide

The action of N-bromosuccinimide on adducts obtained by Diels-Alder reaction of benzo(g)phthalazin-1,4-dione with substituted 1,3-butadienes is reported. Different addition or substitution products are formed depending on the solvent and reaction conditions. The stereochemistry of the most interesting among these compounds has been studied, and a possible mechanism for their formation is proposed.     

Reactions of heteroaromatic thiols with 1,3-butadiene and cyclopentadiene

The formation of 1,2 and 1,4 adducts in the reaction of 5-chloro-2-thiophenethiol, 2-benzofuranthiol, 2-benzothiophenethiol, and 3-methyl-2-benzothiophenethiol with conjugated dienes in the presence of various amounts of ethylsulfuric acid and also without a catalyst was studied. Catalytic acceleration of the reaction with ethylsulfuric acid indicates the heterolytic character of the addition.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1335–1337, October, 1982.     

Synthesis of highly branched sulfur-nitrogen heterocycles by cascade cycloadditions of [1,2]dithiolo[1,4]thiazines and [1,2]dithiolopyrroles

We report the synthesis of some new polysulfur-nitrogen heterocycles by cascade cycloadditions to readily available polycyclic 1,2-dithiole-3-thiones. Thus, treatment of bis[1,2]dithiolopyrrole dithione 1 with dimethyl acetylenedicarboxylate (DMAD) or dibenzoylacetylene (DBA) gave the 1:4 adducts 2a,b and 3a. On the other hand, cycloaddition of bis[1,2]dithiolo[1,4]thiazine dithiones 4a-d with the same dipolarophiles gave the 1:2, 1:3, or 1:4 adducts 5a-c, 6a, 7a, 8a, 9a, and 10a,c,d selectively in fair to high yields. Reaction conditions were crucial for achievement of selectivity in thermal reactions. Catalysis by scandium triflate was used in the reaction of 4a and 2 equiv of DMAD. Treatment of the [1,2]dithiolo[1,4]thiazine dithione 11 with DBA gave the 1:2, 1:3 (two isomers), and 1:4 adducts 12-14 and 15a-d selectively. Cyclic voltammetry of selected examples showed irreversible processes that were not influenced by peripheral groups bonded to the heterocyclic system.     

Synthesis of β‐Arylacyl/β‐Heteroarylacyl‐β‐alkylidene Malonates and Their Application in Substituted Pyridone Synthesis

A novel approach has been developed for the synthesis of β‐arylacyl/β‐heteroarylacyl‐β‐alkylidine malonates in moderate to good yields by the reaction of Stork aryl and heteroaryl enamine with β‐chloroalkylidene malonates. The reaction involves conjugate (Michael) addition of Stork enamine on β‐chloroalkylidene malonates and elimination of chloride ion. These Michael adducts were utilized as intermediates for the synthesis of highly substituted 1,4‐dialkyl‐2‐oxo‐6‐aryl/hetreoaryl‐1,2‐dihydro‐pyridine‐3‐carboxylic acid ethyl esters via 5 + 1 ring annulation protocol.     

A synthesis of di- and tri-substituted β,γ-unsaturated esters from aldehydes by the magnesium carbenoid 1,2-CH and 1,2-CC insertion as the key reaction

Addition reaction of 1-chlorovinyl p-tolyl sulfoxides, which were derived from aldehydes, with lithium enolate of tert-butyl acetate at −78 °C in THF gave adducts in high yields. Treatment of these adducts with Grignard reagents resulted in the formation of magnesium carbenoids via the sulfoxide-magnesium exchange reaction. When the adducts were derived from alkyl aldehydes or electron-deficient aromatic aldehydes, carbenoid 1,2-CH insertion reaction took place from the magnesium carbenoids to afford β,γ-unsaturated butyric esters having a substituent at the β-position. On the other hand, when the adducts were derived from electron-rich aromatic aldehydes, carbenoid 1,2-CC insertion reaction took place from the magnesium carbenoids to give β,γ-unsaturated butyric esters having the aromatic group at the γ-position. Highly stereospecific 1,2-CC insertion reactions were observed in the latter reactions. When the addition reactions were quenched with iodoalkanes, the alkylated adducts were obtained in quantitative yields. Tri-substituted β,γ-unsaturated esters, or in some case γ,δ-unsaturated esters, were obtained by the treatment of the alkylated adducts with EtMgCl. These procedures provide a good way for a new synthesis of di- and tri-substituted β,γ-unsaturated esters from aldehydes with two or three carbon-carbon bond-formations.     

The reactions of aromatic compounds with bromine trifluoride (2): Octafluoronaphthalene

The reaction of bromine trifluoride with octafluoronaphthalene has been investigated, from which was obtained decafluoro-1,2-benzocyclohexa-1,4-diene, 2-bromo-undecafluorotetralin and a mixture of dibromotetradecafluorobicylo [4,4,0] decene isomers. Dehalogenation and reduction gave decafluoro-1,2-benzocyclohexa-1,3-diene in addition to the 1,4-diene and 2$\text{H}$-undecafluorotetralin, a similar mixture being obtained from the dibromo decene. The reactions of the dienes and bromofluorotetralin with methoxide ion have also been studied.     

Regio- and stereochemically controlled formation of hydroxamic acids from indium triflate-mediated nucleophilic ring-opening reactions with acylnitroso-Diels-Alder adducts

Treatment of acylnitroso-Diels-Alder [2.2.1] bicyclic adducts 2a-b with indium triflate in an alcohol solvent induces ring-opening reactions to afford monocyclic anti-1,2-, anti-1,4-, and syn-1,4-hydroxamic acids with good to excellent regio- and stereoselectivity (up to 7:86:7). Treatment of [2.2.2] bicyclic nitroso adducts 2c-d under similar reaction conditions generates only anti-1,2- and anti-1,4-hydroxamic acids with anti-1,4-product being predominant (up to 17:83).     

Synthesis of bis-3-alkyl-5-arylhydantoins and bis-3-alkyl-5-arylthiohydantoins separated by two and four carbon atoms

Synthesis of 1,2- and 1,4-bis-thiohydantoins and hydantoins employing ethylenediamine and 1,4-diaminobutane as spacers is described. Compounds containing a two carbon bridge were synthesized by alkylation of ethylenediamine with two equivalents of N-t-butyl-α-(p-toluenesulfonyloxy)phenylacetamide 3 . The phenyl isothiocyanate adduct of 3 cyclized in refluxing toluene to form 1a . Other isothiocyanate or isocyanate adducts derived from alkylation product 4 required hydrolysis to induce cyclization. Compounds 1b-1f were obtained in this way. Compounds with a four carbon bridge were obtained by reaction of two equivalents of methyl α-bromophenyl acetate and 1,4-diaminobutane to produce N,N'-bis-[(α-phenyl-α-methoxycarbonyl)methyl]butylenediamine 6 . The isothiocyanate or isocyanate adducts from 6 cyclized, without hydrolysis, to form compounds 2a-2e .     

Additive-controlled regioselective direct asymmetric aldol reaction of hydroxyacetone and aldehyde

A structurally simple dipeptide derivative 1b prepared from l-proline and l-valine has been developed for the direct asymmetric aldol reaction of hydroxyacetone and various aldehydes with moderate to high yields and high enantioselectivities. More importantly, this regioselective reaction could be easily regulated by changing the additives in the presence of the same organocatalyst 1b, to afford the normal 1,2-diol adducts and the disfavoured 1,4-diol products, respectively, in a highly regioselective fashion. A possible reaction mechanism has also been proposed.