Cycloaddition reactions of 1-lithio-1,3-dienes with aromatic nitriles affording multiply substituted pyridines, pyrroles, and linear butadienylimines

Fully or partially substituted 1-iodo- or 1-bromo-1,3-dienes could be readily lithiated using t-BuLi or n-BuLi to afford their corresponding 1-lithio-1,3-diene derivatives in quantitative yields. When these in situ generated lithium reagents were treated with organonitriles, depending on the substitution patterns of the butadienyl skeletons, substituted pyridines, pyrroles, and/or linear butadienyl imines were formed in good to excellent yields via N-lithioketimine intermediates. In the cases of 1,2,3,4-tetrasubstituted and 2,3-disubstituted 1-lithio-1,3-dienes, pyridine derivatives or linear butadienyl imines were generally formed depending on the reaction temperatures. When 1,2,3,4-tetrasubstituted 4-halo-1-lithio-1,3-dienes and 1,2-disubstituted 1-lithio-1,3-dienes were treated with organonitriles, pyrrole derivatives or linear butadienyl imines were obtained. Competition between 5-exo and 6-endo cyclization was found to be responsible for the formation of either pyrroles or pyridines. Selective elimination of RLi from the lithiated cyclic N-containing intermediates was observed. The order of elimination was found to be LiCl > Me3SiLi > LiH.     

Concise synthesis of stereodefined dienols and cyclopentadienes via direct addition of 1-bromomagnesiobutadienes and 1-lithiobutadienes to carbonyl compounds

Stereodefined all-cis substituted dienols could be readily prepared in excellent yields by the direct addition of 1-bromomagnesiobutadiene or 1-lithiobutadiene derivatives with aldehydes and ketones. Depending on the nature of substituents and workup procedures, multi-substituted cyclopentadienes could be also formed in high yields from these dienols. It is interesting to note that, unlike normal alkenyl magnesiumbromides, these conjugated butadienyl magnesiumbromide reagents do not react with ketones.     

Polylithiumorganic compounds. Part 29: C,C Bond cleavage of phenyl substituted and strained carbocycles using lithium metal

The reaction of phenyl substituted cyclopropanes phenylcyclopropane and 1,1-diphenylcyclopropane, phenyl substituted bicyclobutanes 1-phenylbicyclobutane, 1-methyl-3-phenylbicyclobutane, 1-methyl-2,2-diphenylbicyclobutane, as well as phenyl substituted spiropentanes phenylspiropentane and 1,1-diphenylspiropentane with lithium metal or lithium di-t-butylbiphenyl (LiDBB) was investigated. Under suitable reaction conditions and choice of solvent in all cases cleavage of the single bond next to the activating phenyl group was observed. The dilithiumorganic compounds thus obtained are sufficiently stable and can be trapped with electrophiles. Lithium hydride elimination is observed as follow-up reaction only in a few cases. The corresponding anions of the strained ring systems 1-lithio-2,2-diphenylcyclopropane, 1-lithio-3-phenylbicyclobutane, 1-lithio-3-methyl-2,2-diphenylbicyclobutane, and 1-lithio-4-phenylspiropentane, which can be obtained by lithium bromine exchange or by metalation of the unsubstituted carbocycle, do not show any cleavage upon reaction with lithium metal.     

Dearomatizing anionic cyclization and novel skeletal rearrangement: high yield formation of multiply substituted bicyclic or polycyclic spirocyclopentadienes and phenanthrene derivatives from 4-aryl 1-lithio-1,3-butadienes

Both 4-phenyl 1-lithio-1,3-butadienes and 4-naphthyl 1-lithio-1,3-butadienes underwent highly efficient and selective intramolecular nucleophilic addition of the butadienyllithium to the aromatic rings, resulting in full dearomatization of the phenyl rings and partial dearomatization of the naphthyl rings. When the reactions were carried out at lower temperatures, ipso intramolecular nucleophilic attack took place exclusively to afford the spirocyclopentadiene derivatives upon hydrolysis or further treatment with a variety of electrophiles. 4-Naphthyl 1-lithio-1,3-butadienes and 4-phenyl 1-lithio-1,3-butadienes were found to proceed in this reaction under similar conditions, with the former being faster even at -78 degrees C. However, when the reaction of 4-naphthyl 1-lithio-1,3-butadienes was carried out at higher temperatures, such as 75 degrees C, an interesting skeletal rearrangement took place to afford the vicinal attack products, tetrasubstituted phenanthrenes, via a dearomatization/rearomatization process. Mechanistic investigation revealed that the kinetically favored ipso attack intermediates might undergo thermal skeletal rearrangement via 1,2-alkyl shift.     

1-aza-1,3-enynes in synthesis of substituted 4H-[1,3]thiazino[3,2-a]benzimidazol-4-ols

Reaction of N-tert-butyl-1-aza-1,3-enynes with symmetrically substituted 2-mercaptobenzimidazoles in water-alcohol solutions afford 4H-[1,3]thiazino[3,2-a]benzimidazol-4-ols. The structure of compounds obtained was proved by the ¹H and ¹³C NMR spectroscopy and X-ray diffraction data.     

Some general characteristic properties of substituted cyclopentadienes

A number of substituted cyclopentadienes display characteristic properties which are representate of all members in the series: (a) the endocyclic double bond isomers are in the thermodynamic equilibrium; the process of establishing the equilibrium being retarded; (b) the transformation of isomeric cyclopentadienes proceeds by steps, i.e. a proton from the methylene group (5th position) passes mainly to the adjacent C-atom (1st position). The proton-cyclopentadienyl anions are probably transitional states in the transformation of isomers. It is assumed that this transformation is a first order reaction. As a result of this investigation it has been shown that the structure of the substituted cyclopentadiene (or the composition of the isomer mixtures) depends mainly on the character of the substituent and not on the method of synthesis.²     

Cycloaddition reactions of ketoimines. Part II. Synthesis of substituted phenanthridines and cyclopenta[c]quinolines

Substituted 4-benzoyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolines 3 and 6-benzoyl-5,6,6a,7,8,10a-hexahydrophenanthridines 10 are obtained through Lewis acid catalyzed addition of 1-phenyl-2-arylamino-2-methoxyethanones 2 to cyclopentadienes and 1,3-cyclohexadiene respectively. Compounds 3 can be converted to the aromatized analogues by reaction with 2,3-dichloro-5,6-dicyanobenzoquinone in refluxing benzene. Compounds 10 are oxidized by sulfur either in decalin or in quinoline to substituted 6-benzoylphenanthridines.     

Mass spectra of substituted uracils

The mechanisms for the major fragmentations obtained with selected substituted uracils are discussed. Interpretation of data was facilitated by use of metastable peaks, high-resolution data, and low-voltage spectra. The major fragmentation obtained with N-alkyl substituted uracils, when the alkyl group contains 2 or more carbons, is due to cleavage of the alkyl substituent. This cleavage is accompanied by a rearrangement of 1 or 2 hydrogens from the alkyl group to the uracil ring. Possible mechanisms for the rearrangements are discussed. It was found that the molecular ion of 1- and 3-alkyl substituted uracils (where the alkyl group has 2 or more carbons) does not undergo the expected ‘retro Diels-Alder Reaction’. Instead, the odd-electron ion formed by loss of the alkyl substituent with a single hydrogen rearrangement undergoes this reaction (loses HNCO). Since it is formed as a secondary reaction product, the relative abundance of the ‘retro Diels-Alder’ fragment is low compared to what is obtained in the spectra of the simple uracils. The ‘retro Diels-Alder Reaction’ can be used to differentiate between 2- and 4-thiouracils, and between 1- and 3-methyl and phenyl substituted uracils. It was found that 1- and 3-alkyl substituted uracils (alkyl group of 2 or more carbons) can be differentiated by the mass of the M-alkyl fragment since the 3-substituted compounds give predominantly a double hydrogen rearrangement and the 1-substituted compound gives mainly a single hydrogen rearrangement. In addition the intensity of the molecular ion, relative to the M-alkyl ion, is considerably stronger in the 1-substituted uracils.     

Synthesis and Structural Characterization of Butadienylcalcium-based Heavy Grignard Reagents and a Ca4[O] Inverse Crown Ether Complex

The structure elucidation of heavy Grignard reagents (RAeX, Ae=Ca, Sr, and Ba, X=halides) has been greatly strived after, mainly because of their inaccessibility and remarkable instability. The synthesis of a series of butadienylcalcium compounds is presented, including 1-calcio-4-lithio-1,3-butadiene, 1,4-dicalcio-1,3-butadiene, and a Ca₄[O] inverse crown ether complex, via the reaction between 1,4-dilithio-1,3-butadienes and calcium iodide in THF. Single-crystal X-ray analysis of these unprecedented heavy Grignard reagents revealed unique structural characteristics and bonding modes. Preliminary reaction chemistry was investigated. This study provides a novel class of alkenyl heavy Grignard reagents and a useful synthetic strategy for otherwise unavailable reactive organometallic compounds.     

Acyl-lithiation of olefins: formation of cyclopentenones from 1-lithio-butadienes and CO

[reaction: see text] Intramolecular acyl-lithiation of C=C double bonds proceeds following carbonylation of 1-lithio-1,3-dienes with CO to afford 2- or 3-cyclopentenone derivatives in good to excellent yields after hydrolysis. Addition of electrophiles to the carbonylation reaction mixtures affords various multiply substituted cyclopentenones.     

Synthesis of Some Novel S- and N,S-Substituted Chlorobutadienes

Abstract

Mono(thio)substituted nitrodienes were synthesized by reactions of 2-nitro-pentachloro-1,3-butadiene with some thiols [(tert-butylbenzyl)thio- and 2,3,5,6-tetra-fluorophenylthio-] either directly or in ethanol in the presence of sodium hydroxide. N,S-Substituted 1,3-butadienes were obtained from the reaction of the mono(thio)substituted nitrodienes with morpholine and some piperazine derivatives in dichloromethane. Also mono- and di(thio)substituted perchlorobutadienes were synthesized from the reactions of hexachloro-1,3-butadiene with o-aminothiophenol in ethanol in the presence of sodium hydroxide. The structures of the new compounds were characterized by microanalysis and spectroscopic data.     

Recyclization of 2-methoxy-5-morpholino-1,3-oxazole-4-carbonitrile by benzylamine, phenethylamine, and phenylhydrazine

Reaction of 2-methoxy-5-morpholino-1,3-oxazole-4-carbonitrile with benzylamine, phenethylamine and phenylhydrazine results in the new substituted 5-amino-2,3-dihydro-1H-imidazol-2-ones.     

N,N-dihalophosphoramides-XV: The addition of diethyl N,N-dichlorophosphoroamidate (DCPA) to conjugated 1,3-dienes

The addition of DCPA to several conjugated 1,3-dienes has been studied. The reaction was found to proceed in dichloromethane and was spontaneously or photolytically initiated depending on the structure of the dienes. N-chloro adducts, formed upon addition, could be reduced “in situ” with sodium sulphite solution to give the corresponding diethyl N-(chloroalkenyl)posphoroamidates. Addition of DCPA to terminal double bond 1,3-dienes (butadiene, isoprene and 2,3-dimethyl-1,3-butadiene) leads regiospecifically to (E)-1,4-adducts. Similarly, 1,4-addition is also observed for 1,3-cyclohexadiene. Reaction of DCPA with nonterminal double bond 1,3-dienes (trans-piperylene, 4-methyl-1,3-pentadiene, 2,5-dimethyl-2,4-hexadiene and 1,4-diphenyl-1,3-butadiene) usually affords a mixture of adducts. Spectral data and chemical transformations pertinent to the proof of structure of DCPA addition products are presented. A possible mechanism for the addition is discussed.     

(4+2)-cycloadditions of substituted arenediazocyanides: A kinetic study of a new dienophile

The rate constants of the (4+2)-cycloaddition reaction between substituted $\text{E}$-arenediazocyanides and 2,3-dimethyl-1,3-butadiene have been determined in several solvents. The reaction displays linear Hammett behavior; the data suggest a concerted reaction mechanism.     

Cleavage of C-Si bond by intramolecular nucleophilic attack: lithiation-promoted formation of siloles from 1-bromo-4-trisubstituted silyl-1,3-butadiene derivatives

Lithiation of 1-bromo-4-trisubstituted silyl-1,3-butadiene derivatives with t-BuLi afforded substituted siloles in high yields. Cleavage of one of the three C-Si bonds took place via intramolecular nucleophilic substitution. Selective cleavage was observed when the silyl group possessed different substituents. Results showed that vinyl and phenyl substituents on Si were substituted much more easily than methyl groups, whilst a methyl group was exclusively deleted from an i-Pr-SiMe₂ moiety.     

1,3-二甲基-5-芳基尿嘧啶的光化学合成

研究了1,3-二甲基-5-碘尿嘧啶与苯和取代苯的偶合反应, 用红外光谱, 核磁共振和质谱测定13个偶合物的结构, 并探讨了反应中取代基的电子效应和空间效应以及5-芳基尿嘧啶的质谱裂介规律, 发现反应可由三重态光敏剂加速.     

Photochemical reactions of substituted cyclobutadieneiron tricarbonyl complexes with acetylenes

When mixtures of monosubstituted cyclobutadieneiron tricarbonyl complexes and propyne are irradiated, substituted toluenes are obtained. The composition of the isomeric mixture is influenced by the nature of the substituent in the metal complex. Electron-withdrawing groups produce mixtures containing a very large percent of the ortho isomer while electron-releasing groups yield mixtures rich in the para isomer. Complex mixtures of isomeric benzene compounds are obtained when substituted acetylenes are allowed to react with methyl- or isopropylcyclobutadieneiron tricarbonyl.     

Synthesis and reactions of the first cyclopentadienyl isonitriles

6-Azidofulvenes without a further substituent in the exocyclic position were transformed into new 1-isocyano- and 2-isocyanocyclopenta-1,3-dienes by photolysis in methanol. These novel functionalized cyclopentadienes are useful building blocks, e.g. as dienes in Diels-Alder reactions.     

Macroexpansion methodology : Medium ring synthesis based on an eight unit ring expansion process

Treatment of 1,2-(E,E)-di(1-buta-1,3-dienyl)cyclohexanol (21) with potassium hydride in tetrahydrofuran at room temperature resulted in the facile formation of a 14-membered ring dienolate which on kinetic protonation provided cyclotetradeca-3,5,7-trien-1-one. This novel rearrangement which provides the basis for an efficient, eight unit ring expansion method was also observed when 5,8-dimethyl-5-hydroxy-1,3,7,9-decapentaene (28), the acyclic analogue of 21, was treated with potassium hydride in tetrahydrofuran. Methodology for the preparation of 21 and 28 including the preparation of 1-lithio-1,3-butadiene is also described.     

Synthesis of perfragilin A, B and some analogues

Synthesis of the cytotoxic isoquinoline quinone perfragilin A, an improved synthesis of perfragilin B and preparation of some analogues of both these compounds are described. Cytotoxicity evaluation of a number of the products is reported. The regioselectivity in Diels-Alder reactions of differently substituted benzoquinones with 2-aza-1,3-bis(t-butyldimethylsilyloxy)-1,3-butadiene is described.