A convenient synthesis of new heterocycles from benzimidazoles and carbon suboxide

The reaction of carbon suboxide with 2-substituted benzimidazoles was investigated. By this reaction 1,3-diazino- (pyrimido-), 1,3-oxazino- and 1,3-thiazinobenzimidazole-1,3-diones are obtained.     

Preparation of 1-silyl- and 1,3-disilyl-adamantanes

1-Dimethylsilyl- and 1,3-bis(dimethylsilyl)adamantane have been prepared in low yield by Wurtz reaction of dimethylchlorosilane with 1-chloroadamantane or 1,3-dichloroadamantane, respectively. On the other hand, reaction of phenyldimethylsilyllithium with 1-bromoadamantane or 1,3-dibromoadamantane gives essentially quantitative yields of 1-phenyldimethylsilyladamantane or 1,3-bis(phenyldimethylsilyl)adamantane, respectively.     

Regioselective synthesis of functionalized 3,5-diketoesters and 2,4-diketosulfones by uncatalyzed condensation of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadienes with alpha,beta-unsaturated acid chlorides and sulfonyl chlorides

The reaction of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadienes with alpha,beta-unsaturated and functionalized acid chlorides afforded a variety of 3,5-diketoesters which are not readily available by other methods. The reaction of 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene with sulfonyl chlorides allows a direct synthesis of 2,4-diketosulfones.     

Domino reaction of 1,3-bis(trimethylsilyloxy)-1,3-dienes with oxalyl chloride: general and stereoselective synthesis of gamma-alkylidenebutenolides

The Lewis acid catalyzed cyclization of oxalyl chloride with 1,3-bis(trimethylsilyloxy)-1,3-dienes 3, derived from 1,3-dicarbonyl compounds 1, provides a new and general approach for the synthesis of gamma-alkylidenebutenolides 4, a pharmacologically and synthetically important class of substances. A variety of butenolides were efficiently prepared in good yields and with very good regio- and stereoselectivities. An up-scaling of the reaction was possible. The use of the Lewis acid trimethylsilyl-trifluoromethanesulfonate (TMSOTf) proved to be superior to other activation conditions. Sterically undemanding gamma-alkylidenebutenolides could be prepared alternatively by reaction of the corresponding 1,3-dicarbonyl dianions with N,N'-dimethoxy-N,N'-dimethylethanediamide (2d). In contrast to the dianion method, the Lewis acid catalyzed reaction also facilitated the cyclization of sterically hindered, base-labile, cyclic and functionalized substrates. From a methodology viewpoint, the dianion reaction represents the first cyclization of a bis-Weinreb amide and the first cyclization of an oxalic acid-synthon with an ambident dianion. The TMSOTf-catalyzed reactions are both the first cyclizations of 1,3bis(trimethylsilyloxy)-1,3-dienes with a C2 dielectrophile and the first cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-dienes with a carboxylic acid dichloride or a related dielectrophile.     

Synthesis of 5-alkynyl-2,2,6-trimethyl-1,3-dioxin-4-ones and 1,4-disubstituted-1,2,3-triazoles

Herein we report an approach to the formation of 5-alkynyl-1,3-dioxin-4-ones using Suzuki-Miyaura cross-coupling reaction of potassium alkynyltrifluoroborate salts with 2,2,6-trimethyl-5-iodo-1,3-dioxin-4-one. The resulting 5-ethynyltrimethylsilyl-1,3-dioxin-4-ones obtained through the Sonogashira reaction were further reacted in a Cu(I)-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition to form functionalized 1,4-disubstituted-1,2,3-triazoles in good yields, using mild conditions and ultrasonic radiation to expedite the reaction.     

Palladium-catalyzed cyclization reactions of 2-vinylthiiranes with heterocumulenes. Regioselective and enantioselective formation of thiazolidine, oxathiolane, and dithiolane derivatives

The first palladium-catalyzed ring-expansion reaction of 2-vinylthiiranes with heterocumulenes to form sulfur-containing five-membered-ring heterocycles is described. This regioselective reaction requires 5 mol % of Pd(2)(dba)(3).CHCl(3) and 10 mol % of bidendate phosphine ligand (dppp, BINAP), at 50-80 degrees C, in THF. The reaction of 2-vinylthiiranes with carbodiimides, isocyanates, and ketenimines affords 1,3-thiazolidine derivatives, whereas the reaction with diphenylketene or isothiocyanates results in the formation of 1,3-oxathiolane or 1,3-dithiolane compounds in good to excellent isolated yields and in up to 78% ee.     

Synthesis of 2-phenylethynyl-1,3-dioxanes and their hydrolysis

2-Phenylethynyl substituted 1,3-dioxanes were obtained by the reaction of 1,3-dioxanium salts with an lotsich reagent. It was shown that they are readily hydrolyzed with the formation of a-acerylenic ketones. A simple new method is proposed for the synthesis of the latter without isolating the intermediate 1,3-dioxanes using the reaction of 4 substituted 2-methyl(phenyl, furyl)-1,3-dioxanium salts with hydroxymethyl- and phenylethynylmagnesium bromide as examples.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 193–197, February, 1996.     

Self-condensation of β-(isoxazol-5-yl) enamines under treatment with acetyl chloride and acids. Synthesis of novel 1,3-diisoxazolyl-1,3-dieneamines and 1,3,5-triisoxazolyl benzenes

Two directions for self-condensation of β-(isoxazol-5-yl) enamines under treatment with either acetyl chloride or acids were found leading to new 1,3-diisoxazolyl-1,3-dieneamines and 1,3,5-triisoxazolyl benzenes. The effect of solvent, acid, temperature and the reaction time on the ratio of reaction products were investigated. Trans-E-cis configuration of prepared 1,3-diisoxazolyl-1,3-dieneamines was unambiguously confirmed by 2D NMR spectra and X-ray analysis. A new mechanism of 1,3-diisoxazolyl-1,3-dieneamines formation was proposed.     

Condensation of aldehydes and ketones

The Mannich reaction with methylene- and benzylidenediacetophenones has given: 1,3-dibenzoyl-4-piperidinobutane, 1,3-dibenzoyl-4-morpholinobutane, 1,3-dibenzoyl-4-diethylamino-2-phenylbutane, 1,3-dibenzoyl-2-phenyl-4-piperidinobutane, 1,3-dibenzoyl-4-diethylaminobutane, and 1,3-dibenzoyl-4-dimethylamino-2-phenylbutane. From the latter two compounds, 3-diethylaminomethyl-2,6-diphenylpyridine and 3-dimethylaminomethyl-2,4,6-triphenylpyridine have been obtained.For part XVII, see [7].     

Preparation and radical ring-opening polymerization of 2-substituted-4-methylene-1,3-dioxolanes

2-Methyl-2-phenyl-4-methylene-1,3-dioxolane ( IIa ), 2-ethyl-2-phenyl-4-methylene-1,3-dioxolane ( IIb ), 2-phenyl-2-(n-propyl)-4-methylene-1,3-dioxolane ( IIc ), 2-phenyl-2-(i-propyl)-4-methylene-1,3-dioxolane ( IId ), 2-(n-heptyl)-2-phenyl-4-methylene-1,3-dioxolane ( IIe ), 2-methyl-2-(2-naphthyl)-4-methylene-1,3-dioxolane ( IIf ), and 2,2-diphenyl-4-methylene-1,3-dioxolane ( IIg ) were prepared and polymerized in the presence of a radical initiator. IIa–IIf were found to undergo vinyl polymerization with ring-opening reaction accompanying the elimination of ketone groups in bulk. IIg was found to undergo the quantitative ring-opening reaction accompanying the elimination of benzophenone in solution to obtain polyketone without any side reaction.     

硅烷基取代苯并二硫杂环戊烯的合成及电化学性质

以苯并-1,3-二硫杂环戊烯为原料,通过金属化反应以及锂化二硫杂环戊烯与氯代硅烷反应合成了系列2-硅烷基取代苯并-1,3-二硫杂环戊烯化合物.测定了化合物的氧化电位,发现硅的引入导致苯并-1,3-二硫杂环戊烯的氧化电位明显降低,给体的给电子能力增强.     

Reductive cleavage of ether and thioether bonds on 1,3-benzodioxole and 1,3-benzoxathiole derivatives

The reaction of lithium and sodium diethylamide with 1,3-benzodioxoles and 1,3-benzoxathioles is here reported. 1,3-Benzodioxoles exhibit selective cleavage of the ether bond with formation of alkoxyphenols; 1,3-benzoxathioles when reacting with sodium diethylamide lead to 2-alkoxybenzenethiols while with lithium diethylamide give 2-alkoxybenzenethiols together with 2-(alkylthio)phenols.     

Synthesis and reactivity of allenes substituted by selenenyl groups at 1- and 3-positions

1,3-Bis(methylseleno)- and 1,3-bis(benzylseleno)-1,3-diphenylpropadienes were synthesized by reaction of Ph(2)C(3) dianion, prepared from 1,3-diphenylpropyne and n-butyllithium, with dimethyl diselenide or benzylselenocyanate in the presence of TMEDA, and reaction of the dianion with a mixture of dimethyl diselenide and benzylselenocyanate yielded 1-benzylseleno-3-methylselenoallene along with the symmetric allenes. Diselenocyclic allenes and tetraselenocyclic bisallenes were also obtained by reacting the dianion with corresponding alkane diselenocyanates. The thermal reaction of the 1,3-bis(alkylseleno)allenes mainly afforded enediynes through radical pathway, and the nine-membered cyclic allene provided intramolecular cyclization product via an intramolecular rearrangement. Heating of the cyclic bisallenes gave compounds derived from intramolecular cyclization products together with a small amount of the enediynes. Irradiation of allenes caused rearrangement of the selenenyl group to give alkynes, and the alkynes also reacted photochemically to yield the enediynes.     

Syntheses of 1,3-Imidazoline-2-thione and 2-Phenylimino-1,3-thiazoline combinatorial libraries through different sequences of the same components

We have developed combinatorial libraries of new 1,3-imidazoline-2-thiones 5 and 2-phenylimino-1,3-thiazolines 7 by way of different reaction sequences of the same three components, gamma-chloroacetoacetanilides 1, amines 2, and isothiocyanates 3 in a parallel synthetic fashion. One of the building blocks, the gamma-chloroacetoacetanilides 1, was prepared by the sequential reaction of 4-methylene-oxetan-2-one (ketene dimer) with chlorine and various anilines. The condensation of 1 with amines gave dihydrofuran 4 intermediates that when reacted with 3 afforded the 1,3-imidazoline-2-thiones 5. On the other hand, reaction of 3 with 2 provided substituted thioureas 6 that were reacted with 1 to yield 2-phenylimino-1,3-thiazolines 7.     

N-thioacyl 1,3-amino alcohols: synthesis via ring-opening of oxiranes with thioamide dianions and applications as key intermediates leading to stereochemically defined 5,6-dihydro-4H-1,3-oxazines and 1,3-amino alcohols

N-Thioacyl 1,3-amino alcohols were synthesized via the ring-opening of oxiranes with thioamide dianions generated from N-benzyl thioamides and BuLi in a highly regio- and stereoselective manner. The diastereomers of N-thioacyl 1,3-amino alcohols were readily separated by column chromatography to give stereochemically defined N-thioacyl 1,3-amino alcohols. They underwent intramolecular cyclization with Bu4F and EtI to give 5,6-dihydro-4H-1,3-oxazines. The reaction was specific with anti-N-thioacyl 1,3-amino alcohols, and cis-5,6-dihydro-4H-1,3-oxazines were obtained with high efficiency, whereas the reaction of a syn-alcohol gave a thioimidate as a major product. The reduction of N-thioacyl 1,3-amino alcohols with LiAlH4gave N-alkyl 1,3-amino alcohols in high yields. The use of optically active propylene oxide as a starting material gave the corresponding oxazine and alcohols in optically pure forms.     

Reaction of C3 and C4 ketoses with alkenals and alkenones in water

Treatment of 1,3-dihydroxyacetone and acrolein with aqueous KOH gave a tetrahydrofuran derivative, 1,4-dihydroxy-3,7-dioxabicyclo[3.3.0]octane, in 80% yield. Similarly, 6-alkyl substituted 1,4-dihydroxy-3,7-dioxabicyclo[3.3.0]octanes were obtained by reaction of 1,3-dihydroxyacetone with various α,β-unsaturated aldehydes. In the cases of long chain alkenals, the reaction was effectively accelerated in the presence of organic co-solvent. On the other hand, the corresponding tricyclic products were synthesized by reaction of 1,3-dihydroxyacetone with cyclic enones, such as 2-cyclopentenone and 2-cyclohexenone. This method was successfully applied to the reaction of a tetrulose in the absence of any protecting groups.     

Nickel-catalyzed addition of C-H bonds of terminal alkynes to 1,3-dienes and styrenes

The C-H bond of a terminal alkyne adds to a carbon-carbon double bond of 1,3-dienes, styrenes, and norbornene at room temperature in the presence of a nickel catalyst in regio- and stereoselective manners. Reaction of triisopropylsilylacetylene with 1-substituted 1,3-butadiene derivatives afforded hydroalkynylation products via introduction of a hydrogen atom and a triisopropylsilylethynyl group to 4- and 3-positions of the dienes, respectively. Likewise, 1-triisopropylsiloxy-1,3-butadiene, 1,3-pentadiene, 1-cyclohexen-1-yl-1,3-butadiene, and 1,3-cyclohexadiene underwent the hydroalkynylation reaction, giving the corresponding 1,4-enyne derivatives in good yields at room temperature. Reaction of p-substituted styrene with triisopropylsilylacetylene also proceeded in the presence of the nickel catalyst, giving the branched hydroalkynylation products in good yields. Norbornene gave a exo-addition product in good yield under the same reaction conditions.     

Preparation and properties of copolymer resin based on polybenzimidazole and bisoxazoline

Reaction between the NH groups in polybenzimidazole (PBI) and bisoxazoline compounds (1,3‐phenylene bisoxazoline, 1,3‐PBO) resulted in the successful preparation of novel network polymers. Adjusting the amount of the bisoxazoline compound, which is a cross‐linking agent for the preparation of network polymers, and obtaining dynamic mechanical measurements, electrical resistivity measurements, thermomechanical measurements, and tensile tests allowed the determination of the heat resistance and mechanical strength of these novel network polymers. Examination of the elementary reaction of PBI and the1,3‐PBO curing reaction by using model compounds revealed that the NH group in the PBI structure reacted with the oxazoline group of 1,3‐PBO. Comparison of noncross‐linked PBI with the PBI network polymers obtained through cross‐linking reaction with bisoxazoline compounds demonstrated improvements in heat resistance and mechanical strength of the PBI‐bisoxazoline network polymers.     

Condensation of Indoline with Some 1,2‐ and 1,3‐Diketones

Bismuth nitrate catalyzed condensation reactions of indoline with 1,2‐ and 1,3‐diketones were investigated and were reported to proceed via different reaction pathways with the involvement of one or two of the carbonyl groups. While the reaction of indoline with cyclohexane‐1,3‐dione ( 4 ) gave solely condensation product, the reaction between the acetylacetone ( 5 ) and indoline provided N‐acetyl indoline as single products on retro‐aldol process. In contrast to 1,3‐diketones, the reaction with benzil ( 17 ) was performed under difficult conditions and proceeded to give secondary products.     

Inter- and intramolecular differentiation of enantiotopic dioxane acetals through oxazaborolidinone-mediated enantioselective ring-cleavage reaction: kinetic resolution of racemic 1,3-alkanediols and asymmetric desymmetrization of meso-1,3-polyols

Acetals derived from racemic 1,3-alkanediols undergo kinetic resolution in chiral oxazaborolidinone-mediated ring-cleavage reaction with nucleophiles such as enol silanes and allylic silanes. Enantioselectivity of the reaction is affected by nucleophiles, the N-sulfonyl groups of oxazaborolidinones, and the substituents attached to the acetal carbon. For disubstituted acetals rac-1 and for trisubstituted acetal rac-2, derived from syn-2,4-dimethyl-1,3-pentanediol, satisfactory enantioselectivity is obtained by using methallylsilane 7b,c as a nucleophile in combination with N-mesyloxazaborolidinone 4a. On the other hand, enantioselective reaction of trisubstituted acetal rac-3b, derived from anti-2,4-dimethyl-1,3-pentanediol, is realized by using silyl ketene acetal 5e in combination with N-tosyloxazaborolidinone 4b. The reaction conditions optimized for the kinetic resolution, or enantiomer differentiating reaction, of the racemic acetals are successfully applied to asymmetric desymmetrization of meso-1,3-polyols through intramolecular differentiation of the enantiotopic acetal moieties of the bis-acetal derivatives. The utility of the ring-cleavage reaction as a method for enantioselective terminal differentiation of prochiral polyols is demonstrated in convergent asymmetric synthesis of pentol derivative 35 corresponding to the C(19)[bond]C(27) ansa-chain of rifamycin S.