Formation of pyrrolidines by the titanocene(II)-promoted intramolecular reaction of N-[3,3-bis(phenylthio)propyl]anilides

The reaction of anilides with the titanium carbene complexes generated by the desulfurization of thioacetals with the titanocene(II) species Cp₂Ti[P(OEt)₃]₂ produced the corresponding enamines. Unusual formation of pyrrolidines was observed when N-[3,3-bis(phenylthio)propyl]anilides were treated with the titanocene(II) reagent.     

Titanium carbene complexes as useful tools in organic synthesis

Various titanium carbene complexes are prepared by the reductive titanation of thioacetals, gem-dihalides, and related organosulfur and organohalogen compounds with the titanocene(II) reagent Cp(2)Ti[P(OEt)(3)](2). Alkylidene-, heteroatom-substituted methylidene-, 2-alkenylidene-, 2-alkynylidene-, and vinylidene-titanocenes thus formed are highly reactive toward organic compounds bearing a multiple bond and are employed for a variety of organic transformations such as carbonyl olefination and olefin metathesis.     

Titanium reagents for the synthesis of 2-substituted benzo[b]thiophenes on the solid phase

Titanium(IV) benzylidenes (Schrock carbenes) bearing a masked sulfur nucleophile in the ortho position were generated from thioacetals with use of low-valent titanocene complex Cp(2)Ti[P(OEt)(3)](2) and alkylidenated Merrifield resin-bound esters to give enol ethers. Treatment of the resin-bound enol ethers with a 5:5:90 mixture of TFA, TFAA, and dichloromethane led to cleavage from resin, removal of the tert-butyldimethylsilyl (TBDMS) protecting group, and concomitant cyclization to complete the traceless solid-phase synthesis (SPS) of benzothiophenes. Switching the nature of the linker from acid-stable to acid-sensitive ensured good purity.     

Titanocene(II)-promoted reductive alkylation of anilides with thioacetals

Titanocene(II)-promoted reaction of anilides with thioacetals followed by treatment with a small amount of water gave reductive alkylation products, anilines with a secondary alkyl group.     

Bis(η-cyclopentadienyl)titanium(II) in the gas phase:: Mass spectrometric and computational study of the structure and reactivity

Bis(η⁵-cyclopentadienyl)titanium(II), titanocene, was generated in the gas phase by a thermolysis of the titanocene complex with bis(trimethylsilyl)acetylene. This elusive compound was characterized by means of mass spectrometric methods. Density functional theory (DFT) calculations indicated that the triplet ground state titanocene is kinetically stable towards the unimolecular isomerizations. Based on a DFT calculated energetics, a mechanism of the formation of a titanocene dimer, was proposed, which was based on a formation of bis(η⁵-cyclopentadienyl)titanium hydride as a key intermediate.     

Titanocene(II)-promoted stereoselective alkenylation utilizing (Z)-alkenyl sulfones

The stereoselective alkenylation of unsaturated compounds by means of a (Z)-alkenyl sulfone-titanocene(II) system is described. Treatment of alkynes and (Z)-alkenyl methyl sulfones with the titanocene(II) reagent Cp2Ti[P(OEt)3]2 produced conjugated dienes. This alkenylation system is also applicable to polar C=O bonds; the simple mixing of carbonyl compounds, (Z)-alkenyl methyl sulfones, and the titanocene(II) reagent formed allylic alcohols. The advantages of alkenylation are that it requires no prepreparation of the alkenylmetal reagent and that it proceeds with complete stereoselectivity.     

Titanocene(II)-promoted carbonyl cyclopropylidenation utilizing 1,1-dichlorocyclopropanes

A variety of alkylidenecyclopropanes bearing various substituents on their cyclopropane ring were obtained by the titanocene(II)-promoted reaction of 1,1-dichlorocyclopropane derivatives with carbonyl compounds including esters and lactones.     

Synthesis of 2-substituted benzofurans and indoles using functionalized titanium benzylidene reagents on solid phase

Titanium(IV) benzylidenes bearing a masked oxygen or nitrogen nucleophile in the ortho position were generated from thioacetals, using low-valent titanocene complex, Cp2Ti[P(OEt)3]2. Methylene acetal, alkyl ether, silyl ether, fluoro, tertiary amino, and N-alkyl, N-benzyl, N-prenyl, and N-silyl tert-butyl carbamate groups were tolerated in the titanium alkylidene reagents (Schrock carbenes). Aryl-chlorine bonds were stable to the titanium benzylidene functionality, but there was poor chemoselectivity for the reduction of the thioacetal in the presence of an aryl chloride. The titanium benzylidenes converted Merrifield and Wang resin-bound esters into enol ethers. The oxygen nucleophile was masked as a TMS ether, and when the resin-bound enol ethers bearing this ortho substituent were treated with 1% TFA in dichloromethane, benzofurans were released from resin in high yields. The chameleon catch strategy ensured excellent purity. In a similar way, N-alkylated and N-silylated tert-butyl carbamates were used for the synthesis of N-alkyl and N-Boc indoles, respectively. These traceless solid-phase syntheses of heterocycles are believed to involve postcleavage modification rather than cyclative termination.     

A Novel One-Pot Synthesis of Polyfunctionally Substituted Thiopyrano(2,3- b )pyridine and Pyrido(2,3- b )pyridine Derivatives under Solid-Liquid Phase-Transfer Catalysis

Ketoketene thioacetals or cyanoketene thioacetals which were formed by treatment of a variety of active methylenes containing f -keto or f -cyano group with CS 2 or with PhNCS were allowed to react with 2-aminoprop-1-ene-1,1,3-tricarbonitrile under PTC conditions to afford thiopyrano(2,3- b )pyridine 3a-12a or pyrido(2,3- b )pyridine 3b-12b derivatives.     

Preparation of enol ethers by carbonyl olefination utilizing an alkoxymethyl chloride-titanocene(II) system

Aldehydes, ketones, esters and lactones are transformed into enol ethers or 1,2-dialkoxy-1-alkenes by treatment with organotitanium species prepared from alkoxymethyl chlorides and a titanocene(II) complex.     

Carbonyl olefination utilizing an alkyl halide-titanocene(II) system

Ketones, aldehydes, esters and lactones are transformed into olefins by treatment with the organotitanium species formed from alkyl halides and titanocene(II).     

Highly diastereoselective addition of allyltitanocenes to α-chiral ketones

The addition of allyltitanium reagents, generated by the desulfurizative titanation of allylic sulfides with the titanocene(II) reagent Cp₂Ti−1-butene, to α-chiral ketones produced tertiary homoallylic alcohols bearing three adjacent chiral centers with high diastereoselectivity.     

Titanocene(II)-promoted multicomponent reactions utilizing alkynyl sulfones, alkenyl sulfones, and carbonyl compounds: a novel method for the synthesis of vinylallenes

Titanocene(II)-promoted cross coupling of alkynyl- and (Z)-alkenyl sulfones affords alpha-(phenylsulfonyl)alkenyltitanium species. Further treatment of these species with the titanocene(II) reagent generates titanium vinylvinylidene complexes, which react with carbonyl compounds in one pot to produce substituted vinylallenes with complete stereoselectivity. By using alpha,beta-unsaturated ketones, 1,3,4,6-tetraenes are also obtained stereoselectively.     

Bis(cyclopentadienyl)titanium complexes of naphthalene-1,8-dithiolates, biphenyl 2,2'-dithiolates, and related ligands

Titanocene 1,8-dithiolato-naphthalene and titanocene 2,2'-dithiolato biphenyl are produced by the reaction of naphtho[1,8-cd]-1,2-dithiole [or the biphenyl] with titanocene dicarbonyl (Ti(II)) in toluene at room temperature. The pro-ligands 2,7-di(tert-butyl)naphtho[1,8-cd]-1,2-dithiole, 5,6-dihydroacenaphtho[5,6-cd]-1,2-dithiole, 4,5-dithioacephenanthrylene, and 13,14-dithiapicene have been used in similar reactions with titanocene dicarbonyl to investigate the effect of steric bulk and of varying the naphthalene backbone on the final complex. The resulting Cp(2)TiS(2)Ar complexes (Ar = naphthalene) have been shown by temperature-dependent (1)H NMR spectroscopy to exist in solution in an envelope conformation with the six-membered TiS(2)C(3) rings undergoing inversion on the NMR time scale while the similar Cp(2)TiS(2)Ar complexes (Ar = biphenyl, binaphthalene) interconvert more rapidly. Titanocene 2,2'-disulfinato biphenyl has been synthesized by the salt elimination reaction of titanocene dichloride (Ti(IV)) and the disodium salt of biphenyl 2,2'-disulfinic acid. Finally, the effect of using pro-ligands where the sulfur atoms have been mono- or di-oxidized has been studied, and an interesting oxygen elimination reaction is observed for the S=O fragments but not for the SO(2) groups. All complexes have been characterized spectroscopically and seven X-ray structures are reported.     

Formation of conjugated dienes by the reaction of titanocene alkenylidene complexes with alkynes

Titanocene alkenylidene complexes, generated by the reductive metallation of 1,1-dichloro-1-alkenes with the titanocene(II) species Cp₂Ti[P(OEt)₃]₂, reacted with alkynes to produce conjugated dienes.     

Preparation of silyl polyenol ethers by carbonyl olefination of silyl esters

Silyl enol ethers were produced by the carbonyl olefination of silyl esters with titanium carbene complexes generated by the desulfurizative titanation of thioacetals. The regioselective preparation of silyl dienol and trienol ethers has been achieved by using unsaturated silyl esters and thioacetals.     

Studies dealing with thionium ion promoted mannich cyclization reactions

Treatment of several amido-substituted thioacetals with dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) produces synthetically useful thionium ions that are intercepted by the adjacent nitrogen atom to afford both five- and six-membered alkylthio-substituted lactams as transient intermediates. Further reaction of the alkylthio-substituted lactam with DMTSF generates an N-acyliminium ion, which undergoes cyclization with the tethered aromatic ring to produce an azapolycyclic ring system. Related cyclization sequences occur when amido thioacetals possessing simple olefinic tethers were used. The overall procedure represents an efficient one-pot approach toward various nitrogen-containing ring systems. The cyclization reaction was employed for a synthesis of the core skeleton of the erythrina alkaloid family.     

Influence of Iodine on Reactivity of Phosphorus Sulfides and Homologues of Davy's Reagent in Organic Reactions

Abstract

The use of iodine results in reactivity enhancement of phosphorus sulfides and homologues of Davy's reagent in the reactions with disulfides, aminals and thioacetals. The reactions β-diiodotetraphosphorus trisulfides with disulfides, aminals and thioacetals were studied.     

Regio- and stereoselective preparation of highly substituted tertiary homoallylic alcohols

The titanocene(II)-promoted reaction of α-(benzyldimethylsilyl)allylic sulfides with ketones proceeded with high regio- and stereoselectivity to give δ-silylhomoallylic alcohols. The following palladium catalyzed cross-couplings with organic halides produced anti-(E)-β,δ-disubstituted tertiary homoallylic alcohols with complete retention of configuration.     

二茂钛全氟有机酸衍生物的合成和抑瘤试验

本文报道了一类新的二茂钛全氟有机酸衍生物的合成,并发现其中1,2,3三个二茂钛全氟二元酸衍生物,对小鼠艾氏腹水癌有明显的抗癌活性。