On the paradox of TiCl4 reducing power: pinacol coupling and two-carbon homologation of carbonyl compounds

TiCl₄/DIPEA/CH₂Cl₂ reducing system promotes pinacol coupling and/or reduction to alcohol of aromatic aldehydes and carbonyl compounds activated towards reduction by an electron withdrawing group. In addition, bis homologation of these substrates is observed. An inner-sphere electron transfer from TiCl₄ to DIPEA accounts for the products distribution.     

Highly efficient and chemoselective direct aldol reaction of acyldiazomethane with aldehydes promoted by MgI2 etherate

College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310032, China MgI₂(Et₂O)_n promoted aldol condensation of various aldehydes with acyldiazomethane was described in the presence of DIPEA in good to excellent yields under mild conditions with high chemoselectivity.     

Stereochemistry of products of aldol condensation of 2-(3-oxo-1,3-diphenylpropyl)cyclohexanone with aromatic aldehydes

The aldol condensation of various aromatic aldehydes with 2-(3-oxo-1,3-diphenylpropyl)cyclohexanone in CH₂Cl₂ in the presence of TiCl₄-Et₃N at 0°C afforded perhydrochromens with two equatorial and one axial substituents whereas the aldol reaction under base catalysis gave perhydrochromens with equatorial substituents.     

On the selective reduction of the distal olefin in geraniol and farnesol derivatives

The selective reduction of the distal olefin of many types of terpenoid-based natural products has been commonly approached using gaseous HCl in CH₂Cl₂. We herein present evidence that this method is inefficient and produces many side products, whose formation, in our hands, was difficult to avoid (over several reaction runs). A more efficient procedure for geranyl acetate using 1 equiv. of TiCl₄ in CH₂Cl₂ at −78°C is reported.     

The intramolecular tandem Michael/Mannich-type reaction of α,β-unsaturated carbonyl compounds with acyliminium ions provides access to chiral indolizidines

The intramolecular tandem Michael/Mannich-type (Michael addition/halo-Mannich-type) reaction using TiCl₄/n-Bu₄NI system between the α,β-unsaturated carbonyl compounds possessing an Evans oxazolidinone as a chiral auxiliary and N-acyliminium ion intermediates is described. The reaction was promoted in a mixed solvent of AcOEt–CH₂Cl₂ to afford indolizidine compounds with three stereogenic centers.     

Cationic polymerization of isobutylene with H2O/TiCl4 initiating system in the presence of electron pair donors

Cationic polymerization of isobutylene (IB) in a mixture of methylene dichloride (CH₂Cl₂) and n-hexane (n-Hex) was conducted by using H₂O as initiator, TiCl₄ as co-initiator in the presence of strong external electron pair donor (ED), such as pyridine (Py), dimethylacetamide (DMA) or triethylamine (TEA). The effects of ED concentration, TiCl₄ concentration, solvent polarity, polymerization temperature (T) and time on IB polymerization, molecular weight (MW) and molecular weight distribution (MWD, M_w/M_n) of polyisobutylene (PIB) products were investigated. The relative amount of polymer formed via uncontrolled initiation by conventional active species (I) decreased with increasing the solvent polarity, TiCl₄ concentration and ED concentration in the polymerization. The desirable polymerization of IB with apparent absence of chain transfer reactions could be obtained by H₂O/TiCl₄ initiating system in the presence of ED under the appropriate reaction conditions. The external electron pair donors and TiCl₄ did specially play important and effective roles on polymerization.     

Versatile One‐Step One‐Pot Direct Aldol Condensation Promoted by MgI2

A true one‐step one‐pot aldol‐reaction procedure has been developed for the synthesis of β‐hydroxy ketones and esters. The reaction can be run at room temperature by simply mixing four components in CH₂Cl₂, with medium‐to‐high yields of aldol products obtained after regular workup. Mechanistically, the process probably proceeds via Mg‐enolate formation of the ketone or ester component, followed by addition to the electrophilic aldehyde.     

Synthese,Eigenschaften und Kristallstruktur des cis-Dichloro-bis(diethyldithiophosphinato)titan(IV)

Synthesis, Properties, and Crystal Structure of cis-Dichloro-bis(diethyldithiophosphinato)-titanium(IV) By reaction of TiCl₄ with dialkyldithiophosphinic acids R₂P(S)SH (R ? CH₃, C₂H₅) red chelates (R₂PS₂)₂TiCl₂ are obtained which are very sensitive to hydrolysis. Crystal structure analysis of the ethyl compound shows a distorted octahedral chromophor TiS₄Cl₂ with cis-configuration.     

Synthesis and structure of a chiral areno-bridged [2.4]metacyclophane

The reductive coupling reaction of 1,4-bis(3-acetyl-5-tert-butyl-2-methoxyphenyl)butane 3 was carried out using TiCl₄-Zn in pyridine followed by a McMurry coupling reaction to afford the compounds anti and syn 1,2-dimethyl[2.4]MCP-1-ene 4. Bromination of 4 with BTMA-Br₃ in dry CH₂Cl₂ afforded the interesting compound 1,2-bis-(bromomethyl)-5,15-di-tert-butyl-8,18-dimethoxy[2.4]MCP-1-ene 6 and consecutive debromination with Zn and AcOH in CH₂Cl₂ solution afforded the stable solid 5,15-di-tert-butyl-8,18-dimethoxy-1,2-dimethylene[2.4]MCP 7 in 89% yield. Compound 7 was conveniently employed in a Diels–Alder reaction with dimethyl acetylenedicarboxylate (DMAD) to provide 2-(3′,6′-dihydrobenzo)-5,15-di-tert-butyl-8,18-dimethoxy[2.4]MCP-4′,5′-dimethylcarboxylate 8 in good yield. Diels–Alder adduct 8 was converted into a novel and inherently chiral areno-bridged compound [2.4]MCP 9 by aromatization. The chirality of the two conformers was characterized by circular dichroism (CD) spectra of the separated enantiomer which are perfect mirror images of each other.     

First total synthesis of salinipyrone A using highly stereoselective vinylogous Mukaiyama aldol reaction

A synthetic approach for the total synthesis of salinipyrone A has been developed. Key steps involve the TiCl₄-mediated vinylogous Mukaiyama aldol reaction (VMAR) of chiral ketene silyl N,O-acetal with propionaldyhyde, an aldol condensation, Witting olefination, and a cyclization. The synthesis proceeds in eight steps.     

1,4-syn-Asymmetric induction in the titanium-mediated aldol reactions of chiral methyl α-silyloxy ketones

Good levels of 1,4-syn asymmetric induction are obtained in the TiCl₄-mediated aldol reaction of methyl α-silyloxy ketones with achiral aldehydes. Such methodology represents a new approach to the substrate-controlled acetate aldol reaction, which can be useful to design more efficient syntheses of natural products.     

A New Synthesis of 2-(6-Methoxycarbonylhexyl)-Cyclopent-2-EN-1-One Using α-Silylallyl Sulphide

Acylation of the α-trimethylsilylallyl phenyl sulphide (2). by reaction with the acid chloride (3), catalyzed by aluminium chloride in CH₂Cl₂ at ?78°C, gave methyl 9-oxo-12-phenylthio-11-dodecene (4). Hydrolysis of (4) followed by aldol condensation gave 2-(6-methoxycarbonylhexyl)-cyclopent-2-en-1-one (6).     

Rate enhancement by water in a TiCl4-mediated stereoselective vinylogous Mukaiyama aldol reaction

A remarkable enhancement in the rate of a TiCl₄-mediated stereoselective vinylogous Mukaiyama aldol reaction (VMAR) using vinylketene silyl N,O-acetal 1 was observed in the presence of water.     

Titanium(IV)-mediated synthesis of 2,3-diisothiocyanato-succinic acid diesters and 3,6-dithioxo-piperazine derivatives

Oxidative homocoupling of titanium(IV) enolates of 2-isothiocyanato-carboxylic esters resulted in the synthesis of 2,3-diisothiocyanato-succinic acid diesters. The reactions were carried out using DIPEA/TiCl₄ oxidizing system and led to chiral dimers (instead of meso) as main products. Titanium(IV) enolates derived from hindered 2-isothiocyanato-carboxylates did not undergo the oxidative homocoupling but gave 3,6-dithioxo-piperazines.     

1,4-Asymmetric induction in the titanium-mediated aldol reactions of α-benzyloxy methyl ketones

Good levels of 1,4-anti asymmetric induction are obtained in the TiCl₃(i-PrO)-mediated aldol reaction of α-benzyloxy methyl ketones with achiral aldehydes. Such methodology represents a new approach to the substrate-controlled acetate aldol reaction, which can be useful to design more efficient synthesis.     

Synthesis of palladium-bidentate complex and its application in Sonogashira and Suzuki coupling reactions

A new palladium-bidentate complex [m-C₆H₄(CH₂ImMe)₂(PdCl₂)] (III) was prepared in two steps. In the first step, [m-C₆H₄(CH₂ImMeAgCl)₂] (II) (Im = imidazole moiety) was obtained by reacting imidazolium salt [m-C₆H₄(CH₂ImMe)₂]Cl₂ (I) (prepared by quaternisation of Nmethylimidazole with 1,3-bis(chloromethyl)benzene) and Ag₂O in CH₂Cl₂. In the next step, treatment of (II) with Pd(CH₃CN)₂Cl₂ afforded complex III which was evaluated for its catalytic activity for C-C bond-formation reactions by examining the coupling reaction of 3-iodoanisole with phenylacetylene in the Sonogashira reaction. In addition, 3-methoxybiphenyls were obtained with good to excellent yields by Suzuki coupling reactions of 3-iodoanisole with phenylboronic acids or phenylborates salts in the presence of this complex.     

DIRECT FORMYLATION OF 9,9′-SPIROBIFLUORENE: 2-CARBOXALDEHYDE-9,9′-SPIROBIFLUORENE AND 2,2′-DICARBOXALDEHYDE-9,9′-SPIROBIFLUORENE

The one-step formylations, using CH₃OCHCl₂/TiCl₄ in CH₂Cl₂, of 9,9′-spirobifluorene to obtain 2-carboxaldehyde-9,9′-spirobifluorene and 2,2′-dicarboxaldehyde-9,9′-spirobifluorene in moderate to good yields are described. Previous works dealt with four-steps synthesis.     

Titanium mediated asymmetric aldol reaction with α-fluoropropionimide enolates

Aldol reaction utilising Evans N-(α-fluoropropyl)-2-oxazolidinones with TiCl₄ have been explored. Reactions of N-(α-fluoropropyl)-2-oxazolidinones with aliphatic aldehydes generated α-fluoro-β-hydroxy-aldol products with high diastereoselectivities. When (αR)- and (αS)-N-(α-fluoropropyl)-2-(4S)-oxazolidinones were explored as substrates they gave rise to identical aldol diastereoisomer products. Examination of the enolates formed in each case by ¹⁹F NMR, after treatment with TiCl₄, indicated that both preparations gave the same predominant enolate. This was assumed to be the E-enolate. The α-fluoro-β-hydroxy-aldol products were removed from the auxiliary either by alcoholysis or reduction and converted to the corresponding α,β-difluoro products by treatment with Deoxofluor™.     

Direct catalytic asymmetric aldol reaction of thioamides: a concise asymmetric synthesis of (R)-fluoxetine

A direct catalytic asymmetric aldol reaction of aromatic aldehydes and thioamides is described. A soft Lewis acid/hard Brønsted base cooperative catalyst comprising (R,R)-Ph-BPE/[Cu(CH₃CN)₄]PF₆/Li(OC₆H₄-p-OMe) promoted the title reaction efficiently, triggered by in situ generation of the active thioamide enolate through a soft–soft interaction of Cu(I) and the thioamide. The aldol product was transformed into (R)-fluoxetine, an antidepressant agent.     

Bis(methoxo)titan(IV)-dichlorid

Bis(methoxo)titanium(IV) Dichloride [CH₃O]₂TiCl₂ has been prepared by reaction between TiCl₄ and methanol. It has been characterized by different methods.