Microwave-assisted cycloadditions of 2-alkynylbenzonitriles with sodium azide: selective synthesis of tetrazolo[5,1-a]pyridines and 4,5-disubstituted-2H-1,2,3-triazoles

Under microwave irradiation (75 W), treatment of 2-alkynylbenzonitriles with 1.5 equiv of sodium azide in DMSO at 140 °C gave 4,5-disubstituted-2H-1,2,3-triazoles in 60-99% yields. Additionally, adding 8 equiv of ZnBr₂ and using 8 equiv of sodium azide in DMF at 100 °C lead to the formation of tetrazolo[5,1-a]isoquinolines up to 87% yield.     

Enantioselective addition of diethylzinc to N-diphenylphosphinoylimines employing cinchonidine and cinchonine as chiral ligands

The use of the `pseudoenantiomeric pair' of cinchonine and cinchonidine as ligands for the addition of diethylzinc to N-diphenylphosphinoylimines has been investigated. With 1 equiv of cinchonidine as ligand, a series of chiral amines was prepared in good yield and enantiomeric excesses of up to 94%. The use of 2.0 equiv of methanol as an achiral additive was found significantly to improve the selectivity of the addition when using 0.2 equiv of ligand, yielding ee's close to those obtained with a stoichiometric amount of ligand.     

gem-Difluoropropargylation of aldehydes using cat. In/Zn in aqueous media

Zn (0.9 equiv) in combination with catalytic amounts of In (0.1 equiv) and I₂ (0.1 equiv) was found to effect the reaction of several difluoropropargyl bromide derivatives with aldehydes to produce gem-difluorohomopropargyl alcohols in aqueous media under conditions suitable for large scale applications.     

Reductive allylation of 1H-pyridine-2-(thio)ones by means of the novel lithium allyldibutylmagnesate reagent

A new, highly efficient allylation reagent—lithium allyldibutylmagnesate (allylBu₂MgLi)—was obtained by mixing allyl-magnesium chloride (1 equiv) and n-BuLi (2 equiv). N-Lithiated and N-methyl substituted 1H-pyridine-2-thiones and -ones were successfully and regioselectively allylated by treatment with allylBu₂MgLi yielding 6-allyl-3,6-dihydro-1H-pyridine-2-(thio)ones and 4-allyl-3,4-di-hydro-1H-pyridine-2-(thio)ones. The latter were formed by a 3,3-sigmatropic Cope rearrangement of the former.     

Stereoselective aldol additions of titanium enolates of N-acetyl-4-isopropyl-thiazolidinethione

The addition of chlorotitanium enolates of N-acetyl isopropyl thiazolidine-2-thione to aldehydes was investigated. The stereoselectivity of the aldol products was controlled by the number of equivalents of base added. The syn aldol product was obtained preferentially when 2 equiv of Lewis acid and 1 equiv of base were employed. The anti aldol product was obtained preferentially when 1 equiv of Lewis acid and 2 equiv of base were employed for unsaturated aldehydes. Unexpected results were found with hindered aldehydes when 2 equiv of base were employed.     

Facile nucleophilic fluorination by synergistic effect between polymer-supported ionic liquid catalyst and tert-alcohol reaction media system

A highly efficient method was developed for nucleophilic fluorination using an alkali metal fluoride through the synergistic effect of the polymer-supported ionic liquid (PSIL) as a catalyst and tert-alcohol as an alternative reaction media. This PSIL/tert-alcohol system not only enhances the reactivity of alkali metal fluorides and reduces the formation of by-products but also allows the use of a polymer-supported catalyst protocol. As an example, the nucleophilic fluorinations of the model compound, 2-(3-bromopropoxy)naphthalene, with CsF using only tert-amyl alcohol as solvent (for 2 h reaction time), 0.5 equiv of PS[hmim][BF₄] in CH₃CN (for 12 h reaction time), and 0.5 equiv of PS[hmim][BF₄] in tert-amyl alcohol (which is a PSIL/tert-alcohol system for the synergistic effect; for 2 h reaction time) provided 18, 40, and 84% yield, respectively. The characteristics of the nucleophilic fluorination reactions of some halo- and alkanesulfonyloxyalkane systems to the corresponding fluoroalkanes using various alkali metal fluorides are also reported.     

Poly(urethaneimides) (PUIs) containing tertiary amine groups as precursors for original PUI cationomers

This paper details the synthesis and characterisation of poly(urethaneimides) (PUIs) containing tertiary amine groups and obtained from a polytetramethylene oxide diol (PTMO1000), N-methyldiethanolamine (MDEA), 4,4′-methylene-bis-phenylisocyanate (MDI) and 4,4′-hexafluoroisopropylidene-bis-phthalic anhydride (6FDA). The polymers PTMO1000 (1 − x equiv.) + MDEA (x equiv.)/MDI (2 equiv.)/6FDA (1 equiv.) were obtained in high yields (>90%) through original synthesis, involving the reaction of macrodiisocyanates with an aromatic dianhydride in two steps only. A wide range of complementary techniques including two-dimensional NMR showed that the new method enabled a very good control of the polymer structure. In particular, the tertiary amine content of the PUI copolymers was easily varied over the whole composition range (x: 0 → 1), with interesting prospects for the design of a wide range of ion-containing poly(urethaneimides) by quaternising the tertiary amine groups. The PUI properties (e.g. solubility, viscosity, film-forming ability, etc.) clearly depended upon their tertiary amine content. Up to a tertiary amine content of x = 0.7 equiv., the very good film-forming character of the PUIs enabled to cast strong films suitable for permeability investigations.     

A convenient preparation of thioether functionalized porphyrins

This paper describes a convenient and high yielding three-step approach for the synthesis of trans-tetraphenylporphyrins possessing two thioethers in the ortho positions, which will facilitate the synthesis of more elaborate and complex porphyrin architectures. Their synthesis is realized by a double nucleophilic aromatic substitution of 2 equiv of a thiolate on 2,6-dichlorobenzaldehyde to generate a bis-thioether substituted benzaldehyde. This aldehyde is then condensed with 2 equiv of pyrrole to give a dipyrromethane, which in the final step reacts with an aromatic aldehyde to give a series of thioether-substituted trans-tetraphenylporphyrins.     

Efficient synthesis of trisubstituted alkenes in an aqueous-organic system using a versatile and recyclable Rh/m-TPPTC catalyst

We have found that the use of [Rh(cod)OH]₂ associated with the water-soluble ligand m-TPPTC was highly efficient for the Rh-catalyzed arylation of alkynes. Aryl and alkyl alkynes were transformed to alkenes using 3 mol % rhodium catalyst and 2.5 equiv of boronic acid at 100 °C in a biphasic water/toluene system in 80-99% yield. The reaction was found to be totally regioselective for alkyl arylalkynes and alkyl silylated alkynes. The Rh/m-TPPTC system was for the first time recycled with no loss of the activity and with excellent purity of the desired alkene.     

Simple and efficient cleavage of the N-(1-phenylethyl) unit of carboxamides with methanesulfonic acid

Cleavage of the N-(1-phenylethyl) unit of carboxamides using less than 1 equiv of MsOH in refluxing toluene was found to be simple and very efficient leading to the desired amides in good to excellent yields, and also proved to be more effective compared with reductive methods using hydrogen sources, or acid hydrolysis reagents such as TFA and TsOH. The method selectively cleaved only the N-(1-phenylethyl) group of N-benzyl-N-(1-phenylethyl)amides.     

A palladium catalyzed atom-efficient cross-coupling reactivity of triarylbismuths with α,β-unsaturated acyl chlorides

An atom-efficient cross-coupling reactivity of triarylbismuths (1 equiv) was demonstrated by cross-coupling reaction with 3 equiv of α,β-unsaturated acyl chlorides under palladium catalysis in the synthesis of a series of functionalized α, β-unsaturated ketones in high isolated yields.     

Regioselective monobromination of (E)-1-(2′-hydroxy-4′,6′-dimethoxyphenyl)-3-aryl-2-propen-1-ones using bromodimethylsulfonium bromide and synthesis of 8-bromoflavones and 7-bromoaurones

A wide variety of monobrominated compounds 2a-l have been prepared in good yields from (E)-1-(2′-hydroxy-4′,6′-dimethoxyphenyl)-3-aryl-2-propen-1-ones (1a-l) through regioselective ring bromination using 1.5 equiv of bromodimethylsulfonium bromide (BDMS) at room temperature. Similarly, some of the 2′-hydroxychalcones can be converted directly into tribromides 3 or dibromides 4 by employing 4.0 equiv of BDMS under different reaction conditions which in turn can be transformed into 8-bromoflavones and 7-bromoaurones on treatment with 0.2 M ethanolic KOH solution. Mild reaction conditions, good yields and no chromatographic separation are some of the salient features of the present protocol.     

An improved procedure for the diastereoselective addition of triorganozincates to N-(tert-butanesulfinyl)imines: use of catalytic dialkylzinc

The addition of triorganozincates to (R)-N-(tert-butanesulfinyl)benzaldimine has been performed with very good results by using a catalytic amount of Me₂Zn (0.15 equiv) to generate the organozincate. Yields and/or diastereoselectivities of the formed α-branched sulfinamides improve in comparison with the values obtained in the same reactions carried out with an excess of a previously formed triorganozincate. On the other hand, the transfer of the two alkyl groups of a dialkylzinc reagent to the imine has been achieved by using 0.5 equiv of dialkylzinc and 1.5 equiv of MeMgBr to generate the trialkylzincate. In both methods, good to excellent yields and diastereomeric ratios (up to 98:2) have been obtained.     

Synthesis, structure, and bridge-terminal alkyl exchange kinetics of pyrazolate-bridged dialuminum complexes containing bridging n-alkyl groups

Treatment of triethylaluminum with 3,5-diphenylpyrazole in a 2:1 stoichiometry afforded the ethyl-bridged complex Et₂Al(μ-Ph₂pz)(μ-Et)AlEt₂ (79%) as a colorless crystalline solid. Treatment of tri-n-propylaluminum with 3,5-di-tert-butylpyrazole in a 2:1 stoichiometry afforded the n-propyl-bridged complex (nPr)₂Al(μ-tBu₂pz)(μ-nPr)Al(nPr)₂ (63%) and the dimeric complex [(nPr)₂Al(μ-tBu₂pz)]₂ (3%), respectively, as colorless crystalline solids. Treatment of tri-n-propylaluminum (1 equiv.) or triisobutylaluminum (1 or 2 equiv.) with 3,5-di-tert-butylpyrazole afforded exclusively the dimeric complexes [(nPr)₂Al(μ-tBu₂pz)]₂ (68%) or [(iBu)₂Al(μ-tBu₂pz)]₂ (96%), respectively, as colorless crystalline solids. The solid state structures of Et₂Al(μ-Ph₂pz)(μ-Et)AlEt₂ and (nPr)₂Al(μ-tBu₂pz)(μ-nPr)Al(nPr)₂ consist of 3,5-disubstituted pyrazolato ligands with a di-n-alkylalumino group bonded to each nitrogen atom. An ethyl or n-propyl group acts as a bridge between the two aluminum atoms. The kinetics of the bridge-terminal exchange was determined for the bridging n-alkyl complexes by ¹³C NMR spectroscopy, and afforded ΔH^‡ = 1.5 ± 0.1 kcal/mol, ΔS^‡ = −46.8 ± 39.0 cal/K mol, and for Et₂Al(μ-Ph₂pz)(μ-Et)AlEt₂ and ΔH^‡ = 1.7 ± 0.1 kcal/mol, ΔS^‡ = −46.6 ± 43.4 cal/K mol, and for (nPr)₂Al(μ-tBu₂pz)(μ-nPr)Al(nPr)₂. The negative values of ΔS^‡ imply ordered transition states relative to the ground states, and rotation along the N-AlR₃ vector without aluminum-nitrogen bond cleavage is proposed.     

4-(tert-Butyldimethylsilyloxy)benzylidene acetal: a novel benzylidene-type protecting group for 1,2-diols

A novel 1,2-diol-protecting group, p-silyloxybenzylidene group, has been developed. In addition to the stepwise deprotection conditions including desilylation and the subsequent acidic hydrolysis of the p-hydroxybenzylidene group in AcOH-THF-H₂O, we have established the one-pot deprotection under basic conditions [K₂CO₃ (5 equiv), NH₂OH·HCl (5 equiv), and CsF (1 equiv) in MeOH-H₂O].     

Palladium-free zinc-mediated hydroamination of alkynes: efficient synthesis of indoles from 2-akynylaniline derivatives

Reaction of 2-phenylethynyl N-tosylanilide prepared by Pd-free procedure with ZnBr₂ (3 equiv) in refluxing toluene gave N-tosyl-2-phenylindole in 93% yield. Treatment of 2-phenylethynylaniline with ZnBr₂ (1 equiv) in refluxing toluene resulted in the formation of 2-phenylindole in 91% yield. Catalytic ZnBr₂ (0.05 equiv) effectively reacted with 2-alkynylanilines to afford 2-substituted indoles in high yields. Thus, complete Pd-free zinc catalyzed hydroamination of 2-alkynylanilines was achieved.     

Mild and efficient deprotection of the amine protecting p-methoxyphenyl (PMP) group

Mild and efficient procedures for deprotection of the amine nitrogen protecting p-methoxyphenyl (PMP) group are described. Periodic acid and trichloroisocyanuric acid (TCCA) were found to be particularly effective in realizing amine liberation using 1 and 0.5 equiv of the oxidant, respectively. Extension of the periodic acid-mediated conditions to simultaneous alcohol oxidation by combination with a catalytic amount of sodium dichromate led to smooth conversion of PMP-protected Mannich products into the corresponding β-amino acids in a one-pot procedure.     

Synthesis of novel multidentate carbohydrate-triazole ligands

Cu(I)-catalyzed 1,3-dipolar cycloaddition (click reaction) of 1 mol equiv of N,N′-di-prop-2-ynyl-phthalamide (1a), N,N′-di-prop-2-ynyl-isophthalamide (1b), and pyridine-2,6-dicarboxylic acid bis-prop-2-ynylamide (1c), respectively with 2 mol equiv of 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl azide (2a), 2-azidoethyl 2,3,4,6-tetra-O-acetyl-β-d-glucopyranoside (2b), and 2-azidoethyl 2,3,4,6-tetra-O-acetyl-α-d-mannopyranoside (2c), respectively, afforded the corresponding bis-cycloadducts 3-5, containing two 1,2,3-triazole moieties each, in 38-76% yield. Reaction of 1 mol equiv of 2c with 1 mol equiv of 1c under otherwise identical conditions gave the mono-cycloadduct 6, containing one 1,2,3-triazole and one 2-propynylamide moiety, in 77% yield. Reaction of 6 with 2a afforded 7, containing two different sugar moieties, in 67% yield.     

New selective O-debenzylation of phenol with Mg/MeOH

Carboxylate-benzyl and nitro-benzyl groups used in phenols protection were selectively debenzylated with 3-25 equiv of Mg in methanol at room temperature. Good yields of the desired phenols were obtained within 3-10 h from a wide variety of O-(carboxylate-benzyl)- or O-(nitro-benzyl)-phenols. Selective O-debenzylation was possible in the presence of O-(carboxylate-benzyl)- or O-(nitro-benzyl)-phenols with Mg/MeOH.     

An atom-efficient palladium-catalyzed cross-coupling reaction of triarylbismuths with acid chlorides: synthesis of diaryl and alkyl aryl ketones

The cross-coupling reaction of triarylbismuths with acid chlorides using a catalytic amount of PdCl₂/PPh₃ afforded the corresponding ketones in high yields. The reactions of aromatic and aliphatic acid chlorides occurred with atom efficiency, as 3 equiv of acid chlorides coupled effectively with 1 equiv of triarylbismuths to yield 3 equiv of the corresponding diaryl and alkyl aryl ketones.