Trifluoroacetic Anhydride Mediated Oxidative Functionalization of Some 2-Dimethylaminoethyl-Substituted Indoles

Summary.  2′-Dimethylamino-1′-trifluoroacetyl-2-vinylindole derivatives were prepared by trifluoroacetic anhydride assisted oxidation. Received July 20, 2001. Accepted (revised) September 24, 2001     

Facile Cu(OTf)2-catalyzed preparation of 9-tosylaminofluorene derivatives from o-arylated N-tosylbenzaldimines

The 9-tosylaminofluorene derivatives were synthesized conveniently by Cu(OTf)₂-catalyzed aza-Friedel-Crafts reaction of o-arylated N-tosylbenzaldimines in high yields. This is an efficient, atom-economic, and green method.     

Regioselective single-step synthesis of 2-aminoimidazole derivatives

A convenient single-step strategy for the regioselective assembly of 2-aminoimidazole derivatives is herein described. Through a transition metal-free domino addition/cyclization process, the reactions of unsymmetrical carbodiimides with propargylic amines mediated by Cs₂CO₃ selectively afforded the corresponding polysubstituted 2-aminoimidazoles in moderate to good yields under very mild conditions. The regioselectivity was reversed in the presence of TEA at a higher temperature. The obtained 2-(o-iodoaryl)amino imidazoles could be easily converted to 2-(2-biphenyl)amino imidazole, 2-(o-alkynylphenyl)amino imidazole, benzoimidazo[1,2-a]imidazole and N-(imidazol-2-yl)indole derivatives.     

Synthesis of substituted 3-methylene-2-pyridones from Baylis-Hillman derivatives and its application for the generation of 2-pyridone substituted spiroisoxazolines

The synthesis of substituted 3-methylene-2-pyridones via S_N2 displacement reaction of nucleophiles bearing a keto group on the acetyl derivative of Baylis-Hillman adducts of acrylonitrile followed by TFA/H₂SO₄-mediated intramolecular cyclization is described. The utility of these pyridone derivatives for the synthesis of new spiroisoxazolines in highly regio- and stereo-selective fashion is also illustrated. The structure of the spiroisoxazolines has been secured via X-ray crystallographic analysis.     

Chiral 2-C-methylene glycosides and carbohydrate-derived pyrano[2,3-b][1]benzopyrans: synthesis via InCl3 catalyzed stereoselective Ferrier rearrangement of 2-C-acetoxymethyl glycal derivatives

2-C-Acetoxymethyl glycal derivatives react with aliphatic alcohols in the presence of InCl₃ (30 mol %) to furnish the corresponding 2-C-methylene glycosides in excellent yields and with exclusive α-selectivity except for the methyl 2-C-methylene glycosides, which are formed in ∼2:1 anomeric ratio in favour of the α-anomer. The reaction of 2-C-acetoxyglycals with phenols, however, produces the corresponding chiral carbohydrate-derived pyranobenzopyran derivatives via initial Ferrier rearrangement followed by tandem cyclization in excellent yields and moderate to high stereoselectivities in favour of the corresponding 10a-R-pyrano[2,3-b][1]benzopyran derivatives.     

A simple conversion of azlactones into indenones via H3PW12O40/Al2O3 catalyzed intramolecular Friedel-Crafts reaction

A rapid and simple procedure for the synthesis of the indenone derivatives, N-(1-oxo-1H-inden-2-yl)benzamides, via intramolecular Friedel-Crafts (IFC) reaction of (Z)-4-arylidene-2-phenyl-5(4)-oxazolones (azlactones) catalyzed by H₃PW₁₂O₄₀ supported on neutral alumina under microwave irradiation has been developed. The reaction is straightforward and allows easy isolation of the product. The catalyst could be re-used up to four times after simple filtration.     

A new and efficient one-pot synthesis of 2-hydroxy-1,4-dihydrobenzoxazines via a three-component Petasis reaction

The secondary amines synthesized by the reaction between 2-aminophenols and aromatic aldehydes, via the reduction of the corresponding imines, were employed in the synthesis of new 2-hydroxy-2H-1,4-benzoxazine derivatives through a one-pot Petasis multicomponent reaction in good to excellent yields.     

Expedient synthesis of 1-vinylpyrrole-2-carbaldehydes

1-Vinylpyrrole-2-carbaldehydes and 1-vinyl-4,5-dihydrobenzo[g]indole-2-carbaldehyde were synthesized in 56-91% yields from their 1-vinyl derivatives by a modified Vilsmeier-Haack reaction. A low temperature (−78 °C) is required to avoid removal of the N-vinyl group, whereas at elevated temperature (reflux in 1,2-dichloroethane) the latter process leads to direct conversion of 1-vinylpyrroles to pyrrole-2-carbaldehydes.     

A rate enhancement of tert-butoxycarbonylation of aromatic amines with Boc2O in alcoholic solvents

A rate enhancement of tert-butoxycarbonylation of aromatic amines by Boc₂O in alcohols compared to aprotic solvents was demonstrated. Kinetic analysis by NMR suggested that the reaction in CD₃OD was faster than in CDCl₃ by a factor of 70. Reactions between Boc₂O and various aliphatic and aromatic amines in ethanol provided the N-Boc derivatives in good to excellent yields in short reaction times.     

Regio- and stereoselective reactions of a rhodanine derivative with optically active 2-methyl- and 2-phenyloxirane

The reaction of a rhodanine derivative (=(Z)-5-benzylidene-3-phenyl-2-thioxo-1,3-thiazolidin-4-one; 1) with (S)-2-methyloxirane (2) in the presence of SiO₂ in dry CH₂Cl₂ for 10 days led to two diastereoisomeric spirocyclic 1,3-oxathiolanes 3 and 4 with the Me group at C(2) (Scheme 2). The analogous reaction of 1 with (R)-2-phenyloxirane (5) afforded also two diastereoisomeric spirocyclic 1,3-oxathiolanes 6 and 7 bearing the Ph group at C(3) (Scheme 3). The structures of 3, 4, 6, and 7 were confirmed by X-ray crystallography (Figs. 1 and 2). These results show that oxiranes react selectively with the thiocarbonyl group (CS) in 1. Furthermore, the nucleophilic attack of the thiocarbonyl S-atom at the SiO₂-activated oxirane ring proceeds with high regio- and stereoselectivity via an S_N2-type mechanism.     

Studies on the reduction of the nitro group in 3-aryl-2-methylene-4-nitro-alkanoates afforded by the Baylis-Hillman adducts: synthesis of 4-aryl-3-methylene-2-pyrrolidinones and 3-(1-alkoxycarbonyl-vinyl)-1H-indole-2-carboxylates

The formation of substituted 2-pyrrolidinones and indoles by the reduction of the secondary nitro group in appropriate 3-aryl-2-methylene-4-nitroalkanoates afforded by Baylis-Hillman chemistry via different reducing agents is described. The 3-aryl-2-methylene-4-nitroalkanoate obtained from S_N2 nucleophilic reaction between the acetate of Baylis-Hillman adducts and ethyl nitroacetate upon reduction with indium-HCl furnishes a mixture of cis and trans substituted phenyl-3-methylene-2-pyrrolidinones. In contrast, similar reductions of analogous substrates derived from nitroethane stereoselectively furnished only the trans substituted phenyl-3-methylene-2-pyrrolidinones. On the other hand the SnCl₂·2H₂O-promoted reductions of substrates derived from nitro ethylacetate give oxime derivatives while the ones obtained from nitroethane yield a mixture of cis and trans 4-aryl-3-methylene-2-pyrrolidinones. Alternatively, the SnCl₂·2H₂O-promoted reduction of substituted 2-nitrophenyl-2-methylene-alkanoate furnished from ethyl nitroacetate yield 3-(1-alkoxycarbonyl-vinyl)-1H-indole-2-carboxylate while indium-promoted reaction of this substrate leads to a complex mixture. Analogous reactions with SnCl₂·2H₂O of substituted 2-nitrophenyl-2-methylene-alkanoate obtained from nitroethane yield 4-alkyl-3-methylene-2-quinolones in moderate yields.     

Synthesis of 3,4-dihydropyridin-2-one derivatives in convergent mode applying bio catalyst vitamin B1 and polymer supported catalyst PEG-SO3H from two different sets of building blocks

Two highly efficient, green protocols have been developed for the synthesis of 3,4-dihydropyridin-2-one derivatives from different starting materials exploring two reaction specific catalysts, vitamin B₁ (VB₁), and PEG-SO₃H. VB₁ catalyzed simple and convenient protocol has been developed for the synthesis of 3,4-dihydropyridin-2-one derivatives by the installation of aldehyde, cyanoacetamide, and 1,3-dicarbonyl compounds. In addition, 3,4-dihydropyridin-2-one derivatives have also been synthesized by simply combining aldehyde, malononitrile, and 1,3-dicarbonyl compounds via the formation of 4H-pyran nucleus and PEG-SO₃H catalyzed one-pot rearrangement.     

Hydrogenation of CO2 Promoted by Silicon-Activated H2S: Origin and Implications

Unlike the usual method of CO_x (x = 1, 2) hydrogenation using H₂ directly, H₂S and HSiSH (silicon-activated H₂S) were selected as alternative hydrogen sources in this study for the CO_x hydrogenation reactions. Our results suggest that it is kinetically infeasible for hydrogen in the form of H₂S to transfer to CO_x at low temperatures. However, when HSiSH is employed instead, the title reaction can be achieved. For this approach, the activation of CO₂ is initiated by its interaction with the HSiSH molecule, a reactive species with both a hydridic H^δ− and protonic H^δ+. These active hydrogens are responsible for the successive C-end and O-end activations of CO₂ and hence the final product (HCOOH). This finding represents a good example of an indirect hydrogen source used in CO₂ hydrogenation through reactivity tuned by silicon incorporation, and thus the underlying mechanism will be valuable for the design of similar reactions.     

[3+2] Cycloaddition of metal-containing azomethine ylides for highly efficient synthesis of mitosene skeleton

Efficient synthesis of tricyclic indole derivatives bearing a substituent at the 3-position of the indole nucleus was achieved by the [3+2] cycloaddition reaction of transition metal-containing azomethine ylides derived from N-(o-alkynylphenyl)imines with vinyl ethers. Third-row transition metal complexes, especially PtCl₂, turned out to be highly efficient for the reaction of internal alkynes and imidate substrates with wide generality. Moreover, as strong support for the reaction mechanism, the intermediate Pt-carbene complex was found to undergo intramolecular C-H bond insertion reaction to give tetracyclic indoline derivatives when benzyl vinyl ether was employed as a dipolarophile. This protocol provided a facile synthesis of highly functionalized tricyclic indole derivatives found as the basic skeleton of the mitosene family, such as mitomycin C.     

EuZn2Si2 and EuZn2Ge2 Grown from Zn or Ga(ln)/Zn Flux

Single crystals of the novel ternary compounds EuZn₂Si₂ and EuZn₂Ge₂ were grown from pure gallium, indium, or zinc metal used as a flux solvent. Crystal properties were characterized using X-ray single-crystal analyses via Gandolfi and Weissenberg film techniques and by four-circle X-ray single-crystal diffractometry. The new compounds crystallize with ternary derivative structures of BaAl₄, i.e., EuZn₂Si₂ with ThCr₂Si₂-type (a=0.42607(2) nm, c=1.03956(5) nm, I4/mmm, R₁=0.038) and EuZn₂Ge₂ with CaBe₂Ge₂-type (a=0.43095(2) nm, c=1.07926(6) nm, P4/nmm, R₁=0.067). XAS and magnetic measurements on EuZn₂Si₂ and EuZn₂Ge₂ revealed in both compounds the presence of Eu²⁺ ions carrying large magnetic moments, which order magnetically at low temperatures. The magnetic phase transition occurs at T_N=16 and 7.5 K for the silicide and the germanide, respectively. In EuZn₂Si₂ there occurs a spin reorientation at 13 K and furthermore some canting of antiferromagnetically ordered moments below about 10 K. In EuZn₂Ge₂ a canted antiferromagnetic structure is formed just at T_N.     

Supercritical CO2 improved phosphine imide reaction on peracetylated β-cyclodextrin

Supercritical CO₂ (sCO₂) was successfully used as solvent and reagent in the ‘one-pot’ phosphine imide reaction. In sCO₂ smooth conditions and with or without assistance of triphenylphosphine-bounded polymer, the reaction efficiently leads to the desired urea β-Cd compounds in a short time, bringing an interesting alternative for solving problems of OVC and hazardous reagent substitution in the synthesis of ureido-Cds and, by extension, of urea derivatives.     

Facile one-pot synthesis of 2-arylbenzothiazoles catalyzed by H3PO4/TiO2-ZrO2 (1/1) under solvent-free conditions

A highly efficient and simple protocol for the preparation of 2-arylbenzothiazoles through condensation of 2-aminothiophenol and different aldehydes in the presence of H₃PO₄/TiO₂-ZrO₂(1/1)-cetyl pyridinium bromide (CPB) is described. The reaction proceeded under mild and solvent-free conditions to afford 2-arylbenzothiazole derivatives. In this method, the title compounds were obtained in good to excellent yields and short reaction times. The structures of synthesized products were identified by infrared, ¹H NMR, ¹³C NMR, and mass spectroscopy.     

A two-step procedure for the preparation of mono-protected bis-N-heterocyclic alkyl ether systems

A two-step convenient sequence for the synthesis of previously inaccessible mono-Boc-protected bis-N-heterocyclic alkyl substituted ether derivatives 4 is described. Mitsunobu protocol was applied to the preparation of pyridinyl ether precursor 5. The reduction of the electron rich pyridinyl system 5 has been achieved catalytically using the combination of PtO₂-H₂SO₄ or PtO₂-pTsOH under a hydrogen atmosphere maintained by a gas balloon at ambient temperature.     

Metal-free synthesis of pyridin-2-yl ureas from 2-aminopyridinium salts

An unprecedented base promoted domino approach has been developed for the synthesis of pyridin-2-yl urea derivatives via the reaction of 2-aminopyridinium salts and arylamines. The developed strategy tolerated a wide range of functional groups and afforded pyridin-2-yl ureas in moderate to good yields. The reaction was postulated to involve tandem cyclization, intermolecular nucleophilic addition, ring opening, and demethylation.     

FeCl3-SiO2 as a reusable heterogeneous catalyst for the synthesis of 5-substituted 1H-tetrazoles via [2+3] cycloaddition of nitriles and sodium azide

An efficient method for the preparation of 5-substituted 1H-tetrazole derivatives is reported using FeCl₃-SiO₂ as an effective heterogeneous catalyst. This method has the advantages of high yields, simple methodology, and easy work-up. The catalyst can be recovered by simple filtration and reused delivering good yields.