Brønsted acid-promoted synthesis of highly functionalized tetrahydrocarbazoles from diethyl ()-5-diazo-4-oxohex-2-enedioate.

Brønsted acid-promoted synthesis of highly functionalized tetrahydrocarbazoles from indoles and easily accessible diethyl ()-5-diazo-4-oxohex-2-enedioate has been achieved. Diethyl ()-5-diazo-4-oxohex-2-enedioate acts as a 1,4-diacceptor and undergoes tandem Michael addition followed by nucleophilic substitution at the diazo carbon with indole in the presence of a strong Brønsted acid.

Silver-Catalyzed Olefination of Aryl Aldehydes Using Propiolates.

Olefination of aldehydes is one of the fundamental reactions in organic synthesis. The commonly used Wittig olefination reaction however uses stoichiometric quantities reagents under basic conditions resulting in stoichiometric amounts of byproducts. Known catalytic alternate to the Wittig reaction requires stoichiometric amounts of silane reducing agents and high temperature.

Gold(I)-Catalyzed Regioselective Hydroarylation of Propiolic Acid with Arylboronic Acids.

A gold-catalyzed intermolecular hydroarylation involving arylboronic acid has been disclosed. This carboxylic acid-directed arylation is highly regioselective and occurs at the less electrophilic carbon to afford α-aryl acrylic acids in attractive yields. This protocol offers easy access to NSAID precursors.

Dodging the Conventional Reactivity of -Alkynylanilines under Gold Catalysis for Distal 7-- Cyclization.

A direct ring-closing strategy involving a less facile 7-- carbacyclization of -alkynylaniline derivatives for the synthesis of benzo[]azepines has been presented. The trivial well-documented 5- cyclization in -alkynylaniline derivatives due to high nucleophilicity of nitrogen has been overcome by using their vinylogous amides under gold catalysis to access a wide array of benzo[]azepines in an atom economical way with excellent functional group compatibility. Deuterium scrambling experiments and DFT studies favor a mechanism involving stabilizing conformational change of the initially formed seven-membered vinyl gold intermediate through a key cyclopropyl gold carbene intermediate and its subsequent protodeauration mediated by the counter anion.

Ag(I)-catalyzed cyclization of -alkynylacetophenones facilitated through acetal formation: synthesis of C3-naphthyl indole derivatives.

A mild method for an efficient synthesis of C3-naphthyl indoles from -alkynylacetophenones has been developed. This Ag-catalyzed transformation is assisted by the acetal formed under the reaction condition employing trimethyl orthoformate (TMOF). The role of acetal in promoting the reaction under ambient conditions has been established with control experiments.

TfOH-promoted synthesis of indoles and benzofurans involving cyclative transposition of vinyl ketone.

A metal-free approach to construct indole rings from vinylogous amides derived from -alkynylanilines involving a cyclization, retro-aza-Michael reaction and amine trapping cascade is reported here. This atom-economical transformation has been extended to synthesize benzofuran derivatives using analogous vinylogous esters derived from -alkynylphenols. The excellent stereochemical outcome of the double bond geometry in the products makes it attractive.

Activation of -Propargyl Alcohol Benzaldehydes under Acetalization Conditions for Intramolecular Electrophile Intercepted Meyer-Schuster Rearrangement.

The reactivity of -propargyl alcohol benzaldehydes has been increased tremendously toward Brønsted acid-catalyzed intramolecular electrophile intercepted Meyer-Schuster (M-S) rearrangement under acetalization conditions using trimethyl orthoformate (TMOF). The in situ formed acetal transfers the methoxy group intramolecularly to generate the M-S intermediate in even less reactive substrates, and the formed oxocarbenium ion makes the carbonyl more electrophilic for an effective intramolecular trapping of the M-S intermediate to furnish the indanone derivatives.

Triflic Acid-Catalyzed Synthesis of Indole-Substituted Indane Derivatives via Formed Acetal-Facilitated Nucleophilic Addition and 4π-Electron-5-Carbon Electrocyclization Sequence.

An efficient protocol for the synthesis of indole-substituted indanes from -alkenylbenzaldehydes under acetalization conditions has been presented. The cyclization occurs via a nucleophilic addition of indole on the oxacarbenium ion generated from acetal formed under the reaction condition followed by a conrotatory 4π-electrocyclization reaction, which takes care of the exclusive diastereoselectivity observed during the cyclization step. Olefin geometry of -alkenylbenzaldehyde and the amount of indole play a decisive role in the success of this cyclization process.

Synthesis of Highly Substituted Biaryls by the Construction of a Benzene Ring via Formed Acetals.

Herein, we present an interesting method for the construction of a benzene ring using propargylic alcohols and 1,3-dicarbonyls, which involves three new C-C bond formations via cascade alkylation, formylation, annulation, and aromatization to make substituted biaryls. This one-pot Brønsted acid-promoted protocol utilizes the unique reactivity of the acetal formed under the reaction conditions. Alkynyl methyl ketones could be employed instead of 1,3-dicarbonyls as they are converted to 1,3-dicarbonyls by hydration under the reaction conditions.

Brønsted/Lewis Acid-Promoted Site-Selective Intramolecular Cycloisomerizations of Aryl-Fused 1,6-Diyn-3-ones for Diversity-Oriented Synthesis of Benzo-Fused Fluorenes and Fluorenones and Naphthyl Ketones.

Herein, a facile diversity-oriented approach to access functionalized benzo[]fluorenes, benzo[]fluorenones, and naphthyl ketones has been demonstrated site-selective intramolecular cyclization of aryl-fused 1,6-diyn-3-ones. Synthesis of benzo[]fluorenes and naphthyl ketones has been achieved selectively using TfOH and AgBF, respectively, in situ-formed acetals. Aryl-fused 1,6-diyn-3-ones undergo triflic acid-mediated intramolecular cyclization, leading to benzo[]fluorenone derivatives a radical intermediate as supported by EPR studies.

Synthetic homoserine lactone analogues as antagonists of bacterial quorum sensing.

Quorum sensing (QS) is a density-dependent form of cell-cell communication that triggers the functional coordination of cooperative behaviors such as the production of virulence factors and biofilm formation. Quorum quenching (QQ) refers to all processes involved in the disruption of QS and is regarded as a promising strategy for treating bacterial infections. Herein, four compounds with closely related chemical structures to homoserine γ-lactone were synthesized and fully characterized.

Annulation of a Highly Functionalized Diazo Building Block with Indoles under Sc(OTf)/Rh(OAc) Multicatalysis through Michael Addition/Cyclization Sequence.

A highly functionalized and easily accessible six-carbon diazo building block has been developed and utilized as a 1,4-diacceptor for an efficient synthesis of functionalized tetrahydrocarbazoles, carbazoles, and tetrahydropyrido[1,2- a]indoles. The synthesis involves concurrent tandem catalysis by Sc(OTf) and Rh(OAc). The role of Sc(OTf) is critical as it facilitates both the initial intermolecular Michael reaction of the indole and the subsequent Rh(II)-catalyzed intramolecular annulation.

Catalyst free synthesis of α-fluoro-β-hydroxy ketones/α-fluoro-ynols via electrophilic fluorination of tertiary propargyl alcohols using Selectfluor™ (F-TEDA-BF).

A facile method for the synthesis of α-fluoro-β-hydroxy ketones/α-fluoro-ynols from tertiary propargyl alcohols under electrophilic fluorination conditions using F-TEDA-BF has been presented. The products bear pharmaceutically important α-fluoro ketone, gem-diaryl and fluorohydrin moieties in the same molecule. Interestingly, this catalyst free protocol results in monofluorination.

Amino Groups of Chitosan Are Crucial for Binding to a Family 32 Carbohydrate Binding Module of a Chitosanase from Paenibacillus elgii.

We report here the role and mechanism of specificity of a family 32 carbohydrate binding module (CBM32) of a glycoside hydrolase family 8 chitosanase from Paenibacillus elgii (PeCsn). Both the activity and mode of action of PeCsn toward soluble chitosan polymers were not different with/without the CBM32 domain of P. elgii (PeCBM32).

The directing group wins over acidity: kinetically controlled regioselective lithiation for functionalization of 2-(2,4-dihalophenyl)-1,3-dithiane derivatives.

Regioselective lithiation followed by functionalization of 2-(2,4-dihalophenyl)-1,3-dithiane derivatives with different electrophiles was achieved in good to excellent yields. When the title compound is treated with n-butyl lithium, lithiation occurs selectively at the aromatic carbon having less acidic proton despite the presence of thermodynamically more acidic 1,3-dithiane proton in the same molecule. Computationally calculated pKa values of the available reactive site protons and the experimental results suggest that the regioselective lithiation in 2-(2,4-dihalophenyl)-1,3-dithiane derivatives is not governed by thermodynamic acidity rather exclusively dictated by the kinetic removal of protons due to cooperative coordination (complex induced proximity effect, CIPE) and inductive effects of the 1,3-dihalo substituents present in the aromatic ring.

In Situ Formed Acetal-Facilitated Synthesis of Substituted Indene Derivatives from o-Alkenylbenzaldehydes.

A new protocol has been developed for the synthesis of indene derivatives in a diastereoselective manner from o-alkenylbenzaldehydes and enolizable ketones in the presence of trimethyl orthoformate and catalytic triflic acid. This method involves tandem in situ formed acetal-assisted Claisen-Schmidt condensation followed by 5-exo-trig cyclization/Michael addition in one-pot. It has also been shown that the chalcones derived from o-alkenylbenzaldehydes and ketones can effectively be transformed into indene derivatives in the presence of TfOH catalyst alone.

Gold-catalysed glycosylation reaction using an easily accessible leaving group.

Gold(III)-catalysed glycosylation reaction has been developed by employing a new and easily accessible leaving group synthesized from ethyl cyanoacetate. Several nucleophiles like alcohols, thiols, allyltrimethylsilane, trimethylsilyl azide and triethylsilane have been reacted to make the corresponding glycosides in good yields and with marginal to excellent α-selectivity.

A facile access to substituted benzo[a]fluorenes from o-alkynylbenzaldehydes via in situ formed acetals.

In situ formed acetal changes the course of Brønsted acid-catalyzed reaction of ortho-alkynylbenzaldehydes with arylalkynes altogether. By utilizing this, an efficient domino approach for the regioselective synthesis of substituted benzo[a]fluorenes has been developed under mild reaction conditions. In situ formed acetal facilitates the intermolecular heteroalkyne metathesis and subsequent trans to cis isomerization of a double bond to effect the intramolecular annulation.

Triflic acid promoted direct α-alkylation of unactivated ketones using benzylic alcohols via in situ formed acetals.

Direct α-alkylation of unactivated ketones using benzylic alcohols as electrophiles has been achieved at room temperature. This reaction takes place via in situ formed acetal using triflic acid and trimethyl orthoformate. It is believed that methyl vinyl ether formed from the in situ generated dimethyl acetal in the presence of triflic acid undergoes alkylation.

Synthesis of naphthalene derivatives from ortho-alkynylacetophenone derivatives via tandem in situ incorporation of acetal and intramolecular heteroalkyne metathesis/annulation.

An interesting domino reaction for the synthesis of substituted naphthyl ketones has been developed using readily accessible starting materials. This domino reaction proceeds via in situ incorporation of an acetal followed by intramolecular heteroalkyne metathesis/annulation in an ortho-alkynylacetophenone derivative. A deuterium incorporation experiment has been carried out to understand the mechanism.

Synthesis of chiral α-diarylacetic esters by stereospecific 1,2-aryl migration promoted by in situ generated acetals from benzoins.

A simple protocol for the synthesis of α-diarylacetic esters from benzoins is described. In situ generated acetal assists rapid 1,2-aryl migration in a stereospecific manner, paving the way to make enantioenriched α-diarylacetic esters from easily accessible enantiopure benzoins.

Synthesis of 1-arylnaphthalenes by gold-catalyzed one-pot sequential epoxide to carbonyl rearrangement and cyclization with arylalkynes.

Intermolecular and intramolecular reactions of a one-pot gold-catalyzed epoxide rearrangement followed by an electrophilic addition to arylalkynes to synthesize 1-arylnaphthalenes have been reported. The intramolecular reaction has been applied to synthesize 1-arylnaphthalenes fused with saturated furan, pyran, pyrrole, and cyclopentane ring systems.

Synthesis of arylnaphthalene lignan scaffold by gold-catalyzed intramolecular sequential electrophilic addition and benzannulation.

An intramolecular approach to generate compounds containing an arylnaphthalene lignan scaffold in high yields is presented. It involves a sequential intramolecular electrophilic attack of carbonyl on arylalkyne followed by benzannulation catalyzed by gold salt. AuCl(3) in combination with AgSbF(6) works better to effect this transformation.

Gold/copper-catalyzed activation of the aci-form of nitromethane in the synthesis of methylene-bridged bis-1,3-dicarbonyl compounds.

Activation of the aci-form of nitromethane using Lewis acids for the attack of carbon nucleophiles was studied. 1,3-Dicarbonyl compounds in the presence of catalytic amounts of AuCl(3) or Cu(OTf)(2) in nitromethane solvent could be converted into methylene-bridged bis-1,3-dicarbonyl compounds.