Hydrodehalogenation of halogenated pyridines and quinolines by sodium borohydride/N,N,N′,N′-tetramethylethylenediamine under palladium catalysis

A protocol for the hydrodehalogenation of halogenated pyridines and quinolines by the sodium borohydride/N,N,N′,N′-tetramethylethylenediamine (NaBH₄-TMEDA) system under palladium catalysts is reported. Catalytic amounts of [1,1′-bis(diphenylphosphino)ferrocene] dichloropalladium(II) in combination with NaBH₄-TMEDA rapidly hydrodehalogenate chloro(bromo)-pyridines and -quinolines at room temperature in quantitative yields. Chemoselective reduction of 4,7-dichloroquinoline affords 7-chloroquinoline as the sole product in almost quantitative yield. Moreover, palladium(II) acetate-triphenylphosphine and NaBH₄-TMEDA are able to reduce efficiently reactive bromo-pyridines and -quinolines.     

N,N-Dimethyl-S-difluoromethyl-S-phenylsulfoximinium tetrafluoroborate: A versatile electrophilic difluoromethylating reagent

Over the past decade, sulfur-based fluoromethyl containing compounds have been exhaustively investigated as versatile fluoroalkylating reagents by our research laboratory as well as many others. Lately, we have designed a novel electrophilic difluoromethylating protocol employing in situ prepared N,N-dimethyl-S-difluoromethyl-S-phenylsulfoximinium salt. The present reagent provides excellent reactivity toward a broad spectrum of nucleophilic species (N-, P-, S-, and O-nucleophiles) to yield the corresponding difluoromethylated products with high efficacy under mild conditions. Additional studies have been performed to elucidate the mechanistic fundamentals of the reactions.     

Palladium-catalyzed aziridination of alkenes using N,N-dichloro-p-toluenesulfonamide as nitrogen source

N,N-Dichloro-p-toluenesulfonamide (TsNCl₂) was found to be an efficient nitrogen source for the aziridination of unfunctionalized alkenes using palladium catalysts. Among the palladium salts, palladium acetate was the most effective catalyst for this reaction. A variety of alkenes were reacted at room temperature with TsNCl₂ to form the desired aziridines in moderate to good yields. This method can complement our previous protocol which is limited to the use of electron-deficient α,β-unsaturated alkenes.     

Enantioselective synthesis of (2S,3′R,7′Z)-N-(3′-hydroxy-7′-tetradecenoyl)-homoserine lactone

A concise enantioselective total synthesis of (2S,3′R,7′Z)-N-(3′-hydroxy-7′-tetradecenoyl)-homoserine lactone is described. Key feature of this protocol is a catalytic asymmetric hydrogenation and a prophenol-zinc-catalyzed diazo addition to imine reaction as genesis of chirality. Moreover, flexibility is built in the synthesis to generate enantioenriched analogs using catalytic amount of enantioenriched C₂-symmetric ligands.     

Synthesis of 6,7-dihydro-5H-dibenzo[c,e]azepines and biaryls by palladium-catalyzed Ullmann reaction

A novel palladium-catalyzed Ullmann protocol is described for the synthesis of 6,7-dihydro-5H-dibenzo[c,e]azepines and biaryls. In the presence of Pd(OAc)₂ and KOAc, intramolecular or intermolecular Ullmann coupling of aryl halides proceeds efficiently under ligand-free and aerobic conditions to afford the corresponding 6,7-dihydro-5H-dibenzo[c,e]azepines and biaryls in moderate to excellent yields.     

Synthesis of 5,6-dihydrophenanthridines via N,O-acetal TMS ethers

A concise and high-yielding protocol for the synthesis of 5,6-dihydrophenanthridines is disclosed. The key feature includes a sequential reduction-cyclization reaction of N-acylcarbamates via N,O-acetal TMS ethers as a stable N-acyliminium ion precursor.     

Palladium-catalyzed carbonylative synthesis of N-cyanobenzamides from aryl iodides/bromides and cyanamide

A novel and convenient protocol for the synthesis of N-cyanobenzamides starting from readily available aryl halides and cyanamide via palladium-catalyzed aminocarbonylation has been developed. The protocol utilizes Mo(CO)₆ as the CO source or CO(gas) and affords the desired N-cyanobenzamides in moderate to good yields.     

Iron-catalyzed aerobic oxidative cross-coupling amidation of N,N-dimethylanilines

An efficient iron-catalyzed dehydrogenative cross-coupling amidation/imidation reaction between N,N-dimethylanilines and amides/imides is reported. The protocol uses an inexpensive and readily available Fe(NO₃)₃·9H₂O/O₂ catalytic system in the absence of additional ligands at room temperature.     

I2-catalyzed one-pot synthesis of benzofuro/thieno[2,3-b]pyrrole motifs

A novel I₂-catalyzed one-pot multicomponent protocol for the synthesis of a variety of elusive furo[2,3-b]pyrrole and thieno[2,3-b]pyrrole libraries has been established. To date, cyclization among alkanone, hydrazine and 2-bromobenzofuran or 2-bromobenzo[b]thiophene has not been explored in one-pot. Thus, the proposed single step protocol provides a versatile alternative to existing routes for accessing useful furo[2,3-b]pyrrole and thieno[2,3-b]pyrrole libraries.     

A rapid, one-pot, four-component route to 2H-indazolo[2,1-b]phthalazine-triones

A new, efficient, and environmentally benign protocol for the one-pot, four-component synthesis of 2,2-dimethyl-13-phenyl-2,3-dihydro-1H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione by condensation of phthalic anhydride, hydrazinium hydroxide, aromatic aldehydes, and dimedone catalyzed by Ce(SO₄)₂·4H₂O as an ecofriendly catalyst with high catalytic activity and reusability at 125 °C under solvent-free conditions is reported. The reaction proceeds to completion within 5-10 min in 71-95% yield. To the best of our knowledge, this new procedure provides the first example of an efficient synthetic method for 2H-indazolo[2,1-b]phthalazine-1,6,11(13H)-trione via a four-component reaction.     

Transesterifications mediated by t-BuNH2

A mild protocol for transesterification of simple esters is described. The method is based on the use of t-BuNH₂/ROH (R = Me, Et, i-Pr, t-Bu) with or without LiBr. The scope of the procedure was explored for aliphatic and aromatic esters. The protocol is particularly useful when going from higher to lower hindered esters and harsh reaction conditions are needed for the reversal process. A rationalization of the mechanism is presented. The scope and limitation of this transformation are also described.     

Indium catalyzed solvent-free multicomponent synthesis of cytotoxic dibenzo[a,h]anthracenes from aldehydes, 2-hydroxy-1,4-naphthoquinone,and 2-naphthol

A series of dibenzo[a,h]anthracene derivatives were synthesized through a straightforward, one-pot protocol based on a three-component reaction with 2-hydroxy-1,4-naphthoquinone, aromatic aldehydes, and 2-naphthol as synthetic inputs, using InCl₃ a catalyst under solvent-free conditions. Most of the obtained ortho-quinonic adducts were cytotoxic against HEL and MCF-7 tumoral cell lines.     

Palladium-catalyzed cross-coupling of aryl chlorides with alkenylboronic acids with low E/Z isomerization

Using a bulky electron-rich monodentate benzoferrocenyl phosphine as supporting ligand, an efficient protocol for stereoselective palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl chlorides with alkenylboronic acids was uncovered. Using this protocol, both trans- and cis-alkenylboronic acids can be coupled with high stereoselectivity giving the corresponding vinylarenes in good to quantitative yields. Electron-poor and -rich aryl chlorides including highly hindered ones are all suitable substrates for the reaction.     

Base-promoted 1,3-dipolar cycloaddition reaction of nitrile oxides with methyl 1,4-dioxo-1,4-dihydronaphthalene-2-carboxylate for the construction of naphtho[2,3-d]isoxazole-4,9(3aH,9aH)-diones

A base mediated 1,3-dipolar cycloaddition reaction of methyl 1,4-dioxo-1,4-dihydronaphthalene-2-carboxylate with nitrile oxides in situ generated from N-hydroximoyl chlorides was achieved. With this developed protocol, a range of structurally diverse naphtho[2,3-d]isoxazole-4,9(3aH,9aH)-dione derivatives were smoothly obtained in high yields (up to 95%) with up to >20:1 regioselectivities and >20:1 diastereoselectivities under mild conditions. The promising applicability of the protocol was also demonstrated by the further transformations.     

Dipyridyl/pyridinium thieno[2,3-b]thiophenes as new atropisomeric systems. Synthesis, conformational analysis and energy minimization

Synthesis of a new class of cofacially oriented dipyridyl(pyridinium)lthieno[2,3-b]thiophenes with or without -CO₂Et and -COMe substituents at C2, and C5 positions of thieno[2,3-b]thiophene ring was readily accomplished using a double Dieckman cyclization protocol as the key step. While C2/C5 substituted dipyridylthieno[2,3-b]thiophenes exhibited syn/anti atropisomerism at least up to 70 °C with Arrhenius energy of activation (ΔG^≠) in the range of 17-18 kcal/mol, on the other hand unsubstituted dipyridylthieno[2,3-b]thiophene and its bis-N-quaternized salt were found to show free conformational rotation with an estimated ΔG^≠ of lower than 10 kcal/mol. Conformational energy minimization using AM1 protocol revealed a slight preference for the anti over syn isomers. Compared to the unsubstituted dipyridylthieno[2,3-b]thiophenes, higher energy barriers to rotation (3.7-5.1 kcal/mol) in substituted dipyridylthieno[2,3-b]thiophenes can be attributed to steric encumbrance resulting from -CO₂Et and -COMe substituents located on the non-rotating thienothiophene platform.     

Efficient, protection-free Suzuki-Miyaura synthesis of ortho-biphenyltetrazoles

We describe an efficient protocol for the Suzuki-Miyaura synthesis of ortho-biphenyltetrazoles from non-protected 2-bromophenyltetrazole and arylboronic acids. The optimised conditions were achieved using [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) as catalyst and Na₂CO₃ as base. A panel of structurally diverse arylboronic acids was used to demonstrate the scope of the coupling procedure.     

A facile approach for the synthesis of 14-aryl- or alkyl-14H-dibenzo[a,j]xanthenes under solvent-free condition

A facile, efficient and environment-friendly protocol for the synthesis of 14-aryl- or alkyl-14H-dibenzo[a,j]xanthenes has been developed by one-pot condensation of 2-naphthol with aliphatic and aromatic aldehydes in the presence of P₂O₅ or InCl₃ as catalysts under solvent-free conditions. The present approach offers the advantages of clean reaction, simple methodology, short reaction time, high yield, easy purification, and economic availability of the catalyst.     

AcOH-catalyzed aza-Michael addition/N-nitrosation: An efficient approach to CF2HCH2-containing N-nitrosoamines

A simple and highly efficient protocol for the AcOH-catalyzed three-component reaction among nitroalkenes, difluoroethylamine and tert-butyl nitrite through cascade aza-Michael addition/N-nitrosation has been developed. A range of CF₂HCH₂-containing N-nitrosoamines were obtained in good to excellent yields. This approach features easily available cheap materials, without using additional organic solvents, simple operation under room temperature, gram scalable preparation and functionally diverse products.     

NH4I/EtOCS2K promoted synthesis of substituted benzils from diphenylacetylene derivatives

A facile protocol is described for the synthesis of benzil derivatives from readily accessible diarylacetylene derivatives using the NH₄I/EtOCS₂K system. This novel protocol results in excellent chemoselectivity and provided good to excellent yields. A control experiment indicated that the reaction proceeds via NH₄I promoted EtOCS₂K dimerization to give the corresponding dixanthogen and subsequent dixanthogen assisted oxidation.     

Total synthesis of maremycins A,B, C1/C2, D1, and D2

The total synthesis of maremycins A, B, C₁/C₂, D₁, and D₂ is achieved starting from the natural amino acids l-isoleucine and S-methyl-l-cysteine, in which the total synthesis of maremycins B, C₁/C₂, and D₂ is accomplished for the first time. The synthesis features a position-selective intramolecular bromination process for the synthesis of key chiral building block, a Pd-catalyzed indole synthesis for the preparation of (2S,3S)-β-methyltryptophan and hydroxylation of oxindoles by molecular oxygen. In addition, the protocol for conversion of maremycins A and B to maremycins C and D was improved.