Metal free amide synthesis via carbon–carbon bond cleavage

A metal-free oxidative coupling of methyl ketones and primary amines to amides has been developed. The reaction tolerates a variety of functional groups, and is operationally simple. The reaction is proposed to go through a radical pathway to form the triiodomethyl ketone intermediate and the amide is formed by the nucleophilic attack of amine on triiodomethyl ketone carbonyl.     

Metal-Free Chemoselective Oxidation of 4-Methylquinolines into Quinoline-4-Carbaldehydes

A convenient protocol for the synthesis of quinoline-4-carbaldehydes via chemoselective oxidation of 4-methylquinolines using hypervalent iodine(III) reagents as oxidant is described. This method highlights metal-free and mild reaction conditions, nice yield, good functional group tolerance, and high chemoselectivity.     

Metal-Free Regioselective Chloroazidation of Internal Alkynes

A metal-free, room temperature protocol for the regioselective chloroazidation of internal alkynes is disclosed. The reactions of internal alkynes with trimethylsilyl azide (TMSN₃) in the presence of 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) afforded the corresponding chloroazidoalkenes in good yields. This reaction has good functional group tolerance and is operationally simple.     

Facile synthesis of methylthiomethyl esters through Pummerer-type rearrangement of carboxylic acids and DMSO under metal-free conditions

A green and cost-effective Pummerer-type rearrangement between readily accessible carboxylic acids and DMSO has been achieved under metal-free conditions in satisfactory to excellent yields. The transformation for the synthesis of valuable methylthiomethyl esters is shown to be a convenient strategy for various (hetero)aromatic acids, α,β-unsaturated carboxylic acids and saturated alkyl carboxylic acids with good functional group tolerance.     

A metal-free C–C/C–O bond formation for the synthesis of 2-amino-5-oxo-4-aryl-4H,5H-pyrano[3,2-c]chromene-3-carboxamide catalyzed by polystyrene-supported p-toluenesulfonic acid (PS-PTSA)

An efficient and eco-friendly procedure for the synthesis of 2-amino-5-oxo-4-aryl-4H,5H-pyrano[3,2-c]chromene-3-carboxamide has been developed through a one-pot three-component condensation of 4-hydroxycoumarin with aldehydes and cyanoacetamide, in the presence of catalytic amount of polystyrene-supported p-toluenesulfonic acid (PS-PTSA) as a highly active and reusable heterogeneous acid catalyst in EtOH at 80?°C conditions. This new procedure offers several advantages such as shorter reaction times, excellent yields, a wide range of functional group tolerance, easy experimental work-up procedure, operationally simple under metal-free reaction conditions and C-C/C-O bond formation. The catalyst can be recovered and reused for at least four runs without any significant impact on the product yields.     

Conversion of Olefins into Ketones by an Iron‐Catalyzed Wacker‐type Oxidation Using Oxygen as the Sole Oxidant

We describe a mild and operationally simple procedure for the oxidation of olefins into ketones. The reaction is catalyzed by the hexadecafluorinated iron–phthalocyanine complex FePcF₁₆ with stoichiometric amounts of triethylsilane as an additive under oxygen atmosphere to give ketones in good to high yields with excellent chemoselectivity and functional group tolerance. Ketone formation proceeds in up to 95 % yield and with 100 % regioselectivity while the corresponding alcohols were observed as side products.     

Metal-free one-pot synthesis of quinoline-2,4-carboxylates via a molecular iodine-catalyzed three-component reaction of arylamines,ethyl glyoxylate,and α-ketoesters

A simple and metal-free method has been developed for the construction of quinoline-2, 4-carboxylates under mild conditions via a molecular iodine-catalyzed three-component tandem reaction of arylamines, ethyl glyoxylate, and α-ketoesters. The present protocol provides a convenient and attractive approach to various quinoline-2, 4-carboxylates in moderate to good yields with excellent functional group tolerance.     

One-pot synthesis of phosphorodiamidothioates using N-heterocyclic phosphine (NHP)-thiourea

N-heterocyclic phosphine (NHP)-thiourea-promoted thiophosphation of thiols has been developed for the synthesis of phosphorodiamidothioates under additive-, metal-free reaction conditions. This reaction takes place at room temperature and exhibits good functional group tolerance. The key to success is that the thiourea group can serve as an excellent leaving group, which is tethered with NHP moiety.     

Coupling of Methyl Ketones and Primary or Secondary Amines Leading to α-Ketoamides

A metal-free oxidative coupling of methyl ketones and primary or secondary amines to α-ketoamides has been developed. Four intermediates, α-iodoketone, α-aminoketone, iminium intermediate, and α-hydroxy amine have been identified through a series of control experiments. The atom-economic methodology can be scaled-up, tolerates a variety of functional groups, and is operationally simple.     

Carbonyl Olefin Metathesis and Dehydrogenative Cyclization of Aromatic Ketones and gem-Difluoroalkenes

The beauty of one-pot cascade reaction lies in the efficient disconnection and construction of several bonds in a single reaction flask, without the isolation of any intermediates. Herein, we report the first photoinduced thermally promoted cascade reactions of readily available aromatic ketones and aromatic gem-difluoroalkenes for the synthesis of phenanthrenes which possess potential utility in drug design and materials science. The reaction combines carbonyl-olefin metathesis (cascade photoinduced [2+2] cyclization and thermally controlled retro [2+2] cyclization) and dehydrogenative cyclization (cascade photoinduced conrotatory 6π electrocyclization and collidine-promoted dehydrogenative aromatization) together in one pot. The oxidant-free, acid-free and metal-free reaction shows broad substrate scope and wide functional group tolerance.     

TBAI/TBHP mediated oxidative cross coupling of ketones with phenols and carboxylic acids: Direct access to benzofurans

TBAI/TBHP mediated oxidative cross coupling of phenols and carboxylic acids with ketones has been reported under metal-free, base free, solvent free conditions enabling environmentally benign synthesis of aryloxyketones, acyloxy ketones and benzofurans. Phenoxyketones and acyloxylcarbonyl compounds were synthesized in good to high yields, where as benzofurans were synthesized in moderate yields. This method is operationally simple, works under mild conditions, using commercially available as well as inexpensive TBAI and an oxidant TBHP.     

Metal-Free Synthesis of Carbamoylated Chroman-4-Ones via Cascade Radical Annulation of 2-(Allyloxy)arylaldehydes with Oxamic Acids

An efficient and straightforward approach for the synthesis of carbamoylated chroman-4-ones has been well-developed. The reaction is triggered through the generation of carbamoyl radicals from oxamic acids under metal-free conditions, which subsequently undergoes decarboxylative radical cascade cyclization on 2-(allyloxy)arylaldehydes to afford various amide-containing chroman-4-one scaffolds with high functional group tolerance and a broad substrate scope.     

Visible‐Light‐Mediated Synthesis of β‐Chloro Ketones from Aryl Cyclopropanes

We report the visible‐light‐mediated synthesis of β‐chloro ketones from aryl cyclopropanes, oxygen, hydrochloric acid, and nitric acid. The operationally simple and catalyst‐free method uses cheap standard laboratory reagents and displays broad functional‐group tolerance. Moreover, scale up of the reaction and late‐stage functionalization of bioactive compounds is possible, providing the opportunity to utilize the cyclopropane ring as a masked β‐chloro ketone in a reaction sequence. We propose a light‐driven radical chain reaction initiated by the reaction of diluted hydrochloric and nitric acid to produce small quantities of molecular chlorine. The mechanistic hypothesis is supported by ¹⁸O labelling and UV/Vis experiments, cyclovoltammetry, and several control reactions.     

TBAI-mediated regioselective sulfenylation of indoles with sulfonyl chlorides in one pot

A versatile method for the synthesis of 3-sulfenylated indoles via TBAI promoted sulfenylation of indoles with sulfonyl chlorides in one pot has been presented. This system features highly regioselective, metal-free, easy operation, and shows a broad functional group tolerance leading to excellent yields. And this reaction could be easily conducted in 10?mmol scale with high effectivity. A plausible mechanism is proposed.     

Intramolecular oxidative diamination and aminohydroxylation of olefins under metal-free conditions

A metal-free procedure that is simple to operate and convenient to handle was developed for the facile intramolecular oxidative diamination of olefins using an iodobenzene diacetate oxidant and a halide additive to furnish bisindolines at room temperature. The present reaction is featured by mild conditions, a broad substrate scope, and excellent functional group tolerance. The same protocol was successfully extended to the aminohydroxylation.     

Visible-light mediated carbonyl trifluoromethylative amination as a practical method for the synthesis of β-trifluoromethyl tertiary alkylamines

We report the development of an operationally straigtforward, visible-light-mediated multicomponent strategy for the construction of β-trifluoromethylated tertiary alkylamines from feedstock aldehydes, secondary amines and a convenient source of trifluoromethyl iodide. The new process does not require a photocatalyst, is metal-free, displays a broad functional group tolerance and offers rapid, one-pot access to trifluoromethylated drug-like compounds that will be of interest in medicinal chemistry.

An operationally straightforward, visible-light-mediated multicomponent strategy for the construction of β-trifluoromethylated tertiary alkylamines from aldehydes, secondary amines and a convenient source of trifluoromethyl iodide is reported.     

Metal-free synthesis of 3,3-disubstituted oxindoles via 1,2-alkylarylation of activated alkenes with alcohols

Metal-free synthesis of 3,3-disubstituted oxindoles utilizing N-arylacrylamides and simple alcohols is developed. It provides an efficient method for preparing a series of hydroxyl-containing oxindole derivatives. This reaction is proposed to proceed through oxidative radical cyclization mechanism. The remarkable features of the reaction are metal-free condition and excellent functional group tolerance.     

Direct, metal-free amination of heterocyclic amides/ureas with NH-heterocycles and N-substituted anilines in POCl3

A POCl(3)-mediated, direct amination reaction of heterocyclic amides/ureas with NH-heterocycles or N-substituted anilines is described. Compared to the existing methods, this operationally simple protocol provides unique reactivity and functional group compatibility because of the metal-free, acidic reaction conditions. The yields are generally excellent.     

Copper‐Catalyzed 1,2‐Addition of α‐Carbonyl Iodides to Alkynes

β,γ‐Unsaturated ketones are an important class of organic molecules. Herein, copper catalysis has been developed for the synthesis of β‐γ‐unsaturated ketones through 1,2‐addition of α‐carbonyl iodides to alkynes. The reactions exhibit wide substrate scope and high functional group tolerance. The reaction products are versatile synthetic intermediates to complex small molecules. The method was applied for the formal synthesis of (±)‐trichostatin A, a histone deacetylase inhibitor.     

Metal-free synthesis of substituted phenols from arylboronic acids in water at room temperature

A convenient,efficient and practical metal-free method for the synthesis of substituted phenols from arylboronic acids has been developed.The protocol uses hydrogen peroxide as a hydroxylating agent ammonium bicarbonate as an additive,and the reactions were conveniently performed in water at room temperature.The method shows an excellent tolerance of functional groups,so it will find a wide variety of applications in academic and industrial research.