Rare Metal‐Free Photo‐Aerobic Intramolecular Dehydrogenative Cyclization Reaction towards Polycyclic Heteroarenes

We have achieved a rare‐metal‐free photo‐aerobic intramolecular dehydrogenative coupling reaction from two C—H bonds of indole with malonate. This catalytic system proceeded at room temperature under visible light irradiation with oxygen in the air as a terminal oxidant, and the cyclization products were obtained in good to excellent yields.

     

Aldehyde‐Catalyzed Transition Metal‐Free Dehydrative β‐Alkylation of Methyl Carbinols with Alcohols

Different to the borrowing hydrogen strategy in which alcohols were activated by transition metal‐catalyzed anaerobic dehydrogenation, the direct addition of aldehydes was found to be an effective but simpler way of alcohol activation that can lead to efficient and green aldehyde‐catalyzed transition metal‐free dehydrative C‐alkylation of methyl carbinols with alcohols. Mechanistic studies revealed that the reaction proceeds via in situ formation of ketones by Oppenauer oxidation of the methyl carbinols by external aldehydes, aldol condensation, and Meerwein–Ponndorf–Verley (MPV)‐type reduction of α,β‐unsatutated ketones by substrate alcohols, affording the useful long chain alcohols and generating aldehydes and ketones as the by‐products that will be recovered in the next condensation to finish the catalytic cycle.     

Metal‐Free Oxidative Cross Esterification of Alcohols via Acyl Chloride Formation

A novel metal‐free oxidative cross esterification of alcohols has been achieved using trichloroisocyanuric acid as an oxidant. The alcohols were converted in situ into their corresponding acyl chlorides, which were then reacted with primary and secondary aliphatic, benzylic and allylic alcohols and phenols. A wide variety of esters was obtained in satisfactory yields.

     

Synthesis of 3‐Benzazepines by Metal‐Free Oxidative C–H Bond Functionalization–Ring Expansion Tandem Reaction

A metal‐free synthesis of biologically important benzazepines is achieved through a single synthetic operation involving an oxidative C–H bond functionalization and ring expansion with diazomethanes as key reagent. This represents a new, strong methodology for the straightforward construction of the seven‐ring N‐heterocyclic structures under mild conditions using a 2,2,6,6‐tetramethylpiperidine 1‐oxyl (TEMPO) oxoammonium salt as oxidant. Moderate to good yields are achieved from simple, readily available tetrahydroisoquinolines, and this methodology has been further successfully applied for the synthesis of the 3‐benzazepine drug Lorcaserin. A possible mechanistic pathway for the ring expansion step, comprising the extrusion of nitrogen in a concerted asynchronic process, is proposed based on both mechanistic proof and density function theory (DFT) calculations.

     

Catching Elusive 2‐Furyl Carbenes with Silanes: A Metal‐Free Microwave‐Assisted Silicon‐Hydrogen Bond Functionalization

An efficient, metal‐free, silicon–hydrogen bond functionalization based on the microwave‐assisted reaction of readily available enynones and silanes is reported. This process seemingly proceeds through a 2‐furyl carbene species, a particularly elusive intermediate. Preliminary studies on the metal‐free oxygen–hydrogen and nitrogen–hydrogen bond functionalization of representative alcohols, azoles and sulfonamides are also provided.

     

Double‐Oxidative Dehydrogenative (DOD) Cyclization of Glycine Derivatives with Dioxane under Metal‐Free Aerobic Conditions

The first carbon tetrabromide‐promoted novel double‐oxidative dehydrogenative cyclization/acidic ring opening/aromatization tandem reaction of glycine derivatives with dioxane for the synthesis of complex quinoline motifs has been developed (up to 71% yield). The use of very inexpensive substrates (glycine derivatives and dioxane) and an extremely simple metal‐free promoter (carbon tetrabromide) with green molecular oxygen (air) as an oxidant make this protocol very attractive for potential synthetic applications. A plausible mechanism involving a radical process is proposed.

     

p‐Toluenesulfonylmethyl Isocyanide (TosMIC) and Indium Manifold Strategy to Access β‐Keto‐(E)‐enamino Esters from 1,3‐Dicarbonyl Compounds

The indium trichloride‐catalyzed C C bond formation between 1,3‐dicarbonyl compounds and p‐toluenesulfonylmethyl isocyanide (TosMIC) to access β‐keto‐(E)‐enamino esters exclusively is reported for the first time. The corresponding products are obtained in good to excellent yields.     

Green and Scalable Aldehyde‐Catalyzed Transition Metal‐Free Dehydrative N‐Alkylation of Amides and Amines with Alcohols

In contrast to the borrowing hydrogen‐type N‐alkylation reactions, in which alcohols were activated by transition metal‐catalyzed anaerobic dehydrogenation, the addition of external aldehydes was accidentally found to be a simple and effective protocol for alcohol activation. This interesting finding subsequently led to an efficient and green, practical and scalable aldehyde‐catalyzed transition metal‐free dehydrative N‐alkylation method for a variety of amides, amines, and alcohols. Mechanistic studies revealed that this reaction most possibly proceeds via a simple but interesting transition metal‐free relay race mechanism.     

Visible Light‐Mediated Metal‐Free Synthesis of Vinyl Sulfones from Aryl Sulfinates

Visible light and eosin Y catalyze the synthesis of vinyl sulfones from aryl sulfinates and alkenes by a photoredox process. The reaction scope is broad in aryl sulfinates and alkenes and the general and simple procedure provides a metal‐free alternative for the synthesis of synthetically valuable vinyl sulfones.

     

Palladium(II)‐Catalyzed Efficient C‐3 Functionalization of Indoles with Benzylic and Allylic Alcohols under Co‐Catalyst,Acid, Base,Additive and External Ligand‐Free Conditions

The bis(acetonitrile)palladium(II) chloride complex, PdCl₂(MeCN)₂, efficiently catalyzes the regioselective alkylation of indoles with various benzylic and allylic alcohols under moisture and air insensitive conditions. Notably the reaction does not require any other co‐catalyst, acid, base, additive, or external ligand.     

Synthesis of Unsymmetrical Diorganyl Chalcogenides under Greener Conditions: Use of an Iodine/DMSO System,Solvent‐ and Metal‐Free Approach

Herein, we report a greener iodine‐catalyzed protocol to access different types of unsymmetrical diorganyl chalcogenides. This new approach works in the absence of solvent and metal. The desired products were obtained in good to excellent yields using one equivalent of arylboronic acids, half an equivalent of various diorganyl dichalcogenides, iodine (10 mol%) as a catalyst and 2 equivalents of dimethyl sulfoxide (DMSO; as oxidant), with a reaction time of 10 min under microwave irradiation.

     

Formation of Acetals under Rhodium‐Catalyzed Hydroformylation Conditions in Alcohols

Hydroformylation of terminal alkenes in alcohol solvents leads to the selective formation of the corresponding acetals. The Xantphos ligand gave the best results as well as acetal selectivities higher than 99% and linear/branched ratios of up to 52 were obtained. The scope of the reaction was studied. Acetals were found to be unreactive under hydroaminomethylation conditions.     

Sulfonic Acid‐Functionalized Ionic Liquids as Metal‐Free,Efficient and Reusable Catalysts for Direct Amination of Alcohols

A series of sulfonic acid‐functionalized (SO₃H‐functionalized) ionic liquids was synthesized and used as metal‐free, highly selective and efficient catalysts for the direct amination of alcohols. Notably, the activities of the series of SO₃H‐functionalized ionic liquids were compared and a 92% isolated yield was obtained using 3‐tetradecyl‐1‐(butyl‐4‐ sulfonyl)imidazolium trifluoromethanesulfonate ([BsTdIM][OTf]) as the catalyst. Importantly, the catalytic system has wide substrate scope including benzylic, allyl, propargylic, aliphatic alcohols with sulfonamide, amide, carbamate, aromatic amine and N‐heterocyclic compounds. Interestingly, the system was also suitable for a multi‐gram scale direct amination of alcohols. Additionally, the reusable nature of [BsTdIM][OTf] makes this protocol more attractive and avoids the disposal and neutralization of acidic catalysts. Moreover, preliminary experiments indicated that this reaction should proceed via an S_N1 pathway.     

Bioinspired,Base‐ and Metal‐Free,Mild Decarboxylative Aldol Activation of Malonic Acid Half Thioesters Under Phase‐Transfer Reaction Conditions

Utilizing ‘off the shelf’ commercially available, cheap, small synthetic molecules that mimic the efficient mediation of important bioreactions utilized by Nature is not only highly sought after but also currently highly topical. This paper details our preliminary efforts at developing a unique base‐ and metal‐free phase‐transfer‐mediated malonic acid thioester (MAHT) ‘activation protocol’ that efficiently generates (±)‐β‐thioesters. Our bioinspired aldol process is exceptionally mild, conducted under near neutral pH reaction conditions, does not require an inert, oxygen‐free atmosphere or anhydrous reaction conditions and is highly atom‐economic. Exemplifying the utility of our protocol, the synthesis of an array of structurally and functionally diverse (±)‐β‐hydroxy thioesters equipped with highly prized functionality, i.e., chlorine, bromine, fluorine, nitrile and nitro groups, is reported, as is the diastereoselective potential of this important reaction.

     

Lewis Acid‐Catalyzed Oxidative Allylation: A New Approach for the Synthesis of Homoallylic Alcohols and Amines Directly from Alcohols

A new approach for the synthesis of homoallylic alcohols and amines directly from alcohols via one‐pot sequential oxidation–Barbier reaction and oxidation–condensation–Barbier reactions, respectively, is reported. The protocol involves the one‐pot ferric chloride‐catalyzed oxidation of alcohols to the corresponding aldehydes with chloramine‐T followed by indium‐mediated Barbier allylation with allyl bromide to afford homoallylic alcohols in 70–90% overall yields. The ferric chloride‐catalyzed condensation of aldehydes and oxidation by‐product p‐toluenesulfonamide followed by indium‐mediated Barbier‐type allylation of the resulting aldimines with allyl bromide affords homoallylic amines in 60–80% overall yields in the same reaction vessel. The present work demonstrates a new one‐pot approach toward homoallylic alcohol and amine synthesis directly from alcohols.     

Transition Metal‐Free Homocoupling of Unactivated Electron‐Deficient Azaarenes

This work has established the first direct homocoupling of unactivated electron‐deficient azaarenes in the presence of TMPMgCl (2,2,6,6‐tetramethylpiperidinylmagnesium chloride) and TMEDA (tetramethylethylenediamine). In this process, no transition metal was used while freely available air was employed as the oxidant. The investigated successful substrates included quinolines, isoquinoline, 3‐phenylated pyridines, and 2‐phenylated quinoxalines, giving moderate to high yields. The homocoupling of quinolines was effectively scaled up to one gram in high yield. Additionally, an iridium complex of 6,6′‐dimethyl‐2,2′‐biquinoline was prepared and characterized as an efficient red‐emitting material.

     

Acetyl Bromide Promoted Sequence via Allene Intermediates: Metal‐Free Construction of 2,3‐Dihydroindenes and Isoindolines

2,3‐Dihydroindenes and isoindolines are important skeletons present in medicinal and synthetic chemistry. In this paper, an acetyl bromide promoted metal‐free construction of 2,3‐dihydroindenes and isoindolines with high synthetic efficiency is developed.

     

Potassium Hydroxide/Dimethyl Sulfoxide Superbase‐Promoted Transition Metal‐Free Synthesis of 2‐Substituted Benzothiophenes under Visible Light

A potassium hydroxide/dimethyl sulfoxide (KOH/DMSO) superbase‐promoted method for the synthesis of 2‐substituted benzothiophenes has been developed via photoinduced intermolecular annulation of 2‐halothioanisoles with terminal alkynes at ambient temperature. The present protocol uses commercially available 2‐halothioanisoles as substrates and visible light as energy force, which offers a wide range of benzothiophenes regioselectively in moderate to good yields. Such a facile and effective transformation will provide an environment‐friendly approach to the synthesis of benzothiophene derivatives.

     

Hydroxylamine as a Source for Nitric Oxide in Metal‐Free 2,2,6,6‐ Tetramethylpiperidine N‐Oxyl Radical (TEMPO) Catalyzed Aerobic Oxidation of Alcohols

The communication reports on the metal‐free 2,2,6,6‐tetramethylpiperidine N‐oxyl radical (TEMPO) catalyzed aerobic oxidation of various alcohols to aldehydes and ketones. A novel catalyst system that uses 1–4 mol% of TEMPO in combination with 4–6 mol% of aqueous hydroxylamine is introduced. No other additives are necessary and corrosive by‐products are not formed during oxidation. Nitric oxide which is important for the catalytic cycle is generated in situ by reaction of the hydroxylamine with TEMPO. A catalytic cycle for the overall oxidation process is suggested.     

Potassium tert‐Butoxide‐Promoted Synthesis of 1‐Aminoisoquinolines from 2‐Methylbenzonitriles and Benzonitriles under Catalyst‐Free Conditions

Herein a practical and efficient protocol for preparing a range of aminoisoquinolines is reported. Various aminoisoquinolines were prepared in moderate to good yields from the corresponding 2‐methylbenzonitriles and benzonitriles upon treatment with potassium tert‐butoxide.