Transition‐Metal‐Free Trifluoromethylthiolation of N‐Heteroarenes

A general and efficient methodology for the direct transition metal free trifluoromethylthiolation of a broad range of biologically relevant N‐heteroarenes is reported employing abundant sodium chloride as the catalyst. This method is operationally simple, exhibits high functional group tolerance, and does not require protecting groups.     

Transition‐Metal‐Free Synthesis of N‐(1‐Alkenyl)imidazoles by Potassium Phosphate‐Promoted Addition Reaction of Alkynes to Imidazoles

The addition reaction of alkynes to N‐heterocycles by simply heating in DMSO with potassium phosphate is reported. Good yields with high stereoselectivity could be achieved for a range of substrates. The scope is quite general for both amines and phenylacetylenes. In addition, internal alkynes and α‐bromostyrene were also examined in this reaction. This process is efficient and useful for the synthesis of (Z)‐N‐(1‐alkenyl)imidazoles and related Z products. Thus, the reaction is useful because of the importance of the imidazole scaffold.     

Transition‐Metal‐Free Synthesis of N‐Hydroxy Oxindoles by an Aza‐Nazarov‐Type Reaction Involving Azaoxyallyl Cations

A novel transition‐metal‐free method to construct N‐hydroxy oxindoles by an aza‐Nazarov‐type reaction involving azaoxyallyl cation intermediates is described. A variety of functional groups were tolerated under the weak basic reaction conditions and at room temperature. A one‐pot process was also developed to make the reaction even more practical. This method provides alternative access to oxindoles and their biologically active derivatives.     

Transition‐Metal‐Free Synthesis of Carbazoles and Indoles by an SNAr‐Based “Aromatic Metamorphosis” of Thiaarenes

Dibenzothiophene dioxides, which are readily prepared through oxidation of the parent dibenzothiophenes, undergo nucleophilic aromatic substitution with anilines intermolecularly and then intramolecularly to yield the corresponding carbazoles in a single operation. The “aromatic metamorphosis” of dibenzothiophenes into carbazoles does not require any heavy metals. This strategy is also applicable to the synthesis of indoles. Since electron‐deficient thiaarene dioxides exhibit interesting reactivity, which is not observed for that the corresponding electron‐rich azaarenes, a combination of a thiaarene‐dioxide‐specific reaction with the S_NAr‐based aromatic metamorphosis allows transition‐metal‐free construction of difficult‐to‐prepare carbazoles.     

Reaction of an N‐Heterocyclic Carbene‐Stabilized Silicon(II) Monohydride with Alkynes: [2+2+1] Cycloaddition versus Hydrogen Abstraction

An in depth study of the reactivity of an N‐heterocyclic carbene (NHC)‐stabilized silylene monohydride with alkynes is reported. The reaction of silylene monohydride 1 , tBu₃Si(H)Si←NHC, with diphenylacetylene afforded silole 2 , tBu₃Si(H)Si(C₄Ph₄). The density functional theory (DFT) calculations for the reaction mechanism of the [2+2+1] cycloaddition revealed that the NHC played a major part stabilizing zwitterionic transition states and intermediates to assist the cyclization pathway. A significantly different outcome was observed, when silylene monohydride 1 was treated with phenylacetylene, which gave rise to supersilyl substituted 1‐alkenyl‐1‐alkynylsilane 3 , tBu₃Si(H)Si(CH?CHPh)(C?CPh). Mechanistic investigations using an isotope labelling technique and DFT calculations suggest that this reaction occurs through a similar zwitterionic intermediate and subsequent hydrogen abstraction from a second molecule of phenylacetylene.     

Transition‐Metal‐Free N‐Arylation of Pyrazoles with Diaryliodonium Salts

A new synthetic method was developed for the N‐arylation of pyrazoles using diaryliodonium salts. The transformation does not require any transition‐metal catalyst and provides the desired N‐arylpyrazoles rapidly under mild reaction condition in the presence of aqueous ammonia solution as a mild base without the use of inert atmosphere. The chemoselectivity of unsymmetric diaryliodonium salts was also explored with large number of examples.     

Concerted and Stepwise Mechanisms in Metal‐Free and Metal‐Assisted [4+3] Cycloadditions Involving Allyl Cations

The thermal [4+3] cycloaddition reaction between allenes and tethered dienes (1,3‐butadiene and furan) assisted by transition metals (Au^I, Au^III, Pd^II, and Pt^II) was studied computationally within the density functional theory framework and compared to the analogous non‐organometallic process in terms of activation barriers, synchronicity and aromaticity of the corresponding transition states. It was found that the metal‐mediated cycloaddition reaction is concerted and takes place via transition structures that can be even more synchronous and more aromatic than their non‐organometallic analogues. However, the processes exhibit slightly to moderately higher activation barriers than the parent cycloaddition involving the hydroxyallylic cation. The bond polarization induced by the metal moiety is clearly related to the interaction of the transition metal with the allylic π* molecular orbital, which constitutes the LUMO of the initial reactant. Finally, replacement of the 1,3‐butadiene by furan caused the transformation to occur stepwise in both the non‐organometallic and metal‐assisted processes.     

Mechanism of the Transition‐Metal‐Catalyzed Hydroarylation of Bromo‐Alkynes Revisited: Hydrogen versus Bromine Migration

A comprehensive mechanistic study of the InCl₃‐, AuCl‐, and PtCl₂‐catalyzed cycloisomerization of the 2‐(haloethynyl)biphenyl derivatives of Fürstner et al. was carried out by DFT/M06 calculations to uncover the catalyst‐dependent selectivity of the reactions. The results revealed that the 6‐endo‐dig cyclization is the most favorable pathway in both InCl₃‐ and AuCl‐catalyzed reactions. When AuCl is used, the 9‐bromophenanthrene product could be formed by consecutive 1,2‐H/1,2‐Br migrations from the Wheland‐type intermediate of the 6‐endo‐dig cyclization. However, in the InCl₃‐catalyzed reactions, the chloride‐assisted intermolecular H‐migrations between two Wheland‐type intermediates are more favorable. These Cl‐assisted H‐migrations would eventually lead to 10‐bromophenanthrene through proto‐demetalation of the aryl indium intermediate with HCl. The cause of the poor selectivity of the PtCl₂ catalyst in the experiments by the Fürstner group was predicted. It was found that both the PtCl₂‐catalyzed alkyne–vinylidene rearrangement and the 5‐exo‐dig cyclization pathways have very close activation energies. Further calculations found the former pathway would lead eventually to both 9‐ and 10‐bromophenanthrene products, as a result of the Cl‐assisted H‐migrations after the cyclization of the Pt–vinylidene intermediate. Alternatively, the intermediate from the 5‐exo‐dig cyclization would be transformed into a relatively stable Pt–carbene intermediate irreversibly, which could give rise to the 9‐alkylidene fluorene product through a 1,2‐H shift with a 28.1 kcal mol^?1 activation barrier. These findings shed new light on the complex product mixtures of the PtCl₂‐catalyzed reaction.     

Metal‐Free Allene‐Based Synthesis of Enantiopure Fused Polycyclic Sultones

The controlled metal‐free preparation of fused δ‐sultone derivatives has been developed starting from hydroxyallenynes. The use of 2‐(3,3‐diethyltriaz‐1‐enyl)‐4‐methylbenzene‐1‐sulfonyl chloride in a sulfonylation/rearrangement sequence gives access to 1,3‐dien‐2‐yl arenesulfonates. These functionalized enynes suffered a direct cyclization/desaturation radical cascade, allowing the synthesis of a variety of enynyl [1,2]oxathiine 1,1‐dioxides. Stereoselective cyclization of the readily formed core through intramolecular Diels–Alder reaction has also been demonstrated, affording β‐lactam‐ and glucofuranoside‐fused δ‐sultone polycycles. These selective reactions have been studied experimentally and additionally, their reaction mechanisms have been investigated computationally by means of density functional theory calculations.     

Chemoselective Switch in the Asymmetric Organocatalysis of 5H‐Oxazol‐4‐ones and N‐Itaconimides: Addition–Protonation or [4+2] Cycloaddition

We report a synthetic strategy for a chemoselective switch and a diastereo‐divergent approach for the asymmetric reaction of 5H‐oxazol‐4‐ones and N‐itaconimides catalyzed by l ‐tert‐leucine‐derived tertiary amine–urea compounds. The reaction was modulated to harness either tandem conjugate addition–protonation or [4+2] cycloaddition as major product with excellent enantio‐ and diastereoselectivities. Subjecting the enantio‐enriched cycloaddition products to a basic silica gel reagent yields the diastereomer vis‐à‐vis the product directly obtained under conditions for addition–protonation, thus opening a diastereo‐divergent route for creating 1,3‐tertiary‐hetero‐quaternary stereocenters. Quantum chemical studies further provide stereochemical analysis for the [4+2] process and a plausible mechanism for this chemoselective switch is proposed.     

Electrochemical Synthesis of Thienoacene Derivatives: Transition‐Metal‐Free Dehydrogenative C−S Coupling Promoted by a Halogen Mediator

The first electrochemical dehydrogenative C?S bond formation leading to thienoacene derivatives is described. Several thienoacene derivatives were synthesized by dehydrogenative C?H/S?H coupling. The addition of ⁿBu₄NBr, which catalytically promoted the reaction as a halogen mediator, was essential.     

Rhodium(II)‐Catalyzed Intramolecular Annulation of 1‐Sulfonyl‐1,2,3‐Triazoles with Pyrrole and Indole Rings: Facile Synthesis of N‐Bridgehead Azepine Skeletons

A convenient and efficient synthetic method has been developed to construct highly functionalized N‐bridgehead azepine skeletons, which are of great importance in biological and pharmaceutical industry. The reaction proceeds through a rhodium(II) azavinyl carbene intermediate, which initiated the intramolecular C? H functionalization with pyrrolyl and indolyl rings. A variety of azepine derivatives were obtained in moderate to good yields under mild reaction conditions with high chemoselectivity. Several interesting derivatizations of the resulting products demonstrate that this method is synthetically valuable and useful.