Highly Efficient Gold‐Catalyzed Synthesis of Dibenzocycloheptatrienes

Dibenzocycloheptatrienes are obtained by a gold‐catalyzed 7‐exo‐dig hydroarylation protocol in a highly efficient manner. The gold‐catalyzed reaction usually gives the products in high yields and excellent selectivity. This procedure provides an easy and efficient access to dibenzocycloheptanoids, which are an interesting and unique class of natural products. This was underlined by the first total synthesis of reticuol.     

Rhodium‐Catalyzed Enantioselective Reductive Arylation: Convenient Access to 3,3‐Disubstituted Oxindoles

A rhodium‐Josiphos(L*) catalyzed enantioselective intramolecular hydroarylation reaction is described. The reductive cyclization of o ‐bromoaniline‐derived acrylamides provides convenient access to 3,3‐disubstituted oxindoles in good yields and with excellent enantioselectivity across a range of substrates. We propose that the key cyclization proceeds via a rhodium(III) intermediate. Overall, this method represents an unusual mode of reactivity for rhodium catalysis and is complementary to palladium(0)‐catalyzed α‐arylation methods.     

Simple Synthesis of Quinoxalin‐2(1H)‐one N‐Oxides from N‐Aryl‐2‐nitrosoanilines and Alkylated Cyanoacetic Esters

N‐Aryl‐2‐nitrosoanilines, available from the reaction of N‐arylamines with nitroarenes, condense under alkaline conditions with alkylated derivatives of cyanoacetic esters furnishing quinoxalin‐2(1H)‐one N‐oxides in good to excellent yields. The reaction involves the condensation of the carbanion with the nitroso group leading to the nitrone intermediate, followed by intramolecular acylation of the amine function.     

Hydroarylation of 2‐Aryloxybut‐1‐en‐3‐ynes via Pd/Acid‐Catalyzed C−H Bond Activation: A Concise Synthesis of 2,3‐Bismethylene‐2,3‐dihydrobenzofurans

An intramolecular exo ‐hydroarylation of 2‐aryloxy‐1,4‐disilylbut‐1‐en‐3‐ynes via ortho ‐C−H bond activation under palladium(0) and acid catalysis was found to give 2,3‐bis(silylmethylidene)‐2,3‐dihydrobenzofurans. The two silyl groups present probably promoted the reaction and played a key role in stabilizing the diene moiety in the product. The products readily led to functionalized condensed cycles by a Diels–Alder reaction.     

One‐Pot Four‐Component Synthesis of N2‐Alkyl‐N3‐[2‐(1,3,4‐oxadiazol‐2‐yl)aryl]benzofuran‐2,3‐diamines

A simple synthesis of N²‐alkyl‐N³‐[2‐(1,3,4‐oxadiazol‐2‐yl)aryl]benzofuran‐2,3‐diamines 5 via a one‐pot four‐component reaction is described (Scheme 1). A mixture of N‐(isocyanoimino)triphenylphosphorane ( 1 ), a 2‐aminobenzoic acid 2 , a 2‐hydroxybenzaldehyde 3 , and an isocyanide 4 in absolute EtOH at room temperature undergoes a smooth reaction to afford 5 in excellent yields (Table).     

Diastereo‐ and Regioselective Addition of Thioamide Dianions to Imines and Aziridines: Synthesis of N‐Thioacyl‐1,2‐diamines and N‐Thioacyl‐1,3‐diamines

Addition reactions of thioamide dianions that were derived from N‐arylmethyl thioamides to imines and aziridines were carried out. The reactions of imines gave the addition products of N‐thioacyl‐1,2‐diamines in a highly diastereoselective manner in good‐to‐excellent yields. The diastereomeric purity of these N‐thioacyl‐1,2‐diamines could be enriched by simple recrystallization. The reduction of N‐thioacyl‐1,2‐diamines with LiAlH₄ gave their corresponding 1,2‐diamines in moderate‐to‐good yields with retention of their stereochemistry. The oxidative‐desulfurization/cyclization of an N‐thioacyl‐1,2‐diamine in CuCl₂/O₂ and I₂/pyridine systems gave the cyclized product in moderate yield and the trans isomer was obtained as the sole product. On the other hand, a similar cyclization reaction with antiformin (aq. NaClO) as an oxidant gave the cis isomer as the major product. The reactions of N‐tosylaziridines gave the addition products of N‐thioacyl‐1,3‐diamines with low diastereoselectivity but high regioselectivity and in good‐to‐excellent yields. The use of AlMe₃ as an additive improved the efficiency and regioselectivity of the reaction. The stereochemistry of the obtained products was determined by X‐ray diffraction.     

Azocinoindole Synthesis by a Gold(I)‐Catalyzed Ring Expansion of 2‐Propargyl‐β‐Tetrahydrocarboline

A new methodology taking advantage of gold(I)‐catalyzed ring expansion has been developed to assemble tricyclic 1H‐azocino[5,4‐b]indoles from 2‐propargyl‐β‐tetrahydrocarbolines. The azocinoindoles were obtained in moderate to excellent yields; the structure of which was established by X‐ray crystallographic analysis. A mechanism involving regioselective intramolecular hydroarylation, [1,2]‐alkenyl migration and carbon–carbon bond‐fragmentation was proposed.     

One‐pot Synthesis of 2,5‐Disubstituted‐1,3,4‐oxadiazoles Based on the Reaction of N,N‐Dimethyl Amides with Acid Hydrazides

Convenient and efficient one pot method for the synthesis of 2,5‐disubstituted‐1,3,4‐oxadiazoles based on the reaction of N,N‐dimethyl amides with acid hydrazides has been developed. The methodology is applied to a wide range of difference aryl hydrazide and difference N,N‐dimethyl amides to 2,5‐disubstituted‐1,3,4‐oxadiazoles yield the in good to excellent yields. It will be possible wide useful application in synthesis.     

The preparation of covalent triazine‐based framework via Friedel‐Crafts reaction of 2,4,6‐trichloro‐1,3,5‐triazine with N,N′‐diphenyl‐N,N′‐di(m‐tolyl)benzidine for capturing and sensing to iodine

The covalent triazine‐based framework (TDPDB) has been prepared by Friedel‐Crafts polymerization reaction of N,N′‐diphenyl‐N,N′‐di(m‐tolyl)benzidine (DPDB) with 2,4,6‐trichloro‐1,3,5‐triazine (TCT) catalyzed by methanesulfonic acid. The yield of the reaction (94.85%) is very high. TDPDB was provided with Brunauer‐Emmett‐Teller specific surface area of 592.18 m² g^?1 and pore volume of 0.5241 cm³ g^?1. TDPDB demonstrated an excellent capacity for capturing iodine (3.93 g g^?1) and an outstanding ability to fluorescent sensing to iodine with Ksv of 5.83 × 10⁴ L mol^?1. It also showed high fluorescent sensing sensitivity to picric acid.     

Tandem Gold/Silver‐Catalyzed Cycloaddition/Hydroarylation of 7‐Aryl‐1,6‐enynes to Form 6,6‐Diarylbicyclo[3.2.0]heptanes

Mixtures of [{PCy₂(o‐biphenyl)}AuCl] and AgSbF₆ catalyze the tandem cycloaddition/hydroarylation of 7‐aryl‐1,6‐enynes with electron‐rich arenes to form 6,6‐diarylbicyclo[3.2.0]heptanes in good yield under mild conditions. Experimental observations point to a mechanism involving gold‐catalyzed cycloaddition followed by silver‐catalyzed hydroarylation of a bicyclo[3.2.0]hept‐1(7)‐ene intermediate.     

Scope and Limitations of the Base‐Free Copper(I) Oxide Catalyzed N‐Heteroarylation of 1H‐(Benz)imidazoles with B‐Heteroarylboronic Acids or 2‐Heteroaryl‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolanes

The known, very efficient base‐free copper(I) oxide catalyzed N‐arylation reaction performed in MeOH at room temperature for the synthesis of N‐substituted azoles and amines was extended to the heterocyclic series, i.e., we report herein the base‐free copper(I) oxide catalyzed N‐heteroarylation of 1H‐(benz)imidazole, by means of electron‐rich or electron‐deficient B‐heteroarylboronic acids or 2‐heteroaryl‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolanes (Schemes 1 and 2). Under these conditions, N‐heteroarylated 1H‐(benz)imidazoles were obtained in good to excellent yields (Tables 1 and 2). This is the first time that 2‐heteroaryl‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolanes were used in this type of reaction.     

N‐Heterocyclic Carbene‐Catalyzed Enantioselective Annulation of Indolin‐3‐ones with Bromoenals

N‐Heterocyclic carbene‐catalyzed reactions of indolin‐3‐ones with 2‐bromoenals opened an asymmetric access to 3,4‐dihydropyrano[3,2‐b]indol‐2(5 H)‐ones in good yields and with good to excellent enantioselectivities. This protocol tolerates a broad substrate scope. In addition, a possible mechanism for the annulation reaction is presented.     

Rhodium(III)‐Catalyzed ortho Alkenylation of N‐Phenoxyacetamides with N‐Tosylhydrazones or Diazoesters through CH Activation

A coupling reaction of N‐phenoxyacetamides with N‐tosylhydrazones or diazoesters through Rh^III‐catalyzed C? H activation is reported. In this reaction, ortho‐alkenyl phenols were obtained in good yields and with excellent regio‐ and stereoselectivity. Rh–carbene migratory insertion is proposed as the key step in the reaction mechanism.     

Cobalt‐Catalyzed C8‐Dienylation of Quinoline‐N‐Oxides

An efficient Cp*Co^III‐catalyzed C8‐dienylation of quinoline‐N‐oxides was achieved by employing allenes bearing leaving groups at the α‐position as the dienylating agents. The reaction proceeds by Co^III‐catalyzed C?H activation of quinoline‐N‐oxides and regioselective migratory insertion of the allene followed by a β‐oxy elimination, leading to overall dienylation. Site‐selective C?H activation was achieved with excellent selectivity under mild reaction conditions, and 30 mol % of a NaF additive was found to be crucial for the efficient dienylation. The methodology features high stereoselectivity, mild reaction conditions, and good functional‐group tolerance. C8‐alkenylation of quinoline‐N‐oxides was achieved in the case of allenes devoid of leaving groups as coupling partners. Furthermore, gram‐scale preparation and preliminary mechanistic experiments were carried out to gain insights into the reaction mechanism.     

7‐Iodo‐5‐aza‐7‐deazaguanine: Syntheses of Anomeric D‐ and L‐Configured 2‐Deoxyribonucleosides

Iodination of N²‐isobutyryl‐5‐aza‐7‐deazaguanine ( 7 ) with N‐iodosuccinimide (NIS) gave 7‐iodo‐N²‐isobutyryl‐5‐aza‐7‐deazaguanine ( 8 ) in a regioselective reaction (Scheme 1). Nucleobase‐anion glycosylation of 8 with 2‐deoxy‐3,5‐di‐O‐toluoyl‐α‐D ‐ or α‐L ‐erythro‐pentofuranosyl chloride furnished anomeric mixtures of D ‐ and L ‐nucleosides. The anomeric D ‐nucleosides were separated by crystallization to give the α‐D ‐anomer and β‐D ‐anomer with excellent optical purity. Deprotection gave the 7‐iodo‐5‐aza‐7‐deazaguanine 2′‐deoxyribonucleosides 3 (β‐D ; ≥99% de) and 4 (α‐D ; ≥99% de). The reaction sequence performed with the D ‐series was also applied to L ‐nucleosides to furnish compounds 5 (β‐L ; ≥99% de) and 6 (α‐L ; ≥95% de).     

A General Proline‐Catalyzed Synthesis of 4,5‐Disubstituted N‐Sulfonyl‐1,2,3‐Triazoles from 1,3‐Dicarbonyl Compounds and Sulfonyl Azide

An efficient proline‐catalyzed synthesis of 4,5‐disubstituted‐N‐sulfonyl‐1,2,3‐triazoles has been accomplished from 1,3‐dicarbonyl compounds and sulfonyl azides. The developed reaction is suitable for various symmetrical and unsymmetrical 1,3‐dicarbonyl compounds, tolerates various functional groups and affords 4,5‐disubstituted‐N‐sulfonyl‐1,2,3‐triazoles in good yield with excellent regioselectivity. Rhodium‐catalyzed denitrogenative functionalization of 4,5‐disubstituted‐N‐sulfonyl‐1,2,3‐triazoles further demonstrates their utility in organic synthesis.     

Microwave‐Assisted Stereoselective 1,3‐Dipolar Cycloaddition of C,N‐Diarylnitrone (i.e., N‐(Arylmethylidene)benzenamine N‐Oxide) and Bis(arylmethylidene)acetone (=1,5‐Diarylpenta‐1,4‐dien‐3‐one): NMR and Crystal Analysis of Diastereoisomeric Bis(isoxazolidines)

Microwave‐assisted stereoselective 1,3‐dipolar cycloaddition of C,N‐diarylnitrones (i.e., N‐(arylmethylidene)benzenamine N‐oxides) 2 to substituted bis(arylmethylidene)acetones (=1,5‐diarylpenta‐1,4‐dien‐3‐ones) 1 leading to diastereoisomer pairs of bis‐isoxazolidines 3 and 4 in good to excellent yield is described (Scheme 2 and Table 2). The configuration outcome of the reaction is discussed based on the NMR and X‐ray data of the products.     

Selective Hydroarylation of 1,3‐Diynes Using a Dimeric Manganese Catalyst: Modular Synthesis of Z‐Enynes

The transition‐metal‐catalyzed selective hydroarylation of unsymmetrical alkynes represents the state‐of‐art in organic chemistry, and still mainly relies on the use of precious late‐transition‐metal catalysts. Reported herein is an unprecedented Mn^I‐catalyzed hydroarylation of unsymmetrical 1,3‐diyne alcohols with commercially available arylboronic acids with predictive selectivity. This method addresses the challenges in regio‐, stereo‐, and chemoselectivity. It offers a general, convenient and practical strategy for the modular synthesis of multisubstituted Z‐configurated conjugated enynes. This protocol is distinguished by its operational simplicity, complete selectivity, excellent functional‐group compatibility, and gram‐scale potential. A dimeric Mn^I species, Mn₂(CO)₈Br₂, was proven to be a much more efficient catalyst precursor than Mn(CO)₅Br.     

Microwave‐Assisted Three‐Component Synthesis of Some Novel 1‐Alkyl‐1H‐indole‐2,3‐dione 3‐(O‐Alkyl­oxime) Derivatives as Potential Chemotherapeutic Agents

A convenient and efficient method for a one‐pot conversion of N‐alkylisatins to N‐alkylisatin O‐alkyloximes 7a – 7n as potential chemotherapeutic agents is described (Scheme) (isatin=1H‐indole‐2,3‐dione). In this method, the microwave‐assisted three‐component reaction of N‐alkylisatins 8 , hydroxylamine hydrochloride, and diverse alkyl halides in the presence of K₂CO₃ and Bu₄NBr furnishes the corresponding N‐alkylisatin O‐alkyloximes under solvent‐free condition in short times (2–10 min) and good to excellent yields (62–83%). The O‐alkylation of in situ generated isatin oximes with alkyl halides was achieved regioselectively, and (Z)‐O‐alkyloximes were produced dominantly. PM3 Semi‐empirical quantum‐mechanic calculations were performed to rationalize the evidences, and the calculations indicated a lower heat of formation for the (Z)‐O‐alkyloximes.     

Regio‐ and Enantioselective Synthesis of N‐Allylindoles by Iridium‐Catalyzed Allylic Amination/Transition‐Metal‐Catalyzed Cyclization Reactions

Regio‐ and enantioselective synthesis of N‐allylindoles was realized through an iridium‐catalyzed asymmetric allylic amination reaction with 2‐alkynylanilines and subsequent transition‐metal‐catalyzed cyclization reactions. The highly enantioenriched allylic amines prepared from Ir‐catalysis were treated with catalytic amount of NaAuCl₄ ? 2 H₂O or PdCl₂ providing various substituted N‐allylindoles in excellent yields and enantioselectivities.