Gold‐Catalyzed Carbenoid Transfer Reactions of Diynes – Pinacol Rearrangement versus Retro‐Buchner Reaction

Aromatic diyne systems bearing one terminal propargylic acetate moiety and one tertiary propargylic alcohol subunit were converted in the presence of a gold catalyst. After an initial 1,2‐migration of the acetoxy group at the terminal alkyne, a gold carbenoid is formed which is then transferred onto the internal alkyne of the propargylic alcohol. This combination enables the use of propargylic acetates as precursors for a gold‐catalyzed pinacol‐type rearrangement. In the final pinacol‐like step the shift of an alkyl or aryl moiety onto an electrophilic gold carbenoid/cation terminates the reaction and 1‐naphthyl ketones are obtained as products. If electron‐rich aromatic backbones are used, a mechanistically interesting alternative pathway including a retro‐Buchner reaction is opened.

     

Ring‐Opening/Expansion Rearrangement of Cycloprop[2,3]inden‐1‐ols Catalyzed by p‐Toluenesulfonic Acid

A divergent approach to generate either 1‐hydroxymethylindenes (which could then be converted to benzofulvenes through a dehydration reaction) or naphthalenes by the rearrangement of cycloprop[2,3]inden‐1‐ols is reported. The effect of the cyclopropyl ring substitution pattern on ring‐opening/expansion rearrangements of the substrates was systemically studied.

     

Palladium‐Catalyzed Tandem Reaction of Alkyne‐Based Aryl Iodides and Salicyl N‐Tosylhydrazones to Construct the Spiro[benzofuran‐3,2′‐chromene] Skeleton

A convenient palladium‐catalyzed tandem reaction of aryl iodides and salicyl N‐tosylhydrazones has been achieved to afford a series of compounds containing the novel spiro[benzofuran‐3,2′‐chromene] scaffold in moderate to good yields. This efficient catalytic reaction, which tolerates various functional groups, combines alkyne‐based 5‐exo‐dig cyclization, palladium(II) carbene migratory insertion and intramolecular cyclization, generating three new bonds in one reaction.

     

An Efficient Route to 3‐Amidylindoles via a Palladium‐ Catalyzed Tandem Reaction of 2‐Alkynylanilines with Isocyanides

A palladium‐catalyzed reaction of 2‐alkynylaniline, isocyanides, and silver acetate is described, leading to 3‐amidylindoles in moderate to good yields. During the process, five new bonds are formed with high reaction efficiency in one‐pot procedure.     

A Rhodium‐Catalyzed Tandem Alkyne Dimerization/ 1,4‐Addition Reaction

A convenient three‐component coupling reaction for the construction of conjugated enynes using rhodium catalysis is reported. Dimerization of a monosubstituted alkyne followed by trapping of the vinyl metal intermediate with an electron‐deficient alkene, such as methyl vinyl ketone, provided moderate to good yields of these enynes. The use of the hindered electron‐rich tris(ortho‐tolyl)phosphine as a ligand for the rhodium catalyst provided the best conversions to these complex products.

     

Silver Triflate‐Catalyzed or Electrophile‐Mediated Tandem Reaction of N′‐(2‐Alkynylbenzylidene)hydrazides with Dimethyl Acetylenedicarboxylate

Different outcomes were generated under different conditions for the tandem reactions of N′‐(2‐alkynylbenzylidene)hydrazides with dimethyl acetylenedicarboxylate (DMAD) catalyzed by silver triflate or in the presence of electrophiles. The unexpected isoquinoline‐based azomethine ylides were obtained when the reaction was catalyzed by silver triflate or in the presence of bromine, while the fused 1,2‐dihydroisoquinolines were afforded when iodine was employed in the above tandem reactions.     

Synthesis of 3‐Iodoquinolines by Copper‐Catalyzed Tandem Annulation from Diaryliodoniums,Nitriles, and 1‐Iodoalkynes

A novel method for the synthesis of 3‐iodoquinolines was developed by copper‐catalyzed tandem annulation from diaryliodoniums, nitriles, and 1‐iodoalkynes. It is a method that is characterized by the most convenient operation and wide molecular diversity.

     

Synthesis of Tricyclic Isoquinoline Derivatives via Palladium‐ Catalyzed Tandem Reactions of 2,7‐Alkadiynylic Carbonates with 2,3‐Allenyl Sulfamides

The palladium‐catalyzed tandem reactions of 2,7‐alkadiynylic carbonates with 2,3‐allenyl sulfamides for the syntheses of fused tricycles such as 1,3,6,7,8,9‐hexahydrofuro[3,4‐h]isoquinoline, 2,3,6,7,8,9‐hexahydro‐1H‐pyrrolo[3,4‐h]isoquinoline, and 2,3,4,7,8,9‐hexahydro‐1H‐cyclopenta[h]isoquinoline derivatives have been developed. A mechanism has been proposed based on the isolation of a by‐product.

     

Palladium‐Catalyzed Three‐Component Tandem Cyclization Reaction of 2‐(2,3‐Allenyl)acylacetates,Organic Halides,and Amines: An Effective Protocol for the Synthesis of 4,5‐Dihydro‐1H‐pyrrole Derivatives

A domino three‐component reaction of 2‐(2′,3′‐allenyl)acylacetates with aryl or alkenyl halides and aryl‐ or benzylamines afforded 4,5‐dihydro‐1H‐pyrrole derivatives highly chemo‐ and regioselectively in one pot through imine formation/imine‐enamine tautomerization under the catalysis of palladium(0) and toluenesulfonic acid monohydrate. A high diastereoselectivity was observed.     

Gold‐Catalyzed Regioselective Meyer–Schuster Rearrangement and Ring Expansion Cascade Leading to α‐Hydroxy‐α‐vinylcyclopentanones

Readily available cyclobutanols having a butyne‐1,4‐diol moiety underwent a sequential regioselective Meyer–Schuster rearrangement and 1,2‐shift, furnishing α‐hydroxy‐α‐vinylcyclopentanones. The reaction mechanism is consistent with the formation of an allenol intermediate that racemizes under the reaction conditions. Subsequent activation of the allenol leads to an enantio‐ and diastereoselective route to this scaffold.

     

Mild and Functional Group Tolerant Method for Tandem Palladium‐Catalyzed Carbocyclization–Coupling of ε‐Acetylenic β‐Ketoesters with Aryl Bromides and Chlorides

We report a new protocol for the annulative difunctionalization of acetylenes via tandem carbocyclization–coupling of ε‐acetylenic β‐ketoesters with aryl and heteroaryl bromides and chlorides catalyzed by the palladium species derived from an air‐ and moisture‐stable palladacyclic precatalyst. In the tandem process, the palladium complex combines appropriate carbophilic Lewis acidity and redox activity to catalyze two mechanistically distinct reactions ‐ nucleophilic addition of the enolate to unactivated alkyne, followed by C C coupling. We found that a broad range of electronically varied aryl and heteroaryl bromides and chlorides underwent this reaction with various ε‐acetylenic β‐ketoesters, providing corresponding substituted vinylidenecyclopentanes in high yield with excellent functional group tolerance.

     

Gold(I)‐Catalyzed Tandem Reaction of γ‐Amino‐Substituted Propargylic Esters to Pyrrolines and its Application in the Formal Synthesis of (±)‐Aphanorphine

An effective synthesis of structurally diverse pyrroline derivatives has been accomplished by a gold(I)‐catalyzed tandem 1,3‐acyloxy rearrangement/intramolecular azacylization reaction of γ‐amino‐substituted propargylic esters in good to excellent chemical yields (52–98%). The reaction proceeds under extremely mild conditions and has also demonstrated its potential in a concise formal synthesis of (±)‐aphanorphine with a catalyst loading as low as 0.5 mol% to provide the key intermediate 5‐(4‐methoxybenzyl)‐1‐tosyl‐2,5‐dihydro‐1H‐pyrrol‐3‐yl pivalate on a gram scale.

     

Assembly of Indeno[1,2‐c]chromenes via a Palladium‐Catalyzed Reaction of 1‐Bromo‐2‐(cyclopropylidenemethyl)benzene with 2‐Alkynylphenol

1‐Bromo‐2‐(cyclopropylidenemethyl)benzenes react with 2‐alkynylphenols under palladium catalysis, leading to indeno[1,2‐c]chromenes in moderate to good yields. The molecular complexity and diversity can be introduced efficiently from easily available starting materials.

     

Synthesis of 2H‐Indazoles via Tandem Palladium‐Catalyzed Deacylative Cross‐Coupling and Denitrogenative Cyclization of 2‐Iodoazoarenes and 2‐Iodoaryltriazenes with Acyldiazoacetates in One‐Pot

A synthetic method to prepare a wide range of 2H‐indazoles was developed via a tandem palladium‐catalyzed deacylative cross‐coupling reaction of 2‐iodoazoarenes and 2‐iodoaryltriazenes with acyldiazoacetates and denitrogenative cyclization reaction of in situ generated diazoacetates having azoaryl and triazenylaryl moieties in one‐pot. Additionally, azoaryl‐substituted diazoacetates underwent palladium‐catalyzed denitrogenative cyclization to produce 2H‐indazoles. The present reaction is a good example in which a Pd(0)‐catalyst is involved in two catalytic cycles in one‐pot.

     

Synthesis of Optically Active 2H‐Thiopyrano[2,3‐b]quinolines with Three Contiguous Stereocenters via an Organocatalytic Asymmetric Tandem Michael–Henry Reaction

Optically active 2H‐thiopyrano[2,3‐b]quinolines with three contiguous stereocenters have been synthesized via a chiral bifunctional squaramide‐catalyzed tandem Michael–Henry reaction between 2‐mercaptoquinoline‐3‐carbaldehydes and nitroolefins. The reactions proceed with excellent diastereo‐ and enantioselectivity to give the title compounds in high yields with high levels of diastereo‐ and enantioselectivity (up to >99/1 dr and >99% ee, respectively).     

Tandem Copper‐Catalyzed N‐Arylation–Condensation and van Leusen Reaction: Synthesis of 1,4‐Benzodiazepines and Imidazobenzodiazepines (ImBDs)

A straightforward, tandem, copper‐catalyzed N‐arylation–condensation has been developed using chiral cyclic 1,2‐diamines and ortho‐haloaryl aldehydes or ketones. The corresponding chiral tricyclic 1,4‐benzodiazepines were synthesized in high yields. Subsequently, the 1,4‐diazepines have been converted to a new class of tetracyclic N‐fused imidazobenzodiazepines (ImBDs) using the van Leusen reaction. A one‐pot sequential strategy has also been demonstrated for the synthesis of ImBDs. The synthetic utility of 1,4‐benzodiazepines and ImBDs is described.

     

A Novel Assembly of Substituted Pyrroles by Acid‐Catalyzed Sequential Three‐Component Reaction of Amines,Alkynoates, and 1,2‐Diaza‐1,3‐dienes

A novel protocol for the assembly of polysubstituted pyrroles has been developed through the acid‐catalyzed, sequential three‐component reaction of primary aliphatic amines, alkynoates and 1,2‐diaza‐1,3‐dienes (DDs). This methodology proceeds with complete chemo‐/regioselectivity involving first formation of an enamino ester intermediate, in situ Michael addition with azo‐ene compounds and subsequent intramolecular ring closure.     

Indium(III) Chloride‐Catalyzed Propargylation/Amination/Cycloisomerization Tandem Reaction: One‐Pot Synthesis of Highly Substituted Pyrroles from Propargylic Alcohols, 1,3‐Dicarbonyl Compounds and Primary Amines

A convenient one‐pot propargylation/amination/cycloisomerization tandem process has been developed for the synthesis of highly substituted pyrroles derivatives from propargylic alcohols, 1,3‐dicarbonyl compounds and primary amines using indium(III) chloride as a multifunctional catalyst. This method provides a flexible and rapid route to substituted pyrroles.     

A Facile Route to Benzo[a]fluorenes via a Palladium‐Catalyzed Reaction of 2‐Alkynylbromobenzene with 2‐(2‐Alkynylphenyl)malonate

A palladium‐catalyzed reaction of 2‐alkynylbromobenzenes with 2‐(2‐alkynylphenyl)malonates gives rise to benzo[a]fluorenes in good yields. This tandem process is efficient with the formation of three bonds from easily available starting materials.     

Tandem Gold(III)‐Catalyzed Amination‐Intramolecular Hydroamination Reactions of 1‐En‐4‐yn‐3‐ols with Sulfonamides: Efficient Approach to Highly Substituted Pyrroles

A simple, convenient and efficient synthetic approach to highly substituted pyrroles has been developed by utilizing a gold(III)‐catalyzed tandem amination‐intramolecular hydroamination reaction. The first examples of gold‐catalyzed, selective amination of 1‐en‐4‐yn‐3‐ols have also been disclosed.