Modular Synthesis of Multisubstituted Furans through Palladium‐Catalyzed Three‐Component Condensation of Alkynylbenziodoxoles,Carboxylic Acids,and Imines

Mild and regiocontrolled synthesis of a multisubstituted furan is achieved through Pd(OAc)₂‐catalyzed room‐temperature condensation of an alkynylbenziodoxole, a carboxylic acid, and an enolizable ketimine, which contribute to C1, CO, and C2 fragments, respectively, to the furan skeleton. The reaction tolerates a broad range of functional groups in each of the reaction components, and enables highly modular and flexible synthesis of variously substituted furans. The reaction is particularly effective for the rapid generation of tri‐ and tetraarylfurans and furan‐containing oligoarylenes without relying on conventional cross‐coupling chemistry.     

Palladium‐Catalyzed One‐Pot Three‐ or Four‐Component Coupling of Aryl Iodides,Alkynes, and Amines through CN Bond Cleavage: Efficient Synthesis of Indole Derivatives

An efficient synthesis of N‐substituted indole derivatives was realized by combining the Pd‐catalyzed one‐pot multicomponent coupling approach with cleavage of the C(sp³)?N bonds. Three or four components of aryl iodides, alkynes, and amines were involved in this coupling process. The cyclopentadiene–phosphine ligand showed high efficiency. A variety of aryl iodides, including cyclic and acyclic tertiary amino aryl iodides, and substituted 1‐bromo‐2‐iodobenzene derivatives could be used. Both symmetric and unsymmetric alkynes substituted with alkyl, aryl, or trimethylsilyl groups could be applied. Cyclic secondary amines such as piperidine, morpholine, 4‐methylpiperidine, 1‐methylpiperazine, 2‐methylpiperidine, and acyclic amines including secondary and primary amines all showed good reactivity. Further application of the resulting indole derivatives was demonstrated by the synthesis of benzosilolo[2,3‐b]indole.     

Palladium‐Catalyzed Three‐Component Cascade Cyclization Reaction of Bisallenes with Propargylic Carbonates and Organoboronic Acids: Efficient Construction of cis‐Fused Bicyclo[4.3.0]nonenes

A bicycle built for two : The title reaction affords cis‐fused bicyclo[4.3.0]nonenes from readily available 1,5‐bisallenes with structurally diverse propargylic carbonates and arylboronic acids (see scheme; X=NTs, C(E¹)₂ with E¹=CO₂Bn, SO₂Ph, dba=trans,trans‐dibenzylidenacetone). The reaction may involve a sequential oxidative addition, two different types of three carbopalladations, and a Suzuki‐type coupling.

     

Palladium‐Catalyzed Carbonylative Four‐Component Synthesis of Thiochromenones: The Advantages of a Reagent Capsule

Multicomponent reactions, especially those involving four or even more reagents, have been a long‐standing challenge because of the issues associated with balancing reactivity, selectivity, and compatibility. Herein, we demonstrate how the use of a reagent capsule provides straightforward access to synthetically valuable thiochromenone derivatives by a palladium‐catalyzed carbonylative four‐component reaction. To the best of our knowledge, this is the first example of applying a capsule to prevent catalyst poisoning and undesired side reactions of the multicomponent reaction.     

A Novel Domino Synthesis of Quinazolinediones by Palladium‐Catalyzed Double Carbonylation

Combining commercially available bromoanilines and bromobenzonitriles in a novel double carbonylation process allows for a straightforward synthesis of isoindolo[1,2‐b]quinazoline‐10,12‐diones. At least five different C?C and/or C?N bonds are selectively formed in this 3‐component reaction, which likely proceeds through sequential carbonylation–cyclization–isomerisation–carbonylation steps. Notably, two molecules of CO are inserted in this highly efficient palladium‐catalyzed process.     

Highly Efficient Four‐Component Synthesis of 4(3H)‐Quinazolinones: Palladium‐Catalyzed Carbonylative Coupling Reactions

Given the importance of quinazolinones and carbonylative transformations, a palladium‐catalyzed four‐component carbonylative coupling system for the synthesis of diverse 4(3H)‐quinazolinone in a concise and convergent fashion has been developed. Starting from 2‐bromoanilines (1 mmol), trimethyl orthoformate (2 mmol), and amines (1.1 mmol), under 10 bar of CO, the desired products were isolated in good yields in the presence of Pd(OAc)₂ (2 mol %), BuPAd₂ (6 mol %) in 1,4‐dioxane (2 mL) at 100 °C, using N,N‐diisopropylethylamine (2 mmol) as the base. Notably, the process tolerates the presence of various reactive functional groups and is very selective for quinazolinones, and was used in the synthesis of the precursor to the bioactive dihydrorutaempine.     

Palladium‐Catalyzed Three‐Component Cascade Reaction: Facial Access to Densely Functionalized Indolizines

A palladium‐catalyzed three‐component cascade reaction of 2‐(2‐enynyl)pyridines with nucleophiles and allyl halides has been developed, enabling the synthesis of densely functionalized indolizines in moderate to good yields. The newly developed methodology offers several practical advantages, including operational simplicity, ready availability of starting materials, and mild reaction conditions.     

Enantioselective Generation of Adjacent Stereocenters in a Copper‐Catalyzed Three‐Component Coupling of Imines,Allenes, and Diboranes

A highly enantio‐ and diastereoselective copper‐catalyzed three‐component coupling affords the first general synthesis of homoallylic amines bearing adjacent stereocenters from achiral starting materials. The method utilizes a commercially available NHC ligand and copper source, operates at ambient temperature, couples readily available simple imines, allenes, and diboranes, and yields high‐value homoallylic amines that exhibit versatile amino, alkenyl, and boryl units.     

Palladium‐Catalyzed Oxidative Cycloisomerization of 2‐Cinnamyl‐1,3‐Dicarbonyls: Synthesis of Functionalized 2‐Benzyl Furans

A new palladium‐catalyzed intramolecular oxidative cycloisomerization of readily available starting materials, 2‐cinnamyl‐1,3‐dicarbonyls, has been demonstrated for the creation of structurally diverse 2‐benzyl furans. The cycloisomerization occurs by a regioselective 5‐exo‐trig pathway. The reaction shows a broad substrate scope with good to excellent yields. Furthermore, a one‐pot procedure has been executed by using readily available cinnamyl alcohols and 1,3‐diketones.     

Rhodium(III)‐Catalyzed Three‐Component Reaction of Imines,Alkynes, and Aldehydes through CH Activation

An efficient rhodium(III)‐catalyzed tandem three‐component reaction of imines, alkynes and aldehydes through C?H activation has been developed. High stereo‐ and regioselectivity, as well as good yields were obtained in most cases. The simple and atom‐economical approach offers a broad scope of substrates, providing polycyclic skeletons with potential biological properties.