Palladium‐Catalyzed Hydroaminocarbonylation of Alkenes with Amines: A Strategy to Overcome the Basicity Barrier Imparted by Aliphatic Amines

A novel and efficient palladium‐catalyzed hydroaminocarbonylation of alkenes with aminals has been developed under mild reaction conditions, and allows the synthesis of a wide range of N‐alkyl linear amides in good yields with high regioselectivity. On the basis of this method, a cooperative catalytic system operating by the synergistic combination of palladium, paraformaldehyde, and acid was established for promoting the hydroaminocarbonylation of alkenes with both aromatic and aliphatic amines, which do not react well under conventional palladium‐catalyzed hydroaminocarbonylation.     

Enantioselective Synthesis of Isoxazolines Enabled by Palladium‐Catalyzed Carboetherification of Alkenyl Oximes

Reported here is a highly efficient Pd/Xiang‐Phos catalyzed enantioselective carboetherification of alkenyl oximes with either aryl or alkenyl halides, delivering various chiral 3,5‐disubstituted and 3,5,5‐trisubstituted isoxazolines in good yields with up to 97 % ee. The sterically bulky and electron‐rich (S,Rs)‐ NMe‐X2 ligand is responsible for the excellent reactivities and enantioselectivities. The salient features of this transformation include mild reaction conditions, general substrate scope, good functional‐group tolerance, good yields, high enantioselectivities, easy scale‐up, and application in the late‐stage modification of bioactive compounds. The obtained products can be readily transformed into useful chiral 1,3‐aminoalcohols.     

A General Synthesis of Fluoroalkylated Alkenes by Palladium‐Catalyzed Heck‐Type Reaction of Fluoroalkyl Bromides

An efficient palladium‐catalyzed Heck‐type reaction of fluoroalkyl halides, including perfluoroalkyl bromides, trifluoromethyl iodides, and difluoroalkyl bromides, has been developed. The reaction proceeds under mild reaction conditions with high efficiency and broad substrate scope, and provides a general and straightforward access to fluoroalkylated alkenes which are of interest in life and material sciences.     

CO/C‐H as an Acylating Reagent: A Palladium‐Catalyzed Aerobic Oxidative Carbonylative Esterification of Alcohols

A palladium‐catalyzed oxidative carbonylative esterification of a variety of functionalized alcohols under base‐ and ligand‐free conditions has been demonstrated. A CO/olefin combination was utilized as the acylating reagent with O₂ as a benign oxidant. Notably, the scope of the substrate alcohols has been greatly broadened.     

Palladium‐Catalyzed Direct Cyclopropylation of Heterocycles

Many 1,3‐azoles and thiophenes are directly cyclopropylated in the presence of a simple palladium catalyst. The relative configuration on the three‐membered rings is retained in the products. Thus, the cyclopropyl–halide bond undergoes concerted oxidative addition to palladium(0) and cyclopropyl radicals are not involved in the productive pathway.     

Palladium‐Catalyzed Synthesis of Ammonium Sulfinates from Aryl Halides and a Sulfur Dioxide Surrogate: A Gas‐ and Reductant‐Free Process

Sulfonyl‐derived functional groups populate a broad range of useful molecules and materials, and despite a variety of preparative methods being available, processes which introduce the most basic sulfonyl building block, sulfur dioxide, using catalytic methods, are rare. Described herein is a simple reaction system consisting of the sulfur dioxide surrogate DABSO, triethylamine, and a palladium(0) catalyst for effective convertion of a broad range of aryl and heteroaryl halides into the corresponding ammonium sulfinates. Key features of this gas‐ and reductant‐free reaction include the low loadings of palladium (1 mol %) and ligand (1.5 mol %) which can be employed, and the use of isopropyl alcohol as both a solvent and formal reductant. The ammonium sulfinate products are converted in situ into a variety of sulfonyl‐containing functional groups, including sulfones, sulfonyl chlorides, and sulfonamides.     

Palladium‐Catalyzed Oxidative Carbonylation of N‐Allylamines for the Synthesis of β‐Lactams

β‐Lactam scaffolds are considered to be ideal building blocks for the synthesis of nitrogen‐containing compounds. A new palladium‐catalyzed oxidative carbonylation of N‐allylamines for the synthesis of α‐methylene‐β‐lactams is reported. DFT calculations suggest that the formation of β‐lactams via a four‐membered‐ring transition state is favorable.     

Synthesis of Spiroheterocycles by Palladium‐Catalyzed Domino Cycloisomerization/Cross‐Coupling of α‐Allenols and Baylis–Hillman Acetates

First insights into the reaction between a Baylis–Hillman adduct and an allene moiety have been obtained from the novel domino heterocyclization/cross‐coupling reaction of α‐allenols and Baylis–Hillman acetates, which furnishes [(2,5‐dihydrofuran‐3‐yl)methyl]acrylate derivatives in moderate to good yields.

     

Palladium-Catalyzed Carbo-Oxygenation of Propargylic Amines using in Situ Tether Formation

1,2-Amino alcohols and α-aminocarbonyls are frequently found in natural products, drugs, chiral auxiliaries, and catalysts. This work reports a new method for the palladium-catalyzed oxyalkynylation and oxyarylation of propargylic amines. The reaction is perfectly regioselective based on the in situ introduction of a hemiacetal tether derived from trifluoroacetaldehyde. cis-Selective carbo-oxygenation was achieved for terminal alkynes, whereas internal alkynes gave trans-carbo-oxygenation products. The obtained enol ethers could be easily transformed into 1,2-amino alcohols or α-amino ketones using hydrogenation or hydrolysis, respectively.     

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 Migratory Insertion of Isocyanides: An Emerging Platform in Cross‐Coupling Chemistry

Isocyanides have been important building blocks in organic synthesis since the discovery of the Ugi reaction and related isocyanide‐based multicomponent reactions. In the past decade isocyanides have found a new application as versatile C₁ building blocks in palladium catalysis. Palladium‐catalyzed reactions involving isocyanide insertion offer a vast potential for the synthesis of nitrogen‐containing fine chemicals. This Minireview discusses all the achievements in this emerging field.     

Palladium‐Catalyzed Insertion of Isocyanides into the C−S Bonds of Heteroaryl Sulfides

Insertion of tert‐butyl isocyanide into the C(sp²)?S bonds of heteroaryl sulfides is catalyzed by a palladium diphosphine complex. Thioimidates generated through this reaction could be readily hydrolyzed under acidic conditions to yield the corresponding thioesters, which are of synthetic use. This insertion is useful because starting heteroaryl sulfides were readily prepared by either conventional ways or through sulfur‐specific extended Pummerer reactions.     

Additive Effects in the Palladium‐Catalyzed Carboiodination of Chiral N‐Allyl Carboxamides

The use of Pd catalysis as a means to synthesize organic halides has recently received increased attention. Among the reported methods is the Pd‐catalyzed carboiodination, which uses extremely bulky ligands to facilitate carbon–halogen reductive elimination from Pd^II as the key catalytic step. When approaching substrates exhibiting low stereoselectivity, catalyst troubleshooting becomes difficult as there are few ligands known to promote the key reductive elimination. Herein, we present our finding that tertiary amines act as weakly coordinating ligands which significantly enhance diastereoselectivity in the Pd/QPhos‐catalyzed carboiodination of chiral N‐allyl carboxamides. This methodology allows efficient access to enantioenriched and densely functionalized dihydroisoquinolinones, and has been applied toward the asymmetric formal synthesis of (+)‐corynoline.