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.     

One‐Pot Palladium‐Catalyzed Borrowing Hydrogen Synthesis of Thioethers

Palladium on magnesium oxide is able to allow a one‐pot reaction to synthesize thioethers from thiols and aldehydes formed in situ from the respective alcohol by means of a borrowing hydrogen method. The reaction is initiated by dehydrogenation of the alcohol to give a palladium hydride intermediate and an aldehyde. The latter reacts with a thiol involving most probably the intermediacy of a thionium ion RCH?S⁺R, which can be reduced in situ by the metal hydride to afford thioethers.     

Palladium‐Catalyzed Asymmetric Benzylic Alkylation of Active Methylene Compounds with α‐Naphthylbenzyl Carbonates and Pivalates

A Pd/(R)‐H₈‐BINAP‐catalyzed asymmetric benzylic alkylation of active methylene compounds has been developed. The reaction proceeds without the use of an external base, and the starting racemic diarylmethyl carbonates are converted into the optically active coupling products which contain the benzylic chiral stereocenter by a dynamic kinetic asymmetric transformation (DYKAT). Additionally, with suitable carbonates bases, the same palladium catalysis allows the corresponding pivalates to be adopted in the same DYKAT process.     

Palladium‐Catalyzed Carbonylations of Aryl Bromides using Paraformaldehyde: Synthesis of Aldehydes and Esters

Carbonylation reactions represent useful tools for organic synthesis. However, the necessity to use gaseous carbon monoxide is a disadvantage for most organic chemists. To solve this problem, novel protocols have been developed for conducting palladium‐catalyzed reductive carbonylations of aryl bromides and alkoxycarbonylations using paraformaldehyde as an external CO source (CO gas free). Hence, aromatic aldehydes and esters were synthesized in moderate to good yields.     

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 Asymmetric Reductive Heck Reaction of Aryl Halides

Asymmetric reductive Heck reaction of aryl halides is realized in high stereoselectivity. Hydrogen‐bond donors, trialkylammonium salts in a glycol solvent, were used to promote halide dissociation from neutral arylpalladium complexes to access cationic, stereoselective pathways.     

Palladium‐Catalyzed Asymmetric Allylic Alkylation of Ketone Enolates

Palladium‐catalyzed asymmetric allylic alkylation of nonstabilized ketone enolates to generate quaternary centers has been achieved in excellent yield and enantioselectivity. Optimized conditions consist of performing the reaction in the presence of two equivalents of LDA as base, one equivalent of trimethytin chloride as a Lewis acid, 1,2‐dimethoxyethane as the solvent, and a catalytic amount of a chiral palladium complex formed from π‐allyl palladium chloride dimer 3 and cyclohexyldiamine derived chiral ligand 4 . Linearly substituted, acyclic 1,3‐dialkyl substituted, and unsubstituted allylic carbonates function well as electrophiles. A variety of α‐tetralones, cyclohexanones, and cyclopentanones can be employed as nucleophiles. The absolute configuration generated is consistent with the current model in which steric factors control stereofacial differentiation. The quaternary substituted products available by this method are versatile substrates for further elaboration.     

Manganese‐Mediated C−H Alkylation of Unbiased Arenes Using Alkylboronic Acids

The alkylation of arenes is an essential synthetic step of interest not only from the academic point of view but also in the bulk chemical industry. Despite its limitations, the Friedel–Crafts reaction is still the method of choice for most of the arene alkylation processes. Thus, the development of new strategies to synthesize alkyl arenes is a highly desirable goal, and herein, we present an alternative method to those conventional reactions. Particularly, a simple protocol for the direct C?H alkylation of unbiased arenes with alkylboronic acids in the presence of Mn(OAc)₃?2H₂O is reported. Primary or secondary unactivated alkylboronic acids served as alkylating agents for the direct functionalization of representative polyaromatic hydrocarbons (PAHs) or benzene. The results are consistent with a free‐radical mechanism.     

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 Trifluoromethylation of (Hetero)Arenes with CF3Br

The CF₃ group is an omnipresent motif found in many pharmaceuticals, agrochemicals, catalysts, materials, and industrial chemicals. Despite well‐established trifluoromethylation methodologies, the straightforward and selective introduction of such groups into (hetero)arenes using available and less expensive sources is still a major challenge. In this regard, the selective synthesis of various trifluoromethyl‐substituted (hetero)arenes by palladium‐catalyzed C?H functionalization is herein reported. This novel methodology proceeds under comparably mild reaction conditions with good regio‐ and chemoselectivity. As examples, trifluoromethylations of biologically important molecules, such as melatonin, theophylline, caffeine, and pentoxifylline, are showcased.     

Synthesis of Acylphosphonates by a Palladium‐Catalyzed Phosphonocarbonylation Reaction of Aryl Iodides with Phosphites

Acylphosphonates are conveniently synthesized from aryl iodides by a palladium‐catalyzed reaction with dialkyl phosphites under an atmospheric pressure of carbon monoxide. The reaction demonstrates the first example of the use of phosphorus nucleophiles in related metal‐catalyzed carbonylation reactions.