Palladium carbon-heteroatom bond

Recently, interest in copper-catalyzed carbon-heteroatom bond-forming reactions has shifted to the use of boronic acids as reactive coupling partners [133], One example of carbon-sulfur bond formation is displayed in Scheme 6.65. Lengar and Kappe have reported that, in contrast to the palladium(0)/copper(l)-mediated process described in Scheme 6.55, which leads to carbon-carbon bond formation, reaction of the same starting materials in the presence of 1 equivalent of copper(II) acetate and 2 equivalents of phenanthroline ligand furnishes the corresponding carbon-sulfur cross-coupled product [113]. Whereas the reaction at room temperature needed 4 days to reach completion, microwave irradiation at 85 °C for 45 min in 1,2-dichloroethane provided a 72% isolated yield of the product. 

A. 1.1. Covalently Functionalized Dendrimers Applied in a CFMR The palladium-catalyzed allylic substitution reaction has been investigated extensively in the preceding decades and provides an important tool for the formation of carbon—carbon and carbon—heteroatom bonds 14). The product is formed after attack of a nucleophile to an (f/ -allyl)Pd(II) species, formed by oxidative addition of the unsaturated substrate to palladium(0) (Scheme 1). To date several nucleophiles have been used, mostly resulting in the formation of carbon—carbon and... 

By far the most common way for organic molecules to enter late transition metal catalyzed reactions is oxidative addition. In this process a low valent palladium(O)3 or nickel(O) atom inserts into a carbon-heteroatom bond, usually of an aryl halide or sulfonate (Figure 1-2). The formation of the carbon-metal bond is accompanied by an increase in the oxidation number of the metal by 2. There are a series of factors determining the speed of the process. 

When reductive elimination from a late transition metal involves the formation of a carbon-carbon bond, the process is intramolecular and the groups have to be aligned cis to one another in the complex. In the formation of carbon-heteroatom bonds the reductive elimination from palladium might take place via competing pathways.16... 

In spite of their relatively young age palladium and nickel catalyzed carbon-heteroatom bond forming reactions, also known as the Buchwald-Hartwig reaction, have gained significant importance amongst synthetic... 

The opening step of the Buchwald-Hartwig reaction, similarly to the previous cases, is the oxidative addition of an aryl halide or sulfonate onto a low oxidation state metal. Although the term Buchwald-Hartwig reaction is usually reserved for palladium catalyzed processes, carbon-heteroatom bond formation also proceeds readily with nickel and copper. The nickel catalyzed processes follow a similar mechanism, while the distinctly different copper catalyzed reactions will be discussed in Chapter 2.5. 

Formally copper catalyzed couplings are analogous to palladium and nickel catalyzed reactions. Carbon-carbon and carbon-heteroatom bonds can be formed in such transformations alike. From the mechanistic point of view there is a significant difference between nickel, palladium and copper catalyzed processes however. While in the former cases the catalyst usually oscillates between the 0 and +2 oxidation states, in copper mediated transformations the common oxidation numbers are +1, +2 and +3. 

A significant part of the examples of transition metal catalyzed formation of five membered heterocycles utilizes a carbon-heteroatom bond forming reaction as the concluding step. The palladium or copper promoted addition of amines or alcohols onto unsaturated bonds (acetylene, olefin, allene or allyl moieties) is a prime example. This chapter summarises all those catalytic transformations, where the five membered ring is formed in the intramolecular connection of a carbon atom and a heteroatom, except for annulation reactions, involving the formation of a carbon-heteroatom bond, which are discussed in Chapter 3.4. 

The palladium catalyzed iminoannulation and carboxyannulation of alkynes and an appropriate aryl/vinyl halide is an efficient tool to construct six membered nitrogen and oxygen heterocycles. The process encompasses the concomitant formation of a carbon-carbon and a carbon-heteroatom bond. 

Carbon-heteroatom bond forming reactions are also efficient in introducing amines onto other five membered heterocycles. 2-, and 3-bromothiophene were both coupled with diphenylamine using the highly active palladium-PlBih catalyst system. The reactions furnished the desired products in both cases, although the yield varied significantly with the substitution pattern (6.75.),106... 

The exchange of a halogen to a classical nitrogen or oxygen nucleophile usually proceeds readily on the purine skeleton, without the necessity of using a transition metal catalyst. There are certain cases, however, where the palladium catalyzed carbon-heteroatom bond formation might take preference over noncatalysed methods. Inosine derivatives, for example,... 

The last example focuses not on the functionalization of heterocycles by a transition metal mediated carbon-heteroatom bond forming reaction, but the palladium catalyzed conversion of primary amines, including amino-heterocycles, into urea derivatives. A representative example, shown in 8.38., includes the reaction of an amino-carbazole derivative with morpholine, carbon monoxide and oxygen in the presence of catalytic amounts of palladium(II) iodide. The formation of the urea moiety proceeds with great selectivity and in high yield.49 The reaction works equally well for primary aliphatic and aromatic amines. 

While the major use for palladium catalysis is to make carbon-carbon bonds, which are difficult to make using conventional reactions, the success of this approach has recently led to its application to forming carbon-heteroatom bonds as well. The Overall result is a nucleophilic substitution at a vinylic or aromatic centre, which would not normally be possible. A range of aromatic amines can be prepared direcdy from the corresponding bromides, iodides, or triflates and the required amine in the presence of palladium(O) and a strong alkoxide base. Similarly, lithium thiolates couple with vinylic triflates to give vinyl sulfides provided lithium chloride is present. 

Among the most important reactions in organic synthesis are those that form carbon-carbon bonds. Classically this was accomplished using base-catalyzed reactions such as the aldol, Claisen, and Knoevenagel condensation reactions. Modem versions of these reactoins often display remarkable stereoselectivity.1 Unfortunately, many types of carbon atoms cannot be joined together by these reactions, for example, an aryl carbon to another aryl carbon. It took the development of transition metal-catalyzed reactions before new types of carbon-carbon and carbon-heteroatom bonds could be created. Of particular note in this regard are the reactions catalyzed by palladium, usually in its 0 or +2 oxidation state.2,3,4,5... 

As with all such palladium-catalyzed carbon-heteroatom bond-forming chemistry, the ancillary ligand(s) (i.e., L often featuring phosphine or A-heterocyclic carbene donors " employed have a direct influence over the course of the elementary transformations. Electron-rich and sterically demanding ligands promote the formation of low-coordinate compounds of type A that are predisposed to undergo Ar—X... 

Chiral bisoxazoline associated with palladium is a very efficient organometallic catalyst for the asymmetric allylic alkylation of allylic acetates and carbonates, allowing the formation of carbon-carbon as well as carbon-heteroatom bond in enantiomeric excesses higher than 95%.[1,2] However one of the problems in organometallic homogeneous catalysis is the separation of the catalyst, often toxic and very expensive, from the product(s) of the reaction. Very recently, a chiral fluorous bisoxazoline (Figure 3.1) has been shown to be an efficient ligand in the... 

Powers DC, Ritter T (2009) Bimetallic Pd(lll) complexes in palladium-catalysed carbon-heteroatom bond formation. Nat Chem 1 302-309... 

Palladium-catalyzed reactions have been widely investigated and have become an indispensable synthetic tool for constructing carbon-carbon and carbon-heteroatom bonds in organic synthesis. Especially, the Tsuji-Trost reaction and palladium(II)-catalyzed cyclization reaction are representative of palladium-catalyzed reactions. These reactions are based on the electrophilic nature of palladium intermediates, such as n-allylpalladium and (Ti-alkyne)palladium complexes. Recently, it has been revealed that certain palladium intermediates, such as bis-7i-allylpalladium, vinylpalladium, and arylpalladium, act as a nucleophile and react with electron-deficient carbon-heteroatom and carbon-carbon multiple bonds [1]. Palladium-catalyzed nucleophilic reactions are classified into three categories as shown in Scheme 1 (a) nucleophilic and amphiphilic reactions of bis-n-allylpalladium, (b) nucleophilic reactions of allylmetals, which are catalytically generated from n-allylpalladium, with carbon-heteroatom double bonds, and (c) nucleophilic reaction of vinyl- and arylpalladium with carbon-heteroatom multiple bonds. According to this classification, recent developments of palladium-catalyzed nucleophilic reactions are described in this chapter. 

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