Carbon-heteroatom bond formation additions

Carbon-heteroatom bond formation by free-radical chain additions to... 

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. 

Metal-mediated intramolecular addition of silyl enolates to alkynes is also valuable for the synthesis of cyclic ketones. A stoichiometric amount of HgCl2 or EtAlCl2 effectively promotes the cycloalkenylation via anti-addition to alkynes (Equations (87) and (88)).319 320a The -addition mode can be explained by a metal coordination to the triple bond and subsequent attack of the enolate moiety from the opposite side to the metal. The resultant alkenylmetals can be used for carbon-carbon and carbon-heteroatom bond formation as well as protonation. 

Carbon-Nitrogen Bond Formation. Apart from the CAN-mediated reactions in which solvent (e.g., acetonitrile) incorporation results in carbon-heteroatom bond formation, the oxidative generation and subsequent addition of heteroatom-centered radicals to alkenes or alkynes provide means of direct construction of carbon-hetereoatom bonds. ... 

In addition to these methods, carbon-heteroatom bond formation can also be coupled with these Heck cyclizations. One of the more straightforward methods to couple carbon-heteroatom bond formation with Heck cyclization is via enamine generation. For example, the reaction of enolizable aldehydes or ketones with 2-haloanilines provides a route to the construction of enamines for subsequent Heck cyclization. A recent example of this reaction was reported by Nazare, who demonstrated that ortho-chloroanilines can react with enolizable ketones to generate indoles (Scheme 6.54) [74]. This chemistry proceeds in good yields with a diverse variety of symmetrical and unsymmetrical ketones, provided there is only one enamine isomer, and can be applied to a range of substituted indoles. Zhu has demonstrated that enolizable aldehydes can be used in the cyclization [75]. This latter approach can provide a very effective method to selectively incorporate a range of alkyl, aryl or functionalized units into the 3-indole position, many of which are not easily accessible via other routes. 

Reactions between a diene and a dienophile yielding cyclohexene derivatives through carbon-carbon or carbon-heteroatom bond formation are referred to as Diels-Alder (DA) reactions. The concerted [4 + 2] cycloaddition was first described in 1928 by Diels and Alder, ° and can be adapted for the efficient conjugation of peptides and proteins to synthetic polymers. Despite being recognized as highly selective and additive-free, DA reactions require elevated temperatures to obtain the desired product. Furthermore, the reversibility of the reaction limits its application in materials science. ... 

As one of the most useful synthetic methods for formation of earbon-carbon or carbon-heteroatom bonds, Michael addition reaction has been frequently used as a fundamental step for establishing tandem protocols, because the aetive enolate species is formed as a key intermediate, which can be trapped by other electfophiles [28]. 

This compilation embraces a wide variety of subjects, such as solid-phase and microwave stereoselective synthesis asymmetric phase-transfer asymmetric catalysis and application of chiral auxiliaries and microreactor technology stereoselective reduction and oxidation methods stereoselective additions cyclizations metatheses and different types of rearrangements asymmetric transition-metal-catalyzed, organocatalyzed, and biocatalytic reactions methods for the formation of carbon-heteroatom and heteroatom-heteroatom bonds like asymmetric hydroamina-tion and reductive amination, carboamination and alkylative cyclization, cycloadditions with carbon-heteroatom bond formation, and stereoselective halogenations and methods for the formation of carbon-sulfur and carbon-phosphorus bonds, asymmetric sulfoxidation, and so on. 

Beletskaya IP, Ananikov VP (2010) The formation of Csp -S and Csp -Se bonds by substitution and addition reactions catalyzed by transition metal complexes. In Yudin AK (ed) Catalyzed carbon-heteroatom bond formation. Wiley-VCH, Weinheim... 

A fundamental solution to the problem is to develop novel synthetic processes that are clean by initial design. Eor carbon-heteroatom bond formation it is the hydrofunctionalization process that opens the possibility for environmentally friendly chemical transformations. Hydrofunctionalization of unsaturated organic molecules via direct addition of H-X to multiple bonds is an atom-economical addition reaction which does not produce wastes. In view of the need of green and sustainable chemical procedures, the role of the metal catalysis is crucial to control the reaction, in particular, regio-, stereo-, and enantioselectivity. 

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. 

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. 

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