Insertion reactions carbon-halogen bonds

The utilization of nickel considerably increased the scope and the practicability of aryl-aryl bond forming reactions. During the course of the reaction, Ni(0) inserts in carbon-halogen bonds before the desired biaryl compound is released after the subsequent reaction of the activated species with the requisite couphng parmer. Nickel-mediated coupling reactions have been carried out with stoichiometric amounts of Ni(0) or, more commonly, with catalytic amounts in the presence of reagents that are suited to efficiently recover the metal. 

The classical Reformatsky reaction consists of the treatment of an a-halo ester 1 with zinc metal and subsequent reaction with an aldehyde or ketone 3. Nowadays the name is used generally for reactions that involve insertion of a metal into a carbon-halogen bond and subsequent reaction with an electrophile. Formally the Reformatsky reaction is similar to the Grignard reaction. 

A very promising synthesis of /3-lactones has been recently reported, involving the palladium-catalyzed carbonylation reaction of halogeno alcohols. For example, 3-phenyl-2-oxetanone was obtained in 63% yield from 2-phenyl-2-bromoethanol in DMF solution at room temperature under 1 atmosphere pressure of carbon monoxide (equation 115). A proposed mechanism, in which palladium metal inserts into the carbon-halogen bond, followed by insertion of a molecule of carbon monoxide into the carbon-palladium bond and then ring closure, fits kinetics data (80JA4193). 

Three approaches to zinc enolates are commonly adopted the process associated to the classical Reformatsky reaction is based on the insertion of Zn(0) into the carbon—halogen bond of an a-haloester. Two additional routes involve (i) transmetallation of a lithium enolate with a Zn(II) salt (Section V.A) and (ii) the transition-metal-catalysed conjugate addition of diethylzinc to Michael acceptors (Section V.B). 

Addition across carbon—halogen bonds. Alkyl iodides48,62,65,109 "3,114 and also activated bromides48,65,107 "3,115 (e.g. methyl bromoacetate) react with la thermally62 or under UV irradiation to give 1,3-disubstituted bicyclo[l. 1. l]pentanes when the reaction is performed in diethyl ether, and the insertion of a single bicyclo[l. 1. l]pentane cage can be viewed as the standard reaction pattern. 

Halogenated hydrocarbons undergo an insertion reaction in the carbon-halogen bond and, in the case of fluorine, the reaction products are explosive, probably because of the large energy of formation of the Si—F bond. 

In a general sense, the Reformatsky reaction can be taken as subsuming all enolate formations by oxidative addition of a metal or a low-valent metal salt into a carbon-halogen bond activated by a vicinal carbonyl group, followed by reaction of the enolates thus formed with an appropriate electrophile (Scheme 14.1).1-3 The insertion of metallic zinc into a-haloesters is the historically first and still most widely used form of this process,4 to which this chapter is confined. It is the mode of enolate formation that distinguishes the Reformatsky reaction from other fields of metal enolate chemistry. 

Support for the proposal of M+ insertion into the carbon-halogen bond came from later work in which the reactivity of the Fe(CO) + ions (n = 0 - 5) towards allyl chloride was investigated using a MS/MS/MS multiquadrupole spectrometer60. Thus, while with the naked Fe+ the only observed products were FeCl+ (minor) and C3H5+ (and the secondary products derived from its reaction with neutral allyl chloride), with the iron carbonyl... 

A reaction sequence starting with bis[phenyltelluro]mcthane leads to the insertion of a methylene group into the carbon-halogen bond of an alkyl halide. The bis[phenyltelluro] methane is reacted with butyl lithium to yield lithiomethyl phenyl telluride, which combines with an alkyl halide. The resulting alkylmethyl phenyl tellurium is converted to the tellurium dihalide, which in turn decomposes to an alkylmethyl halide when kept under vacuum at 250 6 or heated in DMF in the presence of a sodium halide at 100°7. 

The reaction scheme is easy enough to draw, but what is the mechanism Overall it involves an insertion of magnesium into the new carbon-halogen bond. There is also a change in oxidation state of the magnesium, from Mg(0) to Mg(II). The reaction is therefore known as an oxidative insertion or oxidative addition, and is a general process for many metals such as Mg, Li (which we meet shortly), Cu, and Zn. 

Scheme 1 depicts some of the outcomes possible (5) when a metal atom reacts with an organic molecule, which might be a monomer or a substituent on a polymer. Some of the more common reactions are generalized. Oxidative addition is relevant to insertion of a metal atom into a carbon-halogen bond, such as might be found in polyvinyl chloride or the monomer, allyl chloride, or... 

A long-standing success in transition metal catalysis is the carbonylation reaction [66], in particular the synthesis of acetic acid [67]. Formally this is the insertion of CO into another bond, in particular into a carbon-halogen bond. After the oxidative addition to the transition metal (the breaking of the carbon-halogen bond), a reaction with a CO ligand takes place. This reaction is often called an insertion. Mechanistic studies have, however, shown that the actual reaction... 

Fluorovinylcopper reagents are prepared by metathesis reactions, and the corresponding zinc or cadmium species are the most convenient metalated precursors, e.g. formation of 1. Note that attempted insertion of copper metal into the vinyl carbon — halogen bond fails to afford the fluorovinylcopper reagent and instead a dimerization reaction occurs.Fluorovinylcopper reagents exhibit excellent thermal stability in the absence of oxygen or moisture. The thermal... 

This method was originally used by Frankland to prepare diethylzinc. It is described as an oxidative insertion see Insertion) of zinc metal inside the carbon-halogen bond of an organic halide. The initial product of the reaction is an alkylzinc halide derivative (RZnX), from which the diaUcylzinc compound (R2Zn) is formed as the Schlenk-type equilibrium establishes (equations 1 and 2). 

The effect of fluorinated systems on the reaction process shown in Figure 10.67 is of interest [139] it is to be noted that insertion of the palladium catalyst into the carbon-halogen bond may be considered as a nucleophihc attack by the palladium centre, albeit a soft nucleophile, which prefers to attack C—Br over C—F [138]. This process is, of course, aided by the presence of electron-withdrawing groups (EWG) in the organic system. It is likely, however, that co-ordination of the other reactant, e.g. alkyne, to the palladium is the rate-determining step [137], but this will be aided by EWGs attached to the metal. 

Davis, S. R. Ab initio study of the insertion reaction of magnesium into the carbon-halogen bond of fluoro- and chloromethane. J. Am. 

The reaction between benzyl chloride and tin is inhibited by nitrobenzene, suggesting that it involves electron transfer, and a reasonable mechanism for the formation of the tin-carbon bonds is shown in equation 4-41. A direct insertion of tin into the carbon-halogen bond has been proposed for the reaction of tin with a mixture of methyl iodide and water.65... 

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