Alkyl halides from addition reactions

Organometallic compounds or carbanions undergo a number of reactions in which the carbanion or carbanion-like moiety of the organometallic compound acts as a nucleophilic displacing agent. Examples are the formation of hydrocarbons from alkyl halides, alkyl halides from halogens, and ketones from acid chlorides or esters. The latter two reactions are closely related to the base-catalyzed condensations and are perhaps additions as well as displacement reactions. Related addition reactions are the carbonation of organometallic compounds and the addition to ketones or aldehydes. 

Cross coupling between an aryl halide and an activated alkyl halide, catalysed by the nickel system, is achieved by controlling the rate of addition of the alkyl halide to the reaction mixture. When the aryl halide is present in excess, it reacts preferentially with the Ni(o) intermediate whereas the Ni(l) intermediate reacts more rapidly with an activated alkyl halide. Thus continuous slow addition of the alkyl halide to the electrochemical cell already charged with the aryl halide ensures that the alkyl-aryl coupled compound becomes the major product. Activated alkyl halides include benzyl chloride, a-chloroketones, a-chloroesters and amides, a-chloro-nitriles and vinyl chlorides [202, 203, 204], Asymmetric induction during the coupling step occurs with over 90 % distereomeric excess from reactions with amides such as 62, derived from enantiomerically pure (-)-ephedrine, even when 62 is a mixture of diastereoisomcrs prepared from a racemic a-chloroacid. Metiha-nolysis of the amide product affords the chiral ester 63 and chiral ephedrine is recoverable [205]. 

A polymer-bound guanidine base 31 has been used for the formation of aryl ethers from suitable phenols and alkyl halides. In addition to serving as a base to affect deprotonation, reagent 31 also acts as a sequestering agent for excess starting phenol (reaction 11).26... 

N-Alkylation of 3-aroylindole 97 carried out at 80 °C with alkyl halides from ethyl through -hexyl, gives mixtures of products 98 and 99 in yields of 41-90% (Equation 15) <1998JOC4510>. In addition to the expected N-alkylated indoles 98, a substantial fraction of the product was formed by additional replacement of the methoxy group by an alkoxy group. The reaction is very temperature dependent, since a decrease of only 5 °C completely suppresses the formation of the 0-alkylation products with the ethyl or -propyl halide. However, -hexyl bromide provided a 75% yield of hexyl ether 99 under these conditions. 

Isohypsic reactions of alkenes, like electrophilic additions of H2O or HX, represent a conventional pathway for the preparation of alcohols and alkyl halides from alkenes. The scope of their application was originally limited as unsymmetrical alkenes (e.g. 125) gave product mixtures composed of both Markovnikov (M) adducts and anti-Markovnikov (aM) adducts. As was already mentioned above (see Scheme 2.10), an efficient and general method for the conversion of alkenes into alcohols or ethers 126 (Scheme 2.47), with a nearly complete M selectivity, was elaborated using mercury salts as electrophiles in conjunction with the reduction of the formed adducts. It is also... 

Several thiols occur naturally for example, skunk secretion contains 3-methyll-butanethiol and cut onions evolve 1-propanethiol, and the thiol group of the natural amino acid cysteine plays a vital role in the biochemistry of proteins and enzymes (see Introduction, p. 2). Primary and secondary thiols may be prepared from alkyl halides (RX) by reaction with excess sodium thiolate (SN2 nucleophilic substitution by HST) or via the Grignard reagent and reaction with sulfur. Tertiary thiols can be obtained in good yields by addition of hydrogen sulfide to a suitable alkene. Thiols can also be prepared by reduction of sulfonyl chlorides (Scheme l).la,2a... 

In addition to undergoing the nucleophilic substitution reactions described in Chapter 10, alkyl halides undergo elimination reactions. In an elimination reaction, groups are eliminated from a reactant. For example, when an alkyl halide undergoes an elimination reaction, the halogen (X) is removed from one carbon and a proton is removed from an adjacent carbon. 

Preparation of Alkyl Halides from Olefins. There are two general methods for the synthesis of alkyl halides (1) by the interaction of an alcohol with a halogen hydride—a procedure that may reasonably be discussed under esterification or halogenation and, also, under the Friedel-Crafts synthesis when a metal halide is used to catalyze the reactions— and (2) by the addition of a halogen hydride to an unsaturated hydrocarbon. This reaction may be catalyzed by metal halides and by sulfuric acid. In the latter instance, the ethylsulfuric acid first formed is converted to the halide by gaseous chlorine or chlorine liberated in situ by action of sulfuric acid on a halide. 

Aldehydes form addition-products with the magnesium alkyl halides, from which secondary alcohols may be obtained by decomposition with water. These reactions have been much used in the preparation of alcohols of this class. The reactions are indicated by the following equations — H H... 

The synthesis of compounds 55 started from //-phosphinic acid 49b. The formation of the second P-C bond was achieved by in situ generation of the phosphonite species (TMSCl or BSA) followed by a conjugate addition of the appropriate Michael acceptor, or alkyl halides (silyl-Arbuzov reaction), or... 

Tetraalkylammonium cyanides, whidi are soluble in organic solvents, catalyze Michael additions and other base-catalyzed reactions. Under comparable conditions they are more powerful nucleophiles (toward alkyl halides) than NaCN. Reactions s. D. A. White and M. M. Baizer, Soc. Perkin I 1973, 2230 benzoins from aldehydes s. Synth. Meth. 26, 675. 

We ve already seen several methods for preparing alkyl halides from alkenes, including the reactions of HX and X2 with alkenes in electrophilic addition reactions (Sections 7.7 and 8.2). The hydrogen halides HCl, HBr, and HI react with alkenes by a polar mechanism to give the product of Markovnikov... 

Although in this chapter we shall be restricting coverage to reactions of transition-metal complexes, the phenomenon of oxidative addition is not confined to this type of compound. Such reactions are also well established for non-transition metals—a recently reported example concerns the oxidative addition of methyl bromide to indium(i) bromide to give InBr2Me— and for non-metals, as in the reaction of phosphorus trichloride with chlorine, to cite a very familiar example. Likewise, reductive eliminations are known and studied outside the area of transition-metal complexes. One example has been mentioned in Chapter 1 of Part II of this volume, namely the elimination of alkyl halides from the thallium(iii) compounds TlRXa. ... 

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