Alkyl halides, addition

Alkyl halides by themselves are insufficiently electrophilic to react with benzene Aluminum chloride serves as a Lewis acid catalyst to enhance the electrophihcity of the alkylating agent With tertiary and secondary alkyl halides the addition of aluminum chlonde leads to the formation of carbocations which then attack the aromatic ring... 

The usual sulfone synthesis by displacement of halide by sulfmate is assumed to have a nucleophilic 8 2 mechanism However, in special cases of alkyl halides with additional, electron-withdrawing substituents a radical substitution pathway has been observed (equation 32). Correspondingly, substitutions under formation of sulfones take... 

Dialkylamino derivatives of elements located in the periodic table to the left or below those listed above cannot be prepared by the above method due to either the ionic character of some of the inorganic halides or the formation of stable metal halide-amine addition products. Therefore, other methods must be applied. Dialkylamino derivatives of tin7 and antimony8 are conveniently obtained by reaction of the corresponding halides with lithium dialkylamides. Others, such as the dialkylamino derivatives of aluminum,9 are made by the interaction of the hydride with dialkylamines. Dialkylamino derivatives of beryllium10 or lithium11 result from the reaction of the respective alkyl derivative with a dialkylamine. 

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. 

The aforementioned observations have significant mechanistic implications. As illustrated in Eqs. 6.2—6.4, in the chemistry of zirconocene—alkene complexes derived from longer chain alkylmagnesium halides, several additional selectivity issues present themselves. (1) The derived transition metal—alkene complex can exist in two diastereomeric forms, exemplified in Eqs. 6.2 and 6.3 by (R)-8 anti and syn reaction through these stereoisomeric complexes can lead to the formation of different product diastereomers (compare Eqs. 6.2 and 6.3, or Eqs. 6.3 and 6.4). The data in Table 6.2 indicate that the mode of addition shown in Eq. 6.2 is preferred. (2) As illustrated in Eqs. 6.3 and 6.4, the carbomagnesation process can afford either the n-alkyl or the branched product. Alkene substrate insertion from the more substituted front of the zirconocene—alkene system affords the branched isomer (Eq. 6.3), whereas reaction from the less substituted end of the (ebthi)Zr—alkene system leads to the formation of the straight-chain product (Eq. 6.4). The results shown in Table 6.2 indicate that, depending on the reaction conditions, products derived from the two isomeric metallacyclopentane formations can be formed competitively. 

It would be inappropriate, and indeed superfluous, to review here the whole of this very complicated field, since this has been done adequately by several authors [2, 4-7]. For our present purposes we need to pick out only one other aspect, that of co-initiation by alkyl halides. It was proved that with certain olefins and metal halides the addition of an alkyl halide to a mixture of metal halide and olefin would initiate polymerisation [8], and this was interpreted by an extension of the theory of co-initiation, in terms of the reaction scheme (2) ... 

Acrylonitrile, polymerization, 120 Activity of phase-transfer catalysts Sjj2 reactions, 170-175 weak-nucleophile Sj.Ar reactions, 175-182 Acyltetracarbonyl cobalt compound, cleavage in the carboxyalkylation of alkyl halides, 150 Addition reactions, Michael, catalytic asymmetric, 69,70f... 

While a large number of studies have been reported for conjugate addition and Sn2 alkylation reactions, the mechanisms of many important organocopper-promoted reactions have not been discussed. These include substitution on sp carbons, acylation with acyl halides [168], additions to carbonyl compounds, oxidative couplings [169], nucleophilic opening of electrophilic cyclopropanes [170], and the Kocienski reaction [171]. The chemistry of organocopper(II) species has rarely been studied experimentally [172-174], nor theoretically, save for some trapping experiments on the reaction of alkyl radicals with Cu(I) species in aqueous solution [175]. 

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... 

Alkylation of allylic halides and alcohols (8, 334 335). Complete details of the reaction of RC.u BF3 with allylic halides and alcohols are now available. The reagent is probably an ate complex, RBF3 Cu 1, at least at low temperatures. In the case of allylic halides, THF is superior to ether for effecting /-substitution. However use of ether is essential for the direct alkylation. Addition of BF3 (even 2 equivalents) has no effect on reactions of C6II5Cu.5... 

A one-pot PTC reaction procedure for the overall conversion of an alkyl halide into a primary amine via an azide is particularly illustrative.204 Thus the reduction of the azide is effected by the addition of sodium borohydride to a reaction mixture arising from the PTC displacement reaction of an alkyl halide with sodium azide (the preparation of 1-octylamine, Expt 5.193). The reaction appears to be applicable to primary and secondary alkyl halides, alkyl methane-sulphonates and benzylic halides. 

Participating substrates include unactivated aromatic and heteroaromatic halides. In addition to halides, other leaving groups are known (i.e., (EtO)2P(0), RS (R = Ar, alkyl), ArSO, ArS02, PhSe, Ph2S+, RSN2 (R = /-Bu, Ph), N2BF4, R3N+, and N+). 

One of the main issues with the use of magnesium and zinc as inexpensive co-reductants is their reactivity with alkyl halides. Also, additives such as TMSOTf are relatively expensive. In an attempt to address these limitations, Namy utilised mischmetal (La 33%, Ce 50%, Nd 12%, Pr 4%, Sm and other lanthanides 1%) as the stoichiometric reductant for the regeneration of the Sm(II).31,32 This reagent system provides an important alternative since it does not require the use of additives and mischmetal is relatively inexpensive. This system has been utilised successfully in Barbier and Reformatsky reactions, halide reductions and pinacol couplings (Scheme 7.7).31,32... 

Oxidation of ]V-MeTTPFenCl (46, 52). Catalytic alkene oxidation by iron N-alkylporphyrins requires that the modified heme center can form an active oxidant, presumably at the HRP compound I level of oxidation. To show that iron N-alkyl porphyrins could form highly oxidized complexes, these reactive species were generated by chemical oxidation and examined by NMR spectroscopy. Reaction of the (N-MeTTP)FenCl with chlorine or bromine at low temperatures results in formation of the corresponding iron(III)-halide complex. Addition of ethyl- or t-butyl-hydroperoxide, or iodosylbenzene, to a solution of N-MeTTPFenCl at low temperatures has no effect on the NMR spectrum. However, addition of m-chloroperoxybenzoic acid (m-CPBA) results in the formation of iron(III) and iron(IV) products as well as porphyrin radical compounds that retain the N-substituent. 

Asymmetric allylation of cinnamyl halides, alkylation of alkynyl epoxides, and 1,4-addition of nitro olefins" are also successfully demonstrated by combination of an organozinc reagent and a chiral copper phosphoramidite. 

Alkylation of arenes and perfluoro or perchlorofluoro compounds proceeds readily under SbFg catalysis [4,21]. In addition to alkyl halides, alkyl esters and haloesters have also been used to alkylate arenes under these reaction conditions. For example, perfluorotoluene reacts with pentafluorobenzene to form perfluorodiphenylmethane in 68 % yield when the reaction mixture is quenched with HR If H2O is used for quenching, perfluorobenzophenone is obtained in 93 % yield (Eq. 8) [21a]. 

In addition to alkyl halides alkyl tosylates, acyl chlorides, isocyanates and the three-membered ring compounds including some cyclopropanes, oxiranes, thiiranes and aziridines can be used as electrophiles to afford a variety of triorganoarsenic compounds (equations 26 , 27 , 28 , 29 , 30 , 31 and 32 ). 

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