Aryl halides allylic ethers

The method is quite useful for particularly active alkyl halides such as allylic, benzylic, and propargylic halides, and for a-halo ethers and esters, but is not very serviceable for ordinary primary and secondary halides. Tertiary halides do not give the reaction at all since, with respect to the halide, this is nucleophilic substitution and elimination predominates. The reaction can also be applied to activated aryl halides (such as 2,4-dinitrochlorobenzene see Chapter 13), to epoxides, " and to activated alkenes such as acrylonitrile. The latter is a Michael type reaction (p. 976) with respect to the alkene. 

Nickel-bpy and nickel-pyridine catalytic systems have been applied to numerous electroreductive reactions,202 such as synthesis of ketones by heterocoupling of acyl and benzyl halides,210,213 addition of aryl bromides to activated alkenes,212,214 synthesis of conjugated dienes, unsaturated esters, ketones, and nitriles by homo- and cross-coupling involving alkenyl halides,215 reductive polymerization of aromatic and heteroaromatic dibromides,216-221 or cleavage of the C-0 bond in allyl ethers.222... 

Tab. 10.8 summarizes the application of rhodium-catalyzed allylic etherification to a variety of racemic secondary allylic carbonates, using the copper(I) alkoxide derived from 2,4-dimethyl-3-pentanol vide intro). Although the allyhc etherification is tolerant of linear alkyl substituents (entries 1-4), branched derivatives proved more challenging in terms of selectivity and turnover, the y-position being the first point at which branching does not appear to interfere with the substitution (entry 5). The allylic etherification also proved feasible for hydroxymethyl, alkene, and aryl substituents, albeit with lower selectivity (entries 6-9). This transformation is remarkably tolerant, given that the classical alkylation of a hindered metal alkoxide with a secondary alkyl halide would undoubtedly lead to elimination. Hence, regioselective rhodium-catalyzed allylic etherification with a secondary copper(l) alkoxide provides an important method for the synthesis of allylic ethers. 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

Reduction of halides.1 The reagent prepared from NaBH3CN and SnCl2 in a 2 1 ratio does not reduce primary or secondary alkyl halides or aryl halides in ether at 25°, but does reduce tertiary, allyl, and benzyl halides. It is thus comparable to NaBH3CN-ZnCl2 (12, 446). Aldehydes, ketones, and acid chlorides are reduced to alcohols, but esters and amides are inert. 

The method is an extension of the well-known Grignard synthesis in ethers to the use of nonsolvating media, and is a development of procedures previously reported.2-6 A version of it has been employed with straight-chain primary alkyl chlorides, bromides, and iodides from C2 to Cu,5-7 and in solvents (or an excess of the halide) which permit reaction temperatures above 120°, with simple aryl halides such as chlorobenzene and 1-chloro-naphthalene. Branched-chain primary, secondary, and tertiary alkyl halides, allyl, vinyl, and benzyl halides either fail to react or give extensive side reactions. Better results are reported to be obtained in such cases with the use of catalytic quantities of a mixture of an alkoxide and an ether such as diethyl ether or tetrahydrofuran in a hydrocarbon medium, but the products are not, of course, completely unsolvated.4... 

Reduction of tertiary, allylic, and benzylic halides. NaCNBH, and ZnCI. in a 2 1 molar ratio in ether reduce these halides selectively in —70-90% yield in the presence of primary, secondary, vinyl, and aryl halides. I hc selectivity is comparable to that of lithium 9,9-di-/i-butyl-9-borabicyclol3.3.l nonate, the ate complex obtained by reaction of n-butyllithium with 9-BBN. ... 

Blaser and Spencer used aroyl halides in place of aryl halides, with aroyl chlorides being of specific interest as ubiquitous, relatively cheap compounds ( Blaser reaction ) [24], This latter reaction is normally conducted in aromatic solvents phosphines are not used here as catalyst ligands since they fully inhibit the reaction. In the same way, benzoic acid anhydrides can be used as the aryl source in combination with PdCl2 and catalytic amounts of NaBr [79]. In this reaction, one of the arenes is used in the coupling reaction by elimination of CO, whereas the other benzoate serves as the base. The benzoic acid thus formed can easily be recycled into the anhydride. The use of aryl and vinyl triflates according to Cacchi [25] and Stille [26] extends the scope of the Heck coupling to carbonyl compounds phenol derivatives act via triflate functionalization as synthetic equivalents of the aryl halides. The arylation of cyclic alkenes [27], electron-rich vinyl ethers [28], and allylic alcohols [29] is accessible through Heck reactions. Allylic alcohols yield C-C-saturated carbonyl compounds (aldehydes) for mechanistic reasons (y9-H elimination), as exemplified in eq. (6). 

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