Metalation and Halogen-Metal Interconversion Reactions of Some Halogenated Phenyl Ethers

Abstract

The extensive application of the halogen-metal interconversion reaction to aryl halides and the two-stage metalation of a number of halogenated aryl ethers [reactions (I) and (II)] have suggested a study of the effect of orientation, the kind of halogen and the nature of the RLi compound on the reactions of some halogenated phenyl ethers.Orientation.-The first illustrations of the halogen-metal interconversion reaction with bromoaryl ethersla,b,c involved bromine ortho to the ether linkage [reaction (IV)]. In subsequent studies,ld,e however, it was found that it is not necessary to have bromine in the ortho posi-

Focused ortho‐Lithiation and Functionalization of p‐Bromo‐ and p‐Iodoanisole

“…For the most part this has been due to concern that the –Br or –I substituent will preferentially undergo rapid X/Li exchange. Both Gilman and Wittig attempted ortho ‐lithiation of p ‐bromoanisole with both eventually realizing that the transformation illustrated in Equation (1) was occurring. Wittig went on to investigate the use of PhLi for the ortho ‐lithiation of the haloanisoles, ultimately isolating the anticipated triarylcarbinol derived from p ‐BrA and benzophenone in 70 % yield [Equation ].…”

“…This was an achievement at the time in that for seventy years, there was a fear of the intervention of a rapid halogen/lithium exchange followed by a secondary ortho-lithiation [Equation (1)]. Both Henry Gilman [8] and George Wittig, [9] the co-discovers of the ortho-lithiation reaction, also elucidated the sequence shown below.…”

“…Iodo-2-methoxy-phenyl)-phenyl-methanol (9): To a stirred solution of 1.14 M o-Li-p-iodoanisole (15.3 mL) was slowly added benzaldehyde (1.7 mL, 16.8 mmol) via syringe. The crude product was triturated with hexanes (5-6 mL), filtered and washed with cold hexanes to afford 3 8. g, 67 %.…”

Bromine–lithium exchange: An efficient tool in the modular construction of biaryl ligands

“…The bromine–lithium exchange reaction is certainly one of the most fundamental synthetic transformations [ 39 ]. Although this reaction was reported by C. S. Marvel in 1927 [ 40 ], G. Wittig [ 41 ] and H. Gilman [ 42 – 44 ] were the first to apply it in organic synthesis in the late thirties. Since then, this reaction has been considered as a mature method lacking both appeal and surprise [ 33 ], and only new applications of this reaction or mechanistic studies have been reported [ 30 , 32 – 33 45 – 55 ].…”

USE OF METHYLLITHIUM IN METAL/HALOGEN EXCHANGE; A MILD AND EFFICIENT METHOD FOR THE SYNTHESIS OFORTHOSUBSTITUTED TOLUENES

“…6 In the early reports of the metal/halogen exchange reaction methyllithium was described as the least effective of all the alkyllithiums investigated and it was therefore believed to have little synthetic utility in this reaction. 11,12 We have found that if methyllithium is reacted with aryl bromides bearing a suitable ortho substituent it is very effective in the metal/halogen exchange reaction (Scheme 1). 9,10 Included in the small number that are known are examples where the methyl bromide by-product reacted with the newly formed aryllithium to produce the corresponding methyl compound.…”