Facile access to hetero-poly-functional arenes and meta-substituted arenes via two-step dimetalation and Mg/halogen-exchange protocol

Bruña, Sonia and Kennedy, Alan R. and Fairley, Michael and O'Hara, Charles T. (2020) Facile access to hetero-poly-functional arenes and meta-substituted arenes via two-step dimetalation and Mg/halogen-exchange protocol. Chemistry - A European Journal. ISSN 0947-6539 (In Press)

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The Grignard reagent, iPrMgCl and its lithium chloride-enhanced ‘turbo’ derivative iPrMgCl·LiCl have been employed to investigate the single iodo/magnesium exchange reactions of the trisubstituted arenes, 2,5-diiodo-N,N-diisopropylbenzamide 1 , 1,4-diiodo-2-methoxybenzene 2 , and 1,4-diiodo-2-(trifluoromethyl)benzene 3 . These three arenes themselves were initially prepared by a double ortho-, metaʹ-deprotonation of N,N-diisopropylbenzamide, anisole and (trifluoromethyl)benzene respectively, using a sodium magnesiate reagent, and subsequent electrophilic quenching with iodine/THF solution. Thus, by following a combined deprotonation and magnesium/halogen exchange strategy, the simple monosubstituted arenes can be converted to trisubstituted diiodoarenes, which can ultimately be transformed into the corresponding mono-magnesiated arenes, in THF at −40°C, within seconds in good yields. The other functional group (OMe, NiPr2 or CF3 respectively) present on the di-iodoarenes helps direct the exchange reaction to the ortho position whereas subsequent addition of different electrophiles permits the preparation of hetero-poly-functional-arenes, with three different substituents in their structure. Intriguingly, if water is used as the electrophile, a new and facile route to prepare meta-substituted arenes, which cannot be easily obtained by conventional processes, is forthcoming. In contrast to directed ortho-metalation (DoM) chemistry, this reaction sequence can be thought of as InDirect meta-Metalation (IDmM). The scope of the chemistry has been tested further by exposing the initial unreacted iodo-functionality at the meta-position to a second Mg/I-exchange reaction and subsequent functionalization.


Bruña, Sonia, Kennedy, Alan R. ORCID logoORCID: https://orcid.org/0000-0003-3652-6015, Fairley, Michael ORCID logoORCID: https://orcid.org/0000-0002-6021-0339 and O'Hara, Charles T.;