Facile Access to Hetero‐poly‐functional Arenes and meta‐Substituted Arenes via Two‐Step Dimetalation and Mg/Halogen‐Exchange Protocol. Issue 12 (28th January 2021)

• Record Type: Journal Article
• Authors: Bruña, Sonia; Kennedy, Alan. R.; Fairley, Michael; O'Hara, Charles T.
• Is Part Of: Chemistry. Volume 27:Issue 12(2021)
• Page Start: 4134
• Page End: 4140
• Publication Date: 2021-01-28
• Subjects: alkali metals -- magnesium -- meta-activation -- metalation -- metal–halogen exchange; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202004696
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: The Grignard reagent, i PrMgCl and its lithium chloride‐enhanced 'turbo' derivative i PrMgCl⋅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‐, meta ′‐deprotonation of N, N ‐diisopropylbenzamide, anisole and (trifluoromethyl)benzene, respectively, using the sodium magnesiate reagent [Na4 Mg2 (TMP)6 ( n Bu)2 ] (where TMP is 2, 2, 6, 6‐tetramethylpiperidide), 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, N i Pr2 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 (D o M) chemistry, this reaction sequence can be thought of as InDirect meta ‐Metalation (ID m M). 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. Abstract : A tandem template metalation and Mg/I‐exchange strategy has been used to convert simple arenes into the corresponding meta ‐substituted arenes in good yields.