Arene–Metal π-Complexation as a Traceless Reactivity Enhancer for C–H Arylation

Abstract

Current approaches to facilitate C-H arylation of arenes involve the use of either strongly electron-withdrawing substituents or directing groups. Both approaches require structural modification of the arene, limiting their generality. We present a new approach where C-H arylation is made possible without altering the connectivity of the arene via π-complexation of a Cr(CO)3 unit, greatly enhancing the reactivity of the aromatic C-H bonds. We apply this approach to monofluorobenzenes, highly unreactive arenes, which upon complexation become nearly as reactive as pentafluorobenzene itself in their couplings with iodoarenes. DFT calculations indicate that C-H activation via a concerted metalation-deprotonation transition state is facilitated by the predisposition of C-H bonds in (Ar-H)Cr(CO)3 to bend out of the aromatic plane.

ortho‐Directing Chromium Arene Complexes as Efficient Mediators for Enantiospecific C(sp2)–C(sp3) Cross‐Coupling Reactions

“…Further oxidation would lead to removal of the Cr(CO) 3 fragment to give the decomplexed coupled product. An additional attractive feature of chromium arene complexes is that they significantly acidify Ar−H bonds, thus facilitating lithiation, including ortho ‐lithiation, thereby enabling the possibility for ortho ‐selective cross‐coupling. Herein we report our success in achieving this coupling reaction, although it ultimately differed mechanistically from the planned pathway.…”

Reactivity of Para‐Substituted Fluorobenzenes in Palladium‐catalyzed Intermolecular Direct Arylations

“…To enhance the electron‐deficient character of mono‐fluorobenzenes, Larrosa and co‐workers reported its η‐complexation with Cr(CO) 3 and performed its α‐arylation in high yields (Figure 1 D). 19 Nevertheless, these strategies might be not considered as green protocols with respect to the concept of atom economy. More recently, we demonstrated that the introduction of a functional group at meta ‐position to the fluorine atom increased dramatically its reactivity (Figure 1 E).…”

Palladium-catalyzed non-directed C–H bond arylation of difluorobenzenes and dichlorobenzenes bearing benzoxazole or benzothiazole

“…11 Among other improvements, a particular attention has focused on the use of alternative coupling partners to aryl halides (e.g., tosylates, 15-17 diaryliodonium salts, 18 boronic acids, 19,20 ArSO 2 Na, 21 carboxylic acid 22 or simple arenes under oxidative conditions 23 ), or the use of other catalytic systems. 24,25 In order to address the lower reactivity of less-electron deficient fluorobenzenes, 14,26,27 directing group (e.g., carboxylic acid) strategy have been employed. 28,29 On other hand, benzoxazole unit has been employed as directing group for the regioselective C2 arylation of phenyl using a palladium catalyst in the presence of silver carbonate in trifluoroacetic acid ( Figure 2b).…”