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. 2014 Dec 31;136(52):18082-6.
doi: 10.1021/ja510260j. Epub 2014 Dec 16.

Tuning reactivity and site selectivity of simple arenes in C-H activation: ortho-arylation of anisoles via arene-metal π-complexation

Paolo Ricci  1 , Katrina Krämer, Igor Larrosa
Affiliations

Tuning reactivity and site selectivity of simple arenes in C-H activation: ortho-arylation of anisoles via arene-metal π-complexation

Paolo Ricci et al. J Am Chem Soc. .

Abstract

Current approaches to achieve site selectivity in the C-H activation of arenes involve the use of directing groups or highly electron-poor arenes. In contrast, simple arenes, such as anisole, are characterized by poor reactivity and selectivity. We report that π-complexation to a Cr(CO)3 unit enhances the reactivity of anisoles providing an unprecedented ortho-selective arylation. This mild methodology can be used for the late stage functionalization of bioactive compounds containing the anisole motif, allowing the construction of novel organic scaffolds with few synthetic steps.

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Figures

Scheme 1
Scheme 1. Regioselective Ortho-Arylation of Anisole via Arene–Metal π-Complexation
Scheme 2
Scheme 2. Scope of the Direct Arylation of Anisole–Cr(CO)3 Complexes 1a–t with 2a
Reactions carried out on a 0.5 mmol scale with respect to the limiting reagent. Yields are of isolated product. b Performed with p-NMe2–C6H4–CO2H. c o,p-Bisarylated product 3ba′′ (3%) was also obtained. d o,p-Bisarylated product 3ca′′ (4%) was also obtained. e o,p-Bisarylated product 3da′′ (7%) was also obtained. f o,p-Bisarylated product 3ra′′ (3%) was also obtained. g Performed without TMP.
Scheme 3
Scheme 3. Scope of the Direct Arylation of Complex 1k with Iodoarenes 2a–o
Reactions carried out on a 0.5 mmol scale with respect to the limiting reagent. Yields are of isolated product. b Performed with 2.0 equiv of 2 for 40 h.
Scheme 4
Scheme 4. Late-Stage Functionalization of Estradiol Derivatives via Metal–Arene π-Complexation
See this image and copyright information in PMC

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