Iron and Manganese Catalysts for the Selective Functionalization of Arene C(sp²)−H Bonds by Carbene Insertion

Abstract

The first examples of the direct functionalization of non-activated aryl sp 2 C À Hb onds with ethyl diazoacetate (N 2 CHCO 2 Et) catalyzedb yM n-or Fe-based complexes in acompletely selective manner are reported, with no formation of the frequently observed cycloheptatriene derivatives through competing Buchner reaction. The best catalysts are Fe II or Mn II complexes bearing the tetradentate pytacn ligand (pytacn = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane). When using alkylbenzenes,t he alkylic C(sp 3 ) À Hb onds of the substituents remained unmodified, thus the reaction being also selective towardf unctionalization of sp 2 C À Hb onds.

Mechanism of the Selective Fe-Catalyzed Arene Carbon–Hydrogen Bond Functionalization

“…The results collected in this section reveal that [Fe-(OTf) 2 (L1)] is a particularly efficient and chemoselective catalyst for the formal carbene insertion from EDA into the C− H bonds of benzene, reinforcing the findings of the preliminary communication. 12 It is worth noting that the scope of this catalytic system with a series of substituted benzenes showed the complete selectivity toward arene C−H bonds in the presence of alkyl C−H sites of the substituents. The presence of two labile coordination sites appears to be necessary for efficient catalysis.…”

“…Although water was not added in our experiments, the presence of adventitious water molecules was experimentally detected by the formation of a certain amount of ethyl glycolate products. 12 Most importantly, note that this mechanism accounts for the results on the isotopic labeling experiments; in first place, the hydrogen atom at the C−H bond that suffers the attack of the carbene moiety can end up at the benzylic position of the product. In addition, the intermediacy of the enol provides a path for the incorporation of hydrogen atoms from water in the final product.…”

“…Mechanistic considerations from product analysis. Our previous contribution included 12 a Hammett analysis of the carbene transfer reaction, determined by means of competitive Reactions carried out at 80°C with 0.005 mmol of catalyst, 8 equiv of NaBAr 4 F and 20 equiv of ethyl diazoacetate in 1.5 mL of benzene + 1.5 mL of CH 2 Cl 2 . Reaction time: 12 h. b Initial EDA converted into insertion (I) + addition (A) products.…”

“…11 Recently, we reported the first example for a chemoselective functionalization of nonactivated aryl C(sp 2 )−H bonds with the use of the commercially available ethyl diazoacetate (EDA) and iron-or manganese-based catalysts. 12 Fe II and Mn II complexes bearing the tetradentate pytacn ligand (pytacn = L1 = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane) lead to >99% formation of insertion products and no formation of cycloheptatriene derivatives (Scheme 2c). Fumarate and maleate products, resulting from coupling of two carbene units, were also practically absent.…”

Highly para‐Selective C−H Alkylation of Benzene Derivatives with 2,2,2‐Trifluoroethyl α‐Aryl‐α‐Diazoesters

“…[11,12] However,the highly site-selective C(sp 2 ) À Hfunctionalization of aryl rings of monoalkyl-substituted arenes remains elusive [13] because of the several competing reactions which occur when mixing an alkyl benzene with diazo esters in the presence of transition metals (Scheme 1a). [11,12] However,the highly site-selective C(sp 2 ) À Hfunctionalization of aryl rings of monoalkyl-substituted arenes remains elusive [13] because of the several competing reactions which occur when mixing an alkyl benzene with diazo esters in the presence of transition metals (Scheme 1a).…”