Substrate Activation Strategies in Rhodium(III)-Catalyzed Selective Functionalization of Arenes

Abstract

The possibility of developing new methods for the efficient construction of organic molecules via disconnections other than traditional functional group transformations has driven the interest in direct functionalization of C-H bonds. The ubiquity of C-H bonds makes such transformations attractive, but they also pose several challenges. The first is the reactivity and selectivity of C-H bonds. To achieve this, directing groups (DGs) are often installed that can enhance the effective concentration of the catalyst, leading to thermodynamically stable metallacyclic intermediates. However, the presence of a pendant directing group in the product is often undesirable and unnecessary. This may account for the limitation of applications of C-H functionalization reactions in more common and general uses. Thus, the development of removable or functionalizable directing groups is desirable. Another key problem is that the reactivity of the resulting M-C bond can be low, which may limit the scope of the coupling partners and hence limit the reaction patterns of C-H activation reactions. While the first Cp*Rh(III)-catalyzed C-H activation of arenes was reported only 7 years ago, significant progress has been made in this area in the past few years. We began our studies in this area in 2010, and we and others have demonstrated that diversified catalytic functionalization of arenes can be realized using Cp*Rh(III) complexes with high reactivity, stability, and functional group compatibility. This Account describes our efforts to solve some of these challenges using Rh(III) catalysis. We fulfilled our design and activation of the arene substrates by taking advantage of the nucleophilicity, electrophilicity, oxidizing potential, and properties of a participating ligand of the directing groups when the arenes are coupled with relatively reactive unsaturated partners such as alkenes and alkynes. These in situ funtionalizable roles of the DG allowed extensive chemical manipulation of the initial coupled product, especially in the construction of a diverse array of heterocycles. In the coupling of arenes with polar coupling partners, the polar Rh(III)-C(aryl) bond showed higher reactivity as both an organometallic reagent and a nucleophilic aryl source. The polar coupling partners were accordingly activated by virtue of umpolung, ring strain, and rearomatization. All of these transformations have been made possible by integration of the higher reactivity, stability, and compatibility of Rh(III)-C bonds into catalytic systems. We have demonstrated that to date some of these transformations can be achieved only under rhodium catalysis. In addition, by means of stoichiometric reactions, we have gained mechanistic insights into the interactions between the Rh-C bond and the other coupling partners, which have opened new avenues in future direct C-H functionalization reactions.

Diastereoselective [3+2] Annulation of Aromatic/Vinylic Amides with Bicyclic Alkenes through Cobalt‐Catalyzed C−H Activation and Intramolecular Nucleophilic Addition

“…In ad euterium/ hydrogen exchange experiment with 1a under the standard reaction conditions using CD 3 OD as the solvent, no D/H exchange was observed in the absence of either Co(OAc) 2 or Ag 2 CO 3 .H owever,t he ortho-methoxylation product 7 was obtained in 78 %y ield under the standard reaction conditions. [13] These results suggest that the C À Ha ctivation is probably catalyzed by aC o III species that is formed in situ from Co II by oxidation with Ag + .…”

“…[11] Thep roduct yield and NMR analysis of the crude product mixture both suggested that the reaction is highly diastereoselective.The choice of oxidant, base,a nd solvent is crucial for the success of this transformation (see the Supporting Information for details on the optimization studies). Control experiments revealed that no product was formed in the absence of either Co(OAc) 2 or Ag 2 CO 3 .Furthermore, we replaced the quinolyl (Q) moiety by many other groups,b ut none of them were equally effective (see the Supporting Information, Table S5). Ther eaction required ah igh catalyst loading (40 mol %), and we speculate that the 8-aminoquinoline (AQ) that is released during the reaction probably reduces the catalytic activity of the Co catalyst by coordinating to the metal.…”

“…[1,2] Although the use of noble metals,i ncluding Pd, Rh, Ru, and Ir,h as been dominating the field of C À Ha ctivation, [3] cobalt-catalyzed C À Hactivation reactions [4,5] have also received much interest because cobalt is earth-abundant and therefore less expensive than noble metals.M oreover,o wing to its unique reactivity and functional-group tolerance,the use of cobalt catalysts for C À Hactivation provides acomplementary method to noblemetal catalysis.…”

Synthesis of Fluorine-Containing 6-Arylpurine Derivatives <i>via</i> Cp*Co(III)-Catalyzed C–H Bond Activation

“…Once they demonstrated the viability of this C-H/C-F bond cleavage strategy, the scope was rapidly expanded. [21][22][23][24][25][26] A Cp*Co(III) catalyst, [27][28][29][30][31] which is more available than Cp*Rh(III) [32][33][34] but often exhibits similar catalytic activity, was used by Li and colleagues 21) and Ackermann and colleagues 22) for the same transformation. Manganese catalysts were also effective, as reported by Ackermann's group 23) and Feng and Loh's group.…”

Highly Stereoselective Synthesis of Imine‐Containing Dibenzo[b,d]azepines by a Palladium(II)‐Catalyzed [5+2] Oxidative Annulation of o‐Arylanilines with Alkynes

“…[5] In particular, nitrogen-group-assisted heteroannulations of nitrogencontaining coupling partners with alkynes by aC À Hcleavage/ alkyne insertion/cyclization cascade have been widely used to generate structurally diverse N-heterocyclic compounds,such as indoles, [6] pyrroles, [7] isoquinolines, [8] isoquinolinones, [9] and so on. [10] Remarkably,m ost of these transformations were realized by formal [3+ +2] or [4+ +2] cycloadditions to give fiveor six-membered rings,but the construction of larger rings by means of related annulations is quite rare.…”