We report the first room-temperature direct C-2 arylation of indoles with iodoarenes by using a highly electrophilic palladium catalyst generated in situ from Pd(OAc)2 and a silver carboxylate. These mild conditions permit a broad set of functionalities both in the indole and in the aryl iodide units such as free alcohols, phenols, aldehydes, bromides, or nitriles, thus allowing the synthesis of a variety of novel compounds in excellent yields.

The first methodology for Au(I/III)-catalyzed oxidative cross-coupling of arenes via double C-H activation has been developed. The reaction is fully selective for the cross-coupling between electron-rich hetero-/carbocyclic arenes and electron-poor arenes bearing relatively acidic C-H bonds. The inherently high cross-selectivity of the system obviates the need for directing groups or a large excess of one of the coupling partners.

The transition metal-catalysed direct functionalisation of C-H bonds is an increasingly viable alternative to the multi-step strategies traditionally adopted. The use of powerful and environmentally benign gold(I) and gold(III) catalysts in such transformations has highlighted their remarkable reactivity and led to a significant increase in their utilisation. This tutorial review provides an overview of gold-catalysed C-H functionalisation, looking at transformations which rely on the ability of gold to perform C-H activation, as well as those exploiting its potent π-acidity.

ABSTRACT:The use of stoichiometric Ag(I)-salts as additives in Pd-catalyzed C-H functionalization reactions is widespread. It is commonly proposed that this additive acts as an oxidant or as a halide scavenger promoting Pd-catalyst turnover. We demonstrate that, contrary to current proposals, phosphine ligated Ag(I)-carboxylates can efficiently carry out C-H activation on electrondeficient arenes. We show through a combination of stoichiometric and kinetic studies that a (PPh 3 )Ag-carboxylate is responsible for the C-H activation step in the Pd-catalyzed arylation of Cr(CO) 3 -complexed fluorobenzene. Furthermore, the reaction rate is controlled by the rate of Ag(I)-C-H activation, leading to an order zero on the Pd-catalyst. H/D scrambling studies indicate that this Ag(I) complex can carry out C-H activation on a variety of aromatic compounds traditionally used in Pd/Ag-mediated C-H functionalization methodologies.

The direct functionalization of phenols at the ortho and para position is generally facilitated by the electron-donating nature of the hydroxyl group. Accessing meta-functionalized phenols from the parent phenols, on the other hand, generally requires lengthy synthetic sequences. Here, we report the first methodology for the one-pot direct meta-selective arylation of phenols. This methodology is based on a traceless directing group relay strategy. In this process carbon dioxide is used as a transient directing group which facilitates a palladium catalyzed arylation meta to the phenol hydroxyl group with iodoarenes. This transformation proceeds with complete meta-selectivity and is compatible with a variety of functional groups both in the phenol and in the iodoarene coupling partner.

We demonstrate the first Au(I)-mediated C-H activation of arenes. Au(I) salts undergo C-H activation with electron-poor arenes, in stark contrast to Au(III) salts, which activate electron-rich arenes. This operationally simple and highly regioselective process occurs under very mild conditions and gives access to a variety of Au(I)-arene complexes in excellent yields.

The first example of a regioselective β-arylation of benzo[b]thiophenes and thiophenes at room temperature with aryl iodides as coupling partners is reported. This methodology stands out for its operational simplicity: no prefunctionalization of either starting material is required, the reaction is insensitive to air and moisture, and it proceeds at room temperature. The mild conditions afford wide functional group tolerance, often with complete regioselectivity and high yields, resulting in a highly efficient catalytic system. Initial mechanistic studies, including 13C and 2H KIEs, suggest that this process occurs via a concerted carbo-palladation across the thiophene double bond, followed by a base-assisted anti-elimination.

The biological production of FDCA is of considerable value as a potential replacement for petrochemical-derived monomers such as terephthalate, used in polyethylene terephthalate (PET) plastics. HmfF belongs to an uncharacterized branch of the prenylated flavin (prFMN) dependent UbiD family of reversible (de)carboxylases and is proposed to convert 2,5-furandicarboxylic acid (FDCA) to furoic acid in vivo. We present a detailed characterization of HmfF and demonstrate that HmfF can catalyze furoic acid carboxylation at elevated CO2 levels in vitro. We report the crystal structure of a thermophilic HmfF from Pelotomaculum thermopropionicum, revealing that the active site located above the prFMN cofactor contains a furoic acid/FDCA binding site composed of residues H296-R304-R331 specific to the HmfF branch of UbiD enzymes. Variants of the latter are compromised in activity, while H296N alters the substrate preference to pyrrole compounds. Solution studies and crystal structure determination of an engineered dimeric form of the enzyme revealed an unexpected key role for a UbiD family wide conserved Leu residue in activity. The structural insights into substrate and cofactor binding provide a template for further exploitation of HmfF in the production of FDCA plastic precursors and improve our understanding of catalysis by members of the UbiD enzyme family.