Room Temperature and Phosphine Free Palladium Catalyzed Direct C-2 Arylation of Indoles

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

Intermolecular Decarboxylative Direct C-3 Arylation of Indoles with Benzoic Acids

A palladium catalyzed C−H activation of indoles and a silver catalyzed decarboxylative C−C activation of ortho substituted benzoic acids are synergistically combined to synthesize indoles arylated exclusively in the C-3 position. This novel decarboxylative C−H arylation methodology is compatible with electron-donating and -withdrawing substituents in both coupling partners

Stereoselective Synthesis of the Western Hemisphere of Salinomycin

A convergent and module-based strategy for the asymmetric synthesis of the western hemisphere (C1−C17 fragment) of salinomycin has been devised. This new synthetic approach relies on highly stereoselective C-glycosidation and aldol processes

Overriding Ortho–Para Selectivity via a Traceless Directing Group Relay Strategy: The Meta-Selective Arylation of Phenols

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

Au-Catalyzed Cross-Coupling of Arenes via Double C–H Activation

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

Au-Catalyzed Cross-Coupling of Arenes via Double C–H Activation

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

Silver-Catalyzed Protodecarboxylation of Heteroaromatic Carboxylic Acids

A simple and highly efficient protodecarboxylation procedure for a variety of heteroaromatic carboxylic acids catalyzed by Ag2CO3 and AcOH in DMSO is described. This methodology can also perform the selective monoprotodecarboxylation of several aromatic dicarboxylic acids

Direct <i>ortho</i>-Arylation of <i>ortho</i>-Substituted Benzoic Acids: Overriding Pd-Catalyzed Protodecarboxylation

<i>ortho</i>-Arylation of <i>ortho</i>-substituted benzoic acids is a challenging process due to the tendency of the reaction products toward Pd-catalyzed protodecarboxylation. A simple method for preventing decarboxylation in sterically hindered benzoic acids is reported. The method described represents a reliable and broadly applicable entry to 2-aryl-6-substituted benzoic acids

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

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

Mild Cleavage of Aryl Mesylates: Methanesulfonate as Potent Protecting Group for Phenols

A mild protocol for the chemoselective deprotection of aryl methanesulfonates is described. The transformation can be conducted on highly functionalized substrates and renders the methanesulfonate a useful, previously underutilized protecting group for phenols