Experimental and Computational Evidence for Gold Vinylidenes: Generation from Terminal Alkynes via a Bifurcation Pathway and Facile C–H Insertions

Facile cycloisomerization of (2-ethynylphenyl)­alkynes is proposed to be promoted synergistically by two molecules of BrettPhosAuNTf₂, affording tricyclic indenes in mostly good yields. A gold vinylidene is most likely generated as one of the reaction intermediates on the basis of both mechanistic studies and theoretical calculations. Different from the well-known Rh, Ru, and W counterparts, this novel gold species is highly reactive and undergoes facile intramolecular C­(sp³)–H insertions as well as O–H and N–H insertions. The formation step for the gold vinylidene is predicted theoretically to be complex with a bifurcated reaction pathway. A pyridine <i>N</i>-oxide acts as a weak base to facilitate the formation of an alkynylgold intermediate, and the bulky BrettPhos ligand in the gold catalyst likely plays a role in sterically steering the reaction toward formation of the gold vinylidene

Experimental and Computational Evidence for Gold Vinylidenes: Generation from Terminal Alkynes via a Bifurcation Pathway and Facile C–H Insertions

Facile cycloisomerization of (2-ethynylphenyl)­alkynes is proposed to be promoted synergistically by two molecules of BrettPhosAuNTf₂, affording tricyclic indenes in mostly good yields. A gold vinylidene is most likely generated as one of the reaction intermediates on the basis of both mechanistic studies and theoretical calculations. Different from the well-known Rh, Ru, and W counterparts, this novel gold species is highly reactive and undergoes facile intramolecular C­(sp³)–H insertions as well as O–H and N–H insertions. The formation step for the gold vinylidene is predicted theoretically to be complex with a bifurcated reaction pathway. A pyridine <i>N</i>-oxide acts as a weak base to facilitate the formation of an alkynylgold intermediate, and the bulky BrettPhos ligand in the gold catalyst likely plays a role in sterically steering the reaction toward formation of the gold vinylidene

A Micellar Catalysis Strategy for Suzuki–Miyaura Cross-Couplings of 2‑Pyridyl MIDA Boronates: <i>No Copper</i>, in Water, Very Mild Conditions

Suzuki–Miyaura (SM) cross-couplings of 2-pyridyl MIDA boronates can be successfully carried out in the complete absence of copper by attenuation of the Lewis basicity associated with the pyridyl nitrogen using selected substituents (e.g., fluorine or chlorine) on the ring. This strategy imparts additional synthetic options compared with existing approaches based on the use of Lewis acids or <i>N</i>-oxides. Thus, access to highly valued 2-substituted pyridyl rings via an initial Suzuki–Miyaura coupling can be followed by dehalogenation, S_NAr reactions, or a second SM coupling to arrive at 2,6-disubstituted pyridyl arrays, all run in a single pot, enabled by micellar catalysis in water. Accessing targets within drug-like space is demonstrated in a four-step, one-pot sequence. Computational data suggest that the major role being played by electron-withdrawing substituents in promoting these cross-couplings without the need for copper is to slow the rates of protodeboronation of intermediate 2-pyridylboronic acids

[3,3]-Sigmatropic Rearrangement versus Carbene Formation in Gold-Catalyzed Transformations of Alkynyl Aryl Sulfoxides: Mechanistic Studies and Expanded Reaction Scope

Gold-catalyzed intramolecular oxidation of terminal alkynes with an arenesulfinyl group as the tethered oxidant is a reaction of high impact in gold chemistry, as it introduced to the field the highly valued concept of gold carbene generation via alkyne oxidation. The proposed intermediacy of α-oxo gold carbenes in these reactions, however, has never been substantiated. Detailed experimental studies suggest that the involvement of such reactive intermediates in the formation of dihydro­benzo­thiepinones is highly unlikely. Instead, a [3,3]-sigmatropic rearrangement of the initial cyclization intermediate offers a reaction path that can readily explain the high reaction efficiency and the lack of sulfonium formation. With internal alkyne substrates, however, the generation of a gold carbene species becomes competitive with the [3,3]-sigmatropic rearrangement. This reactive intermediate, nevertheless, does not proceed to afford the Friedel–Crafts-type cyclization product. Extensive density functional theory studies support the mechanistic conclusion that the cyclized product is formed via an intramolecular [3,3]-sigmatropic rearrangement instead of the previously proposed Friedel–Crafts-type cyclization. With the new mechanistic insight, the product scope of this versatile formation of mid-sized sulfur-containing cyclo­alkenones has been expanded readily to various dihydro­benzo­thiocinones, a tetrahydro­benzo­cyclo­nonenone, and even those without the entanglement of a fused benzene ring. Besides gold, Hg­(OTf)₂ can be an effective catalyst, thereby offering a cheap alternative for this intramolecular redox reaction

A Micellar Catalysis Strategy for Suzuki–Miyaura Cross-Couplings of 2‑Pyridyl MIDA Boronates: <i>No Copper</i>, in Water, Very Mild Conditions

Suzuki–Miyaura (SM) cross-couplings of 2-pyridyl MIDA boronates can be successfully carried out in the complete absence of copper by attenuation of the Lewis basicity associated with the pyridyl nitrogen using selected substituents (e.g., fluorine or chlorine) on the ring. This strategy imparts additional synthetic options compared with existing approaches based on the use of Lewis acids or <i>N</i>-oxides. Thus, access to highly valued 2-substituted pyridyl rings via an initial Suzuki–Miyaura coupling can be followed by dehalogenation, S_NAr reactions, or a second SM coupling to arrive at 2,6-disubstituted pyridyl arrays, all run in a single pot, enabled by micellar catalysis in water. Accessing targets within drug-like space is demonstrated in a four-step, one-pot sequence. Computational data suggest that the major role being played by electron-withdrawing substituents in promoting these cross-couplings without the need for copper is to slow the rates of protodeboronation of intermediate 2-pyridylboronic acids