Silver-Promoted Benzannulations of Siloxy Alkynes with Pyridinium and Isoquinolinium Salts.

We describe the development of efficient benzannulations of siloxy alkynes with pyridinium and isoquinolinium salts. Such reactions are successfully promoted by a stoichiometric amount of silver(I) benzolate under mild reaction conditions. This process proceeds via a formal inverse-electron demand Diels-Alder reaction, followed by fragmentation of the initially produced bicyclic adducts to deliver a range of synthetically useful phenols and naphthols.

Label-assisted mass spectrometry for the acceleration of reaction discovery and optimization.

The identification of new reactions expands our knowledge of chemical reactivity and enables new synthetic applications. Accelerating the pace of this discovery process remains challenging. We describe a highly effective and simple platform for screening a large number of potential chemical reactions in order to discover and optimize previously unknown catalytic transformations, thereby revealing new chemical reactivity.

Assembly of four diverse heterocyclic libraries enabled by Prins cyclization, Au-catalyzed enyne cycloisomerization, and automated amide synthesis.

We describe a unified synthetic strategy for efficient assembly of four new heterocyclic libraries. The synthesis began by creating a range of structurally diverse pyrrolidinones or piperidinones. Such compounds were obtained in a simple one-flask operation starting with readily available amines, ketoesters, and unsaturated anhydrides.

Modular and stereoselective synthesis of tetrasubstituted helical alkenes via a palladium-catalyzed domino reaction.

A highly modular and stereoselective synthesis of tetrasubstituted helical alkenes is accomplished by a Pd-catalyzed norbornene-mediated domino reaction. This protocol features the rapid assembly of four C-C bonds via sequential C-H activations and carbopalladations along with efficient access to enantiopure bromoalkyl aryl alkyne precursors using homologative alkynylation as the key transformation. Three distinct elements of stereoselectivity were observed in the preparation of the chiral helical alkenes: retention of stereochemistry of the substrates, induced helical diastereoselectivity in the alkene formation, and the exclusive exo-facial selectivity of the norbornene incorporation.

Mechanistic studies of Pd-catalyzed regioselective aryl C-H bond functionalization with strained alkenes: origin of regioselectivity.

Mechanistic studies of a palladium-catalyzed regioselective aryl C-H functionalization of 2-pyrrole phenyl iodide with norbornene are presented. Kinetic and spectroscopic analyses together with crystallographic data provide evidence for intermediates in a proposed stepwise mechanism. On the basis of the mechanistic studies, the origin of the regioselectivity is due to a ligand exchange between I(-) and HO(-) on the norbornyl palladium complex.

Synthesis of 2-oxazolones and α-aminoketones via palladium-catalyzed reaction of β,β-dibromoenamides.

β,β-Dibromoenamides show two different interesting reactivities based on the choice of R group under the reaction conditions. On the basis of mechanistic studies, both reactions proceed via an intermolecular Suzuki-Miyaura C-C coupling and an intramolecular C-O coupling.

Tandem Pd-catalyzed double C-C bond formation: effect of water.

A highly efficient water-accelerated palladium-catalyzed reaction of gem-dibromoolefins with a boronic acid via a tandem Suzuki-Miyaura coupling and direct arylation is reported. A wide range of aryl, alkenyl, and alkyl boronic acids, as well as a variety of substitution patterns on the phenyl ring, are tolerated. Additionally, mechanistic studies were conducted to ascertain the order of the couplings as well as the role(s) of water.

The norbornene shuttle: multicomponent domino synthesis of tetrasubstituted helical alkenes through multiple C--H functionalization.

Shall we dance? Within the proposed mechanism for the palladium-catalyzed title reaction, the strained alkene norbornene (or norbornadiene) enters and exits the catalytic cycle in a catalytic "square dance", acting as both a promoter and a coupling partner in the formation of four carbon-carbon bonds, two of them by challenging C--H activation processes.