Li-Na Guo

Palladium-Catalyzed Cyclization of Propargylic Compounds

Many groups have explored the scope of the palladium-based cyclization of propargylic compounds since Tsujis first report in 1985. Through the proper positioning of an internal nucleophilic center and the judicious selection of an appropriate external nucleophile, the synthetic chemist can effectively assert control over the course of the reaction and its products. However, initial investigations were very limited: only heterocyclic compounds were originally synthesized. We have found the palladium-catalyzed cyclization of propargylic compounds to be a very efficient method for producing both carbocyclic and heterocyclic compounds. In this Account, we discuss the cyclization reactions of functionalized propargylic compounds with a variety of nucleophiles that we have developed over the past few years. We also review similar reactions reported by other groups. We focus here on the cyclization of functionalized propargylic compounds containing a carbon nucleophilic center that is in close proximity to the propargylic moiety. We conducted a detailed investigation of their cyclizations with carbon nucleophiles, with nitrogen nucleophiles, with oxygen nucleophiles, and without nucleophiles. We have developed several efficient and useful methods for the synthesis of indenes, naphthalenes, polycycles, and spirocyclic compounds. All of these reactions proceed satisfactorily under very mild conditions; high regio- and stereoselectivity have been observed as well. In the course of our studies, we provided the first demonstration of a novel tandem C-H activation/bis-cyclization reaction of propargylic compounds with terminal alkynes. In addition, we used external nucleophiles to investigate the cyclization of functionalized propargylic compounds that bear an unsaturated carbon-carbon or carbon-heteroatom bond. We presented the first report of the use of external nucleophiles to initiate a novel cyclization of functionalized propargylic compounds containing an electrophile. This revelation provided a fresh perspective through the discovery of a new type of domino cyclization of propargylic compounds. Metal-catalyzed cyclization of propargylic compounds can provide indenes, cyclopentanones, cyclic carbonates, benzofurans, and a range of other cyclic molecules. A thorough understanding of the mechanisms involved in this class of reaction affords exceptional synthetic control, as shown here by our development of efficient procedures and reagents for palladium-catalyzed propargylic cyclizations.

Decarboxylative acylation of cyclic enamides with α-oxocarboxylic acids by palladium-catalyzed C-H activation at room temperature.

An efficient catalytic decarboxylative acylation of unactivated sp(2) (alkenyl) C-H bonds has been developed. Various substituted α-oxocarboxylic acids with different electronic properties react under mild conditions to afford a diverse range of β-acyl enamide products in good yields. The reaction is proposed to proceed via a cyclic vinylpalladium intermediate, facilitating the decarboxylative dehydrogenative process with enamide coupling partners.

Metal-free oxidative hydroxyalkylarylation of activated alkenes by direct sp3 C–H functionalization of alcohols

A metal-free tandem radical addition/cyclization reaction of activated alkenes and alcohols has been developed. The process provides an efficient and atom economical access to various valuable hydroxyl-containing oxindoles through the direct sp(3) C-H functionalization of alcohols.

Copper‐Catalyzed Oxidative Benzylarylation of Acrylamides by Benzylic CH Bond Functionalization for the Synthesis of Oxindoles

Radically changing benzyls: An efficient method for the benzylarylation of activated alkenes has been developed through a copper-catalyzed tandem radical addition/cyclization strategy (see scheme). This oxidative coupling between acrylamides and benzylic hydrocarbons provides access to diverse alkyl-substituted oxindoles in good to excellent yields. A variety of functional groups were tolerated in this transformation (TBPB = tert-butylperoxy benzoate).

Sulfoxide–Alkene Hybrids: A New Class of Chiral Ligands for the Hayashi–Miyaura Reaction

Sulfoxide-alkene hybrids are introduced as a new class of chiral heterodentate ligands for the Hayashi-Miyaura reaction. The synthesis of these ligands was achieved without the use of protecting groups. A chiral resolution was performed via simple column-chromatographic separation of the diastereomeric ligands. Both diastereomers proved to be excellent ligands in Rh-catalyzed 1,4-addition reactions, furnishing chiral products with high enantioselectivities and, remarkably, opposite stereoconfigurations.

Metal-Free Oxidative Spirocyclization of Hydroxymethylacrylamide with 1,3-Dicarbonyl Compounds: A New Route to Spirooxindoles

A metal-free oxidative spirocyclization of hydroxymethylacrylamide with 1,3-dicarbonyl compounds is described. The reaction proceeds through tandem dual C-H functionalization and intramolecular dehydration, in which two new C-C bonds and one C-O bond were formed. This method affords a novel and straightforward access to various spirooxindoles under mild conditions.

Copper-catalyzed tandem oxidative cyclization of cinnamamides with benzyl hydrocarbons through cross-dehydrogenative coupling

The copper-catalyzed tandem oxidative cyclization of cinnamamides with benzyl hydrocarbons through the direct cross-dehydrogenative coupling of sp(3) and sp(2) C-H bonds has been developed. Satisfactorily, ethers, alcohols and alkanes could also be used instead of benzyl hydrocarbons in this transformation, which allows rapid access to diverse dihydroquinolinones in one step.

Bu4NI-catalyzed decarboxylative acyloxylation of an sp3 C–H bond adjacent to a heteroatom with α-oxocarboxylic acids

A novel metal-free decarboxylative acyloxylation of an sp(3) C-H bond in formamides and ethers has been explored. A variety of N-acyloxymethylamides and α-acyloxy ethers could be easily synthesized by this method. Preliminary mechanistic studies have shown that the reaction proceeded via a radical process.

Decarboxylative Alkynylation of α-Keto Acids and Oxamic Acids in Aqueous Media

A mild K2S2O8 promoted decarboxylative alkynylation of α-keto acids and oxamic acids has been developed. This process features mild reaction conditions, a broad substrate scope, and good functional-group tolerance, therefore providing a new and efficient access to a wide range of ynones and propiolamides. Furthermore, this radical process could also be successfully applied to alkynylation of the Csp(2)-H bond in DMF with hypervalent alkynyl iodide reagents.

Transition-Metal-Free Tandem Radical Thiocyanooxygenation of Olefinic Amides: A New Route to SCN-Containing Heterocycles

A novel transition-metal-free tandem radical thiocyanooxygenation of olefinic amides with potassium thiocyanate has been developed under mild conditions. This method allows a reliable and practical access to diverse SCN-containing heterocycles bearing a wide range of functional groups in good to excellent yields. Furthermore, this tandem reaction provides a simple method for the construction of C-O and C-S bonds in one step.