Intramolecular Palladium(II)-Catalyzed Regioselective 6-endo or 6-exo C-H Benzannulation: An Approach for the Diversity-Oriented Synthesis of Quinolinone Derivatives from Pyridones.

Herein, a new intramolecular palladium(II)-catalyzed regioselective 6-endo-trig or 6-exo-trig annulation through direct C-H activation is presented as a method for the diversity-oriented synthesis of highly substituted quinolinones from pyridones. The reaction occurs under mild conditions and exhibits excellent regioselectivity, good functional group tolerance, and broad applications. This innovative approach has been successfully utilized in the synthesis of Glycopentanolone A and an intermediate of (R)-(+)-Tipifarnib.

Regioselective [2 + 1] photocycloaddition of 2-pyridones with diazo compounds.

Herein, we report a novel regioselective [2 + 1] cyclization reaction of 2-pyridones with carbenes generated in situ via visible light irradiation, without the requirement for catalysts or additives. The diverse functional groups of 2-pyridones and diazo compounds exhibit good tolerance, enabling the rapid synthesis of highly valuable cyclopropanated dihydro-2-pyridone scaffolds with exceptional regio- and stereoselectivity. Furthermore, DFT calculations provide a comprehensive explanation for the regio- and stereoselectivity observed in the reaction.

Palladium-catalyzed [4 + 3] annulation of 2-bromobiphenyls and epoxides for the assembly of dihydrodibenzo[b,d]oxepines.

A palladium-catalyzed [4 + 3] annulation of 2-bromobiphenyls and epoxides for the construction of dihydrodibenzo[b,d]oxepines is reported. This approach involves direct C-H and C-O bond activation followed by a ring annulation and features readily available starting materials, a broad substrate scope, good step economy and good scalability.

Catalytic Synthesis of Atropisomeric o-Terphenyls with 1,2-Diaxes via Axial-to-Axial Diastereoinduction.

Herein, we report a modular and convergent strategy for the assembly of atropisomeric o-terphenyls with 1,2-diaxes via palladium/chiral norbornene cooperative catalysis and axial-to-axial diastereoinduction. Readily available aryl iodides, 2,6-substituted aryl bromides, and potassium aryl trifluoroborates are used as the building blocks, laying the foundation for diversity-oriented synthesis of these scaffolds (46 examples). Other features include the unique axial-to-axial diastereoinduction mode, construction of two axes in a single operation, and step economy. DFT calculations are performed to rationalize the axial-to-axial diastereoinduction process. Synthetic utilities of this method in preparation of atropisomeric oligophenyls, chiral catalysts, and ligands are demonstrated.

A Concise Total Synthesis of (-)-Berkelic Acid.

Reported here is a concise total synthesis of (-)-berkelic acid in eight linear steps. This synthesis features a Catellani reaction/oxa-Michael cascade for the construction of the isochroman scaffold, a one-pot deprotection/spiroacetalization operation for the formation of the tetracyclic core structure, and a late-stage Ni-catalyzed reductive coupling for the introduction of the lateral chain. Notably, four stereocenters are established from a single existing chiral center with excellent stereocontrol during the deprotection/spiroacetalization process. Stereocontrol of the intriguing deprotection/spiroacetalization process is supported by DFT calculations.

Epoxides as Alkylating Reagents for the Catellani Reaction.

We report a cooperative catalytic system comprising a PdII complex, XPhos, and the potassium salt of 5-norbornene-2-carboxylic acid that enables the use of epoxides as alkylating reagents in the Catellani reaction, thereby expanding the existing paradigm of this powerful transformation. The potassium salt of inexpensive 5-norbornene-2-carboxylic acid acts as both mediator and base in the process. This mild, chemoselective, scalable, and atom-economical protocol is compatible with a wide variety of readily available functionalized aryl iodides and epoxides, as well as terminating olefins. The resulting products undergo facile oxa-Michael addition to furnish ubiquitous isochroman scaffolds.

Reaction of Diazo Compounds with Difluorocarbene: An Efficient Approach towards 1,1-Difluoroolefins.

A transition-metal-free difluoromethylenation of diazo compounds that proceeds under mild conditions has been developed and is based on the use of TMSCF2 Br as the difluoromethylene source and tetrabutylammonium bromide (TBAB) as the promoter. The chemoselective formal carbene dimerization reaction is achieved owing to the electronic properties and the relative stability of the difluorocarbene intermediate.

Construction of All-Carbon Quaternary Centers through Cu-Catalyzed Sequential Carbene Migratory Insertion and Nucleophilic Substitution/Michael Addition.

A Cu-catalyzed three-component cross-coupling reaction of terminal alkyne, α-diazo ester, and alkyl halide has been developed. This transformation involves sequent migratory insertion of copper-carbene and nucleophilic substitution, in which a C(sp)-C(sp(3)) bond and a C(sp(3))-C(sp(3)) bond are formed successively on a carbenic center. Michael addition acceptors can also be employed instead of alkyl halides that enable Michael addition to be an alternative way to build C(sp(3))-C(sp(3)) bond. This transformation represents a highly efficient method for the construction of all-carbon quaternary centers.

Photoinduced [3+2] Cycloaddition of Alkyl-Acceptor Diazoalkanes: Diversity-Oriented Synthesis of Pyrazolines Containing a Quaternary Center.

We present a new [3+2] cycloaddition reaction between alkyl-acceptor diazoalkanes under visible light irradiation. By employing easily accessible alkyl-acceptor-type diazoalkanes or their precursor hydrazones as both 1,3-dipoles and dipolarophiles, a diverse range of pyrazoline derivatives featuring a quaternary center have been efficiently synthesized in a predictable manner, with excellent functional group tolerance and good yields. Furthermore, scale-up experiments and downstream transformations of the product were also detailed.

Photoinduced Cobalt Catalyzed Radical Heck-Type Reaction of Alkyl Electrophiles.

We report here a general alkylation reaction of terminal alkenes with nucleophilic cobaloxime complex catalysis under visible light irradiation. A broad range of vinyl arenes and heteroarenes, as well as a diverse set of alkyl(pseudo)halides or strained rings as alkyl electrophiles, can efficiently undergo the transformation up to the gram scale. Mechanistic study reveals the radical nature of the reaction and corroborates our design involving alkylcobaloxime as the key intermediate.

Diversity-oriented functionalization of 2-pyridones and uracils.

Heterocycles 2-pyridone and uracil are privileged pharmacophores. Diversity-oriented synthesis of their derivatives is in urgent need in medicinal chemistry. Herein, we report a palladium/norbornene cooperative catalysis enabled dual-functionalization of iodinated 2-pyridones and uracils. The success of this research depends on the use of two unique norbornene derivatives as the mediator. Readily available alkyl halides/tosylates and aryl bromides are utilized as ortho-alkylating and -arylating reagents, respectively. Widely accessible ipso-terminating reagents, including H/DCO2Na, boronic acid/ester, terminal alkene and alkyne are compatible with this protocol. Thus, a large number of valuable 2-pyridone derivatives, including deuterium/CD3-labeled 2-pyridones, bicyclic 2-pyridones, 2-pyridone-fenofibrate conjugate, axially chiral 2-pyridone (97% ee), as well as uracil and thymine derivatives, can be quickly prepared in a predictable manner (79 examples reported), which will be very useful in new drug discovery.

Synthesis of Benzofused Dioxabicycle Scaffolds via a Catellani Strategy.

Reported is a modular strategy for the preparation of the unique benzofused dioxabicycle scaffolds involving a Catellani reaction of aryl iodides, epoxides, and terminal alkynes and an oxa-cyclization. This is a mild, scalable, chemoselective, and atom-economical protocol, compatible with various functionalized aryl iodides, epoxides, and terminal alkynes. With the ability to build up the molecular complexity rapidly and efficiently from feedstock chemicals, this method will have wide applications in organic synthesis.

Ag(I)-Catalyzed Tandem Reaction of Conjugated Ene-yne-ketones in the Presence of PhI(OAc)2 and Triethylamine: Synthesis of 2-Alkenylfurans.

Silver-catalyzed tandem cyclization-elimination reactions of conjugated ene-yne-ketones in PhI(OAc)2/triethylamine system lead to the formation of 2-alkenylfurans. 2-Furylsilver carbene and phenyliodonium ylide are proposed as the key intermediates in these transformations.