Rh(III) and Ru(II)-Catalyzed Site-Selective C–H Alkynylation of Quinolones

C2- and C5-alkynylated quinolone scaffolds are core structures of numerous biologically active molecules. Utilizing TIPS-EBX as an alkynylating agent, we have developed an efficient and site-selective C5 alkynylation of 4-quinolones that is directed by the weakly coordinating carbonyl group. In addition, Ru­(II) catalyzed C2-selective alkynylation was successfully realized via <i>N</i>-pyrimidyl group-directed cross-couplings to access valuable C2-alkynylated 4-quinolones. This strategy provides direct access to the C2 or C5 alkynylated 4-quinolones. Furthermore, the reaction was applied to isoquinolones for C3-selective alkynylation

Palladium(II)-Catalyzed Direct Intermolecular Alkenylation of Chromones

A new efficient method for the direct alkenylation of chromones via a palladium(II)-catalyzed C–H functionalization reaction was developed. The use of pivalic acid with Cu(OAc)3/Ag2CO3 provided superior reactivity in the cross-coupling of chromones with alkene partners. This approach represents a significant advance over the existing two-step method and afforded various 3-vinylchromone derivatives, which are privileged structures in many biologically active compounds and versatile synthetic building blocks

Enantioselective Syntheses of Georgyone, Arborone, and Structural Relatives. Relevance to the Molecular-Level Understanding of Olfaction

Georgyone (1) and arborone (2), powerful woody odorants, have been synthesized enantioselectively along with their enantiomers. Several structural relatives of 1 and 2 have also been made enantioselectivity in order to probe the molecular details of the binding of 1 and 2 to the olfactory G-protein-coupled receptors which they activate. These studies have led to a number of conclusions regarding the structural requirements for woody odor, including absolute configuration, critical methyl substitution, and the spatial orientation of the key methyl groups. Odorants 1 and 2 bind to at least 10 mouse olfactory receptors, lending support to the combinatorial model for odor perception/differentiation. The implications of this work with regard to possible receptor binding modes are discussed

Enantioselective Syntheses of Georgyone, Arborone, and Structural Relatives. Relevance to the Molecular-Level Understanding of Olfaction

Georgyone (1) and arborone (2), powerful woody odorants, have been synthesized enantioselectively along with their enantiomers. Several structural relatives of 1 and 2 have also been made enantioselectivity in order to probe the molecular details of the binding of 1 and 2 to the olfactory G-protein-coupled receptors which they activate. These studies have led to a number of conclusions regarding the structural requirements for woody odor, including absolute configuration, critical methyl substitution, and the spatial orientation of the key methyl groups. Odorants 1 and 2 bind to at least 10 mouse olfactory receptors, lending support to the combinatorial model for odor perception/differentiation. The implications of this work with regard to possible receptor binding modes are discussed

Three-Component Cyclobutylation via Silver(I)-Catalyzed Carbene Transfer Reactions with [1.1.1]Propellane

In this study, we report an innovative Ag(I)-catalyzed carbene transfer reaction that employs [1.1.1]propellane as a precursor to form the methylene cyclobutyl carbene complex for a controllable three-component reaction. The key strategy of this method involves the formation of Ag-bound oxonium ions as intermediates, which are generated by the reaction between the Ag-carbene complex and cyclic ether-type solvents such as THF and 1,4-dioxane. The subsequent nucleophile-induced C–O bond cleavage leads to a three-component etherification of methylene cyclobutane. Employing this strategy, we successfully coupled various amine and alcohol partners, demonstrating the method’s potential for the late-stage functionalization of intricate, biologically relevant molecules and synthetic manipulations of the resulting products. To further explore the mechanism driving selective three-component reactions, we have conducted comprehensive experimental and computational studies

A Short Enantioselective Pathway for the Synthesis of the Anti-Influenza Neuramidase Inhibitor Oseltamivir from 1,3-Butadiene and Acrylic Acid

A short synthetic pathway has been developed for the synthesis of oseltamivir (1) or the enantiomer (ent-1). The intermediates and conditions for this process are summarized in Scheme . The synthesis provides a number of advantages:  (1) use of inexpensive and abundant starting materials; (2) complete enantio-, regio-, and diastereocontrol; (3) avoidance of explosive, azide-type intermediates; (4) good overall yield (ca. 30%, still not completely optimized); and (5) scalability

DataSheet1_Nucleophilic C4-selective (hetero) arylation of pyridines for facile synthesis of heterobiaryls.docx

The synthesis of heterobiaryl compounds holds significant value in organic chemistry due to their extensive range of applications. Herein, we report a highly efficient strategy for conducting C4-selective (hetero) arylation of pyridines using N-aminopyridinium salts. The reaction proceeds readily at room temperature in the presence of a base, thus eliminating the requirement for catalysts or oxidants. This method allows for the installation of various electron-rich (hetero) aryl groups on pyridines, resulting in the streamlined synthesis of highly valuable C4-(hetero) aryl pyridine derivatives, which are otherwise challenging to acquire via conventional methods. This simple and straightforward method will facilitate access to a range of heterobiaryl compounds thereby promoting their application in various scientific disciplines.</p

Strategic Approach to the Metamorphosis of γ‑Lactones to NH γ‑Lactams via Reductive Cleavage and C–H Amidation

A new approach has elaborated on the conversion of γ-lactones to the corresponding NH γ-lactams that can serve as γ-lactone bioisosteres. This approach consists of reductive C–O cleavage and an Ir-catalyzed C–H amidation, offering a powerful synthetic tool for accessing a wide range of valuable NH γ-lactam building blocks starting from γ-lactones. The synthetic utility was further demonstrated by the late-stage transformation of complex bioactive molecules and the asymmetric transformation

Enantioselective Synthesis of Bridged- or Fused-Ring Bicyclic Ketones by a Catalytic Asymmetric Michael Addition Pathway

Efficient methodology has been developed for the conjugate addition of ketene acetals to cyclic α,β-enones. The chiral adducts allow access to fused- or bridged-ring structures such as those shown

A Short Enantioselective Pathway for the Synthesis of the Anti-Influenza Neuramidase Inhibitor Oseltamivir from 1,3-Butadiene and Acrylic Acid

A short synthetic pathway has been developed for the synthesis of oseltamivir (1) or the enantiomer (ent-1). The intermediates and conditions for this process are summarized in Scheme . The synthesis provides a number of advantages:  (1) use of inexpensive and abundant starting materials; (2) complete enantio-, regio-, and diastereocontrol; (3) avoidance of explosive, azide-type intermediates; (4) good overall yield (ca. 30%, still not completely optimized); and (5) scalability