Total synthesis of diplofuranone A and diapolic acid A.

The first and concise syntheses of the anticancer agent diplofuranone A and the fatty acid-derived metabolite diapolic acid A have been demonstrated using easily accessible and commercially available starting materials. The key feature of these syntheses is the efficient diversification of highly stereo- and chemoselectively constructed (E,E)-1,6-dioxo-2,4-dienes using ruthenium catalytic conditions, which enabled straightforward access to diversely substituted bioactive molecules.

Asymmetric Ru/Cinchonine Dual Catalysis for the One-Pot Synthesis of Optically Active Phthalides from Benzoic Acids and Acrylates.

Herein, we report the asymmetric Ru/cinchonine dual catalysis that provides straightforward access to enantioselective synthesis of C-3 substituted phthalides via tandem C-H activation/Michael addition cascade. The use of readily accessible and less expensive [RuCl2(p-cym)]2 and cinchonine catalyst for the one-pot assembly of chiral phthalides greatly overcomes the present trend of using highly sophisticated catalysts. The developed method provides access to both enantiomers of a product using pseudoenantiomeric cinchona alkaloids as catalysts streamlining the synthesis of phthalide in both the optically active forms.

Diversification of (E,E)-1,6-Dioxo-2,4-Dienes for the Synthesis of (+)-Aspicillin, Isolaurepan, and ß-Parinaric Acid.

A divergent formal synthesis of polyhydroxylated macrocyclic lactone (+)-aspicillin and polyene bioactive natural product ß-parinaric acid and the total synthesis of non-terpenoid metabolite isolaurepan have been achieved using a ruthenium-catalyzed stereo- and chemoselective oxidative coupling reaction of easily accessible vinyl ketones and acrylates. The crucial transformation involves the efficient synthesis and functionalization of stereodefined (E,E)-1,6-dioxo-2,4-dienes using simple reaction protocols, which enabled straightforward access to a diverse range of bioactive natural products.

Ruthenium-Catalyzed Oxidative Cross-Coupling Reaction of Activated Olefins with Vinyl Boronates for the Synthesis of (E,E)-1,3-Dienes.

An oxidative cross-coupling reaction between activated olefins and vinyl boronate derivatives has been developed for the highly stereoselective construction of synthetically useful (E,E)-1,3-dienes. The highlight of this reaction is that exclusive stereoselectivity (only E,E-isomer) was achieved from a base-free, ligand-free, and mild catalytic condition with a less expensive [RuCl2(p-cymene)]2 catalyst.

Ru(II)-Catalyzed Deoxygenative Formal [3 + 1 + 2] Benzannulation of Allyl Alcohols and Acetylenediesters via C-H Activation and Selective Carbon-Carbon Triple Bond Cleavage.

An unprecedented Ru(II)-catalyzed deoxygenative, site-selective formal [3 + 1 + 2] benzannulation reaction for the efficient synthesis of highly substituted benzene molecules is reported. This reaction between allyl alcohols and acetylenedicarboxylate esters proceeds via cascade C-H activation, consecutive double migratory insertion with alkynes, and cycloaromatization followed by an unusual specific C-C triple bond cleavage.

Synthesis of Polyene Bioactive Natural Products: FR252921 and Vitamin A.

A formal synthesis of FR252921, a potent macrocyclic immunosuppressive agent, and a six-step synthesis of vitamin A have been demonstrated. The application of a ruthenium-catalyzed step-economic and environmentally benign strategy for the highly stereo- and chemoselective construction of valuable polyene motifs of FR252921 and vitamin A highlights the syntheses. The key features for the synthesis FR252921 include preparation of the triene moiety followed by two consecutive peptide couplings of the three fragments.

Ruthenium-catalyzed stereo- and chemoselective oxidative coupling of vinyl ketones: efficient access to (E,E)-1,6-dioxo-2,4-dienes.

A Ru-catalyzed direct oxidative coupling reaction of vinyl ketones was developed. It offers a straightforward and atom-economical protocol for the synthesis of functionalized (E,E)-1,6-dioxo-2,4-diene derivatives in moderate to good yields with excellent stereo- and chemoselectivities. In addition, the synthetic utility of this method was further demonstrated by its application to the synthesis of bioactive natural products such as (7E,9E)-henicosa-7,9-diene-6,11-dione (sex pheromone), ostopanic acid (plant anticancer agent), JA (anti-tumor agent) and the southern part (C1-C13) of the antibiotic macrolactin-T.

Weakly Coordinating, Hydroxyl Directed Ruthenium Catalyzed C-H Alkylation of Ubiquitous Benzyl Alcohols with Maleimides.

Benzyl alcohols have been employed as effective coupling partners in Ru-catalyzed C-H functionalization reactions, and their annulation with maleimides then offers efficient synthesis of useful ortho substituted succinimide aromatic aldehydes and ketones. Detailed mechanistic studies have been demonstrated by performing preliminary reactions, deuterium studies, and competitive experiments.

Ruthenium-catalyzed formal sp3 C-H activation of allylsilanes/esters with olefins: efficient access to functionalized 1,3-dienes.

Ru-catalysed oxidative coupling of allylsilanes and allyl esters with activated olefins has been developed via isomerization followed by C(allyl)-H activation providing efficient access to stereodefined 1,3-dienes in excellent yields. Mild reaction conditions, less expensive catalysts, and excellent regio- and diastereoselectivity ensure universality of the reaction. In addition, the unique power of this reaction was illustrated by performing the Diels-Alder reaction, and enantioselective synthesis of highly functionalized cyclohexenone and piperidine and finally synthetic utility was further demonstrated by the efficient synthesis of norpyrenophorin, an antifungal agent.