Concise Total Synthesis of Salimabromide.

We achieved a concise total synthesis of salimabromide by using a novel intramolecular radical cyclization to simultaneously construct the unique benzo-fused [4.3.1] carbon skeleton and the vicinal quaternary stereocenters. Other notable transformations include a tandem Michael/Mukaiyama aldol reaction to introduce most of the molecule's structural elements, along with hidden information for late-stage transformations, an intriguing tandem oxidative cyclization of a diene to form the bridged butyrolactone and enone moieties spontaneously, and a highly enantioselective hydrogenation of a cycloheptenone derivative (97% ee) that paved the way for the asymmetric synthesis of salimabromide.

Optically Active Flavaglines-Inspired Molecules by a Palladium-Catalyzed Decarboxylative Dearomative Asymmetric Allylic Alkylation.

With the aid of a class of newly discovered Trost-type bisphosphine ligands bearing a chiral cycloalkane framework, the Pd-catalyzed decarboxylative dearomative asymmetric allylic alkylation (AAA) of benzofurans was achieved with high efficiency [0.2-1.0 mol% Pd2(dba)3/L], good generality, and high enantioselectivity (>30 examples, 82-99% yield and 90-96% ee). Moreover, a diversity-oriented synthesis (DOS) of previously unreachable flavaglines is disclosed. It features a reliable and scalable sequence of the freshly developed Tsuji-Trost-Stoltz AAA, a Wacker-Grubbs-Stoltz oxidation, an intra-benzoin condensation, and a conjugate addition, which allows the efficient construction of the challenging and compact cyclopenta[b]benzofuran scaffold with contiguous stereocenters. This strategy offers a new avenue for developing flavagline-based drugs.

Palladium-Catalyzed Asymmetric (2+3) Annulation of p-Quinone Methides with Trimethylenemethanes: Enantioselective Synthesis of Functionalized Chiral Spirocyclopentyl p-Dienones.

A novel asymmetric catalytic (2+3) annulation of p-quinone methides with CN-substituted trimethylenemethane is described under palladium catalysis, providing an alternative approach for the enantioselective construction of highly functionalized chiral spirocyclopentyl p-dienones. Driven by the significant improvement in the reactivity and enantioselectivity, a novel type of non-C2-symmetric phosphoramidite ligand from the chirality-matched combination of (S)-BINOL and sterically demanding amine derived from l-hydroxyproline is evolved and explored for the protocol presented here.

Enantioselective Synthesis of Functionalized 4-Aryl Hydrocoumarins and 4-Aryl Hydroquinolin-2-ones via Intramolecular Vinylogous Rauhut-Currier Reaction of para-Quinone Methides.

A novel strategy for the asymmetric construction of functionalized 4-aryl-3,4-dihydrocoumarins and 4-aryl-3,4-dihydroquinolin-2-ones via an intramolecular vinylogous Rauhut-Currier reaction of para-quinone methides (p-QMs) under the bifunctional catalysis of chiral amine-phosphine is described. This intramolecular mode for the catalytic enantioselective 1,6-conjugate addition of p-QMs has been explored for the first time, delivering two types of synthetically important heterocycles in high yields and enantioselectivites.

Tandem Spirocyclopropanation/Rearrangement Reaction of Vinyl p-Quinone Methides with Sulfonium Salts: Synthesis of Spirocyclopentenyl p-Dienones.

A novel base-mediated tandem spirocyclopropanation/rearrangement reaction of vinyl p-quinone methides (p-VQMs) with sulfonium salts is described. The unprecedented reactivity of p-VQMs was explored for the first time in the spiroannulation cascade, providing a stereoselective approach to the construction of synthetically interesting, densely functionalized spirocyclopentenyl p-dienones.