Asymmetric total synthesis of caribenol A via an intramolecular Diels-Alder reaction.

A total synthesis of the caribenol A (1), a novel natural product with an intriguing tetracyclic framework, has been achieved. The synthesis features an intramolecular Diels-Alder (IMDA) reaction for the facile construction of the tricyclic [5-7-6] skeleton of caribenol A (1) and a biomimetic oxidation reaction for the formation of the 2-hydroxyfuran-2(5H)-one motif of caribenol A (1) as key steps. This synthetic approach also reveals that the sp(2) carbon at C(2) in substrate 8 is a critical factor for the formation of the tricyclic [5-7-6] skeleton in 7.

Access to electron-rich arene-fused hexahydroquinolizinones through a gold-catalysis-initiated cascade process.

Golden Cascade: With a tethered, electron-rich arene as the internal nucleophile, a gold-catalyzed amide cyclization to an alkyne initiates a cascade process that ends with a Ferrier rearrangement. Electron-rich arene-bearing hexahydroquinolizin-2-ones are formed in good yields and can be converted into indole alkaloids in only a few steps.

Formal synthesis of cortistatins.

A unified strategy toward the asymmetric facile construction of the [6.7.6.5]oxapentacyclic skeleton of cortistatins is reported, featuring intramolecular Diels-Alder (IMDA), oxidative dearomatization, and an oxy-Michael addition reaction.

Asymmetric total synthesis of caribenol A.

A unified strategy toward the asymmetric total synthesis of carbenol A is reported, featuring intramolecular Diels-Alder (IMDA) and biomimetic oxidation reactions as key steps.

A model study for the concise construction of the oxapentacyclic core of cortistatins through intramolecular Diels-Alder and oxidative dearomatization-cyclization reactions.

A unified strategy towards the facile construction of the [6.7.6.5] oxapentacyclic skeleton of cortistatins is reported, featuring intramolecular Diels-Alder (IMDA) and oxidative dearomatization-cyclization reactions as key steps.

Combining Zn Ion Catalysis with Homogeneous Gold Catalysis: An Efficient Annulation Approach to N-Protected Indoles.

The Fischer indole synthesis is perhaps the most powerful method for indole preparation, but it often suffers from low regioselectivities with unsymmetric aliphatic ketone substrates and strong acidic conditions and is not suitable for α,ß-unsaturated ketones. In this article, we disclose an efficient synthesis of N-protected indoles from N-arylhydroxamic acids/N-aryl-N-hydroxycarbamates and a variety of alkynes via a cooperative gold and zinc catalysis. The zinc catalysis is similar to the related zinc ion catalysis in metalloenzymes such as human carbonic anhydrase II and substantially enhances the O-nucleophilicity of N-acylated hydroxamines by forming the corresponding Zn chelates. The Zn chelates can attack gold-activated alkynes to form O-alkenyl-N-arylhydroxamates, which can undergo facile 3,3-sigmatropic rearrangements and subsequent cyclodehydrations to yield N-protected indole products. This new chemistry offers several important improvements over the Fischer indole synthesis: a) the reaction conditions are mildly acidic and can tolerate sensitive groups such as Boc; b) broader substrate scopes including substrates with pendant carbonyl groups (reactive in the Fischer chemistry) and alkyl chlorides (e.g., 3f); c) better regioselectivities for the formation of 2-substituted indoles under much milder conditions; d) 2-alkenylindoles can be prepared readily in good to excellent yields, but the Fischer chemistry could not; e) with internal alkynes both steric and electronic controls are available for achieving good regioselectivities, while the Fischer chemistry is in general problematic.

Asymmetric, protecting-group-free total synthesis of (+)-caribenol A.

Caribenol Queen: A new asymmetric, protecting-group-free synthesis of the marine tetracyclic diterpenoid (+)-caribenol A (1) has been achieved. The enantioselective synthesis employed (S)-methyl 1-methyl-2-oxocyclopent-3-enecarboxylate as a chiral scaffold, and an intramolecular Diels-Alder (IMDA) reaction of substrate 3 afforded the [5.7.6] tricyclic core in compound 2.

Formal synthesis of 7-methoxymitosene and synthesis of its analog via a key PtCl2-catalyzed cycloisomerization.

A formal synthesis of 7-methoxymitosene is achieved via a key platinum-catalyzed cycloisomerization. The precursor for the Pt catalysis, a fully functionalized benzene intermediate, was prepared via a regioselective electrophilic bromination followed by a chemoselective Sonogashira cross-coupling. It underwent the PtCl2-catalyzed cycloisomerization smoothly despite its hindered and highly electron-rich nature. Analogs of 7-methoxymitosene can be accessed in an expedient manner by following a similar synthetic sequence.

Construction of all-carbon quaternary center by R2AlCl-mediated ring-opening reaction of oxacycles.

An unexpected R(2)AlCl-mediated ring-opening reaction of oxacycles for the formation of all-carbon quaternary centers was discovered, and a possible mechanism is proposed. The developed chemistry provides a concise approach to synthesize structural diverse of dolastane-type compounds.