Shao-Hua Wang

Organocatalytic Asymmetric Direct C sp 3H Functionalization of Ethers: A Highly Efficient Approach to Chiral Spiroethers

and pharmaceuticals, is an important endeavor in organic synthesis. Tremendous efforts have been made during the past few years toward developing methods for the synthesis of spiroethers, although of the methods developed, many involve multiple steps and only a few are enantioselective. Therefore, the development of methods that are highly efficient, catalytic, and enantioselective is still required. The direct and selective functionalization of inactive Csp3 H bonds is not only a significant and actively studied subject in fundamental organic chemistry, it is also becoming a practical method for organic synthesis because of its atomand step economy. Among the reported transformations, intramolecular redox processes for the direct functionalization of Csp3 H bonds that are a to heteroatoms are important for the synthesis of structurally diverse amine and ether derivatives. Furthermore, since the pioneering work of Kim and co-workers, there have many good results reported in the area of intramolecular redox processes for the direct enantioselective Csp3 H functionalization at positions a to nitrogen atoms. However, examples of the corresponding enantioselective reaction of ethers are scarce. In 2005, Sames and co-workers. reported that Sc(OTf)3 or BF3·Et2O could initiate a direct functionalization of Csp3 H bonds of cyclic ethers 1 to give racemic spiroethers 2’ (Scheme 1). This

Total Synthesis of (−)-FR901483†

A total synthesis of the immunosuppressive alkaloid (-)-FR901483 (1) has been described. The intriguingly azatricyclic structure of 1 was constructed by the semipinacol-type rearrangement and intramolecular Schmidt reaction of an azido cyclohexanone derivative. This strategy provides a distinctive and competitive approach to the natural product 1.

Tandem Semipinacol-Type 1,2-Carbon Migration/Aldol Reaction toward the Construction of [5-6-7] All-Carbon Tricyclic Core of Calyciphylline A-Type Alkaloids

A Lewis acid promoted tandem semipinacol-type 1,2-carbon migration/aldol reaction of trimethylsilane-protected vinylogous α-ketols with aldehyde or dimethyl acetals is reported. This reaction provides a direct and rapid way for the construction of 6-substituted spiro[4.5]decanes which extensively exist in Daphniphyllum alkaloids. By the use of this method, further construction of a [5-6-7] all-carbon tricyclic core of Calyciphylline A-type alkaloids was also completed.

Palladium-Catalyzed Cascade Process To Construct 1,2,5-Trisubstituted Pyrroles

A novel palladium-catalyzed cascade allylic amination/intramolecular hydroamination/isomerization process of protected enynol 1 and primary amine 2 has been explored, which constructs the important 1,2,5-trisubstituted pyrroles. This transformation offers an alternative synthetic methodology capable of generating substituted pyrroles in a straightforward way.

Divergent and Efficient Syntheses of the Lycopodium Alkaloids (-)-Lycojaponicumin C, (-)-8-Deoxyserratinine, (+)-Fawcettimine, and (+)-Fawcettidine

Four from one: The four title alkaloids (structures shown in blue box) have been synthesized by using a common versatile intermediate with a 6/5/5 tricyclic skeleton. This tricyclic intermediate could be easily assembled by using an intramolecular carbene addition/cyclization and a Dieckmann condensation/Tsuji-Trost allylation as key steps.

Cascade oxidative dearomatization/semipinacol rearrangement: an approach to 2-spirocyclo-3-oxindole derivatives.

A novel cascade reaction involving oxidative dearomatization/semipinacol rearrangement of indol-2-yl cyclobutanols is explored with N-sulfonyloxaziridine (Davis oxaziridines) as oxidant, generating various 2-spiroquaternary 3-oxindoles in modest to good yields. This method might be useful in the synthesis of indole-based alkaloids bearing 2-spiroquaternary carbon centers. PTS=p-toluenesulfonic acid monohydrate.

The Synthesis of Multisubstituted Pyrroles via a Copper-Catalyzed Tandem Three-Component Reaction

An unprecedented nucleophilic addition/cyclization/aromatization cascade of basic chemicals, i.e., aromatic alkenes/alkynes, trimethylsilyl cyanide and N,N-disubstituted formamide, has been developed to give a series of multisubstituted pyrroles in moderate to good yields with high regioselectivities. This reaction not only reveals a new reaction mode for α-aminonitriles, but also provides a new and efficient cyclization pattern for the synthesis of multisubstituted pyrroles as well as their derivatives, which might facilitate related biological studies.

Tandem C-H oxidation/cyclization/rearrangement and its application to asymmetric syntheses of (-)-brussonol and (-)-przewalskine E

Natural products are a vital source of lead compounds in drug discovery. Development of efficient tandem reactions to build useful compounds and apply them to the synthesis of natural products is not only a significant challenge but also an important goal for chemists. Here we describe a tandem C–H oxidation/cyclization/rearrangement of isochroman-derived allylic silylethers, promoted by DDQ and InCl3. This method allows the efficient construction of tricyclic benzoxa[3.2.1]octanes with a wide substrate scope. We employ this tandem reaction to achieve the asymmetric total syntheses of (−)-brussonol and (−)-przewalskine E.

Catalytic intermolecular carbon electrophile induced semipinacol rearrangement

A catalytic intermolecular carbon electrophile induced semipinacol rearrangement was realized and the asymmetric version was also preliminarily accomplished with 92% and 82% ee. The complex tricyclic system architecture with four continuous stereogenic centers could be achieved from simple starting materials in a single step under mild conditions.

Efficient Oxa-Diels–Alder/Semipinacol Rearrangement/Aldol Cascade Reaction: Short Approach to Polycyclic Architectures

A novel carbon electrophile induced intermolecular oxa-Diels-Alder/semipinacol rearrangement/aldol cascade reaction of allylic silyl ether with β,γ-unsaturated α-ketoester has been developed under the promotion of SnCl4. This highly efficient transformation enables the quick construction of polycyclic architectures with up to five contiguous stereogenic centers in a single operation with moderate to good yields as well as high diastereoselectivity and would provide versatile short approaches to frameworks and/or analogues of numerous biologically important polycyclic natural products.