Renxiao Liang

Silver-Catalyzed Reaction of Enynals with Alkenes: A Tandem 1,3-Dipolar Cycloaddition/Cyclopropanation

A silver-catalyzed reaction of enynals with alkenes to synthesize a series of polycyclic compounds has been developed. The reaction occurred smoothly using enynals with electron-deficient alkynes or terminal alkynes as substrates. The reaction was proposed to proceed through a tandem 1,3-dipolar cycloaddition/cyclopropanation process. The preliminary investigations of the asymmetric catalytic version revealed that the biphosphine ligand could be used as the potential efficient chiral ligand.

An Efficient Route to Polysubstituted Tetrahydronaphthols: Silver‐Catalyzed [4+2] Cyclization of 2‐Alkylbenzaldehydes and Alkenes

( )-podophyllotoxine (1) is an important member of the lignan class of natural products and it has shown potent cytotoxic activity against various cancer cell lines. Aklavinone (2) is one of the very important precursors common to the formation of the clinically significant anthracyclines, daunomycin, doxorubicin, carminomycin, aklavin, and aclacinomycin A. However, because of the easy elimination of the benzylic hydroxy group and the difficulties in controlling the stereoselectivities of substituents on the tetrahydronaphthol ring, the efficient and stereoselective synthesis of this group of compounds remains a challenge in organic synthesis. Therefore, methods for the synthesis of tetrahydronaphthol derivatives, especially the polysubstituted ones, would be of great importance. It is well known that [4+2] cyclization reactions are the most efficient and atom-economic way to construct a sixmembered ring. We therefore based our retrosynthetic analysis on a [4+2] approach. As shown in Scheme 2, there are four different [4+2] approaches, namely paths a–d. Path a requires the generation of benzyne and 1,3-butadienol, both of which are unstable chemical species. Paths b and c involve the disruption of the aromaticity of the benzene ring during the course of the reaction, which is energetically unfavorable. Path d involves an alkene and benzo-1,3-butadienol (also called hydroxy-o-quinodimethane) as synthons. Although the aromaticity of the benzene ring remains intact for path d, the hydroxy-o-quinodimethane, which is also an unstable chemical species, could rearrange quickly to 2-alkylbenzaldehyde. The success of this strategy would rely strongly upon the generation of the unstable hydroxy-o-quinodimethane species from 2-alkylbenzaldehyde. Although photoinduced enolization of 2-alkylbenzaldehyde has been reported in the literature to produce the corresponding hydroxy-o-quinodimethane, the photolysis reaction is highly limited because the reaction conditions are not applicable for irradiation-sensitive groups or substrates such as styrene derivatives and the halides. The reported reactions typically involve very simple substrates or rather special reaction conditions. In the past decades, transition metals have shown exceptional efficiency in catalyzing a variety of chemical transformations such as cross-coupling, ring-closing metathesis, and Diels–Alder reactions, as well as the enolization of carbonyl compounds. And we were curious about the possibility of producing hydroxy-o-quinodimethanes by the transition-metal catalyzed enolization of 2-alkylbenzaldehyde with the ultimate aim of synthesizing polysubstituted tetrahydronaphthol (Scheme 2, path d). We anticipated this method development to lead to the development of a practical and general method for the synthesis of benzannulated systems such as those found in the lignans. Scheme 1. Naturally occurring compounds containing tetrahydronaphthol.

Rapid Access to 2‐Methylene Tetrahydrofurans and γ‐Lactones: A Tandem Four‐Step Process

A one-pot tandem process involving hydrolysis, Knoevenagel condensation, Michael addition, and Conia-ene (HKMC) reactions has been developed for the rapid synthesis of indanone-fused 2-methylene tetrahydrofurans from the reaction of enynals and propynols. In this process, two rings and four bonds are generated with 100 % atom-economy and high step-efficiency. The resulting tetrahydrofurans were readily oxidized into α-methylene γ-lactones, which are one of the most important substructures in natural and bioactive compounds.

A silver-catalyzed three-component reaction via stabilized cation: synthesis of polysubstituted tetrahydronaphthols and tetrahydronaphthylamines

An efficient and stereoselective method for the synthesis of polysubstituted tetrahydronaphthols and tetrahydronaphthylamines through a silver-catalyzed three-component reaction of enynals/enynimines, alkenes and H2O via a stabilized cation intermediate has been developed.