Facile [7C+1C] Annulation as an Efficient Route to Tricyclic Indolizidine Alkaloids

Abstract

A handle on annulation: The two alkenoyl moieties of the cyclic dithiolane are parallel to each other and enables the [7C+1C] annulation with ethyl isocyanoacetate to occur. As a result, tricyclic indolizidine alkaloids are constructed by a two‐step, base‐catalyzed [7C+1C] annulation/intramolecular cyclization with subsequent reduction/cyclization.

Tandem Cyclization−Annulation of α‐Acidic Isocyanides with 2‐Methyleneaminochalcones: Synthesis of Pyrrolo[2,3‐c]quinoline Derivatives

“…In recent years, our research efforts have been devoted to the domino transformation of functionalized isocyanides ,. Accordingly, a range of structurally complex heterocycles, including pyrrolizidines, C 2 ‐tethered pyrrole/oxazole pairs, tricyclic indolizidines, 8‐azabicyclo[5.2.1]dec‐8‐enes and bi‐/tricyclic oxazolines, were efficiently constructed from the domino reaction of α‐acidic isocyanides with all‐carbon 1,4‐, 1,5‐ or 1,7‐dielectrophiles (Scheme , top). In continuation of our studies on isocyanide‐based reactions, as well as inspired by Xu's work wherein 2‐methyleneaminochalcones were used as aza‐dielectrophiles, we herein report the tandem cyclization‐annulation of α‐acidic isocyanides with 2‐methyleneaminochalcones for the straightforward and efficient synthesis of 3 H ‐pyrrolo[2,3‐ c ]quinolines and tetrahydro‐3 H ‐pyrrolo[2,3‐ c ]quinolines, respectively (Scheme , bottom).…”

[3+2] Cycloaddition of Propargylic Alcohols and α‐Oxo Ketene Dithioacetals: Synthesis of Functionalized Cyclopentadienes and Further Application in a Diels–Alder Reaction

“…Since the first report by Kelber in 1910,1 α‐oxo ketene dithioacetals have been shown to be versatile intermediates in organic synthesis because of the characteristic bis(alkylthio) groups, which are strongly electron‐donating moieties and easily cleaved 2. α‐Oxo ketene dithioacetals and their extended conjugated derivatives are important 1,3‐,3 1,5‐,4 and 1,7‐electrophilic synthons5 and have been extensively investigated in cyclization reactions. As α‐oxo ketene dithioacetals are polar functionalized alkenes, they can be used as a two‐carbon fragment in cyclization reactions.…”

Direct Synthesis of Pyrrolo[3,4‐c]quinolines from the Domino Reaction of Tosylmethyl Isocyanides and Aminochalcones

“…In this context, the domino reaction of methyl isocyanides (such as isocyanoacetate and tosylmethyl isocyanide) with polar multiple bonds is a powerful tool for the synthesis of five‐membered heterocycles 2. Recently, we developed a new strategy on the basis of bicyclization of methyl isocyanides for the efficient construction of bicyclic heterocycles, such as pyrrolizidines,3 C 2 ‐tethered pyrrole/oxazole pairs,4 8‐azabicyclo[5.2.1]dec‐8‐enes5 and 7‐azatetrahydroindoles 6. Extension of this domino bicyclization strategy for complex heterocycles synthesis is highly desirable due to its high efficiency and productivity, facile execution and step economy.…”