Synthesis and Reactivity of o‐Enoyl Arylisocyanides: Access to Phenanthridine‐8‐Carboxylate Derivatives

Abstract

Various o-enoyl arylisocyanides were prepared from readily available reactants and found to undergo a double annulation with glutaconate to provide straightforward access to phenanthridine-8-carboxylates and hydrophenanthridine-8carboxylates under mild aerobic conditions. In this domino transformation, two rings and three bonds were successively created. A mechanism involving tandem [3 + 3]-annulation/intramolecular cyclization/ demethoxycarbonylation/aerobic oxidative aromatization sequence was proposed.

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

“…On the basis of above observations and the related work, [16][17][18][19]21] a possible pathway for this domino reaction is proposed in Scheme 5. The tandem cyclization-annulation may involve the following domino sequence: Michael addition of isocyanides 2 to 2methyleneaminochalcone 1 under basic conditions provides the anion I; [21] proton shift takes place to generate anion II, followed by intramolecular Mannich reaction to form the bicyclic nitrogen anion III (this step may be reversible based on the results of eq 6 in Scheme 4); sequential proton shift and cyclization give the tricyclic intermediate V, which undergoes 1,3-proton shift to produce tetrahydropyrroloquinolines 4 (EWG = CO 2 Et) or intermediate VI (EWG = Ts).…”

“…[15] In recent years, our research efforts have been devoted to the domino transformation of functionalized isocyanides. [16,17] Accordingly, a range of structurally complex heterocycles, including pyrrolizidines, [ were efficiently constructed from the domino reaction of a-acidic isocyanides with all-carbon 1,4-, 1,5-or 1,7dielectrophiles (Scheme 1, top). In continuation of our studies on isocyanide-based reactions, [18] as well as inspired by Xu's work [19] wherein 2-methyleneaminochalcones were used as aza-dielectrophiles, we herein report the tandem cyclization-annulation of a-acidic isocyanides with 2-methyleneaminochalcones for the straightforward and efficient synthesis of 3H-pyrrolo [2,3-c]quinolines and tetrahydro-3H-pyrrolo[2,3-c]quinolines, respectively (Scheme 1, bottom).…”

Tandem Access to Acridones and their Fused Derivatives: [1+2+3] Annulation of Isocyanides with Unsaturated Carbonyls

“…In 2018, we prepared various o-enoyl arylisocyanides from readily available 1-(2-aminophenyl)prop-2-en-1ones, and used them as versatile synthons for the efficient synthesis of phenanthridines. [18] Herein, we chose o-cinnamoyl arylisocyanide 1 a and 5benzylidene dimethylbarbituric acid 2 a as model substrates to screen the reaction conditions (Table 1). As expected, when a mixture of arylisocyanide 1 a (0.25 mmol) and 2 a (1.2 equiv.)…”

“…Functionalized isocyanides, as versatile building blocks, have been widely applied in synthesis of Ncontaining heterocycles. [14] During the past decade, our research group has been working on the double annulation of functionalized isocyanides, such as active methylene isocyanides, [15] trifluoromethylated isocyanides [16] o-alkenylarylisocyanides, [17] and o-enoyl arylisocyanides, [18] as a novel strategy for the efficient construction of polycyclic azaheterocycles. Last year, we developed a formal [1 + 2 + 3] annulation of oalkenylaryl isocyanides with unsaturated ketones as a new strategy for the expeditious synthesis of carbazole derivatives.…”

Recent Trends in the Synthesis and Mechanistic Implications of Phenanthridines

“…The same group reported the construction of phenanthridine‐8‐carboxylate 375 and dihydrophenanthridine‐8‐carboxylate derivatives 376 from a range of o ‐enoyl arylisocyanides 373 and glutaconate 374 via annulation method under mild aerobic conditions [108] . The key assets of this protocol were easily available substrates, environmentally benign method, mild conditions, and good to excellent product yields (Scheme 130).…”