Synthesis of Dialkyl 2‐(Alkylamino)‐4,9‐dihydro‐9‐oxocyclohepta[b]pyran‐3,4‐dicarboxylates

Abstract

Dialkyl 2-(alkylamino)-4,9-dihydro-9-oxocyclohepta [b]pyran-3,4-dicarboxylates are prepared in a one-pot three-component reaction of alkyl isocyanide, dialkyl acetylenedicarboxylate, and a-tropolone (¼ 2-hydroxycyclohepta-2,4,6-trienone). The reaction proceeds smoothly at room temperature and under neutral conditions to afford tropolone derivatives in high yield.Introduction. -Heterocycle-fused tropolones, an important class of compounds with varied pharmacological and biological properties have attracted great attention since the beginning of tropoid chemistry [1 -4]. The cyclohepta [b]pyran ring system is the backbone of some natural products such as paulitine (Fig.), which displays several biological activities, and some derivatives of this system exhibit platelet anti-aggregating, HIV protease inhibition, anesthetic, histaminic response-reducing, antimalarial, anti-inflammatory, and analgesic activities [5 -8]. . Also the reaction of chloro(phenyl)ketene with 2-(aminomethylidene)cycloheptanones, followed by dehydrochlorination of the primary adducts, yields 4-amino-6,7,8,9-tetrahydro-3-phenylcyclohepta[b]pyran-2(5H)-ones [14].

Isocyanide-based multicomponent reactions in the synthesis of heterocycles

“…Moreover, this process requires no external oxidant and only gave HBr as byproduct which could be easily handled. 237 The plausible mechanism involves the reaction of dialkyl acetylenedicarboxylate and alkyl isocyanide to give a zwitterionic intermediate 487 which is protonated. Subsequently, a ketenimine 488 is generated from the reaction of nitrilium ion 489 and deprotonated tropolone 490 which undergoes tautomerization and annulations to afford the nal product (Scheme 126).…”

Dimethyl Acetylenedicarboxylate: A Versatile Tool in Organic Synthesis

“…The reaction proceeded smoothly at room temperature and under neutral conditions to afford tropolone derivatives 591 in good to high yields (Scheme 150). 201 Chemoselective reaction of isocyanides with DMAD in the presence of relatively strong cyclic C-H acids 592, such as 4-hydroxy-6-methyl-2H-pyran-2-one or 4-hydroxycoumarin, led to a facile synthesis of highly functionalized chromeno or pyrano derivatives 593, respectively, in good yields (Scheme 150). 202 A three-component reaction of an isocyanide, DMAD and tetronic acid (594) in dichloromethane at room temperature afforded 4H-furo [3,4-b]pyran derivatives 595 (Scheme 150).…”

In situ generation and protonation of the isocyanide/acetylene adduct: a powerful catalyst-free strategy for multicomponent synthesis of ketenimines, aza-dienes, and heterocycles

“…The reaction proceeds smoothly at room temperature and under neutral conditions to afford pyrano-tropolone heterocycles in high yield. 58 Again, the corresponding cyclization (Nair's product) was not reported. aromatic carboxylic acids, the nal product was unsaturated linear imides 103, while the amido-aminofuran 104 synthesized aliphatic and heterocyclic aromatic carboxylic acids (Fig.…”