[5C + 1N] Annulations: Two Novel Routes to Substituted Dihydrofuro[3,2-c]pyridines

Abstract

Two novel routes based on [5C + 1N] annulations for the synthesis of 2,3-dihydrofuro[3,2-c]pyridines are described. Ammonium acetate (NH(4)OAc) is used as an ammonia source in both routes. The first route utilizes 1-acyl-1-[(dimethylamino)alkenoyl]cyclopropanes as a five-carbon 1,5-bielectrophilic species and combines the [5C + 1N] annulation and regioselective ring-enlargement of cyclopropyl ketone into one pot, whereas the second route utilizes 3-acyl-2-[(dimethylamino)alkenyl]-4,5-dihydrofurans as the five-carbon synthons, which involves a sequential intermolecular aza-addition, intramolecular aza-nucleophilic addition/elimination, and dehydration reaction.

Zinc‐Catalyzed Multicomponent Reactions: Easy Access to Furyl‐Substituted Cyclopropane and 1,2‐Dioxolane Derivatives

“…The results of this experiment revealed that the desired compound 5a was not isolated following the quenching of the reaction, and that compound 4a was recovered instead in 97% yield (Scheme ). Taken together with the results of similar studies from the literature, this result allowed us to propose a possible mechanism for the current reaction, which is shown in Scheme 11c–e,12a. According to this mechanism, amine 2 would initially attack the doubly activated cyclopropane 1 to generate the quaternary ammonium analogue A , which would undergo a cyclization reaction through intermediate B to give the multi‐substituted dihydropyrrole D 12a.…”

“…Dong’s group developed two new routes for the synthesis of substituted dihydrofuro[3,2‐ c ]pyridines, which were reported in 2011 and 2012. The first of these routes involved the Vilsmeier‐type reaction of 1‐aminoalkenoyl‐1‐carbamoylcyclopropanes in the presence of Tf 2 O in DMF,11d whereas the second route used 1‐carbamoyl‐1‐dimethylaminoalkenoylcyclopropanes as the starting materials and ammonium acetate (NH 4 OAc) as the ammonia source (Scheme ) 11e. In 2007, our group established an approach for the divergent construction of γ‐iminolactones, dihydroquinolin‐2‐ones and γ‐lactams using three different types of Lewis acid.…”

“…Notably, all three of these products started from β‐hydroxymethylcyclopropanylamides, which were themselves derived from 1‐acryloyl‐1‐ N ‐arylcarbamylcyclopropanes via a reduction reaction in the presence of NaBH 4 13. Based on a combination of research from the literature11c–e,12a–h and our related research towards the synthesis of nitrogen‐containing compounds from doubly activated cyclopropane precursors,11a,12h,14 it was envisioned that novel N , N ‐bicyclic 1 H ‐pyrrolo[3,2‐ c ]pyridin‐4(5 H )‐one derivatives 3 could be prepared from the reaction of doubly activated cyclopropanes 1 with amines 2 (Scheme ).…”

Cloke–Wilson rearrangement: a unique gateway to access five-membered heterocycles

“…The mechanism of their one-pot synthesis involved the intermolecular addition of ammonia, regioselective thermal Cloke–Wilson rearrangement of cyclopropylketone, intramolecular aza-nucleophilic addition/elimination, and dehydration reaction (Scheme 5). 48…”

Formal [4+2] annulation of enaminones and cyanomethyl sulfur ylide: one-pot access to polysubstituted pyridin-2(1H)-ones

“…10,11 Since the identification of sulfur ylides as methylene transfer agents, 12 these intermediates have been widely used in the synthesis of three-membered ring compounds, such as epoxides, aziridines and cyclopropanes. [13][14][15] During the course of our studies on b-oxo amides, we achieved facile synthesis of pyridones, 16 pyrimidinones, 17 pyridines, 18 isoxazoles, 19 cyclophosphamides 20 and pyrrolin-4-ones 21 via the reactions of various enaminones derived from b-oxo amides. Most recently, we developed an efficient synthesis of g-lactams by the Corey-Chaykovsky reaction of a,a-dialkyl b-oxo amides and trimethylsulfoxonium iodide.…”