[3+2] Anionic Cycloaddition of Isocyanides to Acyclic Enamines and Enaminones: A New, Simple, and Convenient Method for the Synthesis of 2,4‐Disubstituted Pyrroles

Abstract

We herein demonstrate a new approach for the synthesis of 2,4‐disubstituted pyrroles by [3+2] cycloaddition reaction of isocyanides to the activated double bond of various enamines and enaminones. This process paved the way for the synthesis a series of 2,4‐disubstituted pyrroles, which are known to be intermediates in the synthesis of biologically active compounds, in good to excellent yields from simple and commercially available starting materials. The process is carried out efficiently using a strong base, tBuOK, at low temperatures (0 °C). The described method is simple, proceeds in one step, does not require additional catalysts and hence, has a wide scope.

Recent Advances in the Chemistry of Isocyanides with Activated Methylene Group

“…Recently, the first example of [3+2] anionic cycloaddition of isocyanides to acyclic enamines and enaminones was discovered by Efimov and co-workers (Scheme 27). [28] Scheme 27. Isocyanide-enamine cycloaddition.…”

Potassium tert‐Butoxide‐Catalyzed Synthesis of α‐Methylene‐β‐Lactams from Propiolamides

“…[6] The combination of dimethyl sulfoxide and potassium tert-butoxide (pK a [DMSO] = 35.0; pK a [t-BuOH] = 32.2) [7] is one of the most successful examples of base-mediated cyclization of alkynes. [8] Even though it is considered very efficient, the reaction conditions are usually carried out using a high base loading, offering a new opportunity to develop protocols that use a base in a catalytic amount. We described our success in the investigation of this possibility by using the base-catalyzed intramolecular cyclization of N-benzyl-N-methyl-propiolamides 1 affording the α-methylene-β-lactam 2 derivatives (Scheme 1).…”

Synthesis of 6,7-Dihydro-1H,5H-pyrazolo[1,2-a]pyrazoles by Azomethine Imine-Alkyne Cycloadditions Using Immobilized Cu(II)-Catalysts

“…With ambident nucleophiles, enaminones undergo cyclization into different heterocyclic systems [ 28 , 29 , 30 , 31 , 32 , 33 ]. Enaminones are also used as alkenes in cycloaddition reactions [ 34 , 35 , 36 , 37 , 38 ] and as bidentate N, O ligands [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ] and tetradentate acacen-type ligands [ 27 , 50 , 51 , 52 , 53 , 54 ] to coordinate metal ions.…”