Cycloaddition Reactions of Alkyl Cyclopropenecarboxylates Generated in situ with Nitrones: Construction of Substituted Pyrroles and 1,2‐Oxazinanes

Abstract

A highly regioselective [3+2] cycloaddition reaction of nitrones 1 with alkyl 2‐aroylcyclopropenecarboxylates generated in situ from alkyl 2‐aroyl‐1‐chlorocyclopropanecarboxylates 2 under basic conditions is described. The reaction proceeded readily to afford ring‐fused isoxazolidines 3 in moderate‐to‐high yields. The strained ring‐fused cycloaddition products were selectively transformed into the corresponding polysubstituted pyrroles, for example, pyrrolizine derivatives, through N–O bond cleavage or 1,2‐oxazinane derivatives through ring‐opening by treatment with HCl·pyridine in alcoholic solvents.

Small Ring Compounds and N‐oxides: Cycloadditions and Related Processes

“…Interestingly, for pyrroline N ‐oxide 121 , the observed major product was pyrrole 123 ( cf . 118 ), though the mechanism of its formation deserves separate elucidation (Scheme ) …”

A straightforward route to alkyl 5‐arylthiophene‐2‐thiocarboxylates from alkyl 2‐aroyl‐1‐chlorocyclopropanecarboxylates

“…Recently, our group focused on the chemistry of reactive cyclopropene derived from simple 1,2‐elimination of alkyl 1‐aroyl‐1‐halocyclopropanecarboxylates under basic conditions [15]. We have successfully developed their cascade reactions with various substrates like nitrones, acylhydrazones, and 1,3‐dicarbonyl compounds to constructing fused isoxazolidines [16], functionalized pyrroles [17], and polyfunctionalized fulvene derivatives [18], respectively. Under acidic conditions, 1‐aroyl‐1‐alkoxycyclopropanecarboxylates were smoothly converted into substituted furans [19] (Scheme 1, route a).…”

Synthesis of methyl 1,5‐diaryl‐1H‐pyrrole‐2‐carboxylates via acid‐catalyzed ring‐opening/ring‐closure sequence

“…On the other hand, the chemistry of reactive cyclopropene species generated from 1,2‐elimination of alkyl 1‐aroyl‐1‐halocyclopropanecarboxylates has been carefully studied in our group [21]. The cascade reaction of this reactive cyclopropene species with nucleophilic reagent like acylhydrazones afforded functionalized pyrroles [22–24]. The reaction of alkyl 1‐aroyl‐1‐halocyclopropanecarboxylates with amines was also assessed in the presence of Cs 2 CO 3 [25].…”