Regioselective Synthesis of Nitrofuran Containing Novel Spiropyrrolidine Library through 1,3‐Dipolar Cycloaddition Reactions

Abstract

A novel series of nitrofuran containing spiropyrrolidines has been synthesized with high regioselectivity in moderate to excellent yields via 1,3‐dipolar cycloaddition reaction of azomethine ylides with various substituted chalcones.

Microwave Assisted Neat Synthesis of Spiropyrrolidine Library

“…In presence of 5-nitro-2-thienyl group, β-carbon of the chalcone becomes electron rich due to the presence of electron withdrawing nitro group attached to thiophene ring, which results in the formation of compounds 4 (The possible attack is shown with solid arrows, the other possible attack, which is not favored, is shown by dotted arrows). This result was similar to our earlier observation with respect to chalcones carrying nitrofuran moiety [22], which indicates that the change of hetroatom from oxygen to sulfur did not affect the regiochemistry of product, which further proved that it was the presence of electron withdrawing nitro group that caused the change in regioselectivity.…”

Study of Regiochemical Trends During the Synthesis of Furan and 5‐(p‐chlorophenyl)Furan Containing Novel Spiropyrrolidine Library Through 1,3‐dipolar Cycloaddition Reactions

“…As described in Scheme , the 1,3‐dipole generated in situ from decarboxylative cyclocondensation of ninhydrin 1 and sarcosine 2 reacted readily with the aryl furan containing chalcones 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j as dipolarophiles under refluxing conditions in absolute ethanol medium to give only one regioisomer as cycloadducts 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j in high yield, in which the benzoyl group was connected to C‐4 of the newly constructed pyrrolidine, thus showing that when strong electron‐withdrawing nitro group was replaced by weaker electron‐withdrawing group such as p ‐chlorophenyl, we were still able to reproduce the regiochemical trends similar to those of nitrofuran . But in the case of cycloaddition of azomethine ylides to furfuryl chalcone derivatives, 6a , 6b , 6c , 6d , 6e (Scheme ), a pair of regioisomers 7a , 7b , 7c , 7d , 7e and 8a , 8b , 8c , 8d , 8e were obtained with a modest yield and a poor regioisomeric ratio.…”

“…The 1,3‐dipolar cycloaddition of azomethine ylides with olefinic dipolarophiles offers an excellent route for the construction of nitrogen containing five membered substituted pyrrolidine derivatives . Although highly substituted spiropyrrolidines are known , there seems to be a very sparse report on the study of substituent effect on the regioselectivity of spiropyrrolidines . The regiochemistry and stereochemistry of spiropyrrolidine formed by 1,3‐dipolar cycloaddition may be controlled either by choosing the appropriate dipole and dipolarophile or by controlling the reaction using a catalyst.…”

“…Our group had recently reported a novel regioselectivity trend during the reaction of 1‐(substituted benzyl)‐3‐(5‐nitrofuryl) prop‐2‐en‐1‐one were employed as dipolarophiles to react with azomethine ylides . The presence of strong electron withdrawing nitro substituents on the substrates significantly affected the regioselectivity of the 1,3‐dipolar cycloaddition, which allowed the formation of (3′R,4′R)‐4′‐(4‐substituted benzoyl)‐1′‐methyl‐3′‐(5‐nitro‐2‐furfuryl) spiro[indene‐2,2′‐pyrrolidine]‐1,3‐dione in good regioselectivity.…”

An Easy Access to the Synthesis of Sugar‐Based N‐Methyl‐Pyrrolidine via [3 + 2] Cycloaddition Methodology

“…For the synthesis of the high‐value heterocyclic framework, in addition to the [3 + 2] cycloadditions and aza Cope Mannich rearrangements , a new catalytic approach via the modular combination of β amino aldehydes and simple olefins using an enantioselective SOMO (singly occupied molecular orbital) activation/cycloaddition was developed by MacMillan and coworkers . The [3 + 2] cycloaddition reaction of azomethine ylide with alkene represents an outstanding tool in organic synthesis to provide five‐membered nitrogen heterocycles, generally with high regio and stereoselectivities . A wide variety of dipoles and dipolarophiles are used to obtain various heterocyclic skeleton.…”