Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

Abstract

SummaryA novel synthetic methodology has been developed for the synthesis of diethyl 5-alkyl/aryl/heteroaryl substituted 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates (also called 2-substituted pyrroline-4,5-dihydro-3,3-dicarboxylic acid diethyl esters) by iodide ion induced ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters in very good to excellent yields under mild reaction conditions. The electronic and steric impact of the substituents on the kinetics of ring expansion of N-vinyl aziridines to pyrrolines has been studied. Various diversely substituted novel pyrroline derivatives have been synthesized by this methodology and the products can be used as key intermediates in the synthesis of substituted pyrrolines, pyrroles and pyrrolidines.

N,N′‐Bis(arylmethylidene)arylmethanediamines: Suitable Precursors for the Synthesis of 1‐Pyrroline Derivatives

“…They are present in important biologically active compounds such as hemes, chlorophylls , and alkaloids . 1‐Pyrrolines also occur in many natural products such as eudistomins, pyracrimycin A, and myosmine (Fig. ).…”

“…Due to the importance of these heterocycles, several methods for the synthesis of 1‐pyrrolines have been reported. For instance, [3 + 2] cycloaddition of isocyanoacetates with electron‐deficient olefins , ring expansion of N ‐vinylaziridine using dipolarophiles , and reaction of γ ‐bromonitrile with aryl Grignard reagents . Most of these methods have some disadvantages, like multistep synthesis, using toxic organic solvent, and moderate yield of products.…”

Divergent Catalytic Approach from Cyclic Oxime Esters to Nitrogen-Containing Heterocycles with Group 9 Metal Catalysts

“…Considering the catalytic cycles proposed for palladium-, ruthenium-, and iridium-catalyzed reactions, the present catalytic cycle also begins from the oxidative addition of isoxazolone 1 to the low-valent metal species to form intermediate A via N–O bond cleavage. − Intermediate A rapidly undergoes decarboxylation to form azametallacyclobutene B rather than alkenylnitrene species B′ , which then undergoes intramolecular cycloaddition or 1,2-insertion of olefinic moieties into the metal–nitrogen double bond to form bicyclic metallacycle C . In the cobalt-catalyzed reaction, C–N bond-forming reductive elimination from intermediate C affords bicyclic aziridine 2 as well as the regenerated catalyst, which is very similar to the palladium-catalyzed system. , In the rhodium-catalyzed reaction, on the other hand, intermediate C would isomerize into aza-η 3 -allylrhodium intermediate D . Then the β-hydride elimination followed by reductive elimination would form 2 H -pyrrole 5 as well as the regenerated catalyst.…”

Potent biological investigation into a new class of sulfone derivatives endowed with quinolinyl–cyclopropane analogue

“…The first step is the acylation of diethyl malonate 1 with cyclopropane carbonyl chloride 2 in presence of magnesium chloride, triethyl amine and acetonitrile as solvent at 0°C to room temperature yielded diethyl-2-(cyclopropane-carbonyl)malonate 3 through reported method of Rathke et al [34]. In the second step chlorination of diethyl-2-(cyclo propane-carbonyl)malonate 3 was occurred via phosphorus oxychloride in presence of triethyl amine at 110°C for 5-6 hours to get compound 4 diethyl-2-(chloro(cycloproryl)methylene)malonate by the reported method of More et al [35]. Then, in third step substitution of -Cl atom has taken place by use for aniline 5 to get compound 6 diethyl-2-(cyclopropyl(phenylamino)methylene) malonate in presence of K2CO3 & DMF.…”