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

A 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.

were recorded on an HP-5989A quadrapole mass spectrometer.
The synthesis of diethyl acyl malonates 18 was carried by the method of Rathke and Cowan [1] and the physical and spectral data were compared with the literature values [1,2]. Compound 18h [3] and 18j [4] have been previously reported, however, since no spectral characterization was given, the spectral data were recorded and results reported below. Compound 18f, 18g, and 18i were novel and were characterized by MS and NMR and IR spectroscopy.
Compounds 19f, 19g, and 19i were novel and were characterized by MS, NMR and IR spectroscopy. Compound 19b and 19c have been previously reported [9], however, since no spectral characterization was given, the spectral data were recorded and results reported below.
The synthesis of N-vinylaziridines 20 was carried out on a maximum of 24 mmol and minimum of 15 mmol scale whereas their rearrangement to pyrroline derivatives 21 was carried out on a maximum of 21 mmol and a minimum of 10 mmol scale.
Compound 23 was reported as perchlorate salt [10], but we isolated 23 in the form of a free base. Compound 24, although reported in literature [11], was not completely characterized. We have carried out characterization of 24 by NMR and MS and HRMS and the spectral results of 24 were found to be similar to its methyl ester analogue [12].

General procedure for preparation of N-vinylaziridines 20a-20j
The chloro alkenyl malonate derivative (16.1 mmol) and THF (40.0 mL) were placed in a round bottom flask and cooled to 0-10 °C. Aziridine (48.2 mmol) was added slowly over 15 minutes through a syringe to the above mixture. The reaction mixture was then raised to room temperature and stirred for 8-13 h. After disappearance of the starting chloro compound (TLC), the reaction was quenched with water (80 mL). The reaction mixture was extracted twice with 80 mL dichloromethane. The combined extracts were washed twice with 80 mL 10% sodium chloride solution. The organic layer was dried over Na 2 SO 4 and concentrated under vacuum to afford the N-vinylaziridines. The products were sufficiently pure for the subsequent reactions; however, the crude products were purified by chromatography on silica gel (60-120 mesh) using a mixture of hexanes and ethyl acetate (90:10) as eluent, and the spectral data recorded for the column purified products, which were used for the next step (for yields see Table 1).

General procedure for the ring expansion of N-vinylaziridines to synthesize pyrrolines 21a-21j
Anhydrous sodium iodide (