Radical cyclizations of conjugated esters and amides with 3-oxopropanenitriles mediated by manganese(III) acetate

Radical cyclizations of conjugated esters and amides with 3-oxopropanenitriles in presence of manganese(III) acetate produced ethyl 4-cyano-2,3-dihydrofuran-3-carboxylates and 4-cyano-2,3-dihydrofuran-3-carboxamides in good yields. The radical cyclizations of conjugated amides gave 2,3-dihydrofurans in better yields than that of conjugated esters. Moreover, the reactions of thienyl substituted amides and esters with 3-oxopropanenitriles afforded 2,3-dihydrofurans more efficiently than phenyl substituted ones.


Introduction
Transition metal salts (Mn +3 , Ce +4 , Ag + ) having single electron transfer ability are widely used in organic reactions for generating C-C bonds. 1 It is well-known that dihydrofurans 2 are synthesized by radical cyclization reactions with alkenes and 1,3-dicarbonyl compounds using manganese(III)acetate 2,3 , cerium(IV) ammonium nitrate 4 and silver(I) nitrate 5 .Also, it is reported that these radical oxidants are widely used in natural product synthesis. 6The dihydrofuran skeleton is accepted as an important class of organic compound in terms of representing biological activity and resembling natural products.
Proposed mechanism for radical cyclization of 3-oxopropanenitriles with conjugated alkenes mediated by Mn(OAc)3 is given in scheme 1.According to the mechanism, Mn(III)-enolate complex C is formed from the reaction of enol form B of 3-oxopropanenitrile with Mn(OAc)3 and an α-carbon radical D is occurred while Mn +3 is reduced to Mn +2 .The addition of the αcarbonyl radical to conjugated alkene gives a radical intermediate product E.This intermediate product is oxidized to carbocation F with Mn(OAc)3 and intramolecular cyclization of F forms 4-cyano-2,3-dihydrofurans G. 1 H NMR spectra of the isolated compounds 3a-w show a single peak for H-3 protons at between 4.11-4.93ppm.
However, we reported the chemical shift values of the H-2 protons in similar structures as 5.73-6.56ppm.2h These results support that 2,3-dihydrofurans G were formed from the addition of radical intermediate D to α,β-unsaturated amides (or esters) regiospecifically followed by the cyclization of F.
According to these results, the reactions of the two diphenyl substituted alkenes 2c and 2d with 3-oxopropanenitriles formed 2,3-dihydrofurans in higher yields than that of the monophenyl substituted alkenes 2a and 2b.This can be explained by the stability of the radical intermediate products formed with the addition of an α-carbon radical to conjugated esters and amides.Since the tertiary radicals obtained from 2c and 2d are conjugated with two phenyl groups, stability of these radicals are higher than that of the tertiary radicals of 2a and 2b.Therefore, the cyclization of more stable intermediate product forms 2,3-dihydrofuran in a higher yield.
a Yields of isolated products based on the alkene.
a Yields of isolated products based on the alkene.

Conclusions
In conclusion, Mn(OAc)3 mediated radical cyclization of conjugated esters and amides with 3oxopropanenitriles was studied in this work comparatively, resulting in formation of various 2,3dihydrofuran-3-carboxylates and 2,3-dihydrofuran-3-carboxamides.Similar results were obtained from the reactions of conjugated esters 2a, 2c, 2e and conjugated amides 2b, 2d, 2f with 3-oxopropanenitriles. On the other hand, a noteworthy increase is observed in product yields

Experimental Section
General.Melting points were determined on a Gallenkamp capillary melting point apparatus.IR spectra (KBr disc, CHCl3) were obtained with a Matson 1000 FT-IR spectrophotometer in the 400-4000 cm -1 range with 4 cm -1 resolution.

procedure for the synthesis of conjugated amides
Conjugated esters 2a, 2c and 2e were synthesized according to the method explained above.To the conjugated ester (100 mmol), a solution of 5 M NaOH (200 mmol) was added and the mixture was refluxed for 2-3 hours until the phases combined.Water was added to sodium salt and then was hydrolyzed with diluted HCl (25%).Carboxylic acid obtained was filtered and washed with water.Then, fresh distillated thionyl chloride (37 mL, 500 mmol) is added drop by drop in the suspension of carboxylic acid in 200 mL chloroform at room temperature.The mixture was allowed to stand for 12 hours.Without purifying the solution of acyl chloride in chloroform, it is added slowly into a solution of 450 mL ammonia (35 %) containing sodium hydroxide (26 g, 0.2 mole) which was cooled in an ice bath and stirred vigorously.Separated amide was filtered, washed with water and dried.Yield 70%.