The enamine derived from cyclopentanone and (2R,5R)-2,5bis(methoxymethyl)pyrrolidine added ethyl N-mesylazidoformimidate [N3C(OEt)NMs] and ethyl azidoformate (N3CO2Et) with high asymmetric induction (>95%), while the corresponding cyclohexanone enamine gave ring contraction products. With the same azides the cyclopentanone enamine, prepared from (S)-2-(methoxymethyl)pyrrolidine gave N-substituted a-amino cyclopentanones in moderate enantiomeric excess. (~) 1997 Elsevier Science Ltd Starting from proline-derived cyclohexanone enamines we observed chiral discrimination in reactions with (ethoxycarbonyl)nitrene (NCO2Et), generated from NsONHCO2Et in the presence of Et3N. The best ee (77%) for the N-substituted e~-amino ketone was observed with enamine bearing (S)-2-(methoxymethyl)pyrrolidine as the chiral auxiliary. The configuration of the major enantiomer was R. The same product was obtained in a better yield but in a lower ee (35%) using ethyl azidoformate (N3CO2Et). The configuration of the major isomer in this case was S. l Enamines from pyrrolidines with C2 symmetry are known to give high asymmetric induction in alkylation reactions. 2 We tested one of these enamines obtained from cyclohexanone and (2R,5R)-2,5dimethylpyrrolidine in reactions with different aminating agents 3 without success. Then we turned our attention to ethyl N-mesylazidoformimidate [N3C(OEt)NMs]. This versatile azide reacts with alkenes of different nucleophilicity. 4 Recently we used the same azide to successfully aziridinate chiral homoallylic ketals. 5
In this paper we report on a comparison of the results obtained on reacting N3C(OEt)NMs or N3CO2Et with cyclohexanone and cyclopentanone enamines derived from (S)-2-(methoxymethyl)and (2R,5R)-2,5-bis(methoxymethyl)pyrrolidine 1, 6, 11 and 14. We started our study testing the cyclohexanone enamines 1 and 6 in reactions with N3C(OEt)NMs. The reactions were performed in CH2C12 at room temperature. Very fast nitrogen evolution has been observed and the first cycloadduct, quite likely a triazoline, could not be detected. The crude reaction mixtures were chromatographed and the products were characterised by spectral data. The main product has been recognised as the product of ring contraction 2 or 7 and was transformed into cyclopentanecarboxylic acid by hydrolysis. 6
The compound 9 from a similar fast rearrangement was the main product isolated in the reaction performed with N3CO2Et on the enamine 6. On the contrary, we isolated the N-substituted ~xaminocyclohexanone 4 in the cycloaddition reaction of the same azide, followed by photolysis.1 In both cases variable amounts of by-products 3, 5, 8 and 10 have been isolated, coming from a nucleophilic attack to the azide C=N or C=O bond by the pyrrolidine nitrogen atom. 7 We like to stress that, although the undesired ring contraction products 7 and 9 were formed, this is the first time an enamine derived from a C2 symmetric amine reacts with azides. 8
With the aim to obtain N-substituted cx-amino ketones, we focused our attention on cyclopentanone enamines 11 and 14, in the hope of minimising the ring contraction.