Prolin‐benzylester als chirale Hilfsgruppen in asymmetrischen 1,3‐dipolaren Cycloadditionen mit Nitriloxiden

Abstract

Proline Benzyl Esters as Chiral Auxiliaries in Asymmetric 1,3‐Dipolar CycloadditionsN‐Acryloylproline benzyl ester (1b) reacts with nitrile oxides at temperatures from −78 to 0°C to give isoxazolines 4/5 with diastereomeric ratios of ca. 3:1 and with the (5S) isomer as the predominating. The corresponding N‐methacryloylproline benzyl ester (1c) gives inferior results. The diastereoselectivity is not influenced by the temperature and the substituents of the nitrile oxides. To prove the absolute configuration of the predominating stereoisomer, a reaction sequence is developed which makes use of an enantioselective hydrolysis with pig liver esterase as the key step to generate an optically active isoxazoline with known stereochemistry. In the reactions of the N,N′‐fumaroylbis(proline benzyl ester) (11) with the nitrile oxides the chiral auxiliaries display synergistic stereodirecting influences and, as a consequence, the cycloadducts 12/13 are formed at −78°C with ratios of ca. 9:1.