Synthesis of novel derivatives of (1S,4S)-2,5-diazabicyclo[2.2.1]heptane and their evaluation as potential ligands in asymmetric catalysis

Thirty-seven (most of them novel) chiral derivatives of (1S,4S)-2,5-diazabicyclo[2.2.1]heptane (2-36, 38, 39) were prepared from (S)-trans-4-hydroxyproline. A selection of these chiral ligands were examined as potential ligands in the preparation of catalysts for the enantioselective addition of diethylzinc to aldehydes and as chiral Lewis acid activators in the asymmetric Diels-Alder reaction. In the former system, diamine 30 induced up to 92% enantiomeric excess in the formation of (S)-phenyl ethyl carbinol, whereas in the case of the cycloaddition reaction between cyclopentadiene and 3 -acryloyloxazolidin-2-one the catalytic complex formed between dimeric derivative 8 and copper triflate [Cu(OTf)(2)] afforded the expected product in a 95:5 endo/exo ratio and up to 72% ee for the major diastereomeric product. Finally, some of the novel chiral diamines prepared in this work were also evaluated as potential organocatalysts in the asymmetric amination of ethyl a-phenyl-a-cyano acetate. Bifunctional derivative 12 provided the aminated product in excellent yield and with up to 40% ee. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008.