Asymmetric Direct Aldol Reactions Promoted By (4R)-(β-Naphthalenyl) Methoxy-(S)-proline

1. The Synthesis of a Novel Chiral Phase-transfer CatalystCyclodipeptide (3S,6S)-dibenzyl-piperazine-2,5-dione, which was prepared in high yield by heating phenylalanine methyl ester directly, was reduced with NaBH4-BF3 in DME to gave the (2S,5S)-2,5-dibenzylpiperazine, which was reacted with ethylene bromide and triethylamine, affording (2S,5S)-2,5-bis(phenylrnethyl)- 1,4-diazabicyclo [2,2,2]octane. Unexpectedly, the preparation of bis-ammonium salt was unsuccessful.2. Asymmetric Direct Aldol Reactions promoted by (4R)-(Naphthalenyl)methoxy-(S)-proline(4R)-hydroxy-(S)-proline was N-protected by the reaction with di-tert-butyl pyrocarbonate to give N-Boc-(4R)-hydroxy-(S)-proline, which was treated with sodium hydride in anhydrous tetrahydrofuran and followed by etherification with 2-bromomethyl-naphthalene to form the N-Boc-(4R)-(Naphthalenyl)methoxy-(S)-proline, which, after removal of the protecting group with trifluoroacetic acid, gave the title compound (4R)-(Naphthalenyl)methoxy-(S)-proline.This compound can serve as an efficient catalyst for the direct asymmetric aldol addition reaction of acetone to a variety of aromatic aldehydes with high yields (60.5%-95.7%) and good ee's (71.1%-89.7%). Both the reaction yields and selectivities were observed to be higher than those of the corresponding reactions catalyzed by proline. The influences of the amount of the catalyst, the temperature and the electronic effects of the substrates were discussed.