PROCESS OF MAKING alpha-AMINOOXYKETONE/alpha-AMINOOXYALDEHYDE AND alpha-HYDROXYKETONE/alpha-HYDROXYALDEHYDE COMPOUNDS AND A PROCESS OF MAKING REACTION PRODUCTS FROM CYCLYC alpha,ß-UNSATURATED KETONE SUBSTRATES AND NITROSO SUBSTRATES

摘要

The present invention is directed to a process of making alpha-aminooxyketone and alpha-­hydroxyketone compounds. The synthetic pathway generally involves reacting an aldehyde or ketone substrate and a nitroso substrate in the presence of a catalyst of formula (IV), wherein X<1>-X<3> represent independently nitrogen, carbon, oxygen or sulfur and Z represents a 4 to 10-membered ring with or without a substituent and optionally a further step to convert the alpha-aminooxyketone compound formed to the alpha-hydroxyketone compound. The present invention results in alpha-aminooxyketone and alpha-hydroxyketone compounds with high enantioselectivity and high purity. The present invention is also directed to a catalytic asymmetric O-nitroso Aldol / Michael reaction. The substrates of this reaction are generally cyclic alpha,ß-unsaturated ketone substrate and a nitroso substrate. This methodology generally involves reacting the cyclic alpha,ß-unsaturated ketone substrate and the nitroso substrate in the presence of a proline-based catalyst, to provide a heterocyclic product.