Process of making α-aminooxyketone/α-aminooxyaldehyde and α-hydroxyketone/α-hydroxyaldehyde compounds and a process making reaction products from cyclic α,β-unsaturated ketone substrates and nitroso substrates

Abstract

The present invention is directed to a process of making α-aminooxyketone and α-hydroxyketone compounds. The synthetic pathway involves reacting an aldehyde or ketone substrate and a nitroso substrate in the presence of a catalyst of the formula (IV): wherein X-Xrepresent 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 α-aminooxyketone compound formed to the α-hydroxyketone compound which results in α-aminooxyketone and α-hydroxyketone compounds with high enantioselectivity and high purity. The present invention is also directed to a catalytic asymmetric O-nitroso Aldol/Michael reaction involving a cyclic α,β-unsaturated ketone substrate and a nitroso substrate. This methodology involves reacting the cyclic α,β-unsaturated ketone substrate and the nitroso substrate in the presence of a proline-based catalyst, to provide a heterocyclic product.