Reaction of N-aryl-2-nitrosoanilines with alkyl arylidenecyanoacetates in the presence of Et 3 N in MeCN leads to substituted 1,2,3,4-tetrahydroquinoxaline derivatives in reasonable yields. The reaction comprises nucleophilic addition of the nitrosoaniline to the Michael acceptor followed by cyclization involving the nitroso group. Since the reactive nitrogen groups in N-aryl-2-nitrosoanilines are of opposite character the reaction is regioselective and additionally it was found to be diastereoselective.The 1,2,3,4-tetrahydroquinoxaline scaffold is present in numerous biologically active and pharmacologically important compounds. 1 As an example compounds A, B, and C have found applications as cholesteryl ester transfer protein inhibitors, 1b vasopressin V2 receptor antagonists, 1c and prostaglandin D2 receptor antagonists, 1d respectively ( Figure 1).
Figure 1Retrosynthetic analysis of the 1,2,3,4-tetrahydroquinoxaline skeleton suggests that it could be synthesized directly from appropriate 2-nitrosoaniline with unsaturated electrophile via Michael addition of the amino group to the activated C=C bond followed by aza-aldol reaction, completed by reduction of the hydroxyloamine formed (Scheme 1).
Scheme 1