Anthracene-fused isoxazolopyrrolo[2,1-a]isoquinolines via an endocyclic N-acyliminium ion cyclization: a joint experimental and theoretical study

Abstract A simple and efficient strategy is reported for the synthesis of anthracene-fused isoxazolopyrrolo[2,1- a ]isoquinolines via an endocyclic N -acyliminium ion cyclization. The cyclization of 18-aryl-21-(2-arylethyl)-22-hydroxy-16-oxa-17,21-diazahexacyclo[6.6.5.3 15,19 .0 2,7 .0 9,14 .0 15,19 ]docosa-2,4,6,9,11,13,17-heptaen-20-ones proceeds with high stereoselectivity, leading to 28-aryl-30-oxa-12,29-diazaoctacyclo[13.6.6.3 2,14 .0 2,14 .0 3,12 .0 4,9 .0 16,21 .0 22,27 ]triaconta-4,6,8,16,18,20,22,24,26,28-decaen-13-ones. The N -acyliminium cyclization of 18-aryl-21-(2-arylethyl)-20-hydroxy-16-oxa-17,21-diazahexacyclo[6.6.5.3 15,19 .0 2,7 .0 9,14 .0 15,19 ]docosa-2,4,6,9,11,13,17-heptaen-22-ones occurs only for substrates with electron-rich aromatic groups in the arylalkyl fragment. In these cases, cyclization also proceeds with a high stereoselectivity with the formation of anthracene-fused isoxazolopyrrolo[2,1- a ]isoquinolines as single diastereomers. To understand the mechanisms that allow for cyclization of N -acyliminium ion a quantum chemical investigation was performed.