Highly selective synthesis of functionalized morphan derivatives through a multi-component cascade reaction of 3-formylchromones, 2-naphthols, and enaminones

A novel protocol for the preparation of highly functionalized 2-azabicyclo[3.3.1]nonane (morphan) derivatives via a multicomponent cascade reaction, involving 3-formylchromones, 2-naphthols, and enaminones in the ionic liquid [BMIM]PF6 as the solvent and promoted by 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU), was developed, which involved the cleavage of one C–O bond and formation of four bonds (1 ​C–O, 1 ​C–N, and 2 ​C–C bonds). As a result, a series of morphan derivatives were produced through a cascade reaction, including a sequence of 1,2-addition, enol-keto tautomerization, Michael addition, dehydration, another Michael addition, imine-enamine tautomerization, and N-alkylation reactions, which were accompanied by a ring-opening reaction. This protocol was suitable for combinatorial and parallel syntheses of natural product-like morphan compounds in a one-pot reaction rather than through tedious multi-step reactions. A novel protocol for the preparation of highly functionalized 2-azabicyclo[3.3.1]nonane (morphan) derivatives via a multicomponent cascade reaction in the ionic liquid [BMIM]PF6 and promoted by DBU, was developed, which involved the cleavage of one C–O bond and formation of four bonds. This protocol was suitable for combinatorial and parallel syntheses of natural product-like morphan compounds in a one-pot reaction rather than through tedious multi-step reactions. [Display omitted]