Diastereoselective Synthesis of Functionalized Angularly-Fused Tetracycles via an Organocatalytic Quadruple Reaction Sequence

An efficient diastereoselective strategy to access complex structural tetracycles was described through an organocascade quadruple reaction sequence between (E)-2-(3-arylallylidene)-1H-indene-1,3(2H)-diones and β-keto esters. The reaction proceeded through remote 1,6-addition followed by sequential 1,4-addition and aldol/aldol reactions to generate angularly-fused carbocyclic motifs with favourable to excellent yields (up to 94%) and diastereoselectivities (up to >20:1 dr). An enantioselective organocascade approach was attempted to yield densely functionalized tetracycles containing seven chiral centres including a quaternary centre. (Figure presented.).