Organocatalytic Cascade Reactions for the Diversification of Thiopyrano‐Piperidone Fused Rings Utilizing Trienamine Activation

An aminocatalytic privileged diversity‐oriented synthesis (ApDOS) strategy utilizing trienamine catalysis for the construction of diverse and complex thiopyrans‐piperidone fused rings through a thia‐Diels–Alder/nucleophilic ring‐closing sequence by using dithioamides as activated heterodienophiles is reported. Following this strategy, a super cascade reaction to assemble nine fused rings can be achieved by employing a bis‐dithioamide. Additionally, by linking an indole moiety on the dithioamide, a Pictet–Spengler type reaction can be promoted once the cascade sequence has been achieved, leading to more complex penta‐ hexa‐ and heptacyclic fused ring derivatives in a one‐pot process. This investigation opens new perspectives for the synthesis of a new class of complex and diverse thiopyrans that contribute to populate new relevant regions in the chemical space. A highly enantioselective thio‐Diels–Alder/nucleophilic ring‐closing cascade reaction utilizing trienamine catalysis with dithioamides is presented. Notably, by linking an indole moiety on the dithioamide, a Pictet–Spengler type reaction can be also promoted, leading to more complex frameworks in a one‐pot process. Additionally, a super cascade sequence to assemble nine fused rings can be achieved by employing a bis‐dithioamide (see scheme).