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

• Published in: Chemistry : a European journal Vol. 27; no. 2; pp. 618 - 621
• Main Authors: Mitkari, Suhas Balasaheb, Medina‐Ortíz, Alberto, Olivares‐Romero, José Luis, Vázquez, Miguel A., Peña‐Cabrera, Eduardo, Villegas Gómez, Clarisa, Cruz Cruz, David
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 07.01.2021; Wiley Subscription Services, Inc
• Subjects: aminocatalysis; bis-dithioamides; Cascade chemical reactions; Catalysis; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; dithioamides; Indoles; one-pot reactions; Physical Sciences; Science & Technology; trienamine catalysis; AZAHETEROCYCLES; DIELS-ALDER; one-pot reactions; trienamine catalysis; DIVERSITY-ORIENTED SYNTHESIS; ANTICANCER; ANALOGS; CONSTRUCTION; dithioamides; aminocatalysis; bis-dithioamides; INDOLES
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202004553

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).