title: Cationic cyclization of 2-alkenyl-1,3-dithiolanes: diastereoselective synthesis of trans-decalins.
abstract: An unprecedented and highly diastereoselective 6-endo-trig cyclization of 2-alkenyl-1,3-dithiolanes has been developed yielding trans-decalins, an important scaffold present in numerous di- and triterpenes. The novelty of this 6-endo-trig cyclization stands in the stepwise mechanism involving 2-alkenyl-1,3-dithiolane, acting as a novel latent initiator. It is suggested that the thioketal opens temporarily under the influence of TMSOTf, triggering the cationic 6-endo-trig cyclization, and closes after C-C bond formation and diastereoselective protonation to terminate the process. DFT calculations confirm this mechanistic proposal and provide a rationale for the observed diastereoselectivity. The reaction tolerates a wide range of functionalities and nucleophilic partners within the substrate. We have also shown that the one-pot 6-endo-trig cyclization followed by in situ 1,3-dithiolane deprotection afford directly the corresponding ketone. This improvement allowed the achievement of the shortest total synthesis of triptophenolide and the shortest formal synthesis of triptolide.
authors: Université de Strasbourg, Faculté de Pharmacie UMR/CNRS 7199, Laboratoire des Systèmes Chimiques Fonctionnels, 74 route du Rhin, BP 60024, 67401 Illkirch, France.
authors: Sylvie
authors: S
authors: Goncalves
authors: Stefano
authors: S
authors: Santoro
authors: Marc
authors: M
authors: Nicolas
authors: Alain
authors: A
authors: Wagner
authors: Philippe
authors: P
authors: Maillos
authors: Fahmi
authors: F
authors: Himo
authors: Rachid
authors: R
authors: Baati
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D011789:Quantum Theory; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000475:Alkenes; D001688:Biological Products; D006571:Heterocyclic Compounds; D009281:Naphthalenes; C012948:1,3-dithiolane; C007229:decalin