Journal of Organic Chemistry 2011-05-06

Cationic cyclization of 2-alkenyl-1,3-dithiolanes: diastereoselective synthesis of trans-decalins.

Sylvie Goncalves, Stefano Santoro, Marc Nicolas, Alain Wagner, Philippe Maillos, Fahmi Himo, Rachid Baati

Index: J. Org. Chem. 76(9) , 3274-85, (2011)

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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.© 2011 American Chemical Society