Enantioselective organocatalytic construction of pyrroloindolines by a cascade addition–cyclization strategy: Synthesis of (–)-flustramine B

doi:10.1073/pnas.0308177101

Enantioselective organocatalytic construction of pyrroloindolines by a cascade addition–cyclization strategy: Synthesis of (–)-flustramine B

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125

Edited by Jack Halpern, University of Chicago, Chicago, IL, and approved February 23, 2004 (received for review December 12, 2003)

Abstract

Pyrroloindoline and bispyrroloindoline are a subclass of alkaloid structural motifs that commonly exhibit biological activity. An enantioselective organocatalytic approach to the synthesis of pyrroloindoline architecture is described. The addition–cyclization of tryptamines with α,β-unsaturated aldehydes in the presence of imidazolidinone catalysts 1 and 8 provides pyrroloindoline adducts in high yield and excellent enantioselectivities. This transformation is successful for a wide range of tryptamine and α,β-unsaturated aldehyde substrates. This amine-catalyzed sequence has been extended to the enantioselective construction of furanoindoline frameworks. Application of this pyrroloindoline-forming reaction to natural product synthesis has been accomplished in the context of the enantioselective synthesis of (–)-flustramine B.

Footnotes

↵ * To whom correspondence should be addressed at: 347 Crellin, Department of Chemistry, MC 163-30, Caltech, Pasadena, CA 91125. E-mail: dmacmill{at}caltech.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviation: BOC, t-butoxycarbonyl; ee, enantiomeric excess; dr, diastereomeric ratio.
Data deposition: The atomic coordinates have been deposited in the Cambridge Structural Database, Cambridge Crystallographic Data Centre, Cambridge CB2 1EZ, United Kingdom (CSD reference nos. 197024 and 234570).