Enantioselective Synthesis of the Tricyclic Core of FR901483 Featuring a Rhodium-Catalyzed [2+2+2] Cycloaddition

Abstract

An efficient approach to the tricyclic framework of FR901483 is described. The sequence features a [3,3]-sigmatropic rearrangement of a cyanate to an isocyanate, followed by its subsequent asymmetric rhodium-catalyzed [2+2+2] cycloaddition with a terminal alkyne for the synthesis of the indolizidine core. The aza-tricyclic core is completed using an intramolecular benzoin reaction to close the last ring of the natural product. Through a model study of the key cycloaddition, we evaluated the impact of different substituents on the tether of the alkenyl isocyanate.

Key words

[3,3]-sigmatropic rearrangement - isocyanate - [2+2+2] cycloaddition - indolizidine - FR901483

• References


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