Synthesis of Highly Substituted N-Hydroxyindoles through 1,5-Addition of Carbon Nucleophiles to In Situ Generated Unsaturated Nitrones

摘要

We recently reported a new method for the construction of substituted N-hydroxyindoles through trapping of unsaturated nitrones by oxygen, sulfur, and nitrogen nucleophiles.[1] Substituted N-hydroxyindoles continue to be of considerable interest to us not only because of our efforts towards the total synthesis of the thiopeptide antibiotic nocathiacin I,[2] whose structure contains such a domain, but also due to the growing interest in their construction as a consequence of the proven biological properties of this unique structural motif.[3], [4] Intrigued by the preference of phenolic substrates to react through their carbon, rather than their oxygen, centers,[1] we investigated the behavior of various carbon nucleophiles in that process. Herein, we report our findings in this area which constitute a new method for generating highly substituted N-hydroxyindoles through carbon-carbon bond formation involving 1,5-addition[5] to ,-unsaturated nitrones.