5-Hydroxyindoles by intramolecular alkynol-furan diels-alder cycloaddition

Abstract

A convergent approach provides a convenient access to synthetically and biologically useful 3,4-disubstituted 5-hydroxyindoles. The one-pot procedure uses microwave heating to initiate an intramolecular [4 + 2]-cycloaddition of an alkynol segment onto a furan followed by a fragmentation, aromatization, and N-Boc deprotection cascade. Yields range from 15 to 74%, with aromatic substituents providing better conversions. 4-Trimethylsilylated analogues undergo a 1,3-silatropic rearrangement to give the O-TMS ethers.

Figure 1

Representative biologically active 5-hydroxy indoles.

Scheme 1

Methods for Formation of 5-Hydroxy Indoles

Scheme 2

Proposed Reaction Pathways for Indole and 5-Hydroxy Indole Formation by Intramolecular Diels-Alder Reaction with Furans

Scheme 3

^a Formation of Propargyl Alcohol and Thermal Cycloaddition Reaction

Scheme 4

^a Formation of 3-Substituted 5-Hydroxy Indoles from Silylated Alkynones.

Scheme 5

^a Formation of 4-Substituted 5-Hydroxy Indoles from Alkynals.