Synthesis of 3,4,5-trisubstituted indoles via iterative directed lithiation of 1-(triisopropylsilyl)gramines

Directed lithiation of 1-(triisopropylsilyl)gramines with tert-butyllithium followed by reaction with trimethylsilylmethyl azide produced 4-amino-1-(triisopropylsilyl)gramines . The N-tert-butoxycarbonyl derivatives were lithiated selectively at C-5 with tert-butyllithium and the lithiated species were reacted with a variety of electrophiles to give 5-functionalized compounds, and . A facile method to produce 3,4,5-trisubstituted indoles from readily available gramine derivatives is thereby established.