Kyle Clagg1, Haiyun Hou1, Adam B Weinstein2, David Russell3, Shannon S Stahl2, Stefan G Koenig1. 1. Small Molecule Process Chemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States. 2. Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States. 3. Small Molecule Analytical Chemistry and Quality Control, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
Abstract
A direct oxidative C-H amination affording 1-acetyl indolecarboxylates starting from 2-acetamido-3-arylacrylates has been achieved. Indole-2-carboxylates can be targeted with a straightforward deacetylation of the initial reaction products. The C-H amination reaction is carried out using a catalytic Pd(II) source with oxygen as the terminal oxidant. The scope and application of this chemistry is demonstrated with good to high yields for numerous electron-rich and electron-poor substrates. Further reaction of selected products via Suzuki arylation and deacetylation provides access to highly functionalized indole structures.
A direct oxidative C-H amination affording 1-acetyl indolecarboxylates starting from n class="Chemical">2-acetamido-3-arylacrylates has been achieved. Indole-2-carboxylates can be targeted with a straightforward deacetylation of the initial reaction products. The C-H amination reaction is carried out using a catalytic Pd(II) source with oxygen as the terminal oxidant. The scope and application of this chemistry is demonstrated with good to high yields for numerous electron-rich and electron-poor substrates. Further reaction of selected products via Suzuki arylation and deacetylation provides access to highly functionalized indole structures.