Substituted heterocycles are of great importance in medicinal chemistry, ligand design, and total synthesis. One unique method for synthesizing substituted heterocycles relies on using hetarynes, or the aryne derivatives of heterocycles.This presentation will describe routes that we have developed to access 4,5-, 5,6-, and 6,7-indolynes and their reactivity with a variety of trapping agents. Observed variations in the regioselectivity of nucleophilic addition to the indolyne can be rationalized in terms of distortion energy. We will present a straightforward model that can be used to predict the regioselectivity of nucleophilic additions to unsymmetrical arynes. Additionally, we will demonstrate how the use of substituents can enhance or overturn the inherent regioselectivities in indolyne reactions. Finally, we will show how this strategy has allowed for a synthesis of indolactam V using our indolyne approach, and allowed progress towards other complex indole-based targets. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/239nm/uploads/16007_abstract_figure.jpg' alt='' />

Understanding, predicting, and modulating aryne regioselectivities

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.