ORGN 103 |
Arylation of 3-haloindoles facilitated by transient protecting group strategies
| Anthony W. Thompson1, Jocelyn Wang2, Marzia Villa1, and Ryan Schoenfeld1. (1) Medicinal Chemistry, Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, (2) Stanford University |
A new method has been developed for the preparation of 3-arylindoles via palladium catalyzed cross coupling of 1-acetyl-3-bromoindoles with arylboronic acids. Most reported routes to 3-arylindoles require either complete syntheses of the indole ring systems, or metal catalyzed arylations of tediously prepared 3-indoleboronic acids or 3-metalloindoles. Here we report that 1,3-unsubstituted indoles may be transformed into 3-arylindoles in three simple steps, the last of which involves the direct Suzuki cross coupling of an arylboronic acid with a 3-haloindole. Through the course of our investigation, it was found that an electron withdrawing substituent was required at the 1-position to facilitate the desired coupling. Although several groups were found to serve that function adequately, acetyl was found to be especially useful in that solvolytic cleavage of the protecting group occurred under the coupling conditions, while still allowing for a high yield of the desired product. |
| |
|
New Reactions and Methodology, Metal-Mediated Reactions, Heterocycles and Aromatics
8:00 PM-10:00 PM, Sunday, March 28, 2004 Anaheim Convention Center -- Hall A, Poster
Division of Organic Chemistry
The 227th ACS National Meeting, Anaheim, CA, March 28-April 1, 2004
|