Catalyst-Dependent Cyclization

  • Author: Li Grundl
  • Published: 28 June 2017
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
  • Source / Publisher: Advanced Synthesis & Catalysis/Wiley-VCH
thumbnail image: Catalyst-Dependent Cyclization

The indole skeleton is often found in bioactive molecules. A common method to synthesize multi-substituted indole derivatives is to install the substituents at the C-2 position via transition-metal-catalyzed C-H activation.


Takanori Shibata, Waseda University, Tokyo, Japan, and colleagues have found that 3-acetyl-N-alkynylindoles (example pictured) undergo a 6-exo-dig cyclization when using [Ir(cod)2]OTf (cod = 1,5-cyclooctadiene) as a catalyst, 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) as a ligand, and NaOAc as an additive. However, the same starting material gives unexpected 7-endo-dig cyclization products when using [Rh(cod)2][B((3,5-CF3)C6H3)4] as a catalyst and 2,2′-bis(diphenylphosphino)diphenyl ether (DPEPHOS) as a ligand in the absence of any additives. Both reactions were carried out in chlorobenzene at 135 oC.


Preliminary mechanistic studies show that the presence of a carbonyl directing group is necessary. In Ir catalysis, an oxidative addition was the major pathway for C-H bond activation, instead of a concerted metalation deprotonation although a base was used. An intramolecular hydrometalation is involved in both Ir- and Rh-catalyzed reactions and a trans addition in this step led to the 7-endo products in Rh catalysis.


 

Article Views: 868

Sign in Area

Please sign in below

Additional Sign In options

Please note that to comment on an article you must be registered and logged in.
Registration is for free, you may already be registered to receive, e.g., the newsletter. When you register on this website, please ensure you view our terms and conditions. All comments are subject to moderation.

Article Comments - To add a comment please sign in

Bookmark and Share

If you would like to reuse any content, in print or online, from ChemistryViews.org, please contact us first for permission. more


CONNECT:

ChemistryViews.org on Facebook

ChemistryViews.org on Twitter ChemistryViews.org on YouTube ChemistryViews.org on LinkedIn Sign up for our free newsletter


A product of ChemPubSoc Europe (16 European Chemical Societies)and Wiley-VCH