ADVERTISEMENT
2 /3 FREE ARTICLES LEFT THIS MONTH Remaining
Chemistry matters. Join us to get the news you need.

If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.

ENJOY UNLIMITED ACCES TO C&EN

Synthesis

Green Aminations Without Palladium

Nucleophilic aromatic substitution of heteroaryl chlorides works just fine by using KF in water as an alternative to standard palladium-catalyzed methods

by Stephen K. Ritter
July 8, 2013 | APPEARED IN VOLUME 91, ISSUE 27

One of the largest classes of reactions used in medicinal chemistry is the palladium-catalyzed cross-coupling of aryl halides with amines to make N-arylamines. During the past 20 years, this efficient method has largely replaced the classical nucleophilic aromatic substitution (SNAr) approach to N-arylations. One team of researchers is now suggesting that chemists have become so dependent on palladium-catalyzed N-arylations that they blindly use the method without giving SNAr a chance. Katie Walsh and Christopher J. Moody at the University of Nottingham, in En­gland, and Helen F. Sneddon of GlaxoSmithKline note that heteroaryl substrates such as chloropyrimidines and chloropyrazines are highly reactive via SNAr, more so than chlorobenzene, and don’t need a palladium catalyst. With their thoughts on green chemistry, the researchers set out to optimize SNAr reactions of the heteroaryl chlorides (ChemSusChem 2013, DOI: 10.1002/cssc.201300239). They found that using potassium fluoride as a base and water as the solvent leads to N-arylamines in yields comparable with the palladium-catalyzed method and avoids the palladium catalyst, phosphine ligand, and organic solvent.

X

Article:

This article has been sent to the following recipient:

Leave A Comment

*Required to comment