Chemoselective Reactions of 4,6-Dichloro-2-(methylsulfonyl)pyrimidine and Related Electrophiles with Amines

Dedicated to Prof. Scott E. Denmark on the occasion of his 60^th birthday

Abstract

Chemoselective S_NAr reactions of 4,6-dichloro-2-(methylsulfonyl)pyrimidine and several related electrophiles with amines and their derivatives are described. In the presence of weak bases anilines and secondary aliphatic amines selectively displace the chloride group. Deprotonated anilines and their carbonyl derivatives displace the sulfone group. Sterically and electronically unbiased primary aliphatic amines selectively displace the sulfone group in 4,6-dichloro-2-(methylsulfonyl)pyrimidine; however, their reactions with other electrophiles generally are less selective. Steric-driven selectivity explanation was proposed.

Key words

pyrimidine - sulfone - chloride - heterocycles - chemoselectivity

• References

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• 22 See Supporting Information for details.
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• 42 Assigned based on the LC-MS data.