Selective functionalization of complex heterocycles via an automated strong base screening platform

August 2017, Merck & Co., Inc., Rahway, NJ, USA

Reaction Chemistry & Engineering, The Royal Society of Chemistry

Knochel – Hauser bases, derived from 2,2,6,6-tetramethylpiperidinyl (TMP) metal amides, offer exceptional selectivity and functional group tolerance in the regioselective metalation of arenes and heteroarenes. The selectivity, stability and yield of these reactions are highly dependent on the nature of the base, additive and deprotonation temperature. We have developed and validated an automated micro-scale high throughput experimentation (HTE) approach to rapidly optimize base and temperature matrices. We describe the application of this approach to the regioselective functionalization of a variety of complex heterocycles and extension to the preparation of organometallic reagents for transition metal catalyzed cross-coupling screens.

For details:

Selective functionalization of complex heterocycles via an automated strong base screening platform*

Sobhana Babu Boga (a), Melodie Christensen (b), Nicholas Perrotto (b), Shane W. Krska (a), Spencer Dreher (a), Matthew T. Tudge (b), Eric R. Ashley (b), Marc Poirier (b), Mikhail Reibarkh (b), Yong Liu (b), Eric Streckfuss (a), Louis-Charles Campeau (b), Rebecca T. Ruck (b), Ian W. Davies (b), and Petr Vachal (a)

a. Department of Discovery Chemistry, MRL, Merck & Co., Inc., Rahway, NJ, USA.

b. Department of Process Research & Development, MRL, Merck & Co., Inc., Rahway, NJ, USA.

* Electronic supplementary information (ESI) available. See DOI: 10.1039/c7re00057j

Reaction Chemistry & Engineering – May 2017
DOI: DOI: 10.1039/c7re00057j
This journal is © The Royal Society of Chemistry 2017

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