In 2016,Hyde, Alan M.; Liu, Zhijian; Kosjek, Birgit; Tan, Lushi; Klapars, Artis; Ashley, Eric R.; Zhong, Yong-Li; Alvizo, Oscar; Agard, Nicholas J.; Liu, Guiquan; Gu, Xiuyan; Yasuda, Nobuyoshi; Limanto, John; Huffman, Mark A.; Tschaen, David M. published ãSynthesis of the GPR40 Partial Agonist MK-8666 through a Kinetically Controlled Dynamic Enzymatic Ketone Reductionã?Organic Letters published the findings.Electric Literature of C5H3BrClN The information in the text is summarized as follows:
A scalable and efficient synthesis of the GPR40 agonist MK-8666 was developed from a simple pyridine building block. The key step to set the stereochem. at two centers relied on an enzymic dynamic kinetic reduction of an unactivated ketone. Directed evolution was leveraged to generate an optimized ketoreductase that provided the desired trans alc. in >30:1 dr and >99% ee. Further, it was demonstrated that all four diastereomers of this hydroxy-ester could be prepared in high yield and selectivity. Subsequently, a challenging intramol. displacement was carried out to form the cyclopropane ring system with perfect control of endo/exo selectivity. The endgame coupling strategy relied on a Pd-catalyzed C-O coupling to join the headpiece chloropyridine with the benzylic alc. tailpiece. After reading the article, we found that the author used 5-Bromo-2-chloropyridine(cas: 53939-30-3Electric Literature of C5H3BrClN)
5-Bromo-2-chloropyridine(cas: 53939-30-3) belongs to pyridine. Pyridine is very deactivated towards electrophilic substitution with respect to benzene. For this reason classical formylation, using methods such as the Gattermann or Vilsmeier reactions, are not generally successful. Electric Literature of C5H3BrClN