Inhibition of Kornblum Reaction with Lithium Salts in S2 Reactions of Sulfonates and a Nucleophile Containing a Pyridine -Oxide Moiety: Convergent and Selective Synthesis of an MRGPRX2 Antagonist.

A critical step in the development of a convergent synthesis of an MRGPRX2 antagonist () was the S2 reaction with a highly functionalized lactamide electrophile and a unique difluoropiperidine nucleophile containing a pyridine -oxide moiety. Initial reactions with sulfonate leaving groups exhibited superb stereoselectivity, but yields were very low due to side reactions originated from competitive Kornblum reactions of the pyridine -oxide and the sulfonates. Markedly improved reaction profiles were achieved by including stoichiometric lithium triflate.

Partners or Opponents? Alcohol Industry Strategy and the 2016 Revision of the U.K. Low-Risk Drinking Guidelines.

Objective: In 2016, the U.K. Chief Medical Officers published revised low-risk drinking guidelines, based on an updated evidence review.