Our two recent P(V)-based projects that were just published in JACS and ACS Central Science were a lesson of teamwork and sometimes “serendipity” that we would like to describe in the following blogpost.Having worked on the P(V) reagent platform since its inception, I have spent a considerable amount of time sitting in front of the only NMR spectrometer at Scripps capable of detecting the 31P nucleus. Since these blog posts are supposed to be the behind the scenes version of papers we publish, I thought I would take this time to walk you through the fun journey from the Baran
lab to the Molecular Biology building where one of our NMR labs is. You begin by leaving the 4th floor of the Beckman Center for The Chemical Sciences, traversing the intricate Hogwarts style staircases down to the lobby. After exiting the building and making a daring leap over the crosswalk between the two buildings, it’s time to go further into the depths of the MBB building. Okay, back to the science…as you can see in the figure below, the loading and coupling events between the P(V) reagents and alcohol nucleophiles proceeds with a rather boring and predictable outcome via 31P NMR. Over the course of ~3 years, hundreds of compounds have undergone this reaction sequence. Regardless of the compound in question, the only observable peaks are 100 ppm for the loading and 55 ppm for the coupling products. The reactions between nitrogen and sulfur nucleophiles were never observed.
This led us to the realization that the P(V) reagents could potentially solve the challenge associated with Serine selective functionalization as highlighted in the chart below.
All in all, both of these papers were the result of many years of work across multiple labs (across the U.S and the Atlantic) and I am indebted greatly to the teams for not only the work but also the lessons and memories.
-Kyle and the P(V) team