Propanephosphonic Acid Anhydride (T3P®) - A Benign Reagent for Diverse Applications Inclusive of Large-Scale Synthesis

Abstract

Propanephosphonic acid anhydride (T3P ® ) is a prevailing coupling and dehydrating agent with many desirable properties which render it a reagent of choice for a plethora of reactions and, befittingly, its application in organic synthesis is rapidly increasing. Since its introduction as a peptide coupling agent in 1980, the realm of applications of T3P has expanded. Currently its use is found in a broad range of reactions, including condensation, functional group transformation, heterocycles preparation, rearrangements, and catalysis. It offers several advantages over traditional reagents, such as high yield, chemical and optical purity, broad functional group tolerance and easy work-up. The reagent is attractive for large-scale synthesis as well, and particularly so for multi-kilogram scale preparations of drug molecules. This article reviews the hitherto reported applications of T3P as a reagent in organic synthesis. Focus is also placed on the use of T3P for large-scale synthesis.

Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer

“…Scheme depicts the synthesis of compound 20 from the advanced intermediate 34 using T3P as the coupling reagent to facilitate formation of the amide linkage with the acid coupling partner. Compounds 21–22 were synthesized in a similar fashion.…”

<strong>The potential and scope of the microwave tool; A case study on the synthesis of phosphinates&nbsp;</strong>

“…Moreover, the method under discussion is not atom efficient. Another possibility is the reaction of phosphinic acids with alcohols in the presence of the cyclic propylphosphonic anhydride, called the T3P ® reagent [15]. Remaining with the heterocyclic models using 1.1 equivalents of the T3P ® reagent at 25 °C, the 1-hydroxy-3-phospholene 1-oxides could be converted in yields of 76-95% to the corresponding phosphinates (Scheme 1/B) [16].…”

Synthesis of Phosphinic Acid Derivatives; Traditional Versus up-to-Date Synthetic Procedures

“…It was shown recently that the alkylating esterification of phenyl-Hphosphinic acid with alkyl halides takes place using triethylamine in a homogeneous medium (Scheme 37) [117]. The propylphosphonic anhydride (T3P ® ) reagent is also a powerful coupling (dehydrating/condensing) agent applied in a wide range of reactions [118]. The senior author of this article together with co-workers reported the fast and efficient esterification of cyclic phosphinic acids with a series of alcohols at 25°C, in the presence of 1.1 equivalent of the T3P ® reagent (Scheme 42).…”