Taming Brønsted Acid Reactivity: Nucleophilic Substitutions of Propargylic Alcohols with N-Nucleophiles Mediated by Phosphorus-Based Brønsted Acid Catalysts.

Lalita Radtanajiravong,Silvia Díez-González

doi:10.1021/acsomega.9b01427

Abstract

The activity of diethyl phosphite and diphenyl phosphate in propargylation reactions with N-nucleophiles of varying basicity is presented. A careful choice of the reaction conditions minimized undesired rearrangements and arylation processes, typical side reactions with Brønsted acid catalysis. These systems are compatible with technical solvents and presence of air, and they are also applicable to C-, O-, and S-nucleophiles.

Highlights

Significant effort has been placed in the development of efficient direct nucleophilic substitution of alcohols, allylic ones, even before it was identified by the ACS Green Chemistry Institute Pharmaceutical Roundtable as a priority area in the preparation of pharmaceutical intermediates.[1]
The transformation of propargylic alcohols is of particular interest because of their synthetic versatility, and, a range of transition-metal and acid catalysts have been reported for this purpose.[2]
Sulfonic acids[4] and phosphomolybdic acid on silica[5] have been used with a wide range of C, N, and O-nucleophiles in SN1 reactions of propargylic alcohols, and we reported the use of aqueous HBF4.6 These catalysts are compatible with air and reagent-grade solvents, but they are obviously limited by the basicity of the chosen nucleophile

Summary

■ INTRODUCTION

Sulfonic acids[4] and phosphomolybdic acid on silica[5] have been used with a wide range of C-, N-, and O-nucleophiles in SN1 reactions of propargylic alcohols, and we reported the use of aqueous HBF4.6 These catalysts are compatible with air and reagent-grade solvents, but they are obviously limited by the basicity of the chosen nucleophile. Only anilines with electron-withdrawing groups are suitable substrates with the reported systems[10] as even catalysts of modest acidity can mediate these arylations.[11]

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ REFERENCES