Zinc-Catalyzed Transacetalization of N,O-Acetals into N,N-Acetals with Benzotriazoles, Indazoles, and Azides

Abstract

Ynamides have recently emerged as key building blocks in organic synthesis, The electron-donating ability of the nitrogen atom strongly polarizes the triple bond, allowing for transformations to proceed with levels of chemo-, regio-, and stereo-selectivities that cannot be reached with classical alkynes. Ynamides are therefore extremely versatile reagents. Recently, it was found that mCPBA oxidize ynamides at the unconventional β-position, leading to N,O-acetals. We studied the reactions of the N,O-acetals and found that they underwent transacetalization with benzotriazoles, leading to N,N-acetals in the presence of Zn(OTf)2 catalyst. We also found that use of Hexafluoroisopropanol significantly accelerated the reaction, improved the N1/N2 regioisomeric ratio. The transacetalization conditions developed could be extended to other N-donors, such as 1H-indazole and TMSN3 to afford the corresponding N,N-acetals.