Xuan Zhou, Yannick Fillon, Xianglin Shi, Firoz Antia, Xiao Zhou, Angela Lin
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Hydrogen Fluoride Imidazole: A Simple, Efficient, Mild, and Cost-Effective Silyl-Ether Deprotection Reagent
Despite the availability of numerous −OH silyl protection and deprotection methods, the selective cleavage of silyl ethers in highly complex molecules can still be a challenge. In this article, we present results from a full investigation of a novel, efficient, and mild desilylation protocol using HF/imidazole. Imidazole significantly enhances the desilylation reaction efficiency of HF, allowing clean and complete deprotection of TBDPS ethers in substrates containing both acid and base sensitive groups. For example, four- and five-mer oligonucleotides were efficiently deprotected where all other conditions failed. HF/imidazole is also an effective reagent for the deprotection of TIPS and TBDMS ethers. The reagent prepared using commercially available HF and imidazole maintained the same reactivity even after 4 years of storage at 4 °C. Residual reagents and byproducts can be readily removed with a simple workup; consequently, deprotection of TBDPS was successfully implemented in a 2.5 kg scale synthesis of a five-mer oligonucleotide.
期刊介绍:
The Journal of Organic Chemistry welcomes original contributions of fundamental research in all branches of the theory and practice of organic chemistry. In selecting manuscripts for publication, the editors place emphasis on the quality and novelty of the work, as well as the breadth of interest to the organic chemistry community.