Preparation of Monotetrahydropyranylated Short-Chain Symmetrical Diols

Abstract

Efficient and robust methods for the monoprotection of 1,3-propanediol, 1,4-butanediol, and 1,5-pentanediol as THP ethers have been developed. The preparation of 4-(tetrahydro-pyran-2-yloxy)-butan-1-ol from 1,4-butanediol and 5-(tetrahydro-pyran-2-yloxy)-pentan-1-ol from 1,5-pentanediol was accomplished using a two-phase system composed of CH₂Cl_2, 3,4-dihydro-2H-pyran, and aqueous 0.1 N HCL. Preparation of 3-(tetrahydro-pyran-2-yloxy)-propan-1-ol from 1,3-propanediol was accomplished using a water-free biphasic mixture composed of 1,3-propanediol, catalytic pyridinium p-toluenesulfonate, 3,4-dihydro-2H-pyran, and 25% ether in hexane. The compounds are very useful three- to five-carbon homologating agents.

Keywords:

• 3-(Tetrahydro-pyran-2-yloxy)-propan-1-ol
• 4-(Tetra-hydro-pyran-2-yloxy)-butan-1-ol
• 5-(Tetrahydro-pyran-2-yloxy)-pentan-1-ol
• Monotetrahydropyranylation
• Symmetrical diols

Acknowledgments

I thank Bruce W. Zilkowski and Robert J. Bartelt for acquiring mass spectral data, David Weisleder for acquiring NMR spectra, and Robert J. Bartelt for helpful discussions.