One-Pot Substitution of Aliphatic Alcohols Mediated by Sulfuryl Fluoride.

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Jia Yi Mo, Maxim Epifanov, Jack W Hodgson, Rudy Dubois, Glenn M Sammis

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Jia Yi Mo: Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British, Columbia, V6T 1Z1, Canada.
Maxim Epifanov: Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British, Columbia, V6T 1Z1, Canada.
Jack W Hodgson: Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British, Columbia, V6T 1Z1, Canada.
Rudy Dubois: Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British, Columbia, V6T 1Z1, Canada.
Glenn M Sammis: Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British, Columbia, V6T 1Z1, Canada. ORCID

PMID: 32074386 DOI: 10.1002/chem.202000721

The Mitsunobu reaction is a powerful transformation for the one-pot activation and substitution of aliphatic alcohols. Significant efforts have focused on modifying the classic conditions to overcome problems associated with purification from phosphine-based byproducts. Herein, we report a phosphine free method for alcohol activation and substitution that is mediated by sulfuryl fluoride. This new method is effective for a wide range of primary alcohols using phthalimide, di-tert-butyl-iminodicarboxylate, and aromatic thiol nucleophiles in 74 % average yield. Activated carbon nucleophiles and a deactivated phenol were also effective for this reaction in good yields. Secondary alcohols were also successful substrates using aryl thiols, affording the corresponding sulfides in 56 % average yield with enantiomeric ratios up to 99:1. This new protocol has a distinct synthetic advantage over many existing phosphine-based methods as the byproducts are readily separable. This feature was exploited in several examples that did not require chromatography for purification. Furthermore, the mild reaction conditions enabled further in situ derivatization for the one-pot conversion of alcohols to amines or sulfones. This method also provides a boarder nucleophile scope compared to existing phosphine-free methods.

alkyl fluorosulfate alkylation amines nucleophilic substitution sulfuryl fluoride

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2015-RGPIN-05856/Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada

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