The Mitsunobu reaction is ap owerful transformation for the one-pota ctivation 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,w er eport ap hosphine free methodf or alcohola ctivationand substitution that is mediated by sulfuryl fluoride. This new method is effective for aw ide range of primary alcohols using phthalimide, di-tert-butyl-iminodicarboxylate, and aromatict hiol nucleophilesi n7 4% average yield. Activatedc arbon nucleophilesa nd ad eactivated phenolw ere also effective for this reaction in good yields. Secondary alcohols were also successful substrates using aryl thiols, affording the corresponding sulfides in 56 % averagey ield with enantiomeric ratios up to 99:1. This new protocol has ad istinct synthetic advantage over many existing phosphine-based methods as the byproducts are readily separable. Thisf eature was exploitedi n severale xamples that did not require chromatographyf or purification. Furthermore, the mild reaction conditions enabled further in situ derivatization for the one-pot conversion of alcohols to amines or sulfones. This methoda lso provides ab oarder nucleophile scope comparedt oe xisting phosphine-free methods.

Sulfuryl fluoride is a valuable reagent for the one-pot activation and derivatization of aliphatic alcohols, but the highly reactive alkyl fluorosulfate intermediates limit both the types of reactions that can be accessed as well as the scope. Herein, we report the SO 2 F 2 -mediated alcohol substitution and deoxygenation method that relies on the conversion of fluorosulfates to alkyl halide intermediates. This strategy allows the expansion of SO 2 F 2 -mediated one-pot processes to include radical reactions, where the alkyl halides can also be exploited in the one-pot deoxygenation of primary alcohols under mild conditions (52−95% yield). This strategy can also enhance the scope of substitutions to nucleophiles that are previously incompatible with one-pot SO 2 F 2 -mediated alcohol activation and enables substitution of primary and secondary alcohols in 54−95% yield. Chiral secondary alcohols undergo a highly stereospecific (90−98% ee) double nucleophilic displacement with an overall retention of configuration.

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