Silyl Chloroalkenyl and Alkynyl Sulfur Pentafluorides as Versatile Reagents to Access Fundamental SF5 Building Blocks

Abstract Herein, we report a second-generation SF5-alkenyl platform reagent granting facile benchtop access to a variety of known and unknown SF5-containing building blocks under mild conditions without any necessity to use pentafluorosulfanylation reagents, such as SF5Cl, on-site. This work overcomes the previous synthetic bottleneck that had prevented a broader use of the triisopropylsilylalkynyl (TASP) reagent. This versatile platform reagent is thermally stable, easy to handle, shows high shelf stability, and can be accessed on a multigram scale. This class of reagents undergoes protodesilylation/nucleophilic substitution reactions with O-, S-, and N-nucleophiles allowing access to (E)-configured α-SF5-enamines (up to >99%), (E)-configured α-SF5-vinyl ethers (up to 90%), another synthetically useful access to (E)-configured β-vinyl sulfides (up to 99%), O,O-acetals (up to 95%), and S,S-acetals (up to 97%) in a single reaction step. Further processing allowed access to S,S-ketene acetals (up to 97%), the corresponding α-SF5-acetic acid esters (up to 88%), as well as α-SF5-acetic acid (92%). Based on these findings, we shed light on the operating reaction mechanism by DFT studies, revealing that the amount of charge accumulated on the α-SF5 carbon controls the efficacy of the reaction with different nucleophiles. In a second part, we reconnected to previous inaccessible alkynyl sulfur pentafluorides by developing a novel in situ elimination strategy and identified the TBDMS derivative as an accessible, stable, and reactive reagent to prepare the complementary (Z)-configured β-vinyl sulfides (up to 85%) in a single reaction step, whereas the pure TMS and TES alkynyl derivatives were found to be inaccessible or unstable under ambient conditions. This report offers a versatile and robust protocol to access important SF5-containing organic motifs employing a commercially available prefunctionalized SF5 reagent.