Transition-Metal-Free Efficient Synthesis of Bisindole Sulfanes Using 2-(Fluorosulfonyl)difluoroacetic Acid

Abstract

By using 2-(fluorosulfonyl)difluoroacetic acid as sulfur ­reagent, bisindole sulfanes were highly efficient synthesized under transition-metal-free conditions. Results indicate that this proceeded not at the relatively acidic C-2 position but rather selectively at the nucleo­philic C-3 position to give the desired compounds with excellent regio­selectivities and good yields.

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

“…Li et al used 2-(fluorosulfonyl)difluoroacetic acid ( 115 ) as the “S” source to synthesize bis(indol-3-yl)sulfides 116 from N -protected indoles 1 or 61 [ 85 ]. The products 116 were formed within a few seconds in the presence of a moderate base at high temperature ( Scheme 16b ), tolerating groups having both electron-donating and withdrawing nature on 1 .…”

“…There are several uses of sulfoxides as a thiol-free sulfur source for introducing sulfur at the indole C3 position [84][85][86]. In 2013, Hamashima reported a synthesis of di(indol-3-yl)sulfide (105a) by reacting indole with DMSO in the presence of trifluoroacetic anhydride (TFAA) in total 6 steps (Scheme 16a) [84].…”

“…Oxidation of sulfur by oxone followed by repetition of the previous steps afford the diindol-3-ylsulfonium salt 114, which in the presence of a base gives product 105a. N-protected indoles 1 or 61 [85]. The products 116 were formed within a few seconds in the presence of a moderate base at high temperature (Scheme 16b), tolerating groups having both electron-donating and withdrawing nature on 1.…”

XtalFluor‐E Enabled Regioselective Synthesis of Di‐Indole Sulfides by C3−H Sulfenylation of Indoles

“…[14] The majority of these reactions form a single CÀ S bond, but it should be noted that 2-(fluorosulfonyl)difluoroacetic acid reacts as an electrophilic sulfur source in a double S E Ar reaction (Scheme 1C). [15] However, the use of S(IV) sulfenylating reagents for forming diaryl sulfide by a double S E Ar process, is not reported to the best of our knowledge. Herein we report the double CÀ H bond functionalization of indoles with XtalFluor-E to form di-indole sulfides (Scheme 1D) and under certain conditions di-aryl aza sulfonium species.…”

“…Aryl sulfide synthesis via S E Ar with sulfonium salts was established by Belenkova and co‐workers, [12] following this numerous isolated sulfonium salts (Scheme 1A), [13] and in situ formed sulfonium salts (Scheme 1B) have been used as electrophiles in S E Ar reactions [14] . The majority of these reactions form a single C−S bond, but it should be noted that 2‐(fluorosulfonyl)difluoroacetic acid reacts as an electrophilic sulfur source in a double S E Ar reaction (Scheme 1C) [15] . However, the use of S(IV) sulfenylating reagents for forming diaryl sulfide by a double S E Ar process, is not reported to the best of our knowledge.…”