Construction of α‐(Hetero)aryl Ethenesulfonyl Fluorides for SuFEx Click Chemistry

Abstract

The construction of α‐(hetero)aryl ethenesulfonyl fluorides was achieved via a Pd‐catalyzed Suzuki coupling of arylboronic acids with 1‐bromoethene‐1‐sulfonyl fluoride (1‐Br‐ESF). The novel α‐aryl ethenesulfonyl fluorides were found to be another selectively addressable bis‐electrophile for wide diversification through SuFEx click chemistry, or Michael addition with excellent chemical discrimination.

Desulfonative Suzuki–Miyaura Coupling of Sulfonyl Fluorides

“…[1,[3][4][5] As highlighted in Sharpless and Arvidssons recent reviews, sulfonyl fluorides are largely inert to hydrolysis, reduction, and transition metal catalysis. [1][2][3] The SO 2 F group is often installed through transition-metal catalyzed processes, [6][7][8][9][10][11][12][13][14][15][16][17][18] and has been reported to be inert under Suzuki-Miyaura coupling (SMC) conditions. [3,[19][20][21] As a result, while sulfonyl fluorides are a powerful tool to access sulfonylated derivatives, their use as SMC electrophiles to form C À C bonds would significantly broaden their synthetic utility.…”

“…Other functional groups on the boronic acid were also found to be tolerated, including vinyl substitution (5), aromatic amines (6), benzyl ethers (8,17,24), aldehydes (10), and dioxy methylene groups (14). Pyridyl sulfonyl fluorides substituted with electron-donating or electron-withdrawing groups displayed good reactivity using Cu(IPr)Cl and KHF 2 as additives (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Substitution ortho to the sulfonyl fluoride leaving group was tolerated (19).…”

Ethenesulfonyl Fluoride (ESF) and Its Derivatives in SuFEx Click Chemistry and More

“…Notably, a series of 1-arylethenesulfonyl fluorides was obtained through Suzuki coupling of 1-Br-ESF and boronic acids, while no competitive Heck-type products were observed (Scheme 39). 53,54 Subsequently, Moses and coworkers reported the development and application of 1-Br-ESF as a new connector, while it was generated in situ by dehydrobromination of bench-stable 1,2-dibromoethane-1-sulfonyl fluoride (DESF) (82). 55 The [3+2] cycloaddition of 1-Br-ESF with N-hydroxyimidoyl chlorides or azides, as well as 1,4-Michael addition with amines, were realized with excellent efficiency and the corresponding novel sulfonyl fluoride products were reacted with aryl silyl ethers to test their reactivity in SuFEx click chemistry (Scheme 40).…”

Radical-mediated vicinal addition of alkoxysulfonyl/fluorosulfonyl and trifluoromethyl groups to aryl alkyl alkynes

“…These tetra-substituted alkenes are challenging to access through known cross-coupling methods. [8][9][10]…”

“…1 d ,7 Alkenylsulfonyl fluorides are of special interest due to the electrophilic character of both the sulfur center and the β-carbon, representing a unique warhead for covalent binders. 1 j To access alkenylsulfonyl fluorides, the groups of Sharpless, Arvidsson, Qin, Yu, Huestis, Willis, and others reported transition-metal catalyzed cross-coupling reactions with ethenesulfonyl fluoride (ESF), 8 1-bromoethenesulfonyl fluoride (BESF), 9 or 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO)/ N -fluorobenzenesulfonimide (NFSI). 10 These reactions work well, but don't provide access to tetra-substituted alkenyl sulfonyl fluorides that should also be valuable for SuFEx click chemistry.…”