Palladium-Catalyzed Domino Heck/Sulfination: Synthesis of Sulfonylated Hetero- and Carbocyclic Scaffolds Using DABCO–Bis(sulfur dioxide)

Abstract

The synthesis of a broad variety of hetero- and carbocyclic scaffolds via a Pd-catalyzed domino Heck/SO2 insertion reaction is reported. This reaction utilizes DABSO, a safe and easy-to-handle alternative to SO2 gas. The reaction proceeds through a sulfinate intermediate, which can act as a lynchpin for the in situ generation of sulfones, sulfonamides, and sulfonyl fluorides. Good yields and scalability are demonstrated.

Palladium‐Catalyzed Domino Cyclization/Direct Aminosulfonylation Between Aryl Iodides and Amines via the Insertion of Sulfur Dioxide

“…was adjusted to 3.0, 4.0, 5.0 and 7.0 equiv. respectively (Table 1, entries [15][16][17][18]. Neither increasing the temperature to 125 °C nor decreasing it to 80 °C or 95 °C would help to enhance the product yield (Table 1, entries 19-21).…”

“…Oxidative addition of Pd(0) catalyst into 1 a generated aryl palladium species A, which would subsequently undergo an intramolecular cyclization to produce alkyl palladium species B. [18] Then, the insertion of SO 2 into intermediate B made sulfinate palladium salt C [15] which would exist in equilibrium with alkyl sulfonyl palladium complex D. In the presence of base, amines 2 a would have anion exchange with complex D to generate intermediate E. [19] Finally, reductive elimination of intermediate E would allow the formation of the desired sulfonamide 3 a and the regeneration of Pd(0) species for the next catalytic cycle.…”

“…On the other hand, palladium‐catalyzed domino cyclization reaction provides an efficient method to construct and functionalize loop systems [14] . Recently, Lautens and co‐works reported a two‐step, one‐pot strategy for the synthesis of oxindole‐based sulfonamides (Scheme 1a) [15] . In their work, domino cyclization/SO 2 insertion reaction of aryl iodides via Pd‐catalysis provided sulfinate salts as an intermediate, followed by the coupling reaction between sulfinate salts and amines mediated by I 2 , and two oxindole‐based sulfonamides were successfully achieved using this method.…”

DABSO – A Reagent to Revolutionize Organosulfur Chemistry

“…40 Lautens and co-workers showed that cyclic sulfonated products could be prepared through a Pd-catalyzed intramolecular Heck reaction followed by a Pd-catalyzed reaction with DABSO to prepare a sulfinate, from which sulfones, sulfonamides and sulfonyl fluorides were obtained. 41…”

“…40 Lautens and co-workers showed that cyclic sulfonated products could be prepared through a Pd-catalyzed intramolecular Heck reaction followed by a Pd-catalyzed reaction with DABSO to prepare a sulfinate, from which sulfones, sulfonamides and sulfonyl fluorides were obtained. 41 Scheme 11 Pd-catalyzed synthesis of sulfonyl derivatives from aryl halides Sulfonyl fluorides are valuable products. They are hydrolytically stable, but under the correct conditions can undergo sulfur(VI) fluoride exchange (SuFEx) 'click chemistry' reactions.…”