Chemodivergent Synthesis of Allylic Sulfones via Ligand-Controlled Coupling of Allenes with Sulfinic Acids

Abstract

Allylic sulfones are important building blocks in organic synthesis and pharmaceutical chemistry. Herein, we disclose a chemodivergent protocol for Pd-catalyzed and ligand-controlled coupling of allenes with sulfinic acids, providing straightforward and atom-economical access to branched allylic sulfones and linear allylic sulfones bearing a conjugated (Z,E)-1,3-diene scaffold in good yields with high selectivities. This strategy features mild conditions, an unprecedented substrate scope, and functional group compatibility.

One-Pot, Metal-Free Synthesis of Allyl Sulfones in Water

“…A common approach employs the reaction of a sulfonyl precursor with an allyl substrate, a method popular due to the versatility of sulfonyl compounds, which possess exceptional electrophilic, nucleophilic, and free radical conversion capabilities. Sulfonyl precursors include sulfinic acid, sodium sulfinate, arylsulfonyl cyanide, and arylsulfonyl hydrazide . Other techniques include transition metal-catalyzed hydrogenation to sulfoxides and the synthesis of allyl sulfone compounds using SO 2 as a source .…”

Pd-catalyzed cascade coupling reaction of cyclopropanols with N-allenyl-2-iodoanilines to construct 3-substituted indole derivatives

“…7 After that, Ma and co-workers disclosed a palladium-catalyzed coupling reaction of 2,3-allenylic carbonates with cyclopropanols, which provided the expected 1,3-diene products efficiently (Scheme 1c). 8 Based on our recent studies on transition metal-catalyzed functionalization of allenes, 9 we are interested in uncovering a concise and useful synthetic protocol for the combination of allenes with cyclopropanols by taking advantage of the special character of metal homoenolates. Herein, we report a Pd/XPhos-catalyzed ring-opening coupling reaction of cyclopropanols with N -allenyl-2-iodoanilines to construct 3-substituted indole derivatives (Scheme 1d).…”

Regiodivergent sulfonylation of terminal olefins via dearomative rearrangement

“…Couplings of allylic alcohols with sulfinyl chlorides, 21 activated by NBS, 22 or catalyzed by Pd 3,23 have afforded allylsulfone. Similarly, allylic amines using Pd, 24 allenes using Pd, 25 activated alcohols using W 26 or Ir, 27 alkynes with Rh, 28 dienes with Pd, 29 and allyl halides 30 have been reported to produce allylsulfones; whereas, a-sulfonylmethyl styrenes have been mainly prepared by radical reactions 13,[31][32][33][34][35] or using stoichiometric ZnI 2 . 36 Despite progress, we sought to develop a complementary and tunable synthetic approach (regiodivergent sulfonylation) that utilizes inexpensive and readily available starting materials and reagent under transition metal-free conditions.…”

“…Couplings of allylic alcohols with sulfinyl chlorides, 21 activated by NBS, 22 or catalyzed by Pd 3,23 have afforded allylsulfone. Similarly, allylic amines using Pd, 24 allenes using Pd, 25 activated alcohols using W 26 or Ir, 27 alkynes with Rh, 28 dienes with Pd, 29 and allyl halides 30 have been reported to produce allylsulfones; whereas, α-sulfonylmethyl styrenes have been mainly prepared by radical reactions 13,31–35 or using stoichiometric ZnI 2 . 36…”