Regio‐ and Stereoselective Thianthrenation of Olefins To Access Versatile Alkenyl Electrophiles

Abstract Herein, we report a regioselective alkenyl electrophile synthesis from unactivated olefins that is based on a direct and regioselective C−H thianthrenation reaction. The selectivity is proposed to arise from an unusual inverse‐electron‐demand hetero‐Diels–Alder reaction. The alkenyl sulfonium salts can serve as electrophiles in palladium‐ and ruthenium‐catalyzed cross‐coupling reactions to make alkenyl C−C, C−Cl, C−Br, and C−SCF3 bonds with stereoretention.


Solvents
Anhydrous acetonitrile and tetrahydrofuran were obtained from Phoenix Solvent Drying Systems. All deuterated solvents were purchased from Euriso-Top.

Chromatography
Thin layer chromatography (TLC) was performed using EMD TLC plates pre-coated with 250 m thickness silica gel 60 F 254 plates and visualized by irradiation UV light or by placing the TLC plate into an iodine chamber for a few minutes. Flash chromatography was performed using silica gel (40-63 µm particle size) purchased from Geduran.

Starting materials
All substrates were used as received from commercial suppliers, unless otherwise stated. Chemicals were 20 mL). The combined mixture was poured into a separatory funnel, and the layers were separated. The CH 2 Cl 2 layer was collected, and the aqueous layer was further extracted with CH 2 Cl 2 (2 × ca. 10 mL). The combined CH 2 Cl 2 solution was washed with aqueous NaBF 4 solution (2 × ca. 20 mL, 5 % w/w). The CH 2 Cl 2 layer was dried over Na 2 SO 4 , filtered, and the solvent was removed under reduced pressure. The residue was purified by chromatography on silica gel eluting with CH 2 Cl 2 /i-PrOH to afford the alkenyl thianthrenium salt.

Synthesis of 2-TT from 2-INT
Under ambient atmosphere, a 20 mL borosilicate vial was charged with cis-4-octene-derived thanthrenium dication 2-INT (100 mg, 160 μmol, 1.00 equiv.). The beige solid was dissolved with CH 2 Cl 2 (10 mL) and poured onto a saturated aqueous NaHCO 3 solution (ca. 10 mL). The combined mixture was poured into a separatory funnel, and the layers were separated. The CH 2 Cl 2 layer was collected, and the aqueous layer was further extracted with CH 2 Cl 2 (2 × ca. 10 mL). The combined CH 2 Cl 2 solution was washed with aqueous NaBF 4 solution (2 × ca. 10 mL, 5 % w/w). The CH 2 Cl 2 layer was dried over Na 2 SO 4 , filtered, and the solvent was removed under reduced pressure. The residue was triturated with Et 2 O (3 ×5.0 mL), and Et 2 O was removed by pipette. The solid was collected and further dried in vacuo to afford 2-TT (E/Z < 50/1, 60.1 mg,

Formation and stability of trans-4-octene adduct
Under an ambient atmosphere, a GC-vial was charged with Teflon coated stir bar, thianthrene-S-oxide (1) (34 mg, 0.15 mmol, 1.0 equiv), trans-4-octene (17 mg, 0.15 mmol, 1.0 equiv) and CD 3 CN (0.5 mL). The reaction mixture was cooled to 0 °C, at which point trifluoroacetic anhydride (0.060 mL, 91 mg, 0.43 mmol, 2.9 equiv) and trifluoromethanesulfonic acid (0.016 mL, 27 mg, 0.18 mmol, 1.2 equiv) were added sequentially. The reaction mixture was warmed to room temperature, transferred to an NMR tube, and analyzed by 1 H NMR (Fig. S5, top). At this point, toluene (14 mg, 0.15 mmol, 1.0 equiv) was added to the NMR tube. After 1.5 h, there was no discernable decomposition by 1 H NMR (Fig S5, middle), and the NMR tube was heated at 60 °C. After 4 h of heating at 60 °C, 1 H NMR analysis showed thianthrene as the primary decomposition product (Fig. S5, bottom). No toluene derived aryl thianthrenium salt could be observed, and the fate of the hydrocarbon motif was not determined.  Becke-Johnson damping (BJ) 9 along with RI approximation, utilizing the def2/J auxiliary basis set 10 and the def2-TZVPP basis set 11 on all atoms. The libint2 library was used for the computation of 2-el integrals 12 . Tight SCF convergence and geometry optimization criterions were chosen. Very tight SCF convergence was chosen for cycloadduct 3-INT. Solvent effects of acetonitrile were taken into account using the conductor-like polarized continuum model (CPCM) 13 . Input files were created using Avogadro 1.

Discussion on six-membered and bicyclo[2.2.0] disulfonium species
The B3LYP geometry optimized structure of the six-membered thianthrene dication ( Figure S10, left) was obtained using thianthrene as a starting geometry with a +2 charge. The B3LYP geometry optimized bicyclo structure ( Figure S10, right) was obtained by using the Avogadro geometry optimization extension with thianthrene as a starting geometry, however, with an explicit S-S bond. The Avogadro generated structure was then optimized using the standard computational method. Both structures converged to an energy minimum, however, the Gibb's free energy for the tricyclo structure was calculated to be -1257.81179186 Eh, while the bicyclo structure had an energy -1257.73675187 Eh. Therefore, the six-membered thianthrene dication is expected to be the more stable conformation by 47.1 kcal•mol -1 . This six-membered ring dication is also evidenced by the isolation and characterization of the dication of 2,3,7,8-tetramethoxythianthrene. 16 1 H-NMR data suggested from a separate publication also proposes six-membered ring dication. 17

Discussion on elimination mechanism
The elimination cannot proceed via an E2 elimination mechanism due to stereoelectronic constraints. Also, the product cannot be formed by E1 elimination because the dication is stable in solution in the absence of base (see Reactivity studies on cycloaducts part). The reaction could proceed via a sulfonium ylide intermediate (E1cB). A reversible E1cB mechanism (E1cB rev ) can be ruled out because we executed an H/D scrambling experiment and did not observe scrambling. Alternatively, the reaction could proceed via an irreversible E1cB irr mechanism, where rate-determining deprotonation is followed by a rapid elimination. 18 All data observed is consistent with an E1cB irr mechanism.