H-phosphonate-mediated sulfonylation of heteroaromatic N-oxides: a mild and metal-free one-pot synthesis of 2-sulfonyl quinolines/pyridines

Abstract

A smart H-phosphonate-mediated synthetic strategy for the sulfonylation of heteroaromatic N-oxides has been developed, by which a large variety of 2-sulfonyl quinolines/pyridines were synthesized starting from easily available sulfonyl chlorides, diisopropyl H-phosphonate and pyridine/quinoline N-oxides in one pot under metal-free conditions at room temperature.

Iodine/TBHP‐Promoted One‐Pot Deoxygenation and Direct 2‐Sulfonylation of Quinoline N‐Oxides with Sodium Sulfinates: Facile and Regioselective Synthesis of 2‐Sulfonylquinolines

“…Based on the above results and relevant literature,, , , a plausible mechanism for this metal‐free‐induced one‐pot deoxygenation and sulfonylation is proposed in Scheme . Under the optimal reaction conditions, the initial process could presumably involve the reaction of I 2 and TBHP to form an electrophilic iodine species (“I + ”) such as hypoiodite (IO – ) or iodite (IO 2 – ) by an in situ iodination .…”

“…2‐[(4‐Chlorophenyl)sulfonyl]quinoline (3c): Yellow solid (229 mg, 76 % yield). 1 H NMR (400 MHz, CDCl 3 ): δ = 8.36 (d, J = 8.4 Hz, 1 H), 8.17 (d, J = 8.4 Hz, 1 H), 8.11 (d, J = 8.4 Hz, 1 H), 8.07–8.03 (m, 2 H), 7.85 (d, J = 8.4 Hz, 1 H), 7.78–7.74 (m, 1 H), 7.65–7.61 (m, 1 H), 7.47 (td, J = 8.4, 2.0 Hz, 2 H) ppm.…”

“…2‐(Thiophen‐2‐ylsulfonyl)quinoline (3m): Yellow solid (69 mg, 25 % yield). 1 H NMR (400 MHz, CDCl 3 ): δ = 8.37 (d, J = 8.4 Hz, 1 H), 8.18 (d, J = 8.4 Hz, 2 H), 7.89–7.86 (m, 2 H), 7.80–7.76 (m, 1 H), 7.70 (dd, J = 4.8, 1.2 Hz, 1 H), 7.67–7.63 (m, 1 H), 7.12–7.09 (m, 1 H) ppm.…”

“…In 2015, Li and co‐workers developed a protocol for the synthesis of 2‐sulfonylquinolines from quinoline N ‐oxides and sulfonyl chlorides under mild conditions. Nonetheless, a stoichiometric amount of toxic H‐phosphonate was necessary for the successful one‐pot sulfonylation and reduction (Scheme d) . In addition, Han and Pan and co‐workers achieved the synthesis of quinoline sulfones by a copper‐catalyzed deoxygenative 2‐sulfonylation of N ‐oxides with sodium sulfinates by using the additive potassium persulfate (K 2 S 2 O 8 ) to promote C–S bond formation and N–O bond cleavage in a one‐pot transformation (Scheme e) .…”

Transition‐Metal‐Free C2‐H Sulfonylation of Quinoline N‐Oxides via Insertion of Sulfur Dioxide

“…While this is a good practice, metal catalyst was required in order to promote the reaction. Later, Li and co‐workers developed a novel and efficient method for the synthesis of sulfonylated quinolines from quinoline N ‐oxides and sulfonyl chlorides . However, excess base and organic solvent were needed in this method.…”