Rhodium-Catalyzed 1,4-Aryl Rearrangement of Sulfur Ylide for the Synthesis of 2-Pyridyl Thioethers

Abstract

We report a novel rhodium-catalyzed rearrangement involving N-substituted 2-thiopyridones and diazoesters. This reaction proceeds through the rhodium-catalyzed formation of sulfur ylides, followed by a direct C−N bond cleavage to achieve N-to-C 1,4-pyridyl migration. The protocol can be used to construct various thiopyridines possessing tetrasubstituted carbon stereocenters in moderate to excellent yields, which expands the transformation pattern of sulfur ylide intermediates in rearrangement reactions.2-Pyridyl thioethers are found in the cores of various biologically active molecules and agrochemicals (Figure 1). 1 These skeletons are conventionally prepared through the catalytic or noncatalytic substitution of the halides in ArX with an RS group 2 or a transition-metal-catalyzed (TM-catalyzed) cross-coupling reaction with a thiol 3 or In(SR) 3 . 4 Such protocols generally require organic halides and stoichiometric amounts of additives. TM-free nucleophilic aromatic substitution (S N Ar) reactions with thiols, 5 thiosulfate salts, 6 disulfides, 7 and PhSSiMe 3 8 have also been reported as preferable methods; however, these protocols mainly require stoichiometric oxidants, strong bases, or high temperatures (above 100 °C).

A ruthenium catalyzed Dolye–Kirmse rearrangement reaction of sulfoxonium ylides with sulfides or selenides

“…Different solvents were screened and DCM gave the highest yield of 81% (Table 1, entries 11-14). In the investigation of reaction temperature, we observed that 1a did not reach full conversion at a lower temperature, and the side reaction significantly increased at a higher temperature, resulting in a decrease in yield (Table 1, entries [15][16][17].…”

“…[11][12][13] And the synthesis of diazo compounds often requires the use of dangerous raw materials. [14][15][16][17] Thereafter, Biju's team described a method of Steven rearrangement of arynes and allylthioethers to obtain β-keto phenyl thioethers (Scheme 1b). 18 But the reaction was limited by low selectivity of the products.…”