Enantioselective Sulfoxidation Catalyzed by a Bisguanidinium Diphosphatobisperoxotungstate Ion Pair

Abstract

The first enantioselective tungstate-catalyzed oxidation reaction is presented. High enantioselectivities were achieved for a variety of drug-like phenyl and heterocyclic sulfides under mild conditions with H2 O2 , a cheap and environmentally friendly oxidant. Synthetic utility was demonstrated through the preparation of (S)-Lansoprazole, a commercial proton-pump inhibitor. The active ion-pair catalyst was identified to be bisguanidinium diphosphatobisperoxotungstate using Raman spectroscopy and computational studies.

Enantioselective remote C–H activation directed by a chiral cation

“…We also examined vicinally dichlorinated (3i) and difluorinated (3j) substrates, which both worked effectively. Substrates 15 bearing electron donating substituents exhibited lower reactivity under our conditions -3-methoxy gave no conversion and 3-methyl gave <5% conversion, likely due to the reaction temperatures being lower than those typically used in C-H borylation. Performing the reactions at room temperature gave conversion, but with moderate enantioselectivity (Fig.…”

“…In 30 contrast, it is far rarer to encounter anionic transition metal complexes as key intermediates. As such, the charge-inverted approach of pairing a chiral cation with an anionic transition metal catalyst has only been demonstrated in a handful of pioneering cases, notably asymmetric oxidation reactions involving anionic diphosphatobisperoxotungstate (15) and peroxomolybdate (16) complexes as catalysts ( Figure 1A, center panel) (17)(18)(19)(20)(21). Due to this scarcity of anionic metal 35 complexes in the most commonly employed processes, the broader potential of uniting chiral cations with the versatile reactivity of transition metals has remained underexplored, despite the obvious potential presented by several privileged classes of chiral cation.…”

“…We envisaged that, in principle, a wide variety of privileged ligand scaffolds for transition metal catalysis could be rendered anionic, creating exciting opportunities to explore the use of chiral cations as chiral controllers in a wealth of powerful transition metal catalyzed reactions. 15 In seeking a rigorous and relevant test of the above-described approach, we targeted a transformation that lies at the cutting edge of what is currently possible in enantioselective catalysis. Whilst enantioselective, desymmetrizing C-H activation of arenes has been extensively explored with palladium (26,27), rhodium (28,29) and iridium (30, 31) catalysis, all but a single case functionalize at the arene ortho position (32).…”

“…Focusing attention on the meta positions of the outer arenes of the teraryl system, we then evaluated a series of substituents (L·1e -L·1i). Trifluoromethyl (L·1e) and methoxy (L·1f) substitution again gave increases (both 60% ee), but the biggest gain came 15 from the tert-butyl substituted L·1g (73% ee). At this point we investigated aryl groups in these positions to extend the reach even further, but both of these proved detrimental (L·1h and L·1i).…”

Recent Advances in Chiral Guanidine‐Catalyzed Enantioselective Reactions

“…The strategy of chiral cation ion-pairing catalysis developed by Tana nd co-workersw as also applied to enantioselective sulfoxidation benzimidazole-derived sulfides in the presence of silver tungstate and dicationic bisguanidinium 27. [70,71] It was found that the use of Ag 2 WO 4 and NaH 2 PO 4 promoted the sulfoxidation reaction moste fficiently. Ad iphosphatobisperoxotungstate, [(PO 2 (OH) 2 ) 2 (WO(O 2 ) 2 )] 2À was proposed to be the active anion in this reaction.…”