Planar Chiral Flavinium Salts – Prospective Catalysts for Enantioselective Sulfoxidation Reactions

Abstract

A novel planar chiral flavinium salt, 3-benzyl-5-ethyl-10-(8-phenylnaphthalen-1-yl)isoalloxazinium perchlorate (2b), which bears a phenyl cap that covers one side of the isoalloxazinium skeleton plane, has been prepared as a potential catalyst for the enantioselective H 2 O 2 oxidation of sulfides. The rate of H 2 O 2 oxidation of sulfides in the presence of racemic 2b is comparable to that of the reaction catalysed by 5-ethyl-3,10-dimethylisoalloxazinium perchlorate, which indicates that the bulky shielding substituent does not influence the catalytic activity of the flavinium unit. The turnover fre-

Convenient Synthesis of Toxoflavin that Targets β‐Catenin/Tcf4 Signaling Activities

“…The starting materials methylurea, malonic acid, and acetic anhydride were reacted in one‐pot to give the pyrimidinetrione 8 with over 80% yield . This compound was then chlorinated by phosphorus oxychloride, catalyzed by a small amount of water, to obtain the pyrimidinedione 9 with 81% yield . Compound 9 was refluxed with methylhydrazine in ethanol to give the hydrazinylpyrimidinedione 10 with 65% yield after isolation.…”

Organocatalytic Asymmetric Oxidations with Hydrogen Peroxide and Molecular Oxygen

“…The flavinium salt was proposed to be converted, by means of hydrogen peroxide, to a chiral flavinium hydroperoxide able to oxidize methyl aryl sulfides in enantioselective manner (Scheme ). A different flavinium salt, 3‐benzyl‐5‐ethyl‐10‐(8‐phenylnaphthalen‐1‐yl)isoalloxazinium perchlorate 26 , featuring a phenyl cap able to shield one side of the isoalloxazinium plane, was recently synthesized by Cibulka and coworkers 73. This organocatalyst was found to promote the enantioselective oxidation of alkyl aryl sulfides in the presence of hydrogen peroxide affording the sulfoxides with modest ee values (Scheme ).…”

Insight into the catalytic activity of alloxazinium and isoalloxazinium salts in the oxidations of sulfides and amines with hydrogen peroxide

“…Although isoalloxazinium and alloxazinium salts are important organocatalysts for sulfoxidations with hydrogen peroxide and several studies of their catalytic activity have been published [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29], there has been no direct comparison of their efficiency under the same reaction conditions. Only individual comparative studies for both groups of flavinium salts have been reported.…”

“…This method is highly chemoselective, producing sulfoxides with no over-oxidation to sulfones [2,[13][14][15][16][17][18][19][20][21][22][23][24]. If a chiral flavinium salt is employed, the sulfoxidation proceeds with high enantioselectivity [25][26][27][28][29]. Flavin-cyclodextrin conjugates are the most efficient metal-free catalysts reported so far, reaching enantioselectivities up to 80% ee for aromatic and 91% ee for aliphatic sulfides [28,29].…”

“…Research into catalysis with flavinium salts was initiated by the investigation of the mode of action of flavin-4a-hydroperoxides, which were recognized as oxidizing agents in flavoenzymes [30][31][32][33][34][35][36]. So far, flavinium salts have been found to catalyze sulfoxidations [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29], N-oxidations [24,37,38], and Baeyer-Villiger oxidations [39][40][41] in the similar way as flavindependent monooxygenases [13,14,[30][31][32][33][34][35][36]. Biomimetic systems utilizing a flavinium salt and oxygen as terminal oxidant have also been designed [42][43][44].…”