Alloxazine–cyclodextrin conjugates for organocatalytic enantioselective sulfoxidations

Abstract

Four structurally different alloxazine-cyclodextrin conjugates were prepared and tested as catalysts for the enantioselective oxidation of prochiral sulfides to sulfoxides by hydrogen peroxide in aqueous solutions. The alloxazinium unit was appended to the primary face of α- and β-cyclodextrins via a linker with variable length. A series of sulfides was used as substrates: n-alkyl methyl sulfides (n-alkyl = hexyl, octyl, decyl, dodecyl), cyclohexyl methyl sulfide, tert-butyl methyl sulfide, benzyl methyl sulfide and thioanisol. α-Cyclodextrin conjugate having alloxazinium unit attached via a short linker proved to be a suitable catalyst for oxidations of n-alkyl methyl sulfides, displaying conversions up to 98% and enantioselectivities up to 77% ee. β-Cyclodextrin conjugates were optimal catalysts for the oxidation of sulfides carrying bulkier substituents; e.g. tert-butyl methyl sulfide was oxidized with quantitative conversion and 91% ee. Low loadings (0.3-5 mol%) of the catalysts were used. No overoxidation to sulfones was observed in this study.

Recent Developments in Flavin‐Based Catalysis

“…However, in recent years, some efforts have been made to carry out asymmetric organocatalyzed sulfoxidations by creating novel systems mimicking flavoenzymes. Thus, a set of β-cyclodextrins have been linked to different neutral N 5 -ethylflavins in order to create chiral flavin catalysts [62,63]. These systems have been employed in the oxidation of thioanisole and its aryl analogues in aqueous medium in the presence of hydrogen peroxide.…”

Cyclodextrins in Asymmetric and Stereospecific Synthesis

“…In recent years, a series of pteridine derivatives-cyclodextrin conjugates for enantioselective oxidation of prochiral aromatic and aliphatic sulfides with hydrogen peroxide has been studied [48][49][50]. The highest optical yield achieved with these catalysts was 91% ee.…”

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

“…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].…”

“…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].…”

“…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].…”