Modern Stereoselective Synthesis of Chiral Sulfinyl Compounds

Abstract

Chiral sulfinyl compounds, sulfoxides, sulfoximines, sulfinamides, and other derivatives, play an important role in asymmetric synthesis as versatile auxiliaries, ligands, and catalysts. They are also recognized as pharmacophores found in already marketed and well-sold drugs (e.g., esomeprazole) and used in drug design. This review is devoted to the modern methods of preparation of sulfinyl derivatives in enantiopure or enantiomerically enriched form. Selected new approaches leading to racemic products for which the asymmetric variant can be developed in the future are mentioned as well.

Imine‐Based Covalent Organic Frameworks as Photocatalysts for Metal Free Oxidation Processes under Visible Light Conditions

“…One of the most interesting oxidation reactions is the sulfoxidation, obtaining sulfoxides from thioethers, due to their relevance in the pharmaceutical and agrochemical industries and also as key intermediates in organic synthesis. [6,7] The principal approach for the synthesis of these compounds is the use of peroxides or peracids, such as m-CPBA, which are explosive reagents and therefore difficult to handle. Moreover, the overoxidation process to sulfone has been also described as a limitation to be overcome.…”

“…Moreover, the overoxidation process to sulfone has been also described as a limitation to be overcome. [6] In the last decade, photocatalysis has emerged as a powerful solution for the activation of different molecules such as oxygen. [8][9][10][11][12][13] Therefore, an alternative oxidation for the use of peracids and peroxides is the application of gaseous reagents that allows the development of greener processes by reducing the waste from purification, because excess of gas can be easily removed from the reaction.…”

Highly Efficient Access to (S)‐Sulfoxides Utilizing a Promiscuous Flavoprotein Monooxygenase in a Whole‐Cell Biocatalyst Format

“…Chiral sulfoxides have gained huge attention as synthons and precursors for the synthesis of APIs, [1,2] flavors and fragrances, [3] or as chiral auxiliaries in chemical syntheses. [4,5] As the potency of one enantiomer often outperforms the one of the antipode (e. g., shown for esomeprazole), [6][7][8] enantiopure sulfoxide preparation is required.…”

“…This can be achieved by costly and labor intensive resolution of racemates [9] or direct asymmetric synthesis. [5] The latter can be accomplished by the application of chemical [2,10] or biological catalysts, with the biocatalysts typically having a selectivity advantage. [11] A number of enzymes such as cytochrome P450 monooxygenases, [12] Baeyer-Villiger monooxygenases (BVMOs), [13,14] peroxidases, [15] and styrene monooxygenases (SMOs) [16] among others catalyze regio-and enantioselective sulfoxidation, which has been pioneered by work on peroxidases and BVMOs.…”

Biocatalytic Preparation of Chiral Sulfoxides through Asymmetric Reductive Resolution by Methionine Sulfoxide Reductase A

“…Chiral sulfoxides are valuable organosulfurc ompounds and have been widely used as important intermediates in asymmetric synthesis and as bioactivei ngredients in the pharmaceuticali ndustry. [1][2][3][4][5][6] In asymmetric synthesis, optically active sulfoxides are used as stereogenic centers and may also induce chirality in successive reaction steps. [1,2] In the medicinal and pharmaceutical industry, enantiopure sulfoxides have significantc ommercialv alue in the synthesis of pharmaceuticals such as the anticarcinogenic compound sulforaphanea nd the antiulcer medicinee someprazole.…”