Asymmetric and Sustainable Synthesis of Cyclic Sulfoxides with Low Loading of Bisguanidinium Peroxomolybdate Ion-Pairing Catalyst

Abstract

Chiral cyclic sulfoxides are valuable heterocyclic building blocks in natural products and pharmaceutically active molecules as well as optoelectronics materials. In view of their manifold applications but limited number of available synthetic methodologies to obtain them, highly enantioselective catalytic approaches to access chiral cyclic sulfoxides are therefore desired. Here, a sustainable and enantioselective oxidation of cyclic sulfides has been developed by employing in situ-generated bisguanidinium peroxomolybdate ion-pairing catalysis. Chiral cyclic sulfoxides bearing different ring sizes and functional groups have been achieved under mild and green conditions with low catalyst loading (0.05–0.5 mol %). The synthetic potentials based on chiral cyclic sulfoxide products have also been demonstrated in preparation of medicinally relevant molecules such as BI 1015550, a candidate drug for the treatment of idiopathic pulmonary fibrosis.

Engineering of Methionine Sulfoxide Reductase A with Expanded Substrate Scope for Deracemization of Sulfinyl Esters

“…Furthermore, this system maintained high enantioselectivity, achieving 97–99% ee for all compounds (Figure ). The atom economy of this system ranged from 34 to 41% (Table S3), which is comparable to the recently reported chemical or biological ways to prepare chiral sulfinyl compounds. , Notably, these reactions were carried out in an aqueous environment, eliminating the need for harmful organic/inorganic solvents like CCl 4 , toluene, or H 2 SO 4 , which are used in other chemical or biological processes. ,, The low-cost d -glucose was used to recycle the expensive cofactor NADPH, and its consumption promoted the production of target products. The absence of expensive catalysts, the use of a water-based reaction medium avoiding toxic reagents, and the utilization of renewable resources such as d -glucose align well with green and sustainable chemistry principles.…”