Chiral <italic>N</italic>,<italic>N</italic>ʹ-dioxide and their metal complexes in asymmetric catalysis

Abstract

Chirality is a fundamental property of nature. Chiral compounds are closely related to life science, human health, material science, and so on. Asymmetric catalysis is one of the most efficient and important synthetic methodologies to obtain chiral compounds, which meets the requirement of green chemistry. Metal-catalyzed asymmetric reactions attract much attention in the past few years, and thousands of chiral ligands have been synthesized, however, widely applicable, so-called privileged chiral ligands are still very limited. Therefore, the design and synthesis of highly efficient and selective chiral ligands becomes the most important and challenging goal. Our group is committed to asymmetric catalysis and develope a novel type of C 2-symmetric chiral ligand of N , N ʹ-dioxide amide compounds which is easily synthesized from cheap chiral amino acids and amines. Such conformationally flexible privileged ligands break through the notion of the rigid feature of previously privileged ligands. Naturally, it would guide the creation of new ideal chiral ligands and catalysts. N , N ʹ-dioxides are not only used as bifunctional organocatalysts, but also provide an arsenal of chiral metal complexes upon coordination with a variety of metal salts, such as alkaline-earth metal salts, transition metal salts and rare-earth metal salts. This powerful catalyst system has been proved to be highly effective for more than fifty types of asymmetric reactions with wide substrate generality under mild conditions, including carbon-carbon bond formation, and carbon-heteroatom bond formation reactions. The concerns of controlling chemo-, regio-, and stereoselectivity of involved reactions are well addressed. Some new and challengling asymmetric reactions are realized, for intances, the first asymmetric Roskamp reaction is achieved with a N , N ʹ-dioxide/Sc(III) complex at low catalyst loading, which updates the comment about β-keto esters in text of Organic Chemistry , Oxford, and the reaction is amended as “Roskamp-Feng reaction” in Elsevier’s Organic Synthesis Based on Name Reactions . The asymmetric amination of ketones with α-diazoesters shed light on the diversity of diazo chemistry. N , N ʹ-dioxide/La(III) complex catalyzed sulfa-Michael reaction exhibits very strong chiral amplification effect. N , N ʹ-dioxide/Ni(II) complex acts as both chiral Lewis catalyst and metal-carbene promotor in Doyle-Kirmse reaction, [ 2 , 3 ] -Stevens rearrangement and Sommelet-Hauser rearrangement of a new type of designed α-diazo pyrazoleamides. Such the creation of catalytic systems and catalytic asymmetric methods provide simple, efficient, precise, green access to several biologically active drug molecules and natural products, such as Paroxetine, Pregabalin, Thiazesim, KAE609 and so on. Now, N , N ʹ-dioxides have become commercially available chiral ligands and have been successfully applied by many research groups and companies. The above original and systematic research achievements make important contribution to the chirality science.