I. Heterogeneous cross-coupling reactions catalyzed by nickel-in-charcoal and copper-in-charcoal. II. Asymmetric 1,2/1,4-reductions catalyzed by copper hydride. III. Atropselective synthesis of the biaryl A-B ring system of vancomycin utilizing an internally tethered, nonracemic ligand.

摘要

Homogeneous transition-metal catalyzed cross-coupling reactions evolved as powerful tools in organic synthesis. Yet, a problem encountered in the use of a soluble catalyst is the separation of the catalyst from the reaction products. Oftentimes, that requires special treatment which usually destroys catalysts and increases costs as well. Therefore, the majority of transition-metal catalysts employed in industry are heterogeneous due to ease of removal. One of our group research interests is to develop solid-supported metal catalysts and investigate their applications. Two heterogeneous catalysts, nickel-in-charcoal and copper-in-charcoal, have been developed recently. Both are reusable, inexpensive, and easy to prepare. Most importantly, their high efficiency has been seen in many different types of reactions which are widely used in synthetic community. In this context, microwave-assisted Negishi cross-coupling reactions catalyzed by nickel-in-charcoal, and tandem diazo transfer/click reactions catalyzed by copper-in-charcoal are described.;Enantiomerically enriched diarylmethanols are broadly used as intermediates for the synthesis of physiologically active compounds such as orphenadrine, neobenodine, cetirizine hydrochloride, and CDP-840. Although much effort has been devoted to this emerging area, a general method remains elusive. In this study, asymmetric hydrosilylations of various diaryl ketones are described using CuH ligated to nonracemic ligands as catalysts that can lead to diarylmethanols in high enantioselectivities. In addition to asymmetric 1,2-reduction, CuH-catalyzed 1,4-reduction has been highlighted in the key steps in the asymmetric synthesis of the C-9 epimer of amphidinoketide I.;Axially chiral scaffolds, usually found in biologically active compounds or used as chiral ligands in asymmetric catalysis, are of great interest. It is not surprising that significant advances have been made in the synthesis of axially chiral compounds with enhanced atropselectivity. In our group, a method using a nonracemic tethered liangd as a chiral auxilary to induce high level of atropselectivity in the biaryl formation reaction has been developed successfully. The present study reveals the significant contribution of our chiral auxiliary to the highly atropselective synthesis of the A-B ring system of vancomycin. In the future, more classical and challenging syntheses of axially chiral biaryl compounds can be accessed efficiently using our method.