Chiral Amines from Transition‐Metal‐Mediated Hydrogenation and Transfer Hydrogenation

Abstract

This chapter focuses specifically on the synthesis of amines of the form HNR Ã R 1 , NR Ã R 1 R 2 , and HN(X)R Ã (R Ã ¼ chiral alkyl group; R 1 , R 2 ¼ alkyl or aryl groups; X ¼ heteroatom such as N, S, or P) via the asymmetric hydrogenation of imines, enamines, and iminiums. Thus, we will discuss the formation of amines that have (i) chirality a to the nitrogen, and (ii) no carbonyl group a to nitrogen. Many reported examples of this reaction use substrates with C¼N moieties in a ring, so cyclic amines will receive considerable attention. We will discuss in detail the formation of chiral amines using the asymmetric reduction of aza-aromatic substrates, which has been a popular topic in recent years, and will cover the use of N-carbonyl groups to facilitate this reaction. However, the hydrogenations of nonaromatic a,b-unsaturated amides will not be discussed. Though chiral amides (HN(R Ã )C(O)R 1 ) can be produced highly enantioselectively using these reactions, the sheer number of publications on the topic places it outside the scope of this chapter. These hydrogenations are, however, well covered in a number of existing books and review articles [1]. In addition, we will not cover the related process, reductive amination, which is discussed elsewhere in this book.6.2 Chiral Amines with a Disubstituted Nitrogen Atom, HNR Ã R 1 Direct Asymmetric Hydrogenation of Alkyl-and Aryl-Substituted IminesThough less developed than the analogous reductions of olefins and ketones, the iridium-catalyzed asymmetric hydrogenation of imines (especially N-benzyl and Naryl amines) has received considerable study. It has therefore been the subject of

Oxidoreductase-Catalyzed Synthesis of Chiral Amines

“…Until recently, transition-metal-mediated homogeneous catalysis and organo-catalytic methods were the main chemical strategies for the enantioselective reductions. ,− However, the application of expensive and toxic metals and the requirement of several deprotection steps are the major challenges faced by chemical methods. , Also, chemically catalyzed imine hydrogenation methods require the starting ketone to react with the activated groups of nitrogen sources …”

Asymmetric Hydrogenation of β-Aryloxy/Alkoxy Cinnamic Nitriles and Esters

“…Substrates containing an alkoxyl group, such as MeO, i PrO, and CF 3 CH 2 O, were completely converted to the desired products with high enantioselectivities, 90–97% ee. Notably, the substrates bearing N or P heteroatoms, 1q and 1r , could also be hydrogenated to the chiral amine and phosphate with full conversions and excellent enantioselectivities (97% ee and 99.5% ee, respectively), which could be used as chiral auxiliaries, resolving reagents and building blocks for synthesis of a variety of natural products, pharmaceuticals, and biologically active compounds …”