The Development of Double Axially Chiral Phosphoric Acids and Their Catalytic Transfer Hydrogenation of Quinolines

Asymmetric Catalysis From a Chinese Perspective

et al. 2011

Catalytic asymmetric hydrogenations of prochiral unsaturated compounds, such as olefins, ketones, and imines, have been intensively studied and are considered as a versatile method of the synthesis of chiral compounds due to atom economy and operational simplicity. Since 2002, we mainly focused on synthesis of new phosphorus ligands, asymmetric hydrogenation of heteroaromatic compounds and palladium-catalyzed asymmetric hydrogenation. Significant contribution was made in the Dalian Institute of Chemical Physics. In this chapter, we hope to share our experience and adventure in the development of chiral monophosphite ligands and phosphine-phosphoramidite ligands, asymmetric hydrogenation of heteroaromatic compounds, and the development of new homogeneous palladium catalytic hydrogenation system, which have a wide range of applications in synthesis of chiral compounds.

Section: Adventure In Asymmetric Hydrogenationsupporting

confidence: 59%

Section: Organocatalyzed Asymmetric Transfer Hydrogenation Of Quinolinesmentioning

confidence: 99%

Adventure in Asymmetric Hydrogenation: Synthesis of Chiral Phosphorus Ligands and Asymmetric Hydrogenation of Heteroaromatics

Asymmetric Catalysis From a Chinese Perspective

et al. 2011

“…For 2,3,6-trisubstituted quinolines, the reactions proceeded well, and excellent reactivities with good enantioselectivities were obtained (Table 10.5, entries 9-11). Interestingly, for the cyclic compounds 11l and 11n, excellent reactivities and diastereoselectivities (up to >20: 1, major in cis isomer) were obtained (Table 10.5, entries 12,14), which was complementary for the trans configuration reported by Du using chiral phosphoric acid as catalyst [28]. The successful hydrogenation of 2,3-disubstituted quinolines provided a new evidence for the hydrogenation of quinolines mechanism suggested by them.…”

supporting

confidence: 56%

Enantioselective Reduction of Nitrogen‐Based Heteroaromatic Compounds

Zhou

2010

Chiral Amine Synthesis

Optically active amines are fundamentally important synthetic intermediates and structural components of biologically active natural products, drugs, and pharmaceuticals. Asymmetric hydrogenation of nitrogen-based heteroaromatic compounds is one of the most attractive and efficient approaches to enantiomerically pure amines, especially for numerous saturated or partially saturated chiral cyclic amines, whose synthesis by direct cyclization is often difficult. In the past decades, some progresses have been achieved in the hydrogenation of nitrogen-containing heteroaromatic compounds [1]. For example, quinolines, quinoxalines, pyridines, indoles, and pyrroles have been hydrogenated successfully with over 90% enantiomeric excess (ee). In this chapter, we focus on the synthesis of chiral amines via enantioselective hydrogenation of nitrogen-based heteroaromatic compounds. Asymmetric Hydrogenation of Quinolines Ir-and Ru-Catalyzed Asymmetric Hydrogenation of QuinolinesAmong these studies on asymmetric hydrogenation of nitrogen-based heteroaromatic compounds, the hydrogenation of quinolines was studied extensively and elaborately. In 2003, Zhou and coworkers reported the first highly enantioselective hydrogenation of quinolines with high enantioselectivities [2]. They employed [Ir(COD)Cl] 2 /MeO-BiPhep as catalyst using iodine as additive, while the hydrogenation reaction could not take place in the absence of iodine. Their studies showed that this reaction was highly solvent dependent, and toluene was the best solvent.Subsequently, some commercially available chiral bidentate phosphine ligands were tested for the asymmetric hydrogenation of quinolines, and (S)-MeO-BiPhep was the best ligand with 94% ee (Scheme 10.1). The optimal conditions are [Ir(COD) Cl] 2 /MeO-BiPhep/I 2 in toluene at 700 psi H 2 .

Biomimetic Organic Synthesis

“…Du reported a similar catalytic system, which made use of double axially chiral phosphoric acids 21 in the reduction of 2-substituted quinolines to give the corresponding tetrahydroquinolines with comparable enantioselectivities [37]. For 2-phenylquinoline, aromatic solvents and diethyl ether gave similar results, but for the n-butyl analog diethyl ether proved superior in terms of selectivity.…”

Section: Asymmetric Organocatalytic Reduction Of Quinolinesmentioning

confidence: 68%

Bio‐Inspired Transfer Hydrogenations

Rueping

Schoepke

Atodiresei

et al. 2011

IntroductionThe demand for chiral molecules, particularly those with hydrogen as part of the stereogenic center, has increased in recent years, and intensive research has been carried out in both industry and academia to develop efficient methods for synthesizing such compounds [1]. In this context, significant attention has been devoted to the asymmetric hydrogenation of unsaturated compounds, for example, olefins, carbonyls, and imines, which is recognized as one of the most important and convenient routes to the corresponding optically active products [2]. So far, most of the enantioselective reductions rely on biological processes or transition metal catalyzed high-pressure hydrogenations, hydrosilylations, and transfer hydrogenations. Beside their high substrate specificity, the enzymatic processes sometimes suffer from undesired by-products, poor catalyst stability under the operational conditions, substrate and/or product inhibition, and problems with catalyst recovery. Likewise, despite the high reactivity and selectivity exhibited by the organometallic complexes employed in the metal-catalyzed processes, most of these protocols suffer from a limited number of substrates and difficulties with catalyst separation and recycling. Hence, an alternative approach to these chiral compounds would be of great value. Nature's Reductions: Dehydrogenases as a Role ModelEnzymes are catalysts that evolve in Nature and one of their characteristics is high selectivity. During biochemical transformations, enzymes are assisted by non-proteinogenic molecules called co-factors. For instance, nicotinamide adenine dinucleotide (NADH), one of the essential co-factors in Nature, serves as a hydride source for various biological reductions. The synthesis of the amino acid glutamate by the glutamate dehydrogenase (GDH) catalyzed reductive amination of 2-ketoglutarate represents one example (Equation 22.1). The reaction is reversible Biomimetic Organic Synthesis, First Edition. Edited by Erwan Poupon and Bastien Nay.