Asymmetric transfer hydrogenation has become a practically useful tool in reduction chemistry in the last decade or so. This was largely triggered by the seminal work of Noyori and co-workers in the mid-1990s and is driven by its complementing chemistry to hydrogenation employing H2. This Focus Review attempts to present a “holistic” overview on the advances in the area, focusing on the achievements recorded around the last three years. These include more-efficient and “greener” metal catalysts, catalysts that enable hydrogenation as well as transfer hydrogenation, biomimetic and organocatalysts, and their applications in the reduction of CO, CN, and CC bonds. Also highlighted are efforts in the development of environmentally benign and reusable catalytic systems.

Broader, Greener, and More Efficient: Recent Advances in Asymmetric Transfer Hydrogenation

Aqueous-phase asymmetric transfer hydrogenation of ketones--a greener approach to chiral alcohols.

The oxidation of secondary alcohols is one of the most common and well-studied reactions in chemistry. Although excellent catalytic enantioselective methods exist for a variety of oxidation processes, such as epoxidation, dihydroxylation, and aziridination, it is surprising that there are relatively few catalytic enantioselective examples of the ubiquitous alcohol oxidation. In connection with a general program dealing with the discovery of new catalytic oxidation systems, we present herein the development of a catalytic oxidative kinetic resolution of secondary alcohols that uses molecular oxygen as the terminal oxidant (see Scheme 1).

The palladium-catalyzed oxidative kinetic resolution of secondary alcohols with molecular oxygen.

Publisher Summary This chapter describes calculations of nuclear spin–spin couplings. The chapter illustrates that nuclear spin–spin couplings are important NMR parameters and are of considerable interest for both theoreticians and experimentalists. Through the interplay of empirical correlations, theoretical interpretations, the specification of more accurate empirical relationships, and so forth, spin–spin couplings have proven to be an invaluable source of experimental information about the nature of bonding and stereochemistry in solution. The chapter attempts to employ the SI system consistently in all equations. The chapter deals with proton–proton couplings, with proton-other-nucleus couplings, with other couplings involving carbon, and with the remaining couplings. The chapter concludes by discussing nuclear spin–spin interaction energy in isotropic fluids.

Calculations of Nuclear Spin-Spin Couplings

The first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (-)-sparteine as a chiral ligand and molecular oxygen as the stoichiometric oxidant. Mechanistic insights regarding the role of the base and hydrogen-bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting rapid resolutions. The use of chloroform as solvent allows the use of ambient air as the terminal oxidant at 23 °C, resulting in enhanced catalyst selectivity. These improved reaction conditions have permitted the successful kinetic resolution of benzylic, allylic, and cyclopropyl secondary alcohols to high enantiomeric excess with good-to-excellent selectivity factors. This catalyst system has also been applied to the desymmetrization of meso-diols, providing high yields of enantioenriched hydroxyketones.

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The Palladium‐Catalyzed Aerobic Kinetic Resolution of Secondary Alcohols: Reaction Development, Scope, and Applications

The enantioselective dehydrogenation of racemic (R-(+) and S-(−)) α-phenylethanol by RuCl2(PPh3)3 and (+)-neomenthyldiphenylphosphine at 180°C showed constant ratios of kR⁄kS in the absence of benzalacetone. The kR⁄kS value increased almost linearly with the benzalaceton concentration and decreased with the larger amounts of the chiral phosphine under the present reaction conditions.

CATALYTIC ENANTIOSELECTION BY CHIRAL TRANSITION-METAL COMPLEXES. I. DEHYDROGENATION OF RACEMIC α-PHENYLETHANOL BY RuCl2(PPh3)3 AND (+)-NEOMENTHYLDIPHENYLPHOSPHINE

The correlation between the gas-phase proton affinities of aliphatic oxygenated compounds (alcohols, acids, and esters and their electronic structures was investigated by means of an INDO-MO theory. There appears to be a satisfactory linear-dependence of the proton affinities with the energy difference between the parent molecule and the energetically most stable protonated species and with the bond energy of the oxygen-proton bond, although the above energies are overestimated in comparison with the proton affinities. The proton affinities are also predicted with a sufficient accuracy using the first ionization potential and the electron density of the oxygen atom (especially, the % p-character in the oxygen lone-pairs) of the parent molecule.

An INDO Molecular Orbital Approach to the Proton Affinity of Oxygenated Compounds

The inversion barriers of CH3−, NH3, CH3NH2, (CH3)2NH, (CH3)3N, NH2OH, NH2CHO, and OH3+ were investigated by means of the MINDO/2′ method. Although the calculated bond lengths are in satisfactory agreement with the experimental values, the calculated bond angles are too large and resulted in relatively low inversion barriers in comparison with the observed values.

A MINDO/2′-MO Study of the Inversion Barriers of Some Molecules Involving First-Row Atoms

Electronic Structures of Dialkyl Peroxides

Several protonated alcohols, acids, and esters were investigated by means of the INDO-MO theory and in connection with their proton and carbon-13 NMR results. The relative stability of the protonated conformers as detected by the NMR spectroscopy, had a good coincidence with the MO-theory and the experimental results. The proton or carbon-13 chemical shifts and coupling constants also showed satisfactory linear correlations between the theory and the experiment; the proton and isotropic (13C) chemical shifts could be well explained by the linear correlation between the diamagnetic shielding constant and the electron density on the proton of the O–H bond and between the calculated paramagnetic shielding effect and the observed isotropic chemical shifts. The observed coupling constants of the proton and carbon-13 NMR had good overall parallelisms with those evaluated by means of the Fermi contact effect.

Masahide Okada

Papers

CATALYTIC ENANTIOSELECTION BY CHIRAL TRANSITION-METAL COMPLEXES. I. DEHYDROGENATION OF RACEMIC α-PHENYLETHANOL BY RuCl2(PPh3)3 AND (+)-NEOMENTHYLDIPHENYLPHOSPHINE

An INDO Molecular Orbital Approach to the Proton Affinity of Oxygenated Compounds

A MINDO/2′-MO Study of the Inversion Barriers of Some Molecules Involving First-Row Atoms

Electronic Structures of Dialkyl Peroxides

An INDO Molecular-orbital Interpretation of the NMR of Several Protonated Heteroaliphatic Compounds