Hydrogenation is a core technology in chemical synthesis. High rates and selectivities are attainable only by the coordination of structurally well-designed catalysts and suitable reaction conditions. The newly devised [RuCl(2)(phosphane)(2)(1,2-diamine)] complexes are excellent precatalysts for homogeneous hydrogenation of simple ketones which lack any functionality capable of interacting with the metal center. This catalyst system allows for the preferential reduction of a C=O function over a coexisting C=C linkage in a 2-propanol solution containing an alkaline base. The hydrogenation tolerates many substituents including F, Cl, Br, I, CF(3), OCH(3), OCH(2)C(6)H(5), COOCH(CH(3))(2), NO(2), NH(2), and NRCOR as well as various electron-rich and -deficient heterocycles. Furthermore, stereoselectivity is easily controlled by the electronic and steric properties (bulkiness and chirality) of the ligands as well as the reaction conditions. Diastereoselectivities observed in the catalytic hydrogenation of cyclic and acyclic ketones with the standard triphenylphosphane/ethylenediamine combination compare well with the best conventional hydride reductions. The use of appropriate chiral diphosphanes, particularly BINAP compounds, and chiral diamines results in rapid and productive asymmetric hydrogenation of a range of aromatic and heteroaromatic ketones and gives a consistently high enantioselectivity. Certain amino and alkoxy ketones can be used as substrates. Cyclic and acyclic alpha,beta-unsaturated ketones can be converted into chiral allyl alcohols of high enantiomeric purity. Hydrogenation of configurationally labile ketones allows for the dynamic kinetic discrimination of diastereomers, epimers, and enantiomers. This new method shows promise in the practical synthesis of a wide variety of chiral alcohols from achiral and chiral ketone substrates. Its versatility is manifested by the asymmetric synthesis of some biologically significant chiral compounds. The high rate and carbonyl selectivity are based on nonclassical metal-ligand bifunctional catalysis involving an 18-electron amino ruthenium hydride complex and a 16-electron amido ruthenium species.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820010105%2940%3A1%3C40%3A%3AAID-ANIE40%3E3.0.CO%3B2-5

Asymmetric Catalysis by Architectural and Functional Molecular Engineering: Practical Chemo‐ and Stereoselective Hydrogenation of Ketones

1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral Auxiliaries in Asymmetric Synthesis

Large-scale oxidations in the pharmaceutical industry.

Asymmetric Synthesis of Active Pharmaceutical Ingredients

Large-Scale Carbonyl Reductions in the Pharmaceutical Industry

A practical enantioselective synthesis of .alpha.,.alpha.-diaryl-2-pyrrolidinemethanol. Preparation and chemistry of the corresponding oxazaborolidines

An asymmetric synthesis of MK-0417. Observations on oxazaborolidine-catalyzed reductions

5,6-Dihydro-4-(R-amino)-4H-thieno[2,3-b]-thiopyran-2-sulfonamide-7,7-dioxide is a potent carbonic anhydrase inhibitor useful in the treatment of ocular hypertension and glaucoma. The S-(+)-enantiomer of that compound, the more active enantiomer, is prepared by a process involving an intermediate step of an enantioselective reduction of a carbonyl group employing an oxazaborolidine chiral catalyst.

Enantiospecific synthesis of s-(+)-5,6-dihydro-4-(r-amino)-4h-thieno[2,3-b] thiopyran-2-sulfonamide-7,7-dioxide

(s)-tetrahydro-1-methyl-3,3-diphenyl-1h, 3h-pyrrolo-1,2-c1,3,2oxazaborole-bor ane complex : (boro, trihydro(tetrahydro-1-methyl-3,3-diphenyl-1h, 3h-py rrolo-1,2-c1,3,2oxazaborol e-n7)-, 1-4-(3as-cis)-)

Julie J. Mohan

Papers

A practical enantioselective synthesis of .alpha.,.alpha.-diaryl-2-pyrrolidinemethanol. Preparation and chemistry of the corresponding oxazaborolidines

An asymmetric synthesis of MK-0417. Observations on oxazaborolidine-catalyzed reductions

Enantiospecific synthesis of s-(+)-5,6-dihydro-4-(r-amino)-4h-thieno[2,3-b] thiopyran-2-sulfonamide-7,7-dioxide

(s)-tetrahydro-1-methyl-3,3-diphenyl-1h, 3h-pyrrolo-1,2-c1,3,2oxazaborole-bor ane complex : (boro, trihydro(tetrahydro-1-methyl-3,3-diphenyl-1h, 3h-py rrolo-1,2-c1,3,2oxazaborol e-n7)-, 1-4-(3as-cis)-)

A Practical Enantioselective Synthesis of α,α-Diaryl-2- pyrrolidinemethanol. Preparation and Chemistry of the Corresponding Oxazaborolidines.