Oxidative stress: Free radical production in neural degeneration

Asymmetric hydrogenation of olefins is one of the most useful reactions for the synthesis of optically active compounds, especially in industry. However, the application range of the catalysts developed so far is limited to alkenes with a coordinating functional group or an aryl substituent next to the double bond. We have found a class of chiral iridium catalysts that give high enantioselectivity in the hydrogenation of unfunctionalized, trialkyl-substituted olefins. Because these catalysts do not require the presence of any particular functional group or aryl substituent in the substrate, they considerably broaden the scope of asymmetric hydrogenation.

https://science.sciencemag.org/content/sci/311/5761/642.full.pdf

Asymmetric hydrogenation of unfunctionalized, purely alkyl-substituted olefins.

Water- and fat-soluble vitamins are essential for human and animal nutrition. Several of them are produced in amounts of well above 1000 t annually worldwide. In this highly competitive field, catalytic methods represent ideal tools to lower production costs, and consequently gain an economical advantage, by the application of environmentally benign processes. Examples of industrially important transformations given in this review are grouped by reaction types, e.g. hydrogenation, oxidation and various alkylation, rearrangement, cycloaddition, and esterification reactions.

Catalytic processes in vitamins synthesis and production

Palladium‐Catalyzed Enantioselective Domino Reaction for the Efficient Synthesis of Vitamin E

Chiral iridium complexes with bicyclic pyridine-based N,P ligands have emerged as efficient catalysts for the enantioselective hydrogenation of unfunctionalized trialkyl-substituted olefins. Optimization of the reaction conditions by variation of the solvent, pressure, and temperature led to enantiomeric excesses of up to 99%. Three pure alkenes, (E)-2-cyclohexyl-2-butene and (E)- and (Z)-3,4-dimethyl-2-pentene were converted into the corresponding chiral alkanes with 97%, 94%, and 93% ee, respectively. Hydrogenation of the three C=C bonds of both α- and γ-tocotrienyl acetate led to α- and γ-tocopheryl acetate with very high diastereoselectivity. The same catalysts were successfully applied in the hydrogenation of trisubstituted alkenes with a carboxylic ester or a keto group in the γ position. This reaction was used as a key step in a highly enantioselective synthesis of the pheromone of the caddisfly Hesperophylax occidentalis. The hydrogenation of a structurally analogous allylic alcohol also gave high enantioselectivities.

Iridium-catalyzed asymmetric hydrogenation of unfunctionalized tetrasubstituted olefins.

All eight stereoisomers of α-tocopheryl acetate have been synthesized in a state of high chemical and stereoisomeric purity. Key chiral side-chain intermediates were prepared from (+)-(S)-3-hydroxy-2-methylpropanoic acid. New routes to (2R, 4′ RS, 8′ RS)-α-tocopheryl acetate, a mixture of four diastereoisomers, were also developed. A sensitive gas chromatographic method was developed to determine the diastereoisomeric and enantiomeric purity of α-tocopherol samples as the methyl ethers. It was established for the first time that naturally occurring α-tocopherol is essentially a single enantiomer (2 R, 4′ R, 8′ R), synthetic all-rac-α-tocopherol an equimolar mixture of four racemates, and that natural (E)-(7 R, 11 R)-phytol is diastereoisomerically and enantiomerically homogeneous.

Total Synthesis of All Eight Stereoisomers of α‐Tocopheryl Acetate. Determination of their diastereoisomeric and enantiomeric purity by gas chromatography

TOTAL SYNTHESIS OF ALL EIGHT STEREOISOMERS OF α-TOCOPHERYL ACETATE. DETERMINATION OF THEIR DIASTEREOISOMERIC AND ENANTIOMERIC PURITY BY GAS CHROMATOGRAPHY

Clifford G. Scott

Papers

Total Synthesis of All Eight Stereoisomers of α‐Tocopheryl Acetate. Determination of their diastereoisomeric and enantiomeric purity by gas chromatography

TOTAL SYNTHESIS OF ALL EIGHT STEREOISOMERS OF α-TOCOPHERYL ACETATE. DETERMINATION OF THEIR DIASTEREOISOMERIC AND ENANTIOMERIC PURITY BY GAS CHROMATOGRAPHY