Enantioselective catalytic isomerisation

An elegant example of a highly efficient catalytic asymmetric synthesis is the Takasago process [128] for the manufacture of 1-menthol, an important flavour and fragrance product. The key step is an enantioselective catalytic isomerisation of a prochiral enamine to a chiral imine (Fig. 1.44). The catalyst is a Rh-Binap complex (see Fig. 1.44) and the product is obtained in 99% ee using a sub-strate/catalyst ratio of 8000 recycling of the catalyst affords total turnover numbers of up to 300000. The Takasago process is used to produce several thousand tons of 1-menthol on an annual basis. 

L = P(CH3)3 or CO, oxidatively add arene and alkane carbon—hydrogen bonds (181,182). Catalytic dehydrogenation of alkanes (183) and carbonylation of bensene (184) has also been observed. Iridium compounds have also been shown to catalyse hydrogenation (185) and isomerisation of unsaturated alkanes (186), hydrogen-transfer reactions, and enantioselective hydrogenation of ketones (187) and imines (188). 

From the viewpoint of industrial utilisation, a major breakthrough in catalytic asymmetric synthesis was the discovery of the BINAP-Rh catalysed enantioselective isomerisation of prochiral allylic amines [35, 36], which led to the Takasago process for production of 1-menthol (Scheme 7.7). An annual production of over 1500 tonnes makes this by far the world s largest scale and most important example of asymmetric synthesis. 

Another novel extension of asymmetric organocatalysis was reported by Hintermann and Schmitz towards the successful development of an organo-catalytic enantioselective double-bond isomerisation, which has been previously associated with the field of metal catalysis. Therefore, an asymmetric synthesis of the 2,5-diphenylphosphol-2-ene fragment was achieved via the enantioselective cinchonine-catalysed double-bond isomerisation of a wc50-2,5-diphenyl-phosphol-3-ene amide into a 2,5-diphenylphosphol-2-ene amide with an enantioselectivity of up to 83% ee (Scheme 10.10). This new asymmetric concept opened the way to a catalytic enantioselective synthesis of 2,5-diarylphospho-lane building blocks for many applications in transition metal catalysis. 

In 2013, Terada and Toda reported a relay catalysis for a ternary reaction sequence composed of double bond isomerisation, protonation of the double bond, and enantioselective Pictet-Spengler-type cyclisation, which was accomplished using a binary catalytic system consisting of a ruthenium hydride complex and a chiral phosphoric acid. As shown in Scheme 7.47, the intramolecular reaction of allylamides led to the corresponding chiral tetrahydroisoquinoline derivatives in moderate to good yields and insufficient enantioselectivities of 18 to 53% ee. 

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