Isomerisations enantioselective

Similar isomerisation reactions have been apphed to other substrates with very high enantioselectivities for many trisubstituted allylic amines. In general, the rearrangement of allylic alcoholsand ethers provides lower enantioselectivity. However, higher ees have been obtained in the isomerisation of cyclic acetals and the desymmetrisation of 4,7-dihydro-1,3-dioxepins such as (12.06) occurs with up to 92% ee in the presence of the nickel-DUPHOS catalyst (12.07). Unfunction-alised alkenes have been isomerised enantioselectively using a titanocene catalyst. ... 

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). 

The intermolecular Pauson-Khand reaction of the resulting S/P-cobalt complexes with norbornadiene was studied under thermal and A -oxide activation conditions. Thus, heating the diastereomerically pure complex (R = Ph, R = Cy) with ten equivalents of norbornadiene at 50 °C in toluene afforded the corresponding exo-cyclopentenone in a quantitative yield and with an enantio-selectivity of 99% ee. Under similar conditions, the analogous trimethylsilyl complex (R = TMS, R = Cy) afforded the expected product in a high yield but with a lower enantioselectivity of 57% ee. In order to increase this enantio-selectivity, these authors performed this reaction at room temperature in dichloromethane as the solvent and in the presence of NMO, which allowed an enantioselectivity of 97% ee to be reached. These authors assumed that the thermal activation promoted the isomerisation of the S/P ligand leading to a nonstereoselective process. 

The synthesis of menthol is given in the reaction scheme, Figure 5. 6. The key reaction [2] is the enantioselective isomerisation of the allylamine to the asymmetric enamine. It is proposed that this reaction proceeds via an allylic intermediate, but it is not known whether the allyl formation is accompanied by a base-mediated proton abstraction or hydride formation. 

Enantioselective isomerisation of the 4,7-dihydro-1,3-dioxepine 232 to (R)-(-)-233 has been achieved using (R,R)-(+)-CHIRAPHOS-(and (R,R)-(-)-Me-DuPHOS-) modified nickel complexes [01AG(E)177],... 

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. 

Aromatic modified oligonucleotides have been used in photochemical reactions, in one case to act as a photochemical switch, in other cases for cleavage reactions. Azobenzene derivatives in ODNs have been used as a molecular switch by taking advantage of the cistrans isomerisation by UV light. The azobenzene moiety has now been introduced into ODNs on an enantioselective-... 

Plant cells show an extensive repertoire of chemical reaction mechanisms epoxi-dation, reduction, oxidation, hydroxylation, isomerisation. It is self-evident that plant cell cultures synthesize as enantioselectively as their mother organisms. Besides the well-known flavour extracts and single substances, also presently unknown naturally flavour chemicals and mixtures of these are in principle obtainable. Therefore the rapid progress in investigating this area is not surprising [26],... 

The isomerisation of allyhc amines into the corresponding enamines is an excellent example of asymmetric catalysis, which has been exploited on a commercial basis. The isomerisation of the aUylamine (12.01) with a rhodium/BINAP complex occurs with excellent yield and enantioselectivity to give the enamine (12.02) as the initial product. ... 

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. 

The BINAP-Rh complex catalyses enantioselective isomerisation of diethylgeranylamine to citronella diethylenamine, which proceeds in 96-99% optical yield, which is the key step (Scheme 7.7). 

Fluorescence spectroscopy-based biophysical studies of the interactions of 9, 43 and 44 with phospholipid vesicles (PLVs) demonstrated their propensity to bind to membranes, supporting the theory that these compounds are located in the cell membrane of the producing mollusc. The photochemical isomerisation and electrocyclisation reactions of the precursors 43 and 44 to form tridachiahydropyrone (9) were conducted in the PLVs. The racemic nature of the product isolated from these experiments indicates that if the cell membrane is the biological site of this transformation, then any enantioselectivity conferred in the natural system must be due to the presence of other bilayer components, such as integral membrane proteins, not present in the membrane models here used. This raises a limitation of liposomes as models of biological membranes—they are very simplistic versions of a far more complex system (Fig. 5.1). 

In 2007, Frauenrath and Flock described the double bond isomerisation of 5-methyl-4//-l,3-dioxin performed upon catalysis with [Nil2(i ,i )-Me-DU-PHOS], which afforded the corresponding chiral dioxins in excellent enantioselectivities of up to 95% ee, along with good yields (Scheme 10.18). These products were further aziridinated and then ring-opened to lead to chiral 4-methyl-l,3-oxazolidine-4-carbaldehydes with 73% de. 

On the other hand, Hayashi et al. have reported the highly enantio-selective formal [3 + 3] cycloaddition of a,p-unsaturated aldehydes with ene-carbamates catalysed by diphenylprolinol silyl ether as an organocatalyst. This reaction consisted of four consecutive reactions including an asymmetric ene reaction, an isomerisation from an imine into an enecarbamate, a hydrolysis and a hemiacetal formation in one pot to afford synthetically important chiral piperidine derivatives with excellent enantioselectivities of up to 99% ee, good yields and moderate to good diastereoselectivities, as shown in Scheme 6.22. 

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. 

In 2010, Jorgensen et al. developed an enantioselective tandem reaction of propargylated malononitriles with cyclic enones sequentially catalysed by a cinchona alkaloid-derived primary amine catalyst in the presence of (J )-mandelic acid as an additive for the first Michael step, and a gold catalyst for the second tandem exo-dig cyclisation-isomerisation reaction. " As shown in Scheme 7.62, the corresponding chiral bicyclic enones were achieved in good yields and high enantioselectivities of up to 96% ee, albeit low to moderate diastereoselectivities (34-66% de). 

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