Palladium-catalysed DKR

The stereochemical course for the racemisation could be explained as follows. First, the oxidative addition to the propargylic phosphate gave an allenylpalla-dium(ii) through the back side attack of palladium(0). Thus, this enantio-enriched allenylpalladium(ii) was stereospecifically formed starting from the 

R = Me, Bn, /-Bu, /-Pr,CH20TBDMS ligand = dppe, dppp, dppb, dppf, (R)-BINAP, (S)-BINAP 

In 1999, Trost and Toste introduced the concept of dynamic kinetic asymmetric transformation (DYKAT) which is frequently referred to as DKR, since it involves the equilibration of diastereomeric intermediates generated from the racemic substrates. This concept allows for the transformation of both enantiomers of a racemic substrate in a highly enantio-enriched product. As an example. Trust s group has demonstrated that exposing butadiene monoepoxide and phthalimide to a catalyst formed in situ from a 7i-allylpalladium chloride dimer and a chiral ligand led to the corresponding chiral phthalimide 

Similar conditions were apphed to a palladium-catalysed asymmetric aUyhc alkylation, effecting a DKR transformation of isoprene monoepoxide and a 

In 2010, Cordova s group reported the first examples of one-pot highly chemo- and enantioselective DYKATs based on the reaetions between a,)S-unsaturated aldehydes and propargylated carbon acids, providing the 

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Scheme 4.56 Palladium-catalysed DKRs of phenylglycine amide derivatives.

Scheme 4.60 Palladium-catalysed DKR of 2-phenyl-2-cyclohexenyl acetate.

Scheme 4.61 Palladium-catalysed DKR of acyclic allylic acetates.

In 2007, Glueck s group reported a catalytic DKR process in which secondary phosphines were converted into the corresponding enantio-enriched tertiary phosphines through palladium-catalysed asymmetric hydrophosphination of aryliodides using secondary phosphines. The key intermediates were diaster-eomeric phosphide complexes with chiral ancillary ligands (L Pd PRR ). Their relative rates of P-inversion and phosphorus-carbon bond formation controlled the enantioselectivity of the prodnct formation. As shown in Scheme 2.63, the reaction allowed moderate enantioselectivities of up to 70% ee to be achieved. 

In 1996, Allen and Williams demonstrated that the DKR of allylic acetates could be accomplished through coupling palladium-catalysed racemisation and enzymatic hydrolysis of allylic acetates in buffer solution. However, the DKR under these conditions was limited to cyclohexenyl acetates to yield symmetrical palladium-allyl intermediates. Among them, 2-phenyl-2-cyclohexenyl acetate was the only substrate to have been resolved with good results (81% yield, 96% ee), as shown in Scheme 4.60. 

Many metal catalysts have been reported that effect the racemization step in DKR processes [61]. While various complexes of ruthenium, rhodium, iridium, palladium and other metals are known to catalyse rapid racemization of different substrates, only a few complexes have been found to be compatible with the enzymatic component of the resolution. A suitable catalyst must not interfere... 

Although this type of catalyst was highly active and selective for the race-misation of benzylic amines, the reaction times for DKR were still longer than 24 hours in some cases and small amounts of side products were formed. In order to improve the performance of these palladium catalysts, the group employed microwave irradiation as a heating source, demonstrating that racemisation reactions of benzylic amines under microwave irradiation catalysed by Pd/CaCOs were faster and more selective. Furthermore, they checked that the microwave irradiation had no influence on the activity and... 

In 2009, Andrade et al. demonstrated that the DKR mediated by palladium and lipase could be efficiently applied to selenium-containing amines. As shown in Scheme 4.55, a series of organoselenium-l-phenylethanamines were submitted to DKR catalysed by a combination of Pd/BaS04 and Candida... 

Palladium nanocatalyst [Pd°/AlO(OH)] was shown by Kim et al. to be able to catalyse, in combination with lipase Novozym 435, the DKR of primary benzyl amines. As shown in Scheme 8.74, the corresponding chiral amides were produced in remarkable yields and enantioselectivities ranging from 90 to >99% ee. 

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