Palladium deracemization

The first example of chemoenzymatic DKR of allylic alcohol derivatives was reported by Williams et al. [37]. Cyclic allylic acetates were deracemized by combining a lipase-catalyzed hydrolysis with a racemization via transposition of the acetate group, catalyzed by a Pd(II) complex. Despite a limitation of the process, i.e. long reaction times (19 days), this work was a significant step forward in the combination of enzymes and metals in one pot Some years later, Kim et al. considerably improved the DKR of allylic acetates using a Pd(0) complex for the racemization, which occurs through Tt-allyl(palladium) intermediates. The transesterification is catalyzed by a lipase (Candida antarctica lipase B, CALB) using isopropanol as acyl acceptor (Scheme 5.19) [38]. 

Scheme 8E.27. Deracemization by alkylation of (2-Aza-7i-allyl)palladium complex.

Quaternary stereocentres in /3-keto esters have been deracemized in an enantio-convergent decarboxylative allylation process, catalysed by palladium(II).202 One catalyst is involved in both C-C bond-breaking and -making steps. 

Scheme 11. Palladium-catalyzed deracemization of Baylis-Hillman adducts (Trost et ai).

The development of efficient, asymmetric versions of the Baylis-Hillman-reaction for the synthesis of enantiomerically pure a-methylene-/ -hydroxycarbonyl and related compounds is still a rewarding issue. Interesting recent approaches for the solution of this problem include the use of chiral Michael acceptors or aldehyde/aldimine components. The use of stoichiometric or catalytic amounts of chiral base is also of great current importance. Besides the development of an asymmetric version of the Baylis-Hillman-reaction, alternative reaction sequences giving nonracemic Baylis-Hillman-adducts have attracted considerable attention. Likewise, the recently reported Palladium-catalyzed deracemization of Baylis-Hillman-adducts appears to be promising. Besides stereoselectivity, the low rate and chemical yields often observed in Baylis-Hillman reactions remain important issues to be carefully addressed in all future studies. 

Reactions with Oxygen Nucleophiles. The hist report of the reaction of oxygen nucleophiles was for the deracemization of cyclic allylic ethers, for example, the palladium(0)-catalyzed reaction of 2-cyclohexeny 1-1 -methyl carbonate with sodium pivalate afforded the pivalate ester in 94% yield and 92% ee. This reaction was extended to other cyclic allylic carbonates. 

With their efficient procedure for deracemization of MBH adducts, Trost and coworkers have applied dynamic asymmetric kinetic transformation (DYKAT) to the total synthesis of furaquinodn E. As shown in Scheme 5.28, the asymmetric palladium-catalyzed alkylation of phenols combined with a reductive Heck reaction delivered an effident approach to the synthesis of the key synthon, which is the core structure of the furaquinocins. A general synthetic route to furaquinocin E was established in 14 steps from MBH adduct 159. Their work highlighted the ability to use racemic MBH adducts for asymmetric synthesis. They further extended the scope of their strategy by developing the synthesis of three more analogs of... 

Recently, Maulide el al. have presented another deracemization process in which the product has more than one stereogenic element and therefore allows the existence of different diastereomers. Each and every one of the four different stereoisomeric products (for diethyl(butyl)malonate enolate as the nucleophile) could be prepared from the racemic ds-cyclobutene lactone 61 with high selectivity by employing the Hgands LI, en Ll, 12, and mt-L2 (Scheme 12.30). The observed overall inversion in the presence of ligand L2 (and mt-L2) is thought to be a result of stereoretentive it-allyl generation caused by internal coordination of the carboxylate, followed by classical nucleophilic attack on the opposite side of palladium [51]. 

The chiral synthesis of allylic alcohols has been the focus of many research works due to the high versatility of these molecules in the preparation of many active com-poimds [58,82], Allen and Williams reported the first example of DKR of allylic alcohols via lipase-palladium catalyst coupling deracemization of cyclic allylic acetates [83]. However, the accumulation of secondary products, as well as the long reaction times required, limited the use of this strategy. 

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