Dynamic kinetic asymmetric carbonate

Trost and coworkers have shown that Baylis-Hillman adducts can be efficiently derace-mized by Pd2dba3-CHCl3 catalyzed reaction of the corresponding carbonates 55 with phenols 56 in the presence of chiral C2-symmetric P,N-ligands (Scheme 11) [44], The strategy follows a dynamic kinetic asymmetric transformation process via jr-allyl palladium chemis-... 

It would be preferable to carry out a dynamic kinetic asymmetric transformation on a zirconaaziridine without having to add the inserting reagent slowly. The fact that the enantiomers of 2i interconvert rapidly makes it possible to carry out such a transformation at maximum de (64% with R,R-DPEC) without having to use a syringe pump for addition of the optically active carbonate. 

Zirconaaziridines, which can be prepared in a few steps from commercially available starting materials, have polar Zr-C bonds that permit the insertion of many electrophilic reagents (C=0, C=N) as well as alkynes (C=C) and alkenes (C=C). Appropriate substituents on their ring carbons make zirconaaziridines chiral and raise the possibility of their use in asymmetric synthesis. The lability of their chiral centers distinguishes zirconaaziridines from other organo-metallic reagents and makes it possible for them to undergo dynamic kinetic asymmetric transformations . 

Later work has shown that a dynamic kinetic asymmetric transformation could be obtained if the acetates were converted into carbonate groups. With the tetra(2,2,2-trichloroethyl) carbonate derivative, reactions with carbon and nitrogen nucleophiles gave exclusively the monosubstituted products in high yield (61-95%) and excellent enantiomeric excesses (95-99%). However, car-boxylate nucleophiles afforded the disubstituted products in high yield and enantiomeric excess (eq 7). This allowed an efficient synthesis of D-myo-inositol-l,4,5-trisphosphate to be devised. 

This methodology has been expanded to geranyl methyl carbonate for the synthesis of the vitamin E nucleus, and to tiglyl methyl carbonate for the synthesis of (—)-calanolide A and B. In the latter example, the anthracenyldiamine -based ligand was required for optimum selectivity. The synthesis of (—)-aflatoxin B lactone utilizes a dynamic kinetic asymmetric transformation, whereby a suitably functionalized phenol reacts with a racemic 5-acyloxy-2-(5//)-furanone to provide a single product in 89% yield. One final example of phenol as a nucleophile is for the deracemization of Baylis-Hillman adducts." ... 

One of the routes leading to P-stereogenic phosphines is electrophilic substim-tion at the phosphorus atom of secondary phosphines, as a result of asymmetric catalysis in which a catalyst activates a phosphorus nucleophile or a carbon electrophile, creating an asymmetric environment, i.e., creating preference for one of Si or Re face sides at the reactive center [103-113]. Upon reaction with chiral metal complexes, racemic secondary phosphines are converted into diaste-reomeric metal-phosphide complexes A or B, which interconvert rapidly through the inversion at phosphorus. If the equilibrium A B is faster than the reaction of A or B with an electrophile E, then P-stereogenic phosphines 196, in which pyramidal inversion is slow, can be formed enantioselectively. The product ratio in this dynamic kinetic asymmetric transformation depends both on and on the rate constants ks and (Scheme 63). 

Recently, some elegant work was reported on the preparation of chiral ortho-substituted phenol derivatives through intramolecular chirahty transfer by Trost et al. [64]. Chiral substrate 78 was prepared in excellent enantiomeric excess from phenol and racemic aUyUc carbonate through asymmetric O-aUylation with dynamic kinetic asymmetric transformation. They showed that a europium(lll) tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate) Eu(fod)3-catalyzed rearrangement proceeds at 50 °C to give product 79 with complete chirahty transfer. 

Fig. 8.33 DYKAT of 1,3-diols via lipase-catalyzed acyl-transfer in combination with Ru-catalyzed epimerization of hydroxyl groups. G=chiral carbon, convertible for equilibration and acyl migration, but not for the irreversible step H=chiral carbon, convertible for equilibration, acyl migration and the irreversible step l=chiral carbon, convertible for acyl migration, stable chirality. (From J. Steinreiber, K. Faber, H. Griengl, De-racemization of enantiomers versus de-epimerization of diastereomers-chssification of dynamic kinetic asymmetric transformations (DYKAT), Chemistry 14 (2(X)8), 8060. Copyright 2008 Wiley).

The integration of a catalyzed kinetic enantiomer resolution and concurrent racemization is known as a dynamic kinetic resolution (DKR). This asymmetric transformation can provide a theoretical 100% yield without any requirement for enantiomer separation. Enzymes have been used most commonly as the resolving catalysts and precious metals as the racemizing catalysts. Most examples involve racemic secondary alcohols, but an increasing number of chiral amine enzyme DKRs are being reported. Reetz, in 1996, first reported the DKR of rac-2-methylbenzylamine using Candida antarctica lipase B and vinyl acetate with palladium on carbon as the racemization catalyst [20]. The reaction was carried out at 50°C over 8 days to give the (S)-amide in 99% ee and 64% yield. Rather surpris-... 

Phenols are used as the nucleophile in the asymmetric aUylation of 7r-aUylpalladium complexes. Trost and Toste attained asymmetric phenyl ether formation in high enantiomeric excess (ee) using diphosphine ligand derived from chiral 1,2-cyclohexanediamine (equation 10). Dynamic kinetic resolution of the racemic secondary aUylic carbonate is conducted in the presence of tetrabutylammonium chloride, which increases the rate of ft—a—ft isomerization of the jr-allyl palladium intermediate (equation 11). Lautens and coworkers cleaved meio-oxabicyclic alkenes with phenol in the presence of a catalytic amount of a chiral ferrocenyldiphosphine and a rhodium complex (equation 12). ... 

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