Dynamic resolution allylic alcohol

Berkessel and co-workers have demonstrated the utility of the bifunctional cyclohexane-diamine catalysts in the dynamic kinetic resolution of azalactones (Schemes 60 and 61) [111, 112]. The authors proposed that the urea/thiourea moiety of the catalyst coordinates and activates the electrophilic azlactone. The allyl alcohol nucleophilicity is increased due to the Brpnsted base interaction with the tertiary amine of the catalyst. 

Kinetic and Dynamic Kinetic Resolution of Allylic Alcohols... 

J. H. Koh, and J. Park, Dynamic kinetic resolution of allylic alcohols mediated by ruthenium- and lipase-based catalysts,... 

Akai S, Tanimoto K et al (2006) A dynamic kinetic resolution of allyl alcohols by the combined use of lipases and [VO(OSiPh3)3]. Angew Chem Int Ed 45 2592-2595... 

In the course of our earlier studies on terpenylboranes we developed a simple transformation of a- into 3-pinene," and a stereoselective synthesis of allylic alcohols by the reduction of vinylic epoxides.12 An extension of these studies to contrathermo-dynamic isomerization of a-thujene, 2- and 3-carene,13 and kinetic resolution of vinylic epoxides by the reduction with terpenylboranes,14 is described. 

The first example of the use of enzyme and metal combinations to provide a dynamic resolution procedure was reported by Allen and Williams in 1996[18. In this case, a palladium (II) catalyst was employed that was able to racemize the allylic acetate substrate, but did not erode the enantioselectivity of the product allylic alcohol (Fig. 9-11). For example, a cyclic acetate was shown to undergo a simple kinetic resolution, affording enantiomerically enriched starting material and product at approximately 50 % conversion. However, performing the reaction in the presence of a palladium (II) catalyst facilitated a dynamic resolution by continuously racemiz-ing the starting material as the reaction progressed. 

Another ruthenium catalyst was used for the dynamic kinetic resolution of allylic alcohols [reaction (24)] by acylation yielding allylic acetates. Again a redox process should be responsible for the racemization. 

An elegant example for a dynamic resolution of an allylic alcohol via enantiose-lective ester hydrolysis is depicted in Scheme 2.66 [463]. Thus, Pseudomonas sp. lipase hydrolyzed the acetate ester with high specificity, while the in-situ racemiza-tion of the substrate enantiomers was effected by a catalytic amount of Pd leading to the product alcohol in 96% e.e. and 81% yield. However, the lipase has to be chosen with great care, since other hydrolytic enzymes such as acetylcholine esterase and lipases from Penicillium roqueforti, Rhizopus niveus, and Chromobacterium viscosum were incompatible with the metal catalyst. 

Scheme 2.66 Dynamic resolution of an allylic alcohol ester using Pseudomonas sp. lipase and catalysis...

Bogar, K., Vidal, P.H., Leon, A.R.A., and Baeckvall, J.-E. (2007) Chemoenzymatic dynamic kinetic resolution of allylic alcohols a highly enantioselective route to acyloin acetates. Org. Lett., 9 (17), 3401-3404. 

Scheme 19.3 Dynamic kinetic resolution of an O-acylated allylic alcohol based on palladium-catalyzed racemization and enzymatic ester hydrolysis.

Moreover, the same authors employed a closely related organocatalyst and the corresponding urea derivative to promote the enantioselective dynamic kinetic resolution of azalactones with allylic alcohol. In this case of substrates, the urea derivatives proved to be superior to their thiourea analogues and, most usefully, these catalysts were insensitive to the steric bulk of the amino acid residue, allowing alanine-, methionine- and phenylalanine-derived azalactones to undergo dynamic kinetic resolution with unprecedented levels of enantioselectivity, as shown in Scheme 9.4. Furthermore, the compatibility of these catalysts with thiol nucleophiles was exploited in the first enantioselective catalytic dynamic kinetic resolution of azalactones by thiolysis to furnish enantioenriched amino acid thioesters of potential use with moderate enantioselectivities (<64% ee). 

Thiourea catalyst turned out to be effective for the kinetic resolution Berkessel et al. have found enantioselective dynamic kinetic resolution of azlactones, leading to natural and unnatural amino acid derivatives with excellent enantioselectivity. On treatment of an azlactone with allyl alcohol in the presence of 5 mol% of (9) led to the ring opening and the corresponding ester was obtained in high ee. NMR spectroscopic experiments elucidated the formation of a substrate-catalyst complex (19) (Figure 2.21) [113]. 

Lihammar, R., Millet, R., and BackvaU, J.-E. (2013). Enzyme- and rutheniumdynamic kinetic resolution of functionalized cyclic allylic alcohols. /. Org. Chem., 78, 12114-12120. 

Akai, S. (2014). Dynamic kinetic resolution of racemic allylic alcohols via hydrolase-metal combo catalysis An effective method for the synthesis of optically active compounds. Chem. Lett., 43,746-754. 

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