Palladium-catalyzed kinetic resolution

Scheme 8.10 Schematic representation of the palladium-catalyzed kinetic resolution of rac-CHA using SUPRAphos ligands.

Finally for this section, as another asymmetric synthesis of cycliphelitol (1), the synthetic effort of Trost s group will be introduced [52]. Their synthesis was conducted based on the palladium-catalyzed kinetic resolution of racemic conduritol B tetraacetate ( )-94. Since racemic... 

Gais H, Jagusch T, Spalthoff N, Gerhards F, Frank M, Raabe G. Highly selective palladium catalyzed kinetic resolution and enantioselective substitution of racemic allylic carbonates with sulfur nucleophiles asymmetric synthesis of allylic sulfides, allylic sulfones, and allylic alcohols. Chem. Eur. J. 2003 9 4202-A221. 

Palladium(0)-catalyzed kinetic resolution of racemic ally acetate 15 which gives rise to unsym-metrically 1,3-disubstituted zr-allyl complexes has been attempted using 0.5 equivalents of sodium azide in the presence of ferrocenylphosphine (R,pS)-BPPFA (B)40. The optical purities of both the resulting ally azide (.S )-16 and the unreacted starting material (A)-15 are close to zero. 

In 2003, Sigman et al. reported the use of a chiral carbene ligand in conjunction with the chiral base (-)-sparteine in the palladium(II) catalyzed oxidative kinetic resolution of secondary alcohols [26]. The dimeric palladium complexes 51a-b used in this reaction were obtained in two steps from N,N -diaryl chiral imidazolinium salts derived from (S, S) or (R,R) diphenylethane diamine (Scheme 28). The carbenes were generated by deprotonation of the salts with t-BuOK in THF and reacted in situ with dimeric palladium al-lyl chloride. The intermediate NHC - Pd(allyl)Cl complexes 52 are air-stable and were isolated in 92-95% yield after silica gel chromatography. Two diaster corners in a ratio of approximately 2 1 are present in solution (CDCI3). 

The allenyl carboxylate 35 was obtained in an enantiomerically enriched form by the palladium-catalyzed reduction of the racemic phosphate 34 using a chiral proton source [53]. The two enantiomers of the (allenyl)samarium(III) intermediate are in rapid equilibrium and thus dynamic kinetic resolution was achieved for the asymmetric preparation of (i )-35 (Scheme 3.18). 

The groups of Sigman and Stoltz have concurrently published the palladium-catalyzed oxidative kinetic resolution of secondary alcohols using molecular oxygen as the stoichiometric oxidant. Both communications also described a single example of a diol desymmetrization using a palladium catalyst in the presence of (—(-sparteine [Eqs. (10.42) ° and (10.43) ] ... 

Palladium-Catalyzed Allylic Alkylation of Sulfur and Oxygen Nucleophiles -Asymmetric Synthesis, Kinetic Resolution and Dynamic Kinetic Resolution... 

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-... 

A 1,3-substituted allene, which has axial chirality instead of carbon central chirality, has been prepared by a palladium-catalyzed cross-coupling of 4,4-dimethylpenta-l,2-dienylzinc chloride (83) with phenyl iodide (5c) or by that of l-bromo-4,4-dimethylpenta- 1,2-diene (84) with phenylzinc chloride [60] (Scheme 8F.20). The highest enantiomeric purity (25% ee) of the allene (S)-85 was obtained in the former combination with (f ,/ )-diop (1) as chiral ligand. It is interesting that the enantiomeric purity was independent of the ratio of the reagents though the reaction seems to involve a kinetic resolution of the racemic 83. 

Chiral N-arylated imidazolinylidene ligands have been employed in the palladium(II) catalyzed aerobic oxidation of secondary alcohols to the corresponding ketones [55]. The chiral variant of this reaction, which does not generate a new element of chirality, is again based on the kinetic resolution of racemic mixtures. The active catalyst is formed in situ by a combination of two precursors, a dinuclear NHC-palladium(II) complex and an achiral (acetate) or chiral base ((-)-sparteine) (Scheme 18). 

M. T. Reetz, K. Schimossek, Lipase-catalyzed dynamic kinetic resolution of chiral amines use of palladium as the racemiza-tion catalyst, Chimia 1996, 50, 668. 

Examples of electrophilic addition of secondary phosphines to alkenes or alkynes were described. [114, 124, 125, 135]. Glueck [124-126] reported enantioselective tandem reaction of alkylated/arylation of primary phosphines catalyzed by platinum complex, proceeding with formation of chiral phosphaace-naphthenes. Palladium-catalyzed hydrophosphination of alkynes 219 tmder kinetic resolution conditions gave access to 1,1-disubstituted vinylphosphine boranes 220. However, despite screening several chiral ligands, temperatures, and solvents, the... 

Aryl alcohols are competent nucleophiles in the palladium-catalyzed dynamic kinetic asymmetric transformation (DYKAT) of racemic MBH derivatives. As an extension of this strategy, the palladium-catalyzed intramolecular DYKAT of MBH adducts was further explored. As shown in Scheme 4.96, reactions were carried out in dioxane at 25 °C with chiral ligand affording 300 in up to 45% yields and 98% ee via a highly selective kinetic resolution interestingly, when reactions were performed at 80 °C, up to 94% yield with 91% ee of 300 was obtained by the DYKAT process. 

The second example involves the kinetic resolution of racemic secondary alcohols, a process that also has been used in a total synthesis. As illustrated in Figure 14.27, the naturally occurring tricyclic diamine sparteine, in combination with palladium dichloride and oxygen as the terminal oxidant, catalyzes the oxidation of one enantiomer of the race mic benzylic alcohol to the ketone faster than it oxidizes the other enantiomer. The desired unreacted alcohol was isolated in 47% yield with 99% ee (s > 47) and was subsequently transformed to (+)-amurensinine. ... 

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

Ferreira, E. and Stoltz, B. (2001). The Palladium-Catalyzed Oxidative Kinetic Resolution of Secondary Alcohols with Molecular Oxygen. J. Am. Chem. Soc., 123, pp. 7725-7726. 

Bagdanoff, J. and Stoltz, B. (2004). Palladium-Catalyzed Oxidative Kinetic Resolution with Ambient Air as the Etoichiometric Oxidation Gas, Angew. Chem. Int. Ed., 43, pp. 353-357. 

The ability of palladium to serve as both nucleophile (Pd(0)) and electrophile (Pd(II)) has led to the development of oxidase-type reactions that exploit the electrophilic nature of Pd(II). One such example is an extension of the above kinetic resolution of secondary alcohols catalyzed by Pd(nbd)Cl2 in the presence of (-)-sparteine (described earlier), for the oxidative cyclization of substituted phenols. This racemic aerobic cyclization utilizes a Pd(II) salt in the presence of pyridine, O2, and SAmolecular sieves. Numerous palladium precatalysts were screened, Pd(TFA)2 was optimal, yielding the desired cyclized product in 87% yield. Pd2(dba)3 also enabled the cyclization but was less effective, providing the desired cyclized product in significantly reduced yield (25%) (eq 48).13 ... 

Carbonyl Compounds by Oxidation of Alcohols and Aldehydes. A critical assessment of the use of palladium catalysts in the aerobic oxidation of alcohols has concluded that Pd(OAc)2-Et3N is the most versatile and convenient catalyst system and that this often functions under especially mild conditions.There have been many other recent advances in this field and such that there is now a wealth of methods available for effecting the palladium-catalyzed oxidation of alcohols. A procedure using pyridine under an oxygen atmosphere has been shown to convert benzylic and aliphatic alcohols into the corresponding aldehydes or ketones. The yields of product are frequently over 90%. Replacing pyridine with (—)-sparteine in such processes allows for the oxidative kinetic resolution of chiral secondary alcohols. 

Miscellaneous Oxidation Reactions. The kinetic resolution of secondary alcohols is achieved by a palladium-catalyzed enan-tioselective oxidation using Pd[(—)-sparteine]Br2/(—(-sparteine or Pd(CH3CN)2(Br)2/chiral diamine sparteine mimic under an oxygen atmosphere. The chiral amine-dibromide complexes are observed to oxidize secondary alcohols more rapidly than the dichloride complexes (eq 7). This has been attributed to a greater counterion distortion from ideal square planar geometry, which could lower the energy barrier to 8-hydride elimination. 

Also with starting compounds containing two oxygen nucleophiles, both alkoxy/ amino carbonylation and cyclocarbonylation (carbonylative cydization to lactone) mechanisms can occur in sequence. Some bicydic y-lactones from parasitic wasps (Hymenoptera Braconidae) were synthesized by hydrolytic kinetic resolution of epoxides and palladium(II)-catalyzed hydroxycyclization-carbonylation-lactoniza-tion of enediols. For example, cis- and trans-5-n-hexyl-tetrahydrofuro[3,2-b]furan-2 (3H)-ones 75 and 76, with the (3aR,5R,6aR) and (3aS,5R,6aS) configurations, respectively, were acquired in six steps from the inexpensive, readily available ridnoleic add 74 (Scheme 13.48) (89). 

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