Benzyl chiral catalyst

Formation of optically active sulphoxides was found to occur during oxidation of sulphides in the presence of chiral catalysts. Thus, the oxidation of benzyl methyl sulphide... 

Asymmetric oxidation of sulfides to sulfoxides occurs in the presence of chiral catalysts. It was found (53) that oxidation of benzyl methyl sulfide with iodine suspended in (i )-2-methyl-2-phenylsuccinate 33 buffer gives optically active benzyl methyl sulfoxide 34 having 6.35% optical purity. Much higher asymmetric... 

Intramolecular rhodium-catalyzed carbamate C-H insertion has broad utility for substrates fashioned from most 1° and 3° alcohols. As is typically observed, 3° and benzylic C-H bonds are favored over other C-H centers for amination of this type. Stereospecific oxidation of optically pure 3° units greatly facilitates the preparation of enantiomeric tetrasubstituted carbinolamines, and should find future applications in synthesis vide infra). Importantly, use of PhI(OAc)2 as a terminal oxidant for this process has enabled reactions with a class of starting materials (that is, 1° carbamates) for which iminoiodi-nane synthesis has not proven possible. Thus, by obviating the need for such reagents, substrate scope for this process and related aziridination reactions is significantly expanded vide infra). Looking forward, the versatility of this method for C-N bond formation will be advanced further with the advent of chiral catalysts for diastero- and enantio-controlled C-H insertion. In addition, new catalysts may increase the range of 2° alkanol-based carbamates that perform as viable substrates for this process. 

It can be seen that the de does not reach zero, as the benzylic chiral center induces diastereoselective imine reduction, depending upon the system thermodynamics (that is catalyst, solvent, and temperature). Since the epimerization is first order with respect to the (IS, 4R) isomer but zero order with respect to the mixture of isomers, the process is unaffected by concentration and was conveniently run at the same high concentration as that of the mother liquors from the resolution process. A critical part of the process was the separation of the catalyst from the product, and its removal after the amine epimerization was preferred as this provided the greatest potential for its recycle. Removal of the catalyst was achieved by forming an insoluble ammonio complex formed by bubbling gaseous... 

The indanone substrate was methylated in 94% enantiomeric excess, by the use of a chiral catalyst, N-(/>-(trifluoromethyl)benzyl)cinchoninium bromide, under phase transfer conditions.1468 In another method enantioselective alkylation can be achieved by using a chiral base to form the enolate.1469... 

This unique phenomenon provides a powerful strategy in the molecular design of chiral catalysts that is, the requisite chirality can be served by the simple binaphthyl moiety, while an additional structural requirement for fine-tuning of reactivity and selectivity can be fulfilled by an easily modifiable achiral biphenyl structure. This certainly obviates the use of two chiral units, and should be appreciated in the synthesis of a variety of chiral catalysts with different steric and/or electronic properties. Actually, quaternary ammonium bromide possessing a sterically demanding substituent such as (S)-12b can be easily prepared, and benzylation with (S)-12b as catalyst gave 9 in 95% yield with 92% ee. Further, theenantioselectivity was enhanced to 95% ee with (S)-12c as a catalyst [12]. 

The chiral quaternary ammonium salt 47a with a single tartrate moiety and free hydroxyl groups gave disappointing results for the Michael addition of Schiff s base 20 with tert-butyl acrylate in the presence of CsOH base. However, the benzyl-protected catalyst 47b promoted Michael addition, and the adduct (S)-49 was obtained in 57% yield, although the enantioselectivity remained low (Table 7.6, entry 2). The use of catalyst 48a,b with two tartrate moieties afforded the best results at —60 ° C, and Michael adduct (S)-49 was obtained in good enantioselectivity up to 77% ee (entries 4 and 5). 

The second approach is particularly suitable for the synthesis of carbonyl and carboxylic compounds bearing /3-aryl/heteroaryl benzylic stereocenters. Both organic [9] and organometallic chiral catalysts provide high levels of chemical and optical yield in these C-H transformations (Table 2). The high regioselectivity normally... 

Catalytic hydrosilylation of alkenes performed in the presence of a chiral catalyst results in the formation of chiral silanes. Initially platinium catalysts of the type L PtCl2, L = (/ )-benzyl-(methyl)phenylphosphine (BMPP) or (/ )-methyl(phenyl)propylphosphine and 1,1-disubstituted prostereogenic alkenes, such as a-methylstyrene, 2,3-dimethyl-l-butene and 2-methyl-l-butene, were used however, the stereoselectivity was low4,5. A slightly higher stereoselectivity is obtained when dichlorobis[(/ )-benzyl(methyl)phenylphosphine]nickel [Ni(BMPP)2Cl2] is used as the catalyst. Note that two chiral silanes are formed in this reaction, both of which are products of anti-Markovnikov addition. The major product is the expected dichlorosilane 3, while the byproduct is an anomalous chlorosilane 4 both products were separated by fractional distillation and the major product methylated to give the trimethylsilanes 56 7. 

The first catalytic asymmetric version of the Darzens reaction was achieved in 1978 by J. Hummelen and H. Wynberg [41]. The treatment of p-chlorobenzaldeh ydc and phenacylchloride with the strong base NaOH in the presence of the benzyl quini-nium chloride 86 as a chiral catalyst (6 mol%) afforded the trans-chalcone epoxide 98 in 68% yield. However, the optical yield achieved was only in the range of 7-9% ee (Scheme 8.33). 

The benzylic oxidation depicted in the second step of Scheme 8.28b is actually a formal group-selective differentiation of diastereotopic C-H bonds, since asymmetric epoxidation occurs prior to hydroxylation [125]. However, the reaction is an interesting example of a kinetic resolution that depends on the fact that the catalyst used reacts with the two epoxides at different rates, apparently because the chiral catalyst system ... 

The dibenzyl ester 27 can be obtained by slowly distilling a mixture of tartaric acid and benzyl alcohol, without adding an acidic catalyst34. It is a key intermediate in the synthesis of mono-O-acylated tartaric acids 28-31 33,35 the benzyl ester groups can be selectively cleaved to the free carboxylic acid groups by catalytic hydrogenation. Such derivatives form acyloxy-boranes with diborane which are used as chiral catalysts in enantioselective Diels-Alder reactions (Section D. 1.6.1.1.1.). 

The synthesis of optically active cyclohex-2-enone oxide (55) from cyclohex-2-enone has been reported. The epoxidizing medium contained a chiral catalyst (quininium benzyl chloride) with Bu OOH and a small amount of solid NaOH in toluene. This heterogeneous mixture avoided the use of the strongly alkaline aqueous phase which may have been responsible for the failure of earlier attempts at direct, chiral synthesis of (55). Chemical yields of 60% were obtained, with an e.e. of 20 3%. 

Kinetic resolution of some secondary allylic and benzylic alcohols has been shown to occur efficiently in the presence of the chiral ligand (—)-sparteine. For example, partial oxidation of the racemic alcohol 43 with a palladium(II) catalyst under an atmosphere of oxygen in the presence of (—)-sparteine occurs to give a mixture of the ketone 44 and recovered alcohol (5)-43 (6.39). Selective oxidation of the (i )-alcohol occurs with the chiral catalyst system. 

Bohn and co-workers also studied diethylzinc addition to benzaldehyde with soluble polymeric catalysts [10]. Dendritic chiral catalysts consisting of poly(benzyl ethers) and chiral pyridyl alcohols (3) were used as organocatalysts for the asymmetric C-C linkage reaction. The enantiocontrol by the dendritic systems was slightly lower than that of the parent pyridyl alcohols (2-3% drop in ee) but the conversion toward the chiral secondary alcohol was actually slightly higher for the largest dendritic catalyst (84% versus 80% yield after 3 h of reaction time). In more... 

Treatment of ethyl (Z)-2-benzylidene-3-bromopropionate with t-butylthiol provides ethyl (2Z)-2-benzylidene-3-(t-butylthio)propionate (333), which has been hydrolyzed and hydrogenated in the presence of chiral catalyst to produce (iS)-2-benzyl-3-(t-butylthio)propionic acid (334) in good yields (Scheme 3.145). This add is a useful intermediate for inhibitors of renin and retrovirus protease. 

In an asymmetric version of the Corey oxirane synthesis, aryl aldehydes are reacted with benzyl bromide in the presence of the cyclic sulfide (cat ) derived from D-camphor as a chiral catalyst to give 1,2-diaryloxiranes with high stereoselectivities [15], for example ... 

The importance of chiral epoxy-ketones is becoming increasingly recognized as physiologically active natural products, as metabolic intermediates, and as chiral synthons. Cyclohex-2-enones (1) have been transformed into optically active epoxycyclohexanones (2) using t-butylhydroperoxide in toluene, to which catalytic quantities of solid sodium hydroxide and the chiral catalyst quininium benzyl chloride were added, under phase-transfer conditions. In the unsubstituted case the yield is 60% with enantiomeric excess of 20% as determined by n.m.r. Substituents at C(2), C(3), and C(4) block the epoxidation reaction but compounds with gem-dimethyl groups at C(5) and C(6) are readily converted. 

Additional examples of nitrile hydration reactions catalyzed by homogeneous ruthenium catalysts in organic media are (Scheme 8) (1) The hydration of benzoxazolylacetonitrile by the arene-ruthenium(II) dimer [ RuCl(p-Cl)(r -p-cymene) 2], which led to benzoxazolylacetamide in high yield [58], and (2) the asymmetric hydration of a-benzyl-a-methylmalononitrile by the chiral catalysts 13 [59]. Modest yields and low enantiomeric excesses were obtained in this latter reaction. However, we must note that this is the first example of a nonenzymatic asymmetric nitrile hydration process reported to date in the literature. 

---