Differentiation enantioface

These categories can be clarified by consideration of specific cases. For more detail, Izumi and Tai s book should be consulted [62] a comprehensive treatment of asymmetric organic reactions is given by Morrison and Mosher [63]. 

An optically active Grignard reagent has the ability to differentiate between the two enantiofaces of a carbonyl compound such as 45 [64], In the example shown, the (S)-enantiomer of the product alcohol, 46, is obtained with a high degree of optical purity (= specific rotation of mixture- - specific rotation of one pure enantiomer X 100 for definitions of other terms used in this work, see [65]). 

45 (+)-1 — Chloro — 2 — pher Form Grignard reagent ylbutane (—) —(S), 82% optical 46 purity 

The chiral influence can also be present in a catalyst many asymmetric hydrogenation reactions have been carried out. The example shown (47 - 48) requires differentiation of the enantiofaces of a double bond [66]. 

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Hydrolysis of Enol Esters. Enzyme-mediated enantioface-differentiating hydrolysis of enol esters is an original method for generating optically active a-substituted ketones (84—86). If the protonation of a double bond occurs from one side with the simultaneous elimination of the acyl group (Fig. 3), then the optically active ketone should be produced. Indeed, the incubation of l-acetoxy-2-methylcyclohexene [1196-73-2] (68) with Pichia... 

The stereochemical course of the enantioface differentiation on the aldehyde is dictated by the configuration of the sulfoxide group sulfinyl-subsdtuted dihydroisoxazoles epimeric at C-5 (e.g., 18) provide aldol adducts 19 with the same configuration at the hydroxy-substituted carbon (C-2 ) independent of the absolute configuration at C-5, however, with different degrees of stereoselectivity23. 

The result of enzymatic decarboxylation was extremely clear. While (S)-compound resulted in C-containing product, (/ )-compound gave the product with C no more than natural abundance. Apparently, the enzyme decarboxylated pro-(/ ) carboxyl group selectively and the reaction proceeds with net inversion of configuration. Thus, the presence of a planar intermediate can be reasonably postulated. Enantioface-differentiating protonation to the intermediate will give the optically active final product (Eig. 12). 

Table 1. Enantioface-Differentiating Hydrogenation of Various Keto Esters and 2-Octanone...

In 2000, Woodward et al. reported that LiGaH4, in combination with the S/ 0-chelate, 2-hydroxy-2 -mercapto-1,1 -binaphthyl (MTBH2), formed an active catalyst for the asymmetric reduction of prochiral ketones with catecholborane as the hydride source (Scheme 10.65). The enantioface differentiation was on the basis of the steric requirements of the ketone substituents. Aryl w-alkyl ketones were reduced in enantioselectivities of 90-93% ee, whereas alkyl methyl ketones e.g. i-Pr, Cy, t-Bu) gave lower enantioselectivities of 60-72% ee. 

The enantioselective hydrogenation of terminal 1,1-disubstituted olefins presents a particular challenge. Enantioface differentiation in the compounds relies on the different interactions of the catalyst with the two substituents which, as in the case of 1 and 2 (Fig. 30.1), are sterically quite similar. 

Enantioselective osmylotion of alkenes. Osmium tetroxide forms a 1 1 wine-red complex with the chiral diamine l2 that effects efficient enantioselective dihy-droxylation of monosubstituted, oww-disubstituted, and trisubstituted alkenes (83-99% ee) at -110° in THF. The enantioface differentiation in all cases corresponds to that observed with t/mr-3-hexene and the complex with (-)-l. Essentially complete asymmetric induction is observed with frans-l-phenylpropene (99% ee). 

The observed enantioface differentiation in the reduction of the phenyl alkyl ketones was rationalized by postulating a 6-membered ring transition state for hydride transfer (Scheme 10). The transition state leading to the (S)-carbinol has an axial phenyl group interacting sterically with the binaphthoxy oxygen. 

Acyl chains of lipid A are often branched double-chain derivatives. Thus 3-0-acyl-(R)-3-hydroxytetradecanoic acid methyl ester 16 was obtained in 85% e.e. by the enantioface-differentiating hydrogenation of methyl 3-oxotetradecanoa-... 

As illustrated in Section 2.3, enantioface differentiation occurs in addition reactions to hetero double bonds (C = X, with X = O, NR, etc.) and olefinic double bonds in achiral substrates. Thus, the enantioface differentiation can only arise from the reagent, either stoichiometrically (eq. I)18 or catalytically, e.g., from an enzymatic partner (eq. 2)19. 

One way method to enantioface differentiation proceeds via a chiral catalyst (+)-3 and gives an enantiomer ratio of 11 1. 

Adamantanediol, which was obtained through a microbial enantioface-differenti-ating reduction of 2,6-adamantanedione85 or by resolution of the racemate86. 

Nozaki et al. [23] characterised the production of (+)-mesifuran [2,5-di-methyl-4-methoxy-3(2H)-furanone], an important flavour compound in arctic bramble, but which also occurs in strawberry and pineapple. After lipase-catalysed (Candida antarctica) enantioface-differentiating hydrolysis of the enol acetate, the pure optically active (+)-mesifuran could be obtained. 

Fig. I. Enantioface-differentialing (asymmetric) hydrogenation of MAA to MHB. TA-MRNi RNi catalyst modified with tartaric acid.

Enantioface-differentiating ability is the most widely studied character of MRNi because MRNi has been studied with the goals of establishing the fundamental concept of stereo-differentiation and developing enantioface-differentiating catalysts for practical use. The EDA is the important parameter indicating the ability of MRNi for the production of optically active... 

Fig. 11. Effect of NaBr concentration of modifying solution on amount of adsorbed TA or NaBr and enantioface-differentialing ability of TA-NaBr-MRNiA ( ) TA ( ) OY (O) Br. Catalyst RNiA (TA) (RNi pretreated with % TA at pH 3.2 and 100 C for I hr). Modifying condition TA (1%) + NaBr, pH 5.0, 0°C. Reaction conditions MAA (11.5 ml), methyl propionate (23 ml), AcOH (0.2 ml), 100 C, 110-130 kg/cm2.

Fig. 14. Effect of water on optical yield in the enantioface-differentiating hydrogenation with MRNi (O) (S)-Glu-MRNi (A) (S)-Val-MRNi ( ) (S)-Ala-MRNi. Modifying conditions isoelectric point, 0 C. Reaction conditions MAA (17.5 ml), water, 60 C, 80 kg/cm2.

By modification with an optically active compound, RNi can acquire both enantiomer-differentiating ability and diastereoface-differentiating ability in addition to the enantioface-differentiating ability. The diastereoface- and enantiomer-differentiating abilities of MRNi can be observed when a substrate containing both chiral and sp2-prochiral centers is used, because such a compound has a diastereoface and a chirality. 4-Hydroxy-2-pentanone is one of the substrates with a chiral and sp2-prochiral center, as shown in Fig. 17. 

Hydrogenation systems frequently contain a variety of catalytically active metal complexes that exhibit different degrees of enantioface differentiation. For example, the reaction of (Z)-a-(benzamido)cinnamic acid in the presence of preformed [Rh((/ )-binap)(CH30H)2]C104 pro-... 

Structural Characteristics. BINAP-Ru(II) complexes catalyze a variety of synthetically useful stereoselective hydrogenations. Although the exact mechanism of the enantioface differentiation is yet to be eluci-... 

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