Hydroxy esters, optically active

Optically Active 3-Hydroxy Esters by Condensation of ferf-Butyl ( + )-(/f)-2-(4-Mcthylphcnylsullinyl)acetate with Carbonyl Compounds General Procedure35,37 ... 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Reaction of optically active a-sulphinyl acetate 298a with prochiral carbonyl compounds proceeds with a high asymmetric induction - , the degree of which depends on the nature of substituents at the carbonyl group (equation 252 Table 22) . The jS-hydroxy sulphoxides 422 formed may be transformed to optically active p-hydroxycarboxylic esters 423 (equation 253) and optically active long-chain lactones 424 99 (equation 254). Corey and coworkers have used this method to introduce a chiral centre at C-3 in their synthesis of maytansin °°, and Papageorgiou and Benezra for the synthesis of chiral a-hydroxyalkyl acrylates 425 ° (equation 255). 

Enzymatic enantioselective oligomerization of a symmetrical hydroxy diester, dimethyl /Lhydroxyglutarate, produced a chiral oligomer (dimer or trimer) with 30-37% ee [24]. PPL catalyzed the enantioselective polymerization of e-substituted-e-hydroxy esters to produce optically active oligomers (DP < 6) [25]. The enantioselectivity increased with increasing bulkiness of the monomer substituent. Optically active polyesters with molecular weight of more than 1000 were obtained by the copolymerization of the racemic oxyacid esters with methyl 6-hydroxyhexanoate. 

Ojima (43) used the same DIOPRh catalyst earlier to add Et2SiH2, PhMeSiH2, Ph2SiH2 and a-naph-PhSiH2 to a-ketoesters to synthesize optically active a-hydroxy carboxylate esters. With diethyl- or phenyl-methylsilane and propyl pyuvate, a double hydrosilation occurred to chiefly make a cyclic product with double asymmetry. 

Chiral 2,5-dihydrofuran can be prepared through the HC1 gas promoted cyclization of the corresponding optically active allenic hydroxy-ester 83 with almost complete axis chirality (87% ee) to center chirality (85% ee) transfer <00TL9613>. 

The unified highly convergent total and formal syntheses of ( + )-macro-sphelides B (441 X = O) and A (441 X = a-OH, p-H), respectively, have been described (483). Key features of the syntheses include the concise synthesis of the optically active S-hydroxy-y-keto a, 3-unsaturated acid fragment 442 via the direct addition of a fra/i.s-vinylogous ester anion equivalent to a readily available Weinreb amide, and the facile construction of the 16-membered macrolide core of the macrosphelide series via an INOC. 

The enantioselective hydrogenation of /(-keto esters is important, because the resulting optically active /(-hydroxy esters are converted to useful chiral building blocks [1-4]. The development of BINAP-Ru(II) catalysts allowed the highly enantioselective hydrogenation of /(-keto esters. As shown in Figure 32.6, methyl-... 

D-a-Hydroxy carboxylic acids.1 These optically active acids can be prepared by a Sn2 reaction between the t-butyl esters of L-2-halo carboxylic acids and cesium p-nitrobenzoate, which proceeds with complete inversion. 

Reduction of a. -epoxy esters to fi-hydroxy esters. Sml2 alone reduces these esters to a mixture of a- and p-hydroxy esters. The reaction rate and yield is increased by addition of HMPT. Addition of a chelating agent, TMEDA or N,N-dimethylaminoethanol (DMAE), results in regioselective reduction to p-hydroxy esters (equation I). The system reduces optically active epoxy esters with complete... 

Not least for the syntheses of natural products, alkoxycarbonylations with formation of allenic esters, often starting from mesylates or carbonates of type 89, are of great importance [35, 137]. In the case of carbonates, the formation of the products 96 occurs by decarboxylation of 94 to give the intermediates 95 (Scheme 7.14). The mesylates 97 are preferred to the analogous carbonates for the alkoxycarbonylation of optically active propargylic compounds in order to decrease the loss of optical purity in the products 98 [15]. In addition to the simple propargylic compounds of type 89, cyclic carbonates or epoxides such as 99 can also be used [138]. The obtained products 100 contain an additional hydroxy function. 

Asymmetric introduction of azide to the a-position of a carbonyl has been achieved by several methods. These include amine to azide conversion by diazo transfer,2 chiral enolate azidation,3 and displacement of optically active trifluoromethanesulfonates,4 p-nitrobenzenesulfonates,5 or halides.6 Alkyl 2-azidopropionates have been prepared in optically active form by diazo transfer,2 p-nitrobenzenesulfonate displacement,5 and the Mitsunobu displacement using zinc azide.7 The method presented here is the simplest of the displacement methods since alcohol activation and displacement steps occur in the same operation. In cases where the a-hydroxy esters are available, this would be the simplest method to introduce azide. 

In these synthesis, the optically active (R)-cyanohydrin is transformed into the corresponding a-hydroxy carboxylic ester and the hydroxyl funchon is achvated by sulfonylahon. The treatment of the corresponding intermediate with tetra-hydrothieno[3,2-c]pyridine stereoselectively yields the (S)-configured clopidogrel (Scheme 10.23). In the second case, a mutant of the recombinant almond (Pmnus amigdalus) (R)-oxynitrilase isoenzyme 5 catalyzes the formation of enantiopure (R)-2-hydroxy-4-phenylbutyronitrile [54]. Reaction of the sulfonylated hydroxyester derivative with the corresponding dipeptide leads to the formation of enalapril or lisinopril (Scheme 10.24). 

Yashima et al. showed an example where the polymer helicity was controlled by enzymatic enantioselective acylation of the monomers [109]. Optically active phenylacetylenes containing hydroxyl or ester groups were obtained by the kinetic resolution of the corresponding racemic hydroxy-functional phenylacetylene (see Scheme 16). Polymerization of the phenylacetylenes afforded an optically active poly(phenylacetylene) with a high molecular weight (Mn = 89kDa PDI = 2.0) and... 

Two endoperoxides, 351 and 352, were obtained from optically active a-phellandrene (550),242,243 indicating that no steric hindrance is exerted by the isopropyl group of 350 on an oxygen attack. Stereoselective oxygenation is observed with ergosterol (555),19,22,23 lumisteryl acetate (555),244 levopimaric acid (557),245,246 and the benzoic ester of 6/3-hydroxy-5,5,9-trimethylhexahydronaphthalene (360),247 to mention... 

In conclusion, we have found a convenient and practical method for the selective reduction of C=0 bond of a wide spectrum of a-keto-)S, -unsaturated esters with Ru(p-cymene)(TsDPEN) as catalyst. The transition metal catalyzed transfer hydrogenation reaction with good selectivity and high efficiency offers possibilities to provide the optically active a-hydroxy-/l, y-unsaturated esters with chiral catalysts. Table 3.8 gives different substrates that can be reduced with Ru(p-cymene) (TsDPEN) complex in isopropyl alcohol. 

Asymmetric synthesis of fi-hydroxy carboxylic estersEsters of 1 in the presence of f-butylmagnesium bromide as base react with aldehydes and ketones to form optically active a-sulfinyl-jS-hydroxy carboxylic esters, which are desulfurized by aluminum amalgam in aqueous THF (equation I). Chemical yields are 75% of... 

For utility of optically active /3-hydroxy esters D. Seebach, S. Roggo, and J. Zimmermann, Biological-Chemical Preparation of 3-Hydroxycarboxylic Acids and Their Use in EPC-Syntheses, in W. Bartmann and K. B. Sharpless, eds., Stereochemistry of Organic and Bioorganic Transformations, p. 85, Verlag Chemie, Weinheim, 1987. 

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