Esters, 2-hydroxy enantioselective

It is possible that hydrogenation of racemic a-mono-substituted yS-keto esters provides four stereoisomers of the corresponding hydroxy esters. Fortunately, enantioselective hydrogenation of such racemic compounds can selectively yield... 

The biotechnological synthesis of lactones has reached a high standard. Besides microbial production, lactones can also be enzymatically produced. For instance, a lipase-catalysed intramolecular transesterification of 4-hydroxy-carboxylic esters leads enantioselectively (ee>80%) to (S)-y-lactones the chain length may vary from C5 to Cl 1 [13]. y-Butyrolactone can be produced in that way with lipase from Mucor miehei [30]. 

Use of the boron azaenolate 3, prepared from achiral 2-ethyl-4,4-dimethyloxazoline and the chiral boryl triflate, undergoes aldol condensation to give mainly threo-fi-hydroxy esters with enantioselectivity of about 80% (equation II). 

The hydrogenation of various P-keto esters was also performed in water in the presence of ruthenium complexes associated with ligands 10 and 11 (23, 24), affording the corresponding hydroxy ester with enantioselectivities up to 94% [Eq. (6)]. The ee values remained imchanged in the first three recycles. 

As the dosage of air is hardly controlled in these protocols and oxygen causes undesired side reactions, Cozzi and coworkers elaborated a procedure that used t-butyl hydroperoxide as an oxidative additive. In addition, the readily available amino alcohol 323 was used as the chiral ligand. Again, the presence of triphenylphosphine oxide was required as shown in the Reformatsky reaction with aldehydes (Scheme 5.88) [166]. The long reaction times over more than 100 h required at -25 °C indicates a rather sluggish conversion. It may be abbreviated by running the reaction at 25 °C, however, at the expense of reduced enantiomeric excess of P-hydroxy esters 316. Enantioselectivity varied considerably, was fair for most aromatic aldehydes, but was low for aliphatic aldehydes, except for pivalalde-hyde that provided 93% ee. The procedure was also applied to prochiral ketones. 

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

The synthesis of 4-alkyl-y-butyrolactones 13 and 5-alkyl-<5-valerolactones 14 can be achieved in high enantiomeric excess by alkylation of ethyl 4-oxobutanoate and ethyl 5-oxopentanoate (11, n = 2, 3). The addition of diethylzinc, as well as dimethylzinc, leads to hydroxy esters 12 in high optical purity. When methyl esters instead of ethyl esters are used as substrates, the enantioselectivity of the addition reaction is somewhat lower. Alkaline hydrolysis of the hydroxy esters 12, followed by spontaneous cyclization upon acidification, leads to the corresponding y-butyro- and -valerolactones32. 

Asymmetric alcoholyses catalyzed by lipases have been employed for the resolution of lactones with high enantioselectivity. The racemic P-lactone (oxetan-2-one) illustrated in Figure 6.21 was resolved by a lipase-catalyzed alcoholysis to give the corresponding (2S,3 S)-hydroxy benzyl ester and the remaining (3R,4R)-lactone [68]. Tropic acid lactone was resolved by a similar procedure [69]. These reactions are promoted by releasing the strain in the four-membered ring. 

The DKRs of a-, (3-, y- and 8-hydroxy esters were also accomplished with PCL and 1 at 60-70°C. In the DKRs, the enantioselectivities were good in most cases though the yields were moderate. The use of H2 was necessary in the DKR of 7- and 8-hydroxy esters to suppress the formation of ketones (Tables 8-10). 

As an extension of this work, these authors have applied this catalyst system to vinylogous asymmetric Mukaiyama-type aldol reactions, involving silyl vinyl ketene acetals and pyruvate esters. These reactions afforded the corresponding y,5-unsaturated a-hydroxy diesters with quaternary centres in high yields and enantioselectivities of up to 99% ee (Scheme 10.25). It was shown that the presence of CF3CH2OH as an additive facilitated the turnover of the catalyst. 

A further example of highly diastereoseleetive and enantioseleetive C-H insertions performed in similar eonditions to those deseribed above was the reaetion between aryldiazoacetates and allylsilyl ethers, yielding p-hydroxy ester derivatives that are equivalents to aldol products. " An illustrative reaction between an aryldiazoacetate and trani-2-butenylsilyl ether is shown in Scheme 10.78. This reaction led to the diastereoseleetive formation of the equivalent of a syn-a do product in both high yield and enantioselectivity. 

The directive effect of allylic hydroxy groups can be used in conjunction with chiral catalysts to achieve enantioselective cyclopropanation. The chiral ligand used is a boronate ester derived from the (VjA jA N -tetramethyl amide of tartaric acid.186 Similar results are obtained using the potassium alkoxide, again indicating the Lewis base character of the directive effect. 

The conversion of 27 to chiral hydroxy acid 26 was envisioned to arise via a sequential reduction protocol where the ketone moiety of 27 would enantioselectively be reduced to give chiral allylic cyclopentenol 46 (Scheme 7.11). Subsequent 1,4-addition of hydride to the a,/J-unsaturated ester of 46, presumably assisted by... 

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. 

In 1992, Thornton et al. reported that Mn(salen) (43) catalyzed the asymmetric oxidation of silyl enol ethers to give a mixture of a-siloxy and a-hydroxy ketones, albeit with moderate enantioselectivity (Scheme 28).135 Jacobsen et al. examined the oxidation of enol esters with Mn(salen) (27) and achieved good enantioselectivity.136 Adam et al. also reported that the oxidation of enol ethers with (27) proceeded with moderate to high enantioselectivity.137 Good substrates for these reactions are limited, however, to conjugated enol ethers and esters. Based on the analysis of the stereochemistry,137 enol ethers have been proposed to approach the oxo-Mn center along the N—Mn bond axis (trajectory c, vide supra). 

The value of 2-acyl-1,3-dithiane 1-oxides in stereocontrolled syntheses has been extended to the enantioselective formation of (3-hydroxy-y-ketoesters through ester enolate aldol reactions <00JOC6027>. 

Vinylstannanes with hydroxy groups in the allylic position undergo enantioselective and diasteroselective hydrogenation in the presence of rhodium catalysts, as illustrated in reaction 19275. Vinylstannanes can be converted into /1-stannylacrylic esters in a two-step synthesis, as shown in reaction 20276. 

The enantioselective hydrogenation of a,fj- or / ,y-unsaturated acid derivatives and ester substrates including itaconic acids, acrylic acid derivatives, buteno-lides, and dehydrojasmonates, is a practical and efficient methodology for accessing, amongst others, chiral acids, chiral a-hydroxy acids, chiral lactones and chiral amides. These are of particular importance across the pharmaceutical and the flavors and fragrances industries. 

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-... 

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