Of P-hydroxy ester

It may be pointed out that dehydration of p hydroxy esters with fused potassium hydrogen sulphate, acetic anhydride, phosphoric oxide or with tliionyl chloride in benzeue solution leads to ap unsiiturated esters containing some PY-unsaturated ester the proportion of the latter depends not only upon the structure of the ester but also upon the dehydrating agent used. Elehydration occasionally occurs during the reaction itself or upon attempted distillation. 

In 2004, Bode and Rovis independently and concurrently reported the catalytic coupling of reducible aldehydes and alcohols. This mode of reactivity is most closely related to the work published by Wallach, who generated dichloroacetic acid from chloral under cyanide catalysis in aqueous media [108]. Bode and coworkers reported the catalytic, diastereoselective synthesis of P-hydroxy esters from a,P-epoxy aldehydes using thiazolium pre-catalyst 173 Eq. 16a [109]. MeOH, EtOH, and BnOH are effective nucleophiles providing upwards of >10 1 diastere-oselectivity. Aziridinylaldehyde 174 has also been shown to provide the desired iV-tosyl-P-aminoester 175 in 53% yield Eq. 16b. 

Some efficient syntheses have been reported such as those of p-hydroxy esters from tris(methylthio)methyllithium and epoxides. The case of a malate derivative from a commercially available chiral epoxide is described [286]. 

The moderate diastereoselectivities observed in the electrophilic amination of P-hydroxy esters with DTBAD were due to the acyclic nature of the substrates. When the P-hydroxybutanoic acid was protected as l,3-dioxan-4-ones, deprotonation and amination afforded the a-hydrazinodioxanones 60 in good yields and high diaster-eomeric excesses [22,29] (Scheme 28). 

An important application of the Reformatsky reaction is the conversion of P-hydroxy esters to a, P-unsaturated esters. Acid-catalyzed dehydration usually leads to a mixture of a, P- and P, y-unsaturated esters. However, conversion of the initially formed p-hydroxy esters to their corresponding acetates by treatment with acetyl chloride, followed by base-catalyzed dehydration with NaOEt, produces conjugated esters in high purity. This sequence of reactions provides an alternative route to the Homer-Wads worth-Emmons olefmation of ketones (see Chapter 8). 

Chao, L.-C., Rieke, R. D. Activated metals. IX. New reformatsky reagent involving activated indium for the preparation of P-hydroxy esters. J. Org. Chem. 1975, 40, 2253-2255. 

A considerable amount of work has been carried out on the animation with azodicarboxylic esters of p-hydroxy esters, a class of compounds where both enantiomers are readily available by asymmetric reduction of 3-keto esters. Yields are in the range of 50-70% for lithium115,415-417 (Eq. 115),417 magnesium,416 zinc,416,418-424 and titanium enolates,416 but diastereoselectivities are highest with zinc enolates (Eq. 116)416 Attack from the less hindered side of zinc enolate 57 accounts for the observed anti selectivity. Similar results are obtained with the other enantiomer 416 The lithium enolate of the rigidized derivative of ester 56 gives higher yields with a somewhat reduced anti selectivity (Eq. 117). 416... 

Dehydration of p-hydroxy esters. /3-Hydioxy esters are dehydrated to a,0-unsaturated esters in 44-56% yield by treatment with aluminum ethoxide or diethoxyaluminum chloride and then with lithium diisopropylamide. Although the yields are moderate, no l3,7-isomers are formed and, in suitable cases, only the E-isomer is obtained. The reaction is considered to proceed through a jS-alanoxy intermediate, which can form a six-membered ring transition state on enolization. 

Storage Moisture-sensitive store in cool, dry place away from heat, sparks, open flame store under nitrogen keep tigthly closed Uses Reducing agent in silylation-reduction-allylation sequence of p-hydroxy esters to homoallylic-substituted 1,3-diols, in silylation-hydrosilation-oxidation of allyl alcohols to 1,3-diols, reduction of p-hydroxy ketones to anti-1,3 diols... 

One of the oldest organozinc reagents known to the synthetic chemist is the Reformatsky reagent. The Reformatsky reaction (Equation 3.8) is one of the standard methods used for the preparation of p-hydroxy esters [10]. The standard conditions generally employ refluxing... 

The highly reactive indium powder reported in Sections 6.1 and 6.2 reacts readily with a-haloesters to give an indium Reformatsky-type reagent which will add to ketones and aldehydes to give p-hydroxy esters. The Reformatsky reaction using zinc metal has been used in the preparation of p-hydroxy esters for many years. Recent improvements have made this reaction a very reliable reaction (see Section 3.10). 

In order to obtain good yields of p-hydroxy esters, several reaction conditions must be carefully controlled. In the preparation of the activated indium, it is very important that the molar ratio of InCls to K be exactly 1 3. If there is an excess of either InCls or K, side reaction products become considerable. The ratio of the carbonyl compound to the a-bromoacetate is also very critical. In order to obtain high yields, a onefold excess of the carbonyl compound is... 

Finally, the results of reactions of a variety of carbonyl compounds with the activated indium and ethyl-a-bromoacetate are summarized in Table 6.5. In general, the yields of p-hydroxy esters are good with ketones and also with benzaldehyde in xylene and diethyl ether. However, alkyl aldehydes give relatively low yields. In conclusion, highly activated indium has been prepared and some interesting new results have been reported. However, it is clear that much work remains to be done to fully explore the utility of this new material. 

Synthesis of p-Hydroxy Esters Using Active Manganese 343... 

Synthesis of p-Hydroxy Esters Using Active Manganese 345 Table 8.21 Reactions of a-bromoester with carbonyl compound using Mn. ... 

In 2000, the group of Stewart in Florida reported the asymmetric synthesis of P-hydroxy esters and a-alkyl-P-hydroxy esters by recombinant E. cdi expressing enzymes from baker s yeast [32]. In all cases, a single diastereomer was produced (Scheme 12.15). Both strains yielded the syn-(3S)-alcohols 20a, 21a, 23a, and 28a, with high ee values and in moderate chemical yields. When racemic a-substituted P-keto esters 20, 21, 23, and 28 were employed as substrates, DKRs resulted in almost complete conversion of the substrate, due to facile racemization at the a-position. 

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. 

SCHEME 2.133 Chemical synthesis of p-hydroxy esters and ketones. 

Caste-specific compounds produced by some male carpenter ants (Camponotus spp.) include 2,4-dimethyl-2-hexenoic acid (396). Brand et al. 176) and Kooenski et al. 177) prepared (396) as a mixture of E-and Z-isomers (Schemes 70 and 71), whereas Katzenellenbogen and Utawanit 178) obtained the pure -isomer (396a) by stereoselective dehydration of p-hydroxy ester (402) via a P-alanoxy enolate (Scheme 72). 

Katzenellenbogen, J. A., and T. Utawanit A highly stereoselective and completely regiospecific method for the dehydration of p-hydroxy esters via p-alanoxy enolates. Application to the synthesis of trisubstituted olefins and two ant mandibular gland secretions. J. Amer. Chem. Soc. 96, 6153—6158 (1974). 

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