Acetic hydroxy- esters

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. 

Carbohydrate-derived titanium cnolates also provide yvn-x-amino-/l-hydroxy esters of high diastcrcomeric and enantiomeric purity. For this purpose, the lithium enolate derived from ethyl (2,2,5,5-tetramcthyl-2,5-disilapyrrolidin-l-yl)acetate is first transmctalated with chloro(cy-clopentadienyl)bis(1,2 5,6-di-0-isopropylidene-a-D-glucofuranos-3-0-yl)titanium and subsequently reacted with aldehydes.. vj-n-a-Amino-/ -hydroxy esters are almost exclusively obtained via a predominant /te-side attack (synjanti 92 8 to 96 4 87-98% ee for the xvn-adducts)623-b. 

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

In the presence of a strong base, the ot carbon of a carboxylic ester can condense with the carbonyl carbon of an aldehyde or ketone to give a P-hydroxy ester, which may or may not be dehydrated to the a,P-unsaturated ester. This reaction is sometimes called the Claisen reaction,an unfortunate usage since that name is more firmly connected to 10-118. In a modem example of how the reaction is used, addition of tert-butyl acetate to LDA in hexane at -78°C gives the lithium salt of ferf-butyl acetate, " (12-21) an enolate anion. Subsequent reaction a ketone provides a simple rapid alternative to the Reformatsky reaction (16-31) as a means of preparing P-hydroxy erf-butyl esters. It is also possible for the a carbon of an aldehyde or ketone to add to the carbonyl carbon of a carboxylic ester, but this is a different reaction (10-119) involving nucleophilic substitution and not addition to a C=0 bond. It can, however, be a side reaction if the aldehyde or ketone has an a hydrogen. 

Davis has described an approach to related 1,3-diol synthons [49] (Eq. 20). Silylation of the -hydroxy ester 129 with diisopropylchlorosilane, followed by fluoride ion-catalyzed intramolecular hydrosilylation generated a 1 1 diastere-omeric mixture of acetals 131. These acetals were shown to undergo diastereo-selective nucleophilic additions vide infra). 

On treatment with acetic anhydride and pyridine, stephadiamine (16) was converted to W-acetylstephadiamine (22), which was hydrolyzed with potassium hydroxide followed by methylation, after acidification with dilute hydrochloric acid, with diazomethane to yield a hydroxy ester (23) in 93%... 

The ft -hydroxy ester resulting from the reaction of the tert-butyldimethylsilyl ketene acetal of ethyl acetate with a lactone under acid conditions can be reduced to the /3-alkoxy ester.306 The overall yields are excellent (Eq. 149). 

Developments after these Ugi derivatives have taken a number of pathways. The MandyPhos family of ligands (32) have been used to reduce enamides to 01-amino acids as well as an enol acetate to produce an a-hydroxy ester [134—140]. The substituents R and R1 can be used for the fine-tuning of a specific substrate. Many of the family have R1 as a secondary amine, relating the family back to PPFA. For confusion, MandyPhos has also been called FerriPhos, while the derivative 32 (R = Rx = Et) is known as FerroPhos. 

Another chiral auxiliary for controlling the absolute stereochemistry in Mukaiyama aldol reactions of chiral silyl ketene acetals has been derived from TV-methyl ephedrine.18 This has been successfully applied to the enantioselec-tive synthesis of various natural products19 such as a-methyl-/ -hydroxy esters (ee 91-94%),18,20 a-methyl-/Miydroxy aldehydes (91% ee),21 a-hydrazino and a-amino acids (78-91% ee),22 a-methyl-d-oxoesters (72-75% ee),20b cis- and trans-l1-lactams (70-96% ee),23 and carbapenem antibiotics.24... 

Covalently bonded chiral auxiliaries readily induce high stereoselectivity for propionate enolates, while the case of acetate enolates has proved to be difficult. Alkylation of carbonyl compound with a novel cyclopentadienyl titanium carbohydrate complex has been found to give high stereoselectivity,44 and a variety of ft-hydroxyl carboxylic acids are accessible with 90-95% optical yields. This compound was also tested in enantioselective aldol reactions. Transmetalation of the relatively stable lithium enolate of t-butyl acetate with chloro(cyclopentadienyl)-bis(l,2 5,6-di-<9-isopropylidene-a-D-glucofuranose-3-0-yl)titanate provided the titanium enolate 66. Reaction of 66 with aldehydes gave -hydroxy esters in high ee (Scheme 3-23). 

The efficiency of catalysts 86-89 for the asymmetric aldol reaction of a series of nucleophiles toward benzyloxyacetaldehyde was studied. For example, compound 89c was found to be an excellent catalyst for the asymmetric aldol reaction of silylketene acetal derivatives of t-butyl thioacetate, ethyl thioacetate, and ethyl acetate with benzyloxyacetaldehyde. In the presence of 0.5 mol% of the catalyst, the asymmetric aldol reaction took place at —78°C in CH2C12, affording the respective /i-hydroxy esters with excellent enantioselectivity (Scheme 3-32). 

The chemical structures of the majority of FMs that have been studied in wastewater treatment are given in Figs. 1-3. Figure 1 shows a variety of FM structures that include alcohols, aldehydes, and ketones, including benzyl acetate (phenylmethyl ester acetic acid), methyl salicylate (2-hydroxy-methyl ester benzoic acid), methyl dihydrojasmonate (3-oxo-2-pentyl-methyl ester cyclopentaneacetic acid), terpineol (4-trimethyl-3-cyclohexene-1-methanol), benzyl salicylate (2-hydroxy-phenylmethyl ester benzoic acid), isobornyl acetate... 

This procedure illustrates the use of lithio esters for the preparation of /3-hydroxy esters. Isopropyl and /-butyl /3-hydroxy-/8,/3-diphenylpropionate may be prepared in approximately 80% yields by using isopropyl or /-butyl acetates in place of ethyl acetate.2 This procedure is generally more convenient than the Reformatsky reaction for the preparation of such esters. Under similar conditions ethyl acetate may conveniently be condensed with various aldehydes or ketones to give the corresponding /8-hydroxy esters.4... 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

Catalytic hydrogenation transforms keto esters to hydroxy esters under very gentle conditions. In cyclic ketones products of different configuration may result. Ethyl 3,3-dimethylcyclohexanone-2-carboxylatC on hydrogenation over platinum oxide in acetic acid gave 96.3% yield of cis, and over Raney nickel in methanol gave 97% yield of trans ethyl 3,3-dimethyl-cyclohexanol-2-carboxylate, both at room temperature and atmospheric pressure [847]. 

Oxazine ring in 212 was formed by spontaneous lactonization in the hydrolysis of 3-aza-5-hydroxy ester 265 (Equation 22) <2005SL693>. The same method was used in the synthesis of 219 <1993LA477>. Oxazine 267 was formed in the hydrolysis of a 3-aza-5-hydroxyaldehyde diethyl acetal 266 <1981JHC825> (Equation 23). 

The most versatile syntheses of 3-unsubstituted-2,4-oxazolidinediones involve either cyclization of a-hydroxy esters with urea or cyclization of a-hydroxy amides with a carbonate or phosgene. A third very useful approach is cyclodehydration of 0-carbamoyloxy acetic acids. Normally, this method affords 3-substituted analogues in which the 3-substitutent is derived from an isocyanate. However, examples in which an a-O-carbamoyloxy ester has been prepared via chlorosulfo-nyl isocyanate or an equivalent will also be described in this section. Extensions of these methodologies together with new approaches to 2,4-oxazolidinediones follow. Many of the analogues prepared, particularly as potential antidiabetic agents, employ a-hydroxy esters or a-hydroxy amides as precursors, which provides clear evidence of the versatility and generality of these classical approaches. A selection of recent examples will illustrate this point. 

This variation was used for an enantioselective synthesis of anti-a-methyl-p-hydroxy esters using the silylketene acetal derived from (1R, 2S)-N-methylephed-rine-O-propionate (equation II).12... 

The Evans Cu(II)- and Sn(II)-catalyzed processes are unique in their ability to mediate aldol additions to pyruvate. Thus, the process provides convenient access to tertiary a-hydroxy esters, a class of chiral compounds not otherwise readily accessed with known methods in asymmetric catalysis. The process has been extended further to include a-dike-tone 101 (Eqs. 8B2.22 and 8B2.23). It is remarkable that the Cu(II) and Sn(II) complexes display enzyme-like group selectivity, as the complexes can differentiate between ethyl and methyl groups in the addition of thiopropionate-derived Z-silyl ketene acetal to 101. As discussed above, either syn or anti diastereomers may be prepared by selection of the Cu(II) or Sn(II) catalyst, respectively. 

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