Hydroxyacids, reaction with

A naive look at the product suggests an oxidation to a ketone followed by a Baeyer-Villiger like reaction. The product is best explained by a fragmentation from an intermediate chromate ester, resulting on an aldehyde and a stabilized tertiary carbocation that is transformed into a tertiary alcohol by reaction with water. The hydroxyaldehyde so obtained may evolve to the final lactone either via a lactol or a hydroxyacid. 

Reaction with nitrous acid Nitrous acid reacts with the amino group of amino acids to form the corresponding hydroxyacids and liberate nitrogen gas. 

This type of reaction can be used to invert the natural series to give a rare and expensive (R) -amino acid. Phenylalanine 4 is converted into the hydroxyacid 22 with retention. Displacement of triflate from 24 with inversion and removal of the benzyl ester gives Boc-protected (R)-Phe 26. In fact this method was used to make 15N-(/ )-Phe so the nitrogen nucleophile was labelled but it is the inversion that matters to us.8... 

Mandelic acid-derived chiral (a-substituted) acetate enolate addition to aldehydes leading to chiral j5-hydroxycarboxylic acids illustrates the versatility of the readily available ester 63. The addition of phenylmagnesium bromide to methyl (i )-mandelate (63) gives the (i )-diol 152, which is acetylated to (i )-2-acetoxy-l,l,2-triphenylethanol (153) [(/ )-HYTRA]. Deprotonation with LDA at — 78 °C provides an enolate that is then transmetallated with magnesium bromide and further cooled to —115 °C before reaction with an aldehyde to produce 154 as the major diastereomer with a yield of 84-95%. Heating 154 in aqueous methanol containing potassium hydroxide provides the optically active j5-hydroxyacid 156 (Scheme 36) [41- 4]. 

Liquid crystal polyesters are made by a different route. Because they are phenoHc esters, they cannot be made by direct ester exchange between a diphenol and a lower dialkyl ester due to unfavorable reactivities. The usual method is the so-called reverse ester exchange or acidolysis reaction (96) where the phenoHc hydroxyl groups are acylated with a lower aHphatic acid anhydride, eg, acetic or propionic anhydride, and the acetate or propionate ester is heated with an aromatic dicarboxyHc acid, sometimes in the presence of a catalyst. The phenoHc polyester forms readily as the volatile lower acid distills from the reaction mixture. Many Hquid crystal polymers are derived formally from hydroxyacids (97,98) and thein acetates readily undergo self-condensation in the melt, stoichiometric balance being automatically obtained. 

Lipases catalyze the polymerization of lactones [Duda et al., 2002 Gross et al., 2001 Kobayashi, 1999 Kobayashi et al., 2001]. The reaction mechanism is similar to that for the enzymatic polymerization of hydroxyacids (Sec. 2-17a-2). Lipase reacts with lactone to produce enzyme-activated hydroxyacid and some of the latter reacts with water to produce hydroxyacid (Eqs. 7-81). Hydroxyacid and enzyme-activated hydroxyacid react to initiate polymerization (Eq. 7-82). Propagation proceeds by nucleophilic attack of... 

Hydrazine hydrate reacts with a-hydroxyacids to give the A -aminodihydrotriazole which is diazotised with sodium nitrite in HCl to the 3,5-disubstituted triazole enantiomer (Scheme 24) <87H(26)989>. These triazoles were converted to macrocyclic derivatives (see Section 4.02.12.3). The ketals of a-oxoesters undergo the same series of reactions to give, after hydrolysis, the 3,5-dicarbonyl derivatives (Scheme 25) <92S398>. 

Asymmetric synthesis in aldol-type reaction involving magnesium ester or lactone enolates has also been reported. Enolate of (—)-menthyl or (-l-)-bornyl acetate reacts with substituted benzophenones or a-naphtophenones to yield, upon hydrolysis of the resulting esters, optically active /3-hydroxyacids. Although these results are interpreted in terms of a steric factor. Prelog s rules are not applicable to these reactions (equation 88). 

In fact, natural tartaric acid (R,R) reacts easily at room temperature with phosphorus trichloride. The main products of the reaction are spirophosphoranes with a P-H bond formed from the a-hydroxyacid linkage (scheme (A)). 

Hydrolysis of the lactone ring in dimethyldecodine (14) was carried out by prolonged refluxing of the alkaloid in aqueous methanolic sodium hydroxide (17). Ferris reported that the starting material could be recovered in 18% yield using thionyl chloride in chloroform. However, in the total synthesis of the biphenyl ether alkaloid decaline, the yield of lactonization of the corresponding hydroxyacid did not exceed 5% (39, 40). This reaction was usually carried out in much better yield in benzene with p-toluenesulfonic acid (39). 

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