Y-Hydroxy acid

It was found later that the electrolytic coupling reaction gave better yield with the acetate corresponding to B, since fragmentation was a major side reaction of the y-hydroxy acid B (Ref. 2). 

CsHi.Os Y-Hydroxy acid Conformation Study(15) T211... 

P-Hydroxy acids, 14 130, 131 y-Hydroxy acids, 14 131 a-Hydroxyadipaldehyde, 1 279 Hydroxyalkyl alkyl peroxides,... 

An early effort to generate a 3-lithiated propionic acid derivative and react it with (external) electrophiles was reported in 1978 [42]. Since simple 3-lithioesters failed to undergo the required reaction, the alkyl carboxylate portion was protected by preceding conversion to the carboxylate anion. Treatment of lithium 3-bromo-propionate with lithium naphthalide generated the desired dilithiated propionic acid, which gave moderate yields of y-hydroxy acid addition products with carbonyl compounds, Eq. (45). 

Preparation. The general preparation of u-hydroxy acids is by the hydrolysis of an a-halo acid or by Ihe acid hydrolysis of the cyanohydrins of an aldehyde or a ketone. 0-Hydroxy acids may be made by catalytic reduction of 0-keut esters followed by hydrolysis. 0-Hydroxy acids can also he prepared by ihe ReformaCsky reaction y-Hydroxy acids are seldom obtained in the free slate because of ihe case wilh which they form... 

PPL suspended in dry ether catalyzes the lactonization of a number of y-hydroxy acids. For example, f. V)-7 11 itt livlbut vn >lact one [19041-15-7] (R = CH, R = H, n = 1), and y-phenylbutyrolactone (R = C6H5, R = H, n = 1) may be produced in nearly quantitative yields (87-89). When prochiral derivatives (70) of y-hydroxypimelic acid were submitted to the action of PPL and Pseudomonasfluorescens Upases, optically active lactones with up to 98% ee were produced. 

For die lactone target L shown below, cleavage of the lactone ring gives a Y -hydroxy acid. This can be disconnected at any one of the three intervening bonds between the hydroxyl group and the carbonyl group (a, b, c). 

Lactonization. Lactonization of -y-hydroxy acids to rrans-fused bicyclic y-lactones generally requires acidic conditions or DCC. Cyclization of hydroxy acids of structure 2 is difficult because of dehydration, but is effected in >95% yield by treatment with excess I and NfCaHs), in refluxing CHjClj. 

Catalytic hydrogenation of the y-hydroxy acid over copjjer chromite catalyst has been employed for the preparation of y-(f-tolyl)-valeric acid. ... 

Aldol-iype Condensation. Dimetalation of (R)-(+)-3-(p-tolylsulfinyl)propionic acid with Lithium Diisopropylamide produces a chiral homoenolate dianion equivalent which reacts with carbonyl compounds to afford p-sulfinyl-y-hydroxy acids these spontaneously cyclize to give the corresponding p-sulfinyl 7-lactones (eq 2) ... 

There are numerous variations of cycloalkylating lactone formations. They may be classified into HGA ring closure of y-hydroxy acids or esters, 5n2 ring closure of y-bromoca xylates, lactonizations under participation of alkenic double bonds or y-lactone formation by carbenium rearrangements. 

Lactonization. Woodward et af. found treatment of the y-hydroxy acid (1) with DCC in pyridine more effective for lactonization than use of acetic anhydride in pyridine. 

Johnson et found the y-hydroxy acid (3) to resist lactonization by usual methods since the transformation requires a flip of the ring into the boat conformation (4). Lactonization with DCC in pyridine succeeded in some trials but the... 

Dehydration. Johnson and co-workers in a study of the energy difference between the chair and boat forms of cyclohexane required the isomeric lactones (2) and (4) and were able to synthesize the required y-hydroxy acids (1) and (3). Lac-tonization of (1) was accomplished by heating a solution of 1 g. of (1) and 0.4 g. of... 

In an attempt to overcome the above-mentioned problems, acrylates bearing pendant androsterone with 6-hydroxy acid (Fig. 133), 3 - (3 - a cry loy loxy a n -drosterone, was polymerized with a radical initiator in THF to 80-90% yield [ 385 ]. The polymer was oxidized with CH3C02H/H202 to form 6-lactone in 95% yield. The lactone ring was hydrolyzed in THF with 0.2 N aqueous NaOH in 85-90% yield. The final polymer contained 25 mol% unreacted lactone, had a good transparency of 0.21/pm at 193 nm, and a much better shelf life than the y-hydroxy acid system. 13C NMR of the polymer treated with methanesulfonic acid in THF and IR studies of the resist film after exposure indicated that the... 

Fig. 132 Intramolecular esterification of y-hydroxy acid for a reverse polarity change...

The dianion reacts with epoxides to form y-hydroxy acid s, which can be dehydrated to trimethylsilyl-7-butyrolactones ... 

---