Pentenoic 3 -hydroxy-, preparation

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

Caution The starting material in this preparation, 3-hydroxy-2,2,4-trimethyl-3-pentenoic acid (i-ladone, is a mild hut deceptively persistent lachrymator. 

Rearrangement of sulfonium ylides constructed on a chiral oxathianone template provides an effective asymmetric entry to optically active 4-pentenoic acids118. The requisite ylides 17 are obtained by intramolecular alkylation of diazoketones 16, which are in turn prepared from the valine derived hydroxy thiol 15. Ylide formation can be accomplished directly by treatment of diazoketones 16 with rhodium(II) acetate or by a two-step sequence involving acid-catalyzed formation of the sulfonium salt and subsequent treatment with base at low temperature, a procedure which affords superior yields and diastereoselectivity. 

In contrast, the latter. ryw-isomer, ethyl (TS,2R)-2-(1 -hydroxymethyl)-4-pentenoate. was recently prepared as the only product of a reduction with an enzyme fraction obtained from baker s yeast176. Introduction of a sulfur-containing functional group into the substrate increases stereocontrol in baker s yeast reduction of many ketonesI2e>. 2-Methylthio-3-keto esters are selectively reduced to the (3S)-3-hydroxy esters (Table 5)123,127. The 2-methylthio group is easily removed by 3-chloroperbenzoic acid oxidation to the corresponding sulfoxide followed by subsequent reduction with aluminum-mercury amalgam. Thus, these compounds can also be used for the preparation of optically pure 2-unsubstituted 3-hydroxy esters. 

A xylan extracted from the holocellulose present in the stalks of Nicotiana tabacum has been purified by ion-exchange chromatography. The results of methylation analysis, partial hydrolysis with acid, and enzymic hydrolysis indicated that the xylan is composed of a straight chain of approximately 100 /S-(l -> 4)-linked D-xylopyranosyl residues. Curie point-g.l.c. of the xylan yielded 2-furaldehyde, which is probably formed via 3-deoxy-D- /ycero-pent-2-ulose. Another major product was identified as 3-hydroxy-2-penteno-1,5-lactone (21) by high-resolution m.s. this lactone has also been prepared by pyrolysis of a hexuronic acid-containing xylan from beech. Since the tobacco-stalk xylan contains no acidic components, the lactone (21) must arise by... 

When the lithium enolate 84 is added to propenal (tvithout transmetala-tion), the diastereomeric esters 87a and 87b are formed in the ratio 92 8. In this reaction the crude mixture 87a/87b tvas hydrolyzed to give the carboxylic acid (R)-88 in 83.5% ee. To obtain the enantiomerically pure 3-hydroxy-4-pentenoic acid, enrichment tvas performed by single recrystallization of the ammonium salt, formed from (S)-l-phenylethylamine. When the amine has been liberated from the salt the carboxylic acid (R)-88 is obtained in >99.8% ee and 41% overall yield (Scheme 1.18) [132]. The (S) enantiomer, but not the ( R) enantiomer, of 3-hydroxy-4-pentenoic acid 88 (both prepared according to this procedure) has been sho vn to be a substrate for the enzyme 3-hydroxybutanoate dehydrogenase - another example of the different biological activity of enantiomeric compounds [133]. 

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