JS-hydroxyketones

Much of the more recent work using isoxazolines involves ste-reocontrolled synthesis. Kozikowski and Ghosh (84JOC2762) used nitrile oxide cycloaddition to prepare the /8-hydroxyester (143) and the jS-hydroxyketone (145) from the dioxolane (S)-(48b) (Schemes 63 and 64). The ester (143) and ketone (145) are masked triols, suitable for use in the synthesis of sugars, as shown through the elaboration of the ester (143)... 

Dehydrahon of jS-hydroxyketones and jS-hydroxyesters with carbodiimides is used to introduce double bonds into organic molecules. For example, Corey and coworkers used this method in the synthesis of prostaglandins." For example. The shown /3-hydroxyketone... 

A very short and elegant synthesis of the 16-rtiembered dilactone ( )-pyrenophorin (515) has been accomplished by the dipolar cycloaddition reaction of a trialkylsilyl nitronate (81TL735). Nitromethane was added to 3-buten-2-one and the carbonyl group of the product reduced with sodium borohydride. The nitro alcohol (511) was converted to the acrylate (512) which was then subjected to a dimerization-cyclization reaction by treatment with chlorotrimethylsilane and triethylamine in dry benzene. Hydrogenation of the mixture of isoxazoline products (513) over palladium on charcoal followed by double dehydration of the intermediate bis-jS-hydroxyketone (514) led to ( )- and mera-pyrenophorin (Scheme... 

Complex reactions involving insertion of a P-X bond, O transfer from C to P, and ring closure occur when PhPCla reacts with jS-hydroxyketones . In contrast, ketene reacts with PBra to yield only a single product involving insertion into the alkene linkage . This result parallels the addition of SF5CI into ketene . 

An aldol addition is a reaction between two molecules of an aldehyde or two molecules of a ketone. When the reactant is an aldehyde, the addition product is a jS-hydroxyaldehyde, which is why the reaction is called an aldol addition ( aid for aldehyde, ol for alcohol). When the reactant is a ketone, the addition product is a jS-hydroxyketone. Because the addition reaction is reversible, good yields of the addition product are obtained only if it is removed from the solution as it is formed. 

In an aldol addition, the enolate of an aldehyde or a ketone reacts with the carbonyl carbon of a second molecule of aldehyde or ketone, forming a j8-hydroxyaldehyde or a jS-hydroxyketone. The new C—C bond forms between the a-carbon of one molecule and the carbon that formerly was the carbonyl carbon of the other molecule. The product of an aldol addition can be dehydrated to give an aldol condensation product. In a Claisen condensation, the enolate of an ester reacts with a second molecule of ester, eliminating an OR group to form a j8-keto ester. A Dieckmann condensation is an intramolecular Claisen condensation. A Robinson annulation is a ring-forming reaction in which a Michael reaction and an intramolecular aldol addition occur sequentially. 

The major rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl Coenzyme A reductase (HMG-CoA reductase), has been a therapeutic target for many research groups. A synthesis of the functionalized thiophene 172, prepared for its biological activity, illustrates the utility of 162 for the introduction of one of the hydroxy chiral centers present in the molecule. This chiral center is then exploited for the introduction of the second chiral hydroxy center. Treatment of aldehyde 169 with the double anion of 162 at —95 °C in THF affords as the major product 170 (98.8 1.2). Treatment of the adduct with excess tert-butylacetate enolate at — 78 °C followed by acidic work-up furnishes the jS-hydroxyketone 171 in 86% isolated yield. Chelation-controlled reduction of the ketone, accomplished by initial complexation of the ketone and the hydroxy group with triethylborane followed by sodium borohydride addition, provides the desired dihydroxyester 172 (Scheme 39) [47]. 

The preparation of some y-fluoro-jS-hydroxyketones (58) by reaction of epifluorohydrin with the lithio derivative 57 has been reported . The dithioacetals prepared from dithiol 56 are reported to be crystalline, odourless compounds , therefore some advantage may be purported for their use. 

Syn 1,3-diols also can be obtained from jS-hydroxyketones using LiI-LiAlH4 at low temperatures. ... 

Unlike alcohols that can be dehydrated only under acidic conditions, jS-hydroxyaldehydes and jS-hydroxyketones can also be dehydrated under basic conditions. Ibus, heating the product of an aldol addition in either acid or base leads to dehydration. 

Because a 1,4-diketone has two different sets of a-hydrogens, two different jS-hydroxyketones can potentially form, one with a five-membered ring and one with a three-membered ring. The greater stability of the five-membered ring causes it to be formed preferentially (Section 3.11). In fact, the five-membered ring product is the only product formed from the intramolecular aldol addition of a 1,4-diketone. 

In the reaction of a-sulfonyl carbanion with lactones, the corresponding hydroxy-co-ketosulfones were obtained " . Thus, various o-hydroxyketones were shown by Umani-Ronchi and coworkers to be formed from the corresponding lactones. For example, the reaction of a, a-dilithioalkyl phenyl sulfones with lactones in THF at low temperatures afforded co-hydroxy-jS-ketosulfones which, upon desulfonylation with aluminium amalgam, gave the corresponding hydroxyketones . This process was applied for the syntheses of cis-jasmone and dihydrojasmone by treating y-valerolactone with ds-3-hexen-l-yl phenyl sulfone and n-hexyl phenyl sulfone. ... 

An investigation has been reported of the enediol anions and products of jS-elimination of cyclic a-hydroxyketones,- the observations were correlated with n.m.r, results. 

Because an aldol addition is reversible, when the product of an aldol addition (the jS-hydroxyaldehyde or 8-hydroxyketone) is heated with hydroxide ion and water, the aldehyde or ketone that formed the aldol addition product can be regenerated. In Section 18.21 we will see that a retro-aldol addition is an important reaction... 

We have seen that alcohols dehydrate when they are heated with acid (Section 11.4). The jS-hydroxyaldehyde and S-hydroxyketone products of aldol addition reactions are easier to dehydrate than many other alcohols because the double bond formed when the compound is dehydrated is conjugated with a carbonyl group. Conjugation increases the stability of the product and therefore makes it easier to form (Section 8.13). 

In an aldol addition, the enolate ion of an aldehyde or a ketone reacts with the carbonyl carbon of a second molecule of aldehyde or ketone, forming a jS-hydroxyaldehyde or a /3-hydroxyketone. The new C—C bond forms between the a-carbon of one molecule and the carbon that formerly was the carbonyl carbon of the other molecule. 

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