Unsaturated, acids, esters

Various trifluoromethyl containing a, -unsaturated acids, esters, ketones, and nitriles have been used as dienophiles Details regarding regiochermstry and stereochemistry have been reported [2S, 98, 99] (equations 82-84)... 

Unsaturated Acids, Esters, Aidehydes, Ketones (see Unsaturated Carbonyl Compounds)... 

Reactions of this type provide major routes to both the monocyclic system and to 1,5-benzothiazepines. In some cases the reactions are single-stage processes but in many cases the intermediate produced by the primary formation of the S—C bond can be isolated. Thus 2-aminoethanethiol reacts with a,/3-unsaturated or j3-halogeno ketones to give (408). Similarly reaction with a,/3-unsaturated acids, esters or acid chlorides and with 3-halogenopropionyl halides gives the 5-oxo derivative (409). 2-Aminoethanethiol also reacts with activated 2-chlorobenzophenones to give 1,4-benzothiazepines. 

Other five-membered heterocyclic enones used in [2 + 2] photocycloadditions are 1//-pyrrole-2,3-diones86-88 and derivatives of maleic anhydride. Some cycloadducts of dimethylmaleic anhydride and unsaturated acid esters have been used as monomers for condensation polymers.89... 

Aminoethanethiol reacts with ot, 3-unsaturated or (3-halo ketones to give (355). Similarly, reaction with a, (3-unsaturated acids, esters or acid chlorides, and with 3-halopropionyl halides, yields 5-oxo derivatives such as (356). Thioglycollic acid (HSCH2C02H) with 3-bromopropylamine gives (357). 

Palladium acetate triarylphosphine complexes catalyze the addition of vinylic groups from vinylic halides to olefinic compounds in the presence of amines. Conjugated dienes are major products from 0,/3-unsaturated acids, esters, or nitriles while unactivated olefinic compounds react best in the presence of secondary amines where allylic amines are major products. The reactions are usually regio- and stereospecific. The synthetic utility of the reaction is illustrated with a wide variety of examples. 

In addition to the work described here, experiments with styrenes and a,)8-unsaturated acids, esters and ketones, as well as related halides (24), suggest certain generalizations concerning the effect of structure on organocobalt complex stability and catalysis. Table IX lists several organocobalt complexes, whose preparations, either by reaction of the halide with pentacyanocobaltate(II) or by addition of hydrido complex to the corresponding unsaturated substrate, have been attempted. In many cases, both methods were used. 

More typical behavior of ketones is a condensation process yielding p-acylamino ketones. This process was first reported by Bruson et al. who reacted cyclohexanone and nitriles in the presence of anhydrous aluminum chloride and obtained products now known to have the structure (35). Such reactions were later studied in more detail by Khorlin using conventional Ritter conditions. p-Acylamino ketones were obtained only from ketones capable of undergoing condensations to produce a,p-unsaturated ketones or ketols, suggesting the intermediacy of such structures in the reaction. This process is shown for acetophenone in Scheme 14. It is well established that a,B-unsaturated acids, esters and ketones yield similar products under Ritter reaction conditions. - ... 

A number of syntheses of 2-pyrazolin-5-ones depend on the reaction of compounds, other than /3-ketoesters, substituted in the /3-position or of a,/8-unsaturated acids, esters and amides. The most frequently used unsaturated compounds are those having a triple bond in the apposition.1023,1024,1075,1548,1680 R2 can be HO,1552 RO1023,1024,1686 or H2N (eq. 8).1023,1024 A similar reaction is the condensation of ethyl... 

This catalyst is useful for selective reduction of the carbon-carbon double bond of a,/3-unsaturated acids, esters, ketones, nitriles, and nitro compounds. Sterically hindered double bonds, however, are not reduced. Selective hydrogenation of a,j8-unsaturated aldehydes is hampered by concomitant decarbonylation this reaction can be suppressed to some extent by carrying out the hydrogenation in absolute ethanol. The hydrogenations were conducted in benzene or ethanol at 40-60° and 60-100 psi pressure for 12-18 hours.5... 

In contrast to the mechanism of equation (d), which is based on hydride transfer from [CoH(CN)j] , detailed kinetic studies with some a,)8-unsaturated acids, esters, and nitriles indicate successive hydrogen atom transfers to uncoordinated substrates from [Co"(CN)5( H)] species equations (e), (f) . 

Conventional organic synthesis procedures are sometimes employed to prepare the simpler types of those molecules included here. Thus, (v/c-dihydroxyalkyl)phosphonic diesters are obtainable through the hydroxylation of the corresponding unsaturated acid esters using OSO4 and standard techniques. The isolation and purification of a diol may prove to be difficult because of possible intramolecular transesterification, sometimes accompanied by dehydration (reaction 12)" ... 

Reactions of Thiazolium Salts. The thiazolium salt (45 R = benzyl, X = OH, Y = Cl) catalyses the addition of aldehydes to activated double-bonds, e.g. a/S-unsaturated acids, esters, and nitriles. A novel route to 4-alkyl-2H-l,4-thiazin-3-ones (46 R = alkyl or benzyl) involves the quaternization of 2-methylthiazole with RI, iodination with I2 and NEta, and treatment of the 2-(iodomethyl)thiazolium iodides with potassium hydroxide. ... 

So far we have shown you conjugate additions mainly of a,P-unsaturated aldehydes and unsaturated a,P-ketones. You won t be at all surprised to learn, however, that unsaturated acids, esters, amides, and nitriles—in fact all carboxylic acid derivatives—can also take part in conjugate addition reactions. Two examples, an amide and an ester, are shown on the right below. But notice how the selectivity of these reactions depends on the structure of the unsaturated compound compare the way butyllithium adds to this a,P-unsaturated aldehyde and a,P-unsaturated amide. Both additions are irreversible, and BuLi attacks the reactive carbonyl group of the aldehyde, but prefers conjugate addition to the less reactive amide. Similarly, ammonia reacts with this acyl chloride to give an amide product that derives from direct... 

Addition of sodium enol malonates to a,)3-unsaturated acid esters (Michael condensation). 

Treatment of [2- C]malonic acid with acetone in the presence of acetic anhydride and catalytic amounts of concentrated sulfuric acids provides [5- C]Meldrum s acid (419). one of the most versatile low molecular weight building blocks . As summarized in Figure 6.124, its reactivity at C2 is analogous with that of the malonate diesters already discussed. However, the reactivity of the initial adducts differs. For example, hydrolysis or alcoholysis (including tert-BuOH) of the initial adducts with alkyl halides , aldehydes and acyl chlorides gives directly the [2- C]carboxylic acids/esters, a,/3-unsaturated acids/esters and /3-keto acids/esters, respectively, with simultaneous elimination of acetone and In contrast, the 2-(alkoxymethylene)[2- C]malonate... 

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