A, 3-unsaturated compounds

The enolate anion 1 may in principle be generated from any enolizable carbonyl compound 4 by treatment with base the reaction works especially well with /3-dicarbonyl compounds. The enolate 1 adds to the a ,/3-unsaturated compound 2 to give an intermediate new enolate 5, which yields the 1,5-dicarbonyl compound 3 upon hydrolytic workup ... 

With a.-bromo Michael acceptors. Condensation reaction of 2-aminothiazoline with a-bromo-a,/3-unsaturated compounds, commercially available or generated in situ, provided a route to functionalized 2,3,5,6-tetrahydro-imidazo[2,l-3]thiazoles 411 (Equation 187) <1994H(38)2593>. 

In contrast to the limited success with vinyl sulfides as components of [2 + 2] cycloadditions, allenyl sulfides show wide applicability. As illustrated in Scheme 8.91, Lewis acid-catalyzed [2 + 2] cycloadditions of l-trimethylsilyl-l-methylthio-1,2-propadiene (333) with a variety of electron-deficient olefins 336 provide cycloadducts 337 with excellent regioselectivity but with moderate stereoselectivity [175c], Nara-saka and co-workers reported the first Lewis acid-catalyzed asymmetric [2 + 2] cycloaddition of C-l-substituted allenyl sulfides 319 with a,/3-unsaturated compounds 338 using a chiral TADDOL-titanium catalyst. The corresponding cycloadducts 339 were obtained with 88-98% ee, but a low level of trans/cis selectivity (Scheme 8.92) [169,175d[. 

The key reaction in these syntheses was the stereoselective introduction of angular cyano groups as latent methyl groups into perhydropolycyclic a, (3-unsaturated compounds. The new hydrocyanation method developed gave excellent chemoselectivity and stereochemical control. 

If the addition of hydrogen takes place in a 1,2-mode the products are oximes, hydroxylamines, amines, and carbonyl compounds resulting from the hydrolysis of the oximes [567], Oximes and carbonyl compounds also result from reductions of a,/3-unsaturated compounds with iron [569, 570] and an oxime was prepared by catalytic hydrogenation of a )S-nitrostyrene derivative over palladium in pyridine (yield 89%) [571]. 

A ketone 302 may be produced from the hydrolysis of an enamine 303 (equation 107). Applying the same retrosynthetic analysis as in the previous examples, an a,/3-unsaturated compound 304 is obtained as the starting material. 

Another cycloaddition to an a,(3-unsaturated compound involves the reaction of nitrile oxides with 3-methoxy- or 3-methylthio-1 -phenyl-2-propene-1 -one (Scheme 6.18) (133,134). The isoxazoles that are isolated are considered to arise from the respective intermediate isoxazolines by subsequent elimination of methanol or methanethiol. The regioselectivity observed was attributed to the presence of substituents with strong electron-donating ability, and this was accommodated in terms of the FMO theory (133,134). 

The functions of flavoprotein enzymes are numerous and diversified.151-1533 A few of them are shown in Table 15-2 and are classified there as follows (A) oxidation of hemiacetals to lactones, (B) oxidation of alcohols to aldehydes or ketones, (C) oxidation of amines to imines, (D) oxidation of carbonyl compounds or carboxylic acids to a,(3-unsaturated compounds,... 

Table 13 A selection of the a, 3-unsaturated compounds synthesized using a silica-supported base 113 and EOF as the pumping mechanism...

Predicting the Products of the Addition of Nucleophiles to a,/3-Unsaturated Compounds... 

For the more reactive nucleophiles, where addition is essentially irreversible, whether 1,2-addition or 1,4-addition occurs depends on the relative rates of addition to the two electrophilic sites, the carbonyl carbon and the /3-carbon. Lithium aluminum hydride usually gives predominantly 1,2-addition and provides a useful way to reduce the carbonyl group of an a,/3-unsaturated compound. Sodium borohydride, on the other hand, often gives a mixture of 1,2-addition and the completely reduced product, where 1,4-addition followed by 1,2-addition has occurred. Thus, the reaction of 2-cyclohexenone with lithium... 

A large number of reactions have been presented in this chapter. However, all of these reactions involve an enolate ion (or a related species) acting as a nucleophile (see Table 20.2). This nucleophile reacts with one of the electrophiles discussed in Chapters 8, 18, and 19 (see Table 20.3). The nucleophile can bond to the electrophilic carbon of an alkyl halide (or sulfonate ester) in an SN2 reaction, to the electrophilic carbonyl carbon of an aldehyde or ketone in an addition reaction (an aldol condensation), to the electrophilic carbonyl carbon of an ester in an addition reaction (an ester condensation) or to the electrophilic /3-carbon of an a,/3-unsaturated compound in a conjugate addition (Michael reaction). These possibilities are summarized in the following equations ... 

Eder E, Henschler D, Neudecker T. 1982. Mutagenic Properties of allylic and a,(3-unsaturated compounds consideration of alkylating mechanisms. Xenobiotica 12 831-848. 

Cellulose reacts with a,/3-unsaturated compounds containing strongly electron-attracting groups to form substituted ethyl ethers. The most common derivative of this type is cyanoethylcellulose. Cyanoethylation requires strongly basic catalysts and is usually carried out in the presence of sodium hydroxide with acrylonitrile as reagent ... 

Michael addition of enolates to a,[3-unsaturated compounds is a good way of making 1,5-difunction-alfeed compounds, and you should look for these 1,5-relationships in target molecules with a view to making them in this way, Our example is rogletimide, a sedative that can be disconnected to a 1,5-diester. Further 1,5-diCO disconnection gives a compound we made earlier by ethylation of the ester enolate. 

The tertiary amine-catalyzed C-C bond forming reaction of aldehydes with a, 3 -unsaturated compounds is known as the Baylis-Hillmann reaction ". The catalytic amount of tertiary amine such as l,4-diazabicyclo(2.2.2)octane (3.28) is used. 

Enamines may be regarded as synthetic equivalents of enolate ions and are closely related to the enolates derived from ketones in their reactions with acyl halides, alkyl halides and a,3-unsaturated compounds. 

Cerium chloride (CeCl3 7H20) in the presence of Nal catalyzes the diastereoselective dehydration of P hydroxyketones and esters such as 4.8 to the corresponding a, (3-unsaturated compound 4.9. 

Selenenyl halides are relatively stable, though moisture sensitive, compounds that are generally prepared by the reactions shown in Scheme 7 and behave as electrophihc selenium species. " They react with ketones and aldehydes via their enols or enolates to afford a-seleno derivatives (e.g. (17) in equation 11). Similar a-selenenylations of /3-dicarbonyl compounds, esters, and lactones can be performed, although the latter two types of compounds require prior formation of their enolates. Moreover, the a-selenenylation of anions stabilized by nitrile, nifro, sulfone, or various types of phosphorus substituents has also been reported (equation 12). In many such cases, the selenenylation step is followed by oxidation to the selenoxide and spontaneous syn elimination to provide a convenient method for the preparation of the corresponding a ,/3-unsaturated compound (e.g. 18 in equation 11). Enones react with benzeneselenenyl chloride (PhSeCl) and pyridine to afford a-phenylselenoenones (equation 13). 

The anions of allyl- and crotylphosphonamides, (2) and (5) respectively, show excellent selectivity toward a variety of a,3-unsaturated compounds, affording the diastereomerically pure or... 

The diphenylalaninol-derived oxazolidinone skeleton was thus effective as a chiral auxiliary, and was then applied to the /3-radical addition of the a,/3-unsaturated compound 39 (Sch. 16) [32]. The high diastereofacial selectivity of the /3-radical addition can be explained by a chelation model XVII similar to XVI for the preceding allylation reaction. 

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