Unsaturated compounds aldehydes

Highly diastereoselective acetate aldol additions using chlorotitanium enolates of mesityl-substituted JV-acetylthiazolidinethione 136 has been documented <07OL149>. These aldol reactions proceed in high yields and diastereoselectivities (94/6 to 98/2) for aliphatic, aromatic, and a,P-unsaturated aldehydes. Compound 136 also undergoes double diastereoselective aldol additions with chiral aldehyde 139 to give adduct 140 in high yields. 

Compound (74) is a useful synthon for 2,3-disubstituted cyclopentanones. Alkylation and deprotection of PhSCH=CHCH20Me provides an approach to a/3-unsaturated aldehydes.Compounds (75 X = S, R = C02Me) can be alkylated and then converted into R CH2C02Me or R CHIC02Me, whilst benzan-nelated analogues of (75 X = 0, R = alkyl) can be converted into derivatives of the type R YCH2R (Y = e.g. NH or 0). ... 

Lipid peroxidation of polyunsaturated fatty acids yields a group of reactive unsaturated aldehydic compounds (enals) such as 2-alkenals (acrolein [Acr], crotonaldehyde [Cro], 2-hexenal), 4-hydroxy-2-alkenals (4-hydroxy-2-nonenal [HNE], 4-hydroxy-2-hexenal [HHE]), and ketoaldehydes (malondialdehyde [MDA], glyoxal, 4-oxo-2-nonenal [ONE]) (Uchida 2003) (Eigure 18.1). 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

Aldol condensation offers an effective route to a p unsaturated aldehydes and ketones These compounds have some interesting properties that result from conjugation of the carbon-carbon double bond with the carbonyl group As shown m Figure 18 6 the rr systems of the carbon-carbon and carbon-oxygen double bonds overlap to form an extended rr system that permits increased electron delocalization... 

The carbonyl group withdraws rr electron density from the double bond and both the carbonyl carbon and the p carbon are positively polarized Their greater degree of charge separation makes the dipole moments of a p unsaturated carbonyl compounds signifi cantly larger than those of comparable aldehydes and ketones... 

P carbon atom of an a 3 unsatu rated carbonyl compound is elec trophilic nucleophiles especially weakly basic ones yield the prod ucts of conjugate addition to a 3 unsaturated aldehydes and ketones... 

Stabilized anions exhibit a pronounced tendency to undergo conjugate addition to a p unsaturated carbonyl compounds This reaction called the Michael reaction has been described for anions derived from p diketones m Section 18 13 The enolates of ethyl acetoacetate and diethyl malonate also undergo Michael addition to the p carbon atom of a p unsaturated aldehydes ketones and esters For example... 

A particularly useful reaction has been the selective 1,2-reduction of a, P-unsaturated carbonyl compounds to aHyUc alcohols, accompHshed by NaBH ia the presence of lanthanide haUdes, especially cerium chloride. Initially appHed to ketones (33), it has been broadened to aldehydes (34) and acid chlorides (35). NaBH by itself gives mixtures of the saturated and unsaturated alcohols. 

AldolRea.ctlons, In the same way, hydroxybenzaldehydes react readily with aldehydes and ketones to form a,P-unsaturated carbonyl compounds in the Claisen-Schmidt or crossed-aldol condensation (60). 

These reversible reactions are cataly2ed by bases or acids, such as 2iac chloride and aluminum isopropoxide, or by anion-exchange resias. Ultrasonic vibrations improve the reaction rate and yield. Reaction of aromatic aldehydes or ketones with nitroparaffins yields either the nitro alcohol or the nitro olefin, depending on the catalyst. Conjugated unsaturated aldehydes or ketones and nitroparaffins (Michael addition) yield nitro-substituted carbonyl compounds rather than nitro alcohols. Condensation with keto esters gives the substituted nitro alcohols (37) keto aldehydes react preferentially at the aldehyde function. 

Other commonly occurring chemical groups ia essential oils iaclude aromatics such as P-phenethyl alcohol, eugenol, vanillin, ben2aldehyde, cinnamaldehyde, etc heterocycHcs such as iadole (qv), pyra2iaes, thia2oles, etc hydrocarbons (Liaear, branched, saturated, or unsaturated) oxygenated compounds such as alcohols, acids, aldehydes, ketones, ethers and macrocyclic compounds such as the macrocyclic musks, which can be both saturated and unsaturated. 

Hydroqulnollnes. Pyrans formed by reactions of a,P-unsaturated aldehydes with 1-ethoxycyclohexene and treated with hydroxjiamine are converted ia good yield to 5,6,7,8-tetrahydroquiQolines (117). These compounds can be dehydrogenated to the corresponding quiaolines. The parent reduced product has been prepared by heating O-aHylcyclohexanone oxime (118). 

Cyclic g-haloacetals and -ketals have been prepared by variations on two basic methods. The most frequently used method involves the combination of an a,B-unsaturated carbonyl compound (acrolein, methyl vinyl ketone, croton-aldehyde, etc.) a diol, and the anhydrous hydrogen halide. All possible sequences of combining these three have been used. In most cases the... 

The procedure described illustrates a general method for the preparation of o ,j3-unsaturated aldehydes and ketones from the enol ethers of 3-dicarbonyl compounds. 

The diminished tt electron density in the double bond makes a,p-unsaturated aldehydes and ketones less reactive than alkenes toward electrophilic addition. Electrophilic reagents—bromine and peroxy acids, for example—react more slowly with the carbon-carbon double bond of a,(3-unsaturated carbonyl compounds than with simple alkenes. 

The reactions of enamines with aldehydes (329,350) are noteworthy in that they provide a route to the monobenzylidene derivatives of five- to seven-membered eyclic ketones as well as a method for the formation of other a, 9-unsaturated carbonyl compounds, in fair to good yields. The condensation of benzaldehyde with enamines is also involved in the formation of 3,5-dibenzylpyridine from piperidine and benzaldehyde (191-193). 

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

Despite the increasing information on the photochemistry of 2,4-dienones and other unsaturated ketones, as well as on the ring-chain valence isomerism of halogen-substituted pyran and dihydi opyran systems,the data are still very scarce. The intermediate formation of pyrans valence-isomeric with unsaturated carbonyl compounds in the pyridine syntheses based on reactions of ammonia with aldehydes or ketones, advocated by various authors (cf. Section II,B,2,f), is still rather speculative. (See also Section II,B,2,e for the valence isomerism of 5-chloro-2,4-dienones with pyrylium chlorides.)... 

More recent work has shown that the 2-unsubstituted compound 40 (R = H, R = Pr ) is an effective formyl anion equivalent which reacts at C2 and undergoes both 1,4-addition to a,(3-unsaturated carbonyl compounds and 1,2-addition to aldehydes (93TL3907 96T4719). 

One of the most important routes to isoxazole and isoxazoline rings involving the formation of the 1—5 and 2—3 bonds involves the condensation of hydroxylamine with a,/8-unsaturated carbonyl compounds. This method was previously widely used, but it is now of no preparative value, though it has been recently applied to determine the configuration of oximes. " The only new modification of this synthesis is the use of the acetals (27) of a,/8-acetylenic aldehydes for preparation of 5-substituted isoxazoles (28)... 

The addition of the a-carbon of an enolizable aldehyde or ketone 1 to the carbonyl group of a second aldehyde or ketone 2 is called the aldol reaction It is a versatile method for the formation of carbon-carbon bonds, and is frequently used in organic chemistry. The initial reaction product is a /3-hydroxy aldehyde (aldol) or /3-hydroxy ketone (ketol) 3. A subsequent dehydration step can follow, to yield an o ,/3-unsaturated carbonyl compound 4. In that case the entire process is also called aldol condensation. 

If the initially formed /3-hydroxy carbonyl compound 3 still has an a-hydrogen, a subsequent elimination of water can take place, leading to an o ,/3-unsaturated aldehyde or ketone 4. In some cases the dehydration occurs already under the aldol reaction conditions in general it can be carried out by heating in the presence of acid ... 

From a mixture of two different aldehydes, each with a-hydrogens, four different aldols can be formed—two aldols from reaction of molecules of the same aldehyde -I- two crossed aldol products not even considering possible stereoisomers (see below). By taking into account the unsaturated carbonyl compounds which could be formed by dehydration from the aldols, eight different reaction products might be obtained, thus indicating that the aldol reaction may have preparative limitations. 

Reduction of unsaturated carbonyl compounds to the saturated carbonyl is achieved readily and in high yield. Over palladium the reduction will come to a near halt except under vigorous conditions (73). If an aryl carbonyl compound, or a vinylogous aryl carbonyl, such as in cinnamaldehyde is employed, some reduction of the carbonyl may occur as well. Carbonyl reduction can be diminished or stopped completely by addition of small amounts of potassium acetate (i5) to palladium catalysts. Other effective inhibitors are ferrous salts, such asferroussulfate, at a level of about one atom of iron per atom of palladium. The ferrous salt can be simply added to the hydrogenation solution (94). Homogeneous catalysts are not very effective in hydrogenation of unsaturated aldehydes because of the tendencies of these catalysts to promote decarbonylation. 

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