Preparations of Unsaturated Aldehydes and Ketones

Claisen-Schmidt condensation org chem A reaction employed for preparation of unsaturated aldehydes and ketones by condensation of aromatic aldehydes with aliphatic aldehydes or ketones in the presence of sodium hydroxide. klas-on jshmit kand-on sa-shon ... 

The preparation and some synthetic applications of lithium dialkylcuprates were described earlier (Section 14 11) The most prominent feature of these reagents is then-capacity to undergo conjugate addition to a p unsaturated aldehydes and ketones... 

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. 

A novel and versatile method for preparing polymer-supported reactive dienes was recently developed by Smith [26]. PS-DES (polystyrene diethyl-silane) resin 28 treated with trifluoromethanesulfonic acid was converted to a polymer-supported silyl triflate 29 and then functionalized with enolizable a,jS-unsaturated aldehydes and ketones to form silyloxydienes 30 and 31 (Scheme 4.4). These reactive dienes were then trapped with dienophiles and the Diels Alder adducts were electrophilically cleaved with a solution of TFA. 

The product is a P-hydroxy aldehyde (called an aldol) or ketone, which in some cases is dehydrated during the course of the reaction. Even if the dehydration is not spontaneous, it can usually be done easily, since the new double bond is in conjugation with the C=0 bond so that this is a method of preparing a,P-unsaturated aldehydes and ketones as well as P-hydroxy aldehydes and ketones. The entire reaction is an equilibrium (including the dehydration step), and a,P-unsaturated and P-hydroxy aldehydes and ketones can be cleaved by treatment with OH (the retrograde aldol reaction). There is evidence that an SET mechanism can intervene when the substrate is an aromatic ketone. ... 

The general mechanistic features of the aldol addition and condensation reactions of aldehydes and ketones were discussed in Section 7.7 of Part A, where these general mechanisms can be reviewed. That mechanistic discussion pertains to reactions occurring in hydroxylic solvents and under thermodynamic control. These conditions are useful for the preparation of aldehyde dimers (aldols) and certain a,(3-unsaturated aldehydes and ketones. For example, the mixed condensation of aromatic aldehydes with aliphatic aldehydes and ketones is often done under these conditions. The conjugation in the (3-aryl enones provides a driving force for the elimination step. 

Me3SiCN reacts with both saturated and unsaturated aldehydes and ketones to given silylated cyanohydrines. This reaction has been particularly useful for the regioselective protection of a carbonyl in p. quinones and p. quinol antibiotic metabolite has been prepared. 

The preparation of a,/ -unsaturated aldehydes and ketones is exemplified by the following four important methods (a) the oxidation of the corresponding unsaturated primary or secondary alcohol (b) the Horner-Emmons or Wadsworth-Emmons modification of the Wittig reaction248 (c) the aldol con-... 

Oxametallacycles are prepared from unsaturated aldehydes or ketones. Oxidative cyclization of 6-hepten-2-one (312) catalysed by the Ti catalyst Cp2Ti to give cyclopentanol 315 has been developed. The key step is the cleavage of the strong Ti—O bond in the oxametallacycle 313 with oxophilic hydrosilane, and the silyl ether 314 is formed with regeneration of Cp2Ti [129,130], Cyclization of 5-hexenal (316)... 

The preparation of enols of simple aldehydes and ketones has been achieved by rDA reactions under FVP conditions. Equation (17) illustrates the formation of enols by this method. The percentage of enol reported shows that the enols of aldehydes appear to be isolated more readily than those of the ketones. The last two entries are preparations of the simplest enediols, ( )- and (Z)-ethylene-l,2-diols. A very similar process was used to unmask the protected ethylene cycloadduct (23) and produce 2-hydroxybu-tadiene (24), an elusive enol form of the more stable unsaturated ketone, as given by equation (18). ... 

The addition of HCN to aldehydes or ketones produces cyanohydrins. This is an equilibrium reaction, and for aldehydes and aliphatic ketones the equilibrium lies to the right therefore the reaction is quite feasible, except with sterically hindered ketones such as diisopropyl ketone. However, ketones ArCOR give poor yields, and the reaction cannot be carried out with ArCOAr since the equilibrium lies too far to the left. With aromatic aldehydes the benzoin condensation (16-55) competes. With ot, 3-unsaturated aldehydes and ketones, 1,4-addition competes (15-38). The reaction has been carried out enantioselectively optically active cyanohydrins were prepared with the aid of optically active catalysts.Hydrogen cyanide adds to aldehydes in the presence of a lyase to give the cyanohydrin with good enantioselectivity. " Cyanohydrins have been formed using a lyase m an ionic liquid. 

Catalytic hydrogenation of a,jS-unsaturated aldehydes and ketones yields saturated alcohols, addition of hydrogen occurring both at carbon-carbon and at carbon-oxygen double bonds. It is for the purpose of ultimately preparing saturated alcohols that the aldol condensation is often carried out. For example, /i-butyl alcohol and 2-ethyl-1-hexanol are both prepared on an industrial scale in this way ... 

Ni-Boride, readily prepared by reduction of Ni(OAc)2 with NaBH4, is more reactive than Raney-Ni." Treatment of NiCl2 with NaBH4 in methanol followed by heating yields a stable suspension of M2B, which catalyzes the regioselec-tive 1,4-reduction of a, 3-unsaturated aldehydes and ketones. ... 

Mixed substituted orthoesters, e.g. (383 equation 180), can be obtained by addition of alcohols to ketene 0,0-acetals. With the aid of phosphoranes containing a ketene O,(7-acetal structure, various orthoesters, e.g. (384) and (385) (Scheme 70) were prepared. " Cyclic orthoesters (386)-(390) (Scheme 71) are formed in cycloaddition reactions of ketene 0,0-acetals with aldehydes, ketones, 7.848 gj.yj cyanides, oxiranes, a-keto esters, o-diketones or ketones (with irradiation), a,3-unsaturated aldehydes and ketones (under pressure or catalyzed by ZnCh), diazoaceto-phenone, 7 diazoacetone and azodicarboxylate. ... 

Carbonylation of the cuprate reagent, R (CN)CuLi2, prepared from copper(I) cyanide and an alkyl-lithium, gives a product which can be used for the direct nucleophilic 1,4-acylation of a,3-unsaturated aldehydes and ketones (equation 16). The reaction works particularly well with cyclic a,p-unsaturated ketones to give high yields of the expected 1,4-diketone. 

Lithiobenzothiazole (230) (see Section 3.06.7.10.1) was described to be a carbonyl anion equivalent by Corey and Boger who used it for the preparation of a,) -unsaturated aldehydes and ketones <78TL5,78TL9). As an example, the reaction of (230) with cyclohexanone and dehydration leads to... 

Phenylhydrazones are best prepared in dilute acetic acid solution use of more concentrated acetic acid can lead to formation of 1-acetyl-1-phenyl-hydrazine, m.p. 130-131° (corr.) if there is a neighboring hydroxyl group, which can lead to osazone formation, and if this is to be avoided, then any acidity is unfavorable and the reaction should be carried out as near the neutral point as possible. Condensation usually occurs in the cold, and almost always on short warming on the water-bath. A solvent is often unnecessary. <%,/ -Unsaturated aldehydes and ketones may cyclize to pyrazole derivatives on reaction with phenylhydrazine. 

Nitrogen- and Sulphur-containing Rings.- The preparation of 1,3-thiazines as intermediates in the synthesis of cephalosporins has been published utilising a [4+2] cycloaddition of the l-thia-3-azadienes (81) with a,3-unsaturated aldehydes and ketones. The reaction proceeds thermally, except where R = CC Et when a Lewis-acid catalyst is required, and yields are generally high. 

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