Unsaturated ketones reactions

Figure 49.2. Catalytic oxidation of the allylic alcohols 11, 16 and 17 with FePcCli -S to the corresponding a, 5-unsaturated ketones. Reaction conditions 0.125 M allylic alcohol in acetone, 0.5 % mol FePcClis-S, 1.3 mmol of dry TBHP, 40T, 3 h.

In order to study the factors determining the regioselectivity of sodium borohydride reduction of a, -unsaturated ketones, reactions with 3-methylcyclohexenone, carvone and cholestenone were carried out in 2-propanol, diglyme, triglyme or pyridine. Mixtures of 1,2- and 1,4-reduction products were obtained in the alcoholic and ether solvents, whereas pure 1,4-reduction was observed in pyridine. Addition of triethylamine to NaBH4 in diglyme led to formation of triethylamine borine, EtsN BHs. Similarly, with pyridine, pyridine borine could be isolated, leading to exclusive 1,4-reductions. 

Dihydroazines based on a,p-unsaturated ketones reactions 06COC297. 

These include the cycloaddition between a ketene and a Schiff base (reaction 1), two addition reactions to a,3 unsaturated ketones (reactions 2 and 3), and the condensation of two molecules of aldehyde to yield an oxirane derivative (reaction 4), see Scheme 2. 

Ammonia and amines add readily to the double bond in a, -unsaturated ketones (reaction 77) and nitro compoimds (reaction 78) catalysis being usually unnecessary even for aromatic amines. 

The aldol reactions of titanium enolates generated in situ were reported by Harrison [27] to give excellent yield and selectivity for syn aldol products, as shown in Table 2.10. However, methyl ketones tended to eliminate under the reaction conditions and provided a,/i-unsaturated ketones. Reactions with propiophenone and benzaldehyde provided excellent yields of aldolates, with syn aldols being the major product (95 5 ratio). The stereochemical outcome was rationalized by Zimmerman-Traxler transition state model 67. 

Similarly Michael additions of thiols and nitroalkanes to a,3— unsaturated ketones [reactions 2 and 3] catalysed by anhydrous potassium fluoride in the presence of the above ammonium salts produces optical yields of up to 35%. Another unambiguous... 

Claisen-Schmidt reaction. Aromatic aldehydes condense with aliphatic or mixed alkyl-aryl ketones in the presence of aqueous alkali to form ap-unsaturated ketones ... 

By catalytic reduction of a p-unsaturated ketones, prepared from aldehydes by the Claisen - Schmidt reaction (see under Aromatic Aldehydes), for example ... 

The addition of active methylene compounds (ethyl malonate, ethyl aoeto-acetate, ethyl plienylacetate, nltromethane, acrylonitrile, etc.) to the aP-double bond of a conjugated unsaturated ketone, ester or nitrile In the presence of a basic catalyst (sodium ethoxide, piperidine, diethylamiiie, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields trlcarballylic acid ... 

An interesting case are the a,/i-unsaturated ketones, which form carbanions, in which the negative charge is delocalized in a 5-centre-6-electron system. Alkylation, however, only occurs at the central, most nucleophilic position. This regioselectivity has been utilized by Woodward (R.B. Woodward, 1957 B.F. Mundy, 1972) in the synthesis of 4-dialkylated steroids. This reaction has been carried out at high temperature in a protic solvent. Therefore it yields the product, which is formed from the most stable anion (thermodynamic control). In conjugated enones a proton adjacent to the carbonyl group, however, is removed much faster than a y-proton. If the same alkylation, therefore, is carried out in an aprotic solvent, which does not catalyze tautomerizations, and if the temperature is kept low, the steroid is mono- or dimethylated at C-2 in comparable yield (L. Nedelec, 1974). 

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

The furo- and pyranobenzopyranones 114 and 115 are prepared by the reaction of 0-enolate of i(-keto lactone 113[132], The isoxazolc 117 is obtained by the oxidation of the oxime 116 of a, /3- or, d, 7-unsaturated ketones with PdCh and Na2C03 in dichloromethane[l 33], but the pyridine 118 is formed with PdCl2(Ph3P)2 and sodium phenoxide[134]. 

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

Aryl or alkenyl halides attack the central carbon of the allene system in the 2,3-butadien-l-ol 120 to form the 7r-allyl intermediate 121, which undergoes elimination reaction to afford the o,/3-unsaturated ketone 122 or aldehyde. The reaction proceeds smoothly in DMSO using dppe as a ligandflOl]. 

Butyl vinyl ether reacts with aroyl chlorides using Pd(OAc)2 without a ligand to give the unsaturated ketone 839, which is a precursor of a 1-aryl-1,3-dicarbonyl compound. The reaction is regioselective /3-attack. Addition of PhjP inhibits the reaction[718]. 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

Ailyl enol carbonates derived from ketones and aldehydes undergo Pd-cat-alyzed decarboxylation-elimination, and are used for the preparation of a, /3-unsaturated ketones and aldehydes. The reaction is regiospecific. The regio-isomenc enol carbonates 724 and 726, prepared from 723, are converted into two isomeric enones, 725 and 727. selectively. The saturated aldehyde 728 can be converted into the a,/3-unsaturated aldehyde 730 via the enol carbonate 729[459]. 

ZnCl2 is essential. The reaction was utilized in the synthesis of strophanthidin. Only the q, /3-alkene in the a, fi- and 7, (5-unsaturated ketone 51 is reduced selectively[47], Triethoxysilane is another reducing agent of the enone 52 and simple alkenes[48]. 

Addition of Carbanions to a B Unsaturated Ketones The Michael Reaction... 

A synthetically useful reaction known as the Michael reaction, or Michael addition, involves nucleophilic addition of carbanions to a p unsaturated ketones The most common types of carbanions used are enolate 10ns derived from p diketones These enolates are weak bases (Section 18 6) and react with a p unsaturated ketones by conjugate addition... 

---