Ketones a./l-unsaturated

The addition of diazomethane to a,/l-unsaturated ketones, e.g., benzalace-tone and benzalacetophenone, results in A -pyrazolines (16) which decompose thermally to the conjugated ketones (17). Cyclopropane formation is not observed in this instance. 

Anionic Diels-Alder reactions have been studied less extensively with the interest having been focused mainly on the cycloaddition of enolates of a,/l-unsaturated ketones with electron-poor olefins [24] (Equations 1.8 and 1.9). These reactions are fast and stereoselective and can be regarded as a sequential double Michael condensation, but a mechanism involving a Diels-Alder cycloaddition seems to be preferred [24b,f, 25]. 

It has long been known that a, l -unsaturated sulfones resemble a, l -unsaturated ketones and aldehydes in undergoing addition reactions with nucleophilic reagents. These reactions are initiated by nucleophilic attack at the carbon jS to the sulfone group ... 

Compounds of this type with an electron-withdrawing substituent at C-a can be easily prepared by condensation of 2-(benzotriazol-l-yl)acetophenone 869 with aldehydes. Exclusively (E) isomers of a,(l-unsaturated ketones 870 are formed. Treatment with hydrazines converts derivatives 870 into pyrazolines 871. Elimination of benzotriazole from 871 in the presence of mild bases furnishes pyrazoles 872. When in these reactions hydroxylamine is used instead of hydrazines, the corresponding isoxazoles are obtained (Scheme 141) <2001JOC6787>. 

The use of a polyamino acid such as polyleucine as a catalyst for the asymmetric epoxidation of a,/l-unsaturated ketones is clearly established. The advantages and disadvantages of this methodology may be summarised as follows ... 

One-electron reduction of a,/l-unsaturated ketones yields, instead of pina-cols, e-diketones formed by coupling of semireduced species at the /3-carbons... 

If a C=C bond is formally substituted for C=N, the reaction could proceed analogously however, it would require accessible aminoacety-lenes. Reagents of this type exist (e.g., N,N-diethylpropin-l-amine 79), and react with a,/l-unsaturated ketones 26 without a catalyst in inert solvents (73JHC165). This is a convenient approach toward 2-N,N-dialkylamino-4H-pyrans 80 and 81, which are formed, probably, via the hetero-Dieh-Alder reaction (Scheme 22). 

These a,/l-unsaturated ketones and aldehydes are used as reactants in Michael additions (Section 1.10) and Robinson annulations (Section 2.1.4), as well as in a number of other reactions that we will encounter later. Entries 8 and 9 in Scheme 2.11 illustrate Michael reactions carried out by in situ generation of a,/ -unsaturated carbonyl compounds from Mannich bases. 

The (Homer-)Wadsworth-Emmons reaction generally is superior to the Wittig reaction, and has found application in many cases for the synthesis of a,/l-unsaturated esters, a,/l-unsaturated ketones and other conjugated systems. Yields are often better then with the original Wittig procedure. However the Wadsworth-Emmons method is not suitable for the preparation of alkenes with simple, non-stabilizing alkyl substituents. 

Recent advances in alcohol oxidations by rhodium and iridium complexes have mainly focused on Oppenauer-type oxidations or reactions in which this type of oxidation is an intermediate step. An independent result is the oxidation of allyhc (Eq. 9) and benzyUc alcohols with f-BuOOH to the corresponding a,/l-unsaturated ketones [38] with [Rh2(p.-OAc)4]. The reactions were carried out at room temperature in dichloromethane and yields of up to 92% (by GC) in 24-48 h have been described. 

Enolates may be derived from a,/l-unsaturated ketones 16 by base-catalyzed proton abstraction. Under kinetic control the a -proton is abstracted and a cross-conjugated metal dienolate is formed, whereas under thermodynamic conditions the extended dienolate is the major product3,, l. Successful alkylations of dienolates derived from cyclic a,/l-unsaturated ketones have been performed (see Section 1.1.1.3.1.1.2.1.). The related a,/ -unsaturated ester systems have also been investigated22-24. Open-chain structures 16 pose a rather complicated... 

Adger, B.M., Barkley, J V. Bergeron, S., Cappi, M.W., Elowerdew, B.E., Jackson, M. R, McCague, R., Nugent, T.C. and Roberts, S.M. Improved Procedure for Julia-Colonna Asymmetric Epoxidation of a,/l-Unsaturated Ketones Total Synthesis of Diltiazem and Taxol Side-chain. J. Chem. Soc., Perkin Trans. 1 1997, 23, 3501-3507. 

Aldol reaction. The reagent (I) adds in a 1,4-fashion to an a,/J-unsaturated ketone lo give an aluminum enolate, which undergoes aldol condensation with an aldehyde. The adduct is converted into an a-substituted-a./l-unsaturated ketone on sulfoxide elimination.1... 

Cerium(IV) ammonium nitrate (CAN) has been reported to catalyse a facile and efficient aza-Michael addition of aromatic and aliphatic amines to a -unsaturated esters in the absence of solvent under ultrasound irradiation.136 a,/l-Unsaturated ketones react in aqueous solutions under these conditions but only with aliphatic (not aromatic) amines.137... 

In 1979, Pelletier and co-workers reported (203) a method for selective reduction of the oxazolidine ring of C20-diterpenoid alkaloids in the presence of a ketone or an a,/ -unsaturated carbonyl group. Reduction of atisinone (225) with sodium cyanoborohydride at pH 6-7 at room temperature furnished dihydroatisinone (441) in almost quantitative yield. They generalized this reduction method by using various alkaloid derivatives containing either an a,/l-unsaturated ketone or a simple ketone moiety. 

The Mannich reaction of an aldehyde enol (example Formula C in Figure 12.14) or a ketonic enol (example Formula C in Figure 12.15) often proceeds beyond the hydrochloride of a /l-aminocarbonyl compound or the Mannich base. The reason is that the secondary amine or its hydrochloride, which has previously been incorporated as part of the iminium ion, is relatively easy to eliminate from these two types of product. The elimination product is an a,fi-unsaturated aldehyde (example Formula E in Figure 12.14) or an a,/l-unsaturated ketone (example Formula D in Figure 12.15)—that is, an a,/l-unsaturated carbowyl compound. Figure 13.51 will show how the Mannich reaction of a carboxylated lactonic enol provides access to an a-methylene lactone, that is, an a,/l-unsaturated carboxyl compound. 

Reactions of optically pure sulfinyl enones with acyclic dienes have never been reported, perhaps as a result of the discouraging results obtained from racemic substrates [56]. The reaction of a-phenylsulfinyl a,/i-unsaturated ketones with butadiene and 2,3-dimethyl butadiene, under Lewis acid catalysis, yielded the cyclohexadienes resulting from spontaneous elimination of sulfenic acid (precluding any conclusion about the stereoselectivity of the reaction). Analogous results were found by Nishio et al. [57] from reactions of /i-phenylsulfinyl a,/l-unsaturated ketones with acyclic dienes. The bicyclic adducts derived from cyclopentadiene are more stable [57]. In this case, the reactions gave only the exo-sulfinyl adduct,but these stereochemical results were neither confirmed nor discussed in the paper. 

Activation of vinyl C-H bonds with RuH2(CO)(PPh3)3 catalyst has allowed the formal insertion of a,/l-unsaturated ketones or esters into the C-H bond of vinylsilanes and led to a regioselective C-C coupling at the -position [9] (Eq. 6). Activation of the sp2 C-H bond occurred with the aid of chelation of a coordinating functional group and provided vinylruthenium hydride 14. Insertion of olefin afforded the tetrasubstituted alkene 13. The ruthenium activation of a variety of inert C-H bonds has now been performed by Murai [10]. 

There is a serious limitation with respect to the structure of ketones that are accessible by 1,4-addition of Gilman or Normant cuprates to a,/l-unsaturated ketones. As a... 

Acceptor-substituted alkenes that are employed as substrates in Michael additions include a./l-unsaturated ketones (for example, see Figure 10.59), a,/3-unsaturated esters (Figure 10.60), and a,/3-unsaturatcd nitriles (Figure 10.61). The corresponding reaction products are bifunctional compounds with C=0 and/or C=N bonds in positions 1 and 5. Analogous reaction conditions allow Michael additions to vinyl sulfones or nitroalkenes. These reactions lead to sulfones and nitro compounds that carry a C=0 and/or a O N bond at the C4 carbon. 

This strategy has been used to control a variety of tandem addition reactions to a./l-unsaturated ketones Single electron reduction of enone 117 using lithium in... 

Cationic carbon of a,/l-unsaturated ketones coordinating to a titanium halide have been alkylated with an intramolecular olefinic bond (Eqs (205) [496] and (206) [497]). The reaction was terminated by incorporation of a chlorine atom from the Lewis acid, TiC. An a,/3,y,d-dienoate underwent a similar cyclization to give different products, depending on the kind of Lewis acid used (Eq. 207) [498]. 

Unsaturated nitriles (1, 876-881).2 A new one-pot conversion of ketones into a,/i-unsaturated nitriles is formulated in equation (I). The synthesis is applicable to hindered and to a./l-unsaturated ketones. 

Wiesner discovered that the photoreaction of an allene to an a/J-unsaturated ketone always shows the regioselectivity illustrated in the example (487 — 488) above. The general reaction shows another interesting feature in polycyclic a/l-unsaturated ketones, the allene often adds highly selectively to one face of the double bond.402 In the case of the ketone (489), the product (490) appeared from models to be more crowded than the alternative (491) also, the lower face of the double bond in 489 appeared to be the more hindered face. On both counts, the alternative product (491) ought to have been formed and was not. 

The reaction of ylides with alkenes proceeds in two steps according to the MIRC reaction mechanism. Dimethylsulfonium trimethylsilylmethylide (2), generated in situ from the corresponding sulfonium salt 1 with ec-butyllithium, reacts with various a,/l-unsaturated ketones to cyclopropanate the activated C-C double bond (see Table 2). The resulting l-acyl-2-trimethylsilylcyclopropanes 3 are isolated as mixtures of diastereomers. 

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