Unsaturated ketones and esters

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. 

The dienol is unstable, and two separate processes have been identified for ketonization. These are a 1,5-sigmatropic shift of hydrogen leading back to the enone and a base-catalyzed proton transfer which leads to the / ,y-enone. The deconjugated enone is formed because of the kinetic preference for reprotonation of the dienolate at the a carbon. Photochemical deconjugation is a synthetically useful way of effecting isomerization of a,) -unsaturated ketones and esters to the j ,y-isomers. 

Protonation of the enolate provides a method for converting a,(3-unsaturated ketones and esters to the less stable (3,y-unsaturated isomers. 

Dialkyl(trimethylsilyl)phosphines undergo 1,4-addition to a,/3-unsaturated ketones and esters to give phosphine-substituted silyl enol ethers and silyl ketene acetals, respectively. A three-component coupling reaction of a silylphosphine, activated alkenes, and aldehydes in the presence of a catalytic amount of GsF affords an aldol product (Scheme 76).290 291... 

Palladium-catalysed C-C bond formation under Heck reaction conditions, which normally requires anhydrous conditions and the presence of copper(I) salts, is aided by the addition of quaternary ammonium salts. It has been shown that it is frequently possible to dispense with the copper catalyst and use standard two-phase reactions conditions [e.g. 18, 19]. Tetra-/i-butylammonium salts catalyse the palladium-catalysed reaction of iodoarenes with alkynes to yield the arylethynes in high yield [20, 21], whereas the reaction with 3-methylbut-1 -yn-3-ol (Scheme 6.30) provides a route to diarylethynes [22]. Diarylethynes are also formed from the reaction of an iodoarene with trimethylsilylethyne [23], Iodoalkynes react with a,p-unsaturated ketones and esters to produce the conjugated yne-eneones [19],... 

Conjugate additions to a, j5-unsaturated ketones and esters are the most important cuprate reactions. Kinetic studies by Krauss and Smith on Me2CuLi and a variety of ketones revealed the following kinetic characteristics (Eq. 10.5), first order both in cuprate dimer and in the enone [60]. 

Perfluoroalkyl lithium reagents undergo reactions typical of their hydrocarbon analogs. For example, perfluoroalkyl lithium reagents generated in situ from perfluoroalkyl iodides and alkyl lithiums reacted readily with aldehydes and ketones to yield the corresponding secondary and tertiary carbinols, and with esters to give either ketones or tertiary carbinols [12]. No 1,4-addition product is observed when a,/ -unsaturated ketones and esters are employed. 

In a closely related reaction, silyl enol ethers add to a,p-unsaturated ketones and esters when catalyzed459 by TiCl,, e.g.,460... 

Buffer catalysis has been applied to induce chiral induction by enantio-selective protonation remarkable enantiomeric excess was achieved in the photodeconjugation of a,/3-unsaturated ketones and esters by using chiral catalysts for the ketonization of photoenols in aprotic solvents.29... 

The use of dimethylsulphoxonium methylide, as a specific methylene insertion reagent for a, /J-unsaturated ketones and esters, is illustrated by its reaction with ethyl crotonate in dimethylformamide solution to form (39) (Expt 7.16).12 The sulphur ylide initially attacks the /J-carbon of the conjugated system (Michael acceptor site), and this is followed by cyclisation and loss of dimethyl sulphoxide. 

RCu-BF3 (8,334-335 9,333). Yamamoto etal.,15 have reviewed and extended their research on the RCu-BF3 system. This system is superior to R2CuLi for conjugate addition to sterically hindered a,/(-unsaturated ketones and esters, but is less useful in reactions with a,/3-unsaturated acids and is unsatisfactory for additions to a,/l-unsaturated nitriles. A typical example is formulated in equation (I). 

This reaction can be used to effect conjugate addition of an alkyl group to a,p-unsaturated sulfoxides, which is generally unsatisfactory with RMgBr or R2CuLi. However, nitroalkanes undergo this 1,4-addition in the presence of a base, particularly DBU, and the product can be selectively reduced to the desired sulfoxide. The same conditions can be used to effect conjugate addition to a,/ -unsaturated ketones and esters.10... 

Disubstituted a -unsaturated ketones and esters are reduced with alkoxylhy-drosilanes in the presence of chiral rhodium(2,6-bisoxazolinylphenyl) complexes to... 

A chiral cationic rhodium complex has been shown to catalyse the enantioselective conjugate addition of silyl anion equivalents to cyclic a,fl-unsaturated ketones and esters, thus providing a facile access to chiral organosilicon compounds.247... 

A A /V /V -Tetramethylelhylcncdiaminc (TMEDA) as catalyst of the Morita-Baylis-Hillman reaction has been found to be more efficient than DABCO in aqueous media.146 1-Methylimidazole 3-/V-oxide promotes the Morita-Baylis-Hillman reaction of various activated aldehydes with ,/i-unsaturated ketones and esters CH2= CHCOR (R = Me, OMe) in solvent-free systems.147 In another study, the Morita-Baylis-Hillman reaction has been successfully performed under aqueous acidic conditions at pH 1, using a range of substrates and tertiary amines as catalysts.148... 

Conjugate reduction of a, -unsaturated carbonyl compounds.1 The HCOOK/ Pd(OAc)2 system is convenient for transfer conjugate reduction of a,f)-unsaturated ketones and esters and of 2-buten-4-olides to the corresponding saturated compounds. The reaction is carried out in DMF at 60° using an excess of HCOOK. 

In intermolecular cyclopropanations [100], it was found better to use a-bromoesters and amides as ylide precursors and a,/ -unsaturated ketones and esters as electron-deficient alkenes - rather than using a-haloketones as the ylide precursor. (For experimental details see Chapter 14.11.4). The reaction gives access to a range of 1,2-dicarbonyl-substituted cyclopropanes (see Fig. 10.5). The al-kene could have an aryl-, alkyl- or indole-substituted ketone, and a-substitution was also tolerated. Notably, Weinreb amides could be used as the ylide precursor and the product subsequently transformed into a diketocyclopropane. Both enan-... 

Thermolysis of 2-halo-2/7-azirincs, as well as of P-azido-a,p-unsaturated ketones and esters, gave rise to new 4-haloisoxazoles in high yields <02S605>. 

A very interesting synthetic application of diethyl dichlorolithiummethylphos-phonate is described by Villieras et al. In a one-step procedure the carbenoid can subsequently be reacted with ethyl carbonochloridate or a carboxylic acid chloride and an aldehyde followed by a Wittig-Homer elimination on warming the reaction mixture. In this way, it is possible to obtain a-chloro-a, J-unsaturated ketones and esters in good yields39) ... 

Lithium divinyl cuprates. The addition of. inylic cuprates to chiral -y-alkoxy-a,p-unsaturated ketones and esters proceeds with high diastercoselectivity the major product is that in which the vinyl group is anti to the ally lie alkoxyl group. The geometry of the unsaturated system docs not affect the stcrcocheiiiistry of the addition. 

RCu BFj is also useful for the conjugate addition to the a,P unsaturated ketones and esters, whose double bonds are sterically crowded. Such conjugated additions occur selectively by a 1,4 manner. Certain a,P-unsaturated carboxylic acids also undergo a 1,4-addition through this reagent (Eq. 88) Methyl sorbate reacts with BuCu BFj to give predominantly the 1,4-adduct (Eq. 89). Two mechanistic... 

Conjugate addition of stannyl anions to acyclic a,/ -unsaturated ketones and esters is also stereoselective, cf. 66, although in some cases (cf. 4 and 5s) the stereoselectivity is low5,6. 

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