Conjugate ketones and esters

Prior to tlie advent of tripbenylpbospbine-stab dized CuH [6a, b, 11], Tsuda and Saegusa described use of Gve mole percent MeCu/DtBAL in THE/HMPA to effect bydtoaluminaiion of conjugated ketones and esters [26], Hie likely aluminium etiolate intermediate could be quendied witli water ot TMSCl, ot alkylated/acylated widi various electrophiles fsudi as Mel, allyl bromide, etc. Sdieme 5.5). Mote... 

Conjugated ketones and esters react with allenylsilanes to yield acylcyclopentenes (Eq. 9.60) [63]. These products are formed by initial 1,4-addition to the conjugated double bond to afford a silyl-stabilized vinyl cation intermediate. 1,2-Silyl migration gives rise to a second silyl-stabilized vinyl cation which cyclizes to the acyl cyclopen-tene (Scheme 9.14). 

Conjugated ketones and esters generally react with chloroform under basic conditions by Michael-type addition of the trichloromethyl anion to the C=C bond or by insertion of dichlorocarbene into the C=C bond, depending on the substitution pattern of the conjugated system (see Sections 6.4 and 7.3). The corresponding reaction with bromoform under basic conditions produces 1,1-dibromocyclopropanes. 

Prior to the advent of triphenylphosphine-stabilized CuH [Ga, b, 13], Tsuda and Saegusa described use of five mole percent MeCu/DIBAL in THF/HMPA to effect hydroalumination of conjugated ketones and esters [26]. The likely aluminium enolate intermediate could be quenched with water or TMSCl, or alkylated/acylated with various electrophiles (such as Mel, alLyl bromide, etc. Scheme 5.5). More... 

In contrast with conjugated ketones and esters, the reaction between conjugated amides and all types of RMgX proceeds through a 1,4-addition [1-4], particularly with the allylic [21,22] and allenylic [6] organomagnesium derivatives [Eq. (7)] ... 

Aryl transfer. The aryl group of ArSnMcj is selectively transferred to aldehydes and to the P-position of conjugated ketones and esters, under the influence of the ionic Rh complex. 

An asymmetric synthesis of functionalized cyclopropanes by condensation of conjugated ketones and esters with chiral y-chloroallylphosphonic bis(amide)s involves the generation of the PfOi-stabilized allyl anions. 

Selective reduction of the olefin unit in conjugated ketones and esters was observed. However, the reactions are often accompanied by side reactions and the reactivity of the complexes toward common functional groups limits their applicability. 

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... 

As with other reactions, silyl esters of phosphorus acids constitute an important and useful category of reagents for conjugate addition reactions. With aldehydes, ketones, and esters, the silyl ester linkage is transferred to the carbonyl oxygen, facilitating the completion of the reaction, generating the free carbonyl or ester upon workup with a protic solvent (Equation 3.25). 

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]. 

In 1998, the rhodium-catalyzed conjugate addition of organostannanes to a,/9-unsatu-rated ketones and esters was reported by Oi [29]. In the reaction, which was carried out in the presence of [Rh(COD)(MeCN)2]BF4 in THF at 60°C, a variety of a,/9-unsatu-rated ketones and esters were transformed into the corresponding conjugate addition products. It is noted that the yield was highly dependent on the substitution pattern of the substrates. For example, /9-substituted enone 40 afforded an 86% yield of 41, whereas methyl vinyl ketone 42 gave only an 18% yield of 43 (Scheme 3.14). The addition of water to the reaction mixture improved the reactivity for the formation of 41 (98%) and 43 (80%) [30]. 

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... 

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... 

We have already established that RCHO and RCOC1 are poor at conjugate addition while ketones and esters are better. An extreme example is the amide 61 that does conjugate addition even with the lithium enolate 60 of cyclohexanone.8... 

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. 

Conjugated aldehydes, ketones and esters may be modeled by acrolein, methylvinyl ketone and methyl acrylate, respectively. Their LUMOs are shown below ... 

Photohydroalkylations are in most cases carbon-centered radical conjugate additions onto electron-deficient olefins [7]. Scheme 3.3 summarizes in detail the pathways for the photogeneration of radicals from R-H(Y) 1. In path a, a photocatalyst P (when excited) cleaves homolytically a suitable C—H bond, and the resultant radical adds to the olefin 2 to form the adduct radical 3. a,(3-Unsaturated nitriles, ketones, and esters... 

The Cp2TiCl/H20 combination can also be used for the chemoselective reduction of aromatic ketones. The reaction discriminates between ketones and alkenes, between ketones and esters and, remarkably, between conjugated and non-conjugated ketones [80]. There is strong evidence that this reduction proceeds via ketyl-type radicals, which are finally reduced by H-atom transfer from 42 [81]. Under dry conditions, titanium-promoted ketyl radicals from aromatic ketones can be used for intermolecular and intramolecular cross-coupling of ketones [82], Thus, depending on whether water is added or not, complementary and versatile synthetic procedure protocols are available. 

Table 4.4 lists some common bases used in organic chemistry. Although butyl-lithium behaves as a very strong base in many reactions, it also exhibits other chemistry, so it is usually used to prepare other strong bases listed in the table. Lithium diisopropylamide, sodium amide, dimsyl anion, and sodium hydride are often used to prepare the conjugate bases of aldehydes, ketones, and esters for use in reactions. Potassium fert-butoxide is employed when a base somewhat stronger than the conjugate bases of most alcohols is needed. 

The conjugated ylides derived from aldehydes, ketones, and esters are all sufficiently stable to be commercially available as the ylids—one of the few examples of specific enol equivalents that you can actually buy. The ylid corresponding to the enolate of acetaldehyde is a solid, m.p. 185-188 °C that reacts well with other aldehydes, even if they are enolizable. 

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... 

The conjugate addition of bis(dimethylphenylsilyl)lithiocuprate to open-chain ,/ -unsaturated aldehydes, ketones and esters, followed by methylation of the intermediate enoiate, is also a highly diastereoselective process the ami-isomer is the predominant product19,zu. 

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. 

The C-H bond cleavage of active methylene compounds with a transition metal catalyst is another method for the functionalization of these C-H bonds. To date, several reactions have been developed. In particular, the asymmetric version of this type of catalytic reaction provides a new route to the enantioselective construction of quaternary carbon centers. One of the most attractive research subjects is the catalytic addition of active methylene C-H bonds to acetylenes, allenes, conjugate ene-ynes, and nitrile C-N triple bonds. The mthenium-catalyzed reaction active methylene compounds with carbonyl compounds involving aldehyde, ketones, and a,y3-unsatu-rated ketones and esters is described in this section. 

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