Enone , conjugate carbonyl from ketones

Michael addition of metal enolates to a,/3-unsaturated carbonyls has been intensively studied in recent years and provides an established method in organic synthesis for the preparation of a wide range of 1,5-dicarbonyl compounds (128) under neutral and mild conditions . Metal enolates derived from ketones or esters typically act as Michael donors, and a,-unsaturated carbonyls including enoates, enones and unsaturated amides are used as Michael acceptors. However, reaction between a ketone enolate (125) and an a,/3-unsaturated ester (126) to form an ester enolate (127, equation 37) is not the thermodynamically preferred one, because ester enolates are generally more labile than ketone enolates. Thus, this transformation does not proceed well under thermal or catalytic conditions more than equimolar amounts of additives (mainly Lewis acids, such as TiCU) are generally required to enable satisfactory conversion, as shown in Table 8. Various groups have developed synthons as unsaturated ester equivalents (ortho esters , thioesters ) and /3-lithiated enamines as ketone enolate equivalents to afford a conjugate addition with acceptable yields. 

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). 

TMM cycloadditions to cyclic and conjugated ketones have also been reported (Scheme 2.22) [31]. The steric nature of the substrate does play a critical role in determining product formation. Thus the cyclic ketone (73) produced 55% yield of the tetrahydrofuran, but no cycloadduct could be obtained from the cyclic ketone (74). The enone (75) gave only carbonyl cycloaddition, whereas enone (76) yielded only olefin adduct. Interestingly, both modes of cycloaddition were observed with the enone (77). The ynone (78) also cycloadds exclusively at the carbonyl function [34]. 

Orthoesters of acrylic acid are converted to y.y-dialkoxyallylzirconocene ethoxides with CpjZr. These latter species serve as 2,2-dialkoxycyclopropyl anion synthon, showing y-addition reactivity toward carbonyl compounds to afford homoallylic alcohols. In the presence of MejSiOTf cyclopropyl carbinols are formed, due to a switch to the -addition mode conjugate addition to enones leads to P-cyclopropyl ketones (e.g., from 2-cyclopen tenone)... 

The electrophile E+ can be an alkyl halide or sulfate, an aldehyde to give aldol products, or an a,P-unsatunited ester when conjugate addition is preferred. Examples from simple alkylation show that the alkyl halide can be primary alkyl, allylic 33, and even an a-bromoester or y-bromo-a,P-unsaturated ester 31. The original carbonyl compound that forms the chiral imine with SAMP or RAMP can be an aldehyde 27 or 29, a ketone (symmetrical 32 or blocked on one side 35), or an enone. Only the reagents and products are shown with oxidative [O] or hydrolytic [H20] workup. Notice that SAMP is used for the formation of either enantiomer of 28 by using different starting materials but that RAMP is used to enter the other enantiomeric series from 32. 

This adduct is in equilibrium with the stable enolate from the keto-ester and elimination now gives an unsaturated carbonyl compound. Such chemistry is associated with the aldol reactions we discussed in Chapter 27. The new enone has two carbonyl groups at one end of the double bond and is therefore a very good Michael acceptor (Chapter 29). A second molecule of enolate does a conjugate addition to complete the carbon skeleton of the molecule. Now the ammonia attacks either of the ketones and cyclizes on to the other. As ketones are more electrophilic than esters it is to be... 

The preparation of silyl enol ethers from carbonyl compounds represents one of the major uses of TMSOTf. Recently, the stereochemistry and regiospeciflcity of such transformation has been addressed for aldehydes and Q -(lV-alkoxycarbonylamino) ketones, respectively. On the other hand, enantiopure silyl enol ethers can be formed by addition of TMSOTf to zinc enolates, which are obtained from the copper-catalyzed enantioselective conjugate addition of dialkyIzinc reagents to cyclic (eq 36) and acyclic enones. ... 

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