Ketones, unsaturated enolates from

Lithium-ammonia reduction of a,/ -unsaturated ketones (entry 6, Scheme 1.4) provides a very useful method for generating specific enolates.26 The desired starting materials are often readily available, and the position of the double bond in the enone determines the structure of the resulting enolate. This and other reductive methods for generating enolates from enones will be discussed more frilly in Chapter 5. Another very important method for specific enolate generation, the addition of organometallic reagents to enones, will be discussed in Chapter 8. 

A synthetically useful reaction known as the Michael reaction, or Michael addition, involves nucleophilic addition of carbanions to a,(3-unsaturated ketones. The most common types of carbanions used are enolate ions derived from p-di ketones. These enolates are weak bases (Section 18.6) and react with a, 3-unsaturated ketones by conjugate addition. 

A new method of kinetically controlled generation of the more substituted enolate from an unsymmetrical ketone involves precomplexation of the ketone with aluminium tris(2,6-diphenylphenoxide) (ATPH) at —78°C in toluene, followed by deprotonation with diisopropylamide (LDA) highly regioselective alkylations can then be performed.22 ATPH has also been used, through complexation, as a carbonyl protector of y./)-unsaturated carbonyl substrates during regioselective Michael addition of lithium enolates (including dianions of /i-di carbonyl compounds).23... 

Fig. 13.20. Generation of enolates from a,/3-unsaturated ketones via Birch reduction (top line) or by reduction with L-Selectride (bottom line).

Aryl-substituted enolizable keto compounds initiate the copolymerization of unsaturated polyesters with styrene. Gel times of the same order as those obtained with conventional peroxide initiators can be attained exotherms, however, are considerably lower, this latter effect being of technological interest—e.g., casting resins. Since a radical mechanism has been proved, it is postulated that radicals result from keto hydroperoxides which have been formed from the aryl-substituted enols via autoxidation. Steric effects and resonance may partly account for differences in the catalytic activity of some and for the inhibiting effect of other ketones and enols. NMR spectroscopy indicates further that cis-trans isomerism may influence the catalytic effectiveness of pure enols. 

Introduction The extended enolate problem Kinetic and thermodynamic control Wittig and Horner-Wadsworth-Emmons Reactions Extended Aza-Enolates Extended Lithium Enolates of Aldehydes Summary a-Alkylation of Extended Enolates Reaction in the y-Position Extended Enolates from Unsaturated Ketones Diels-Alder Reactions Extended Enolates from Birch Reductions The Baylis-Hillman Reaction The Synthesis of Mniopetal F... 

Simple stereoselective aldol reactions (chapter 3) can also be controlled by tandem conjugate addition. Addition of Me2CuLi to the simple unsaturated ketone 27 gives the lithium enolate 28. It would be very difficult to produce this enolate from the parent ketone MhiCO.Me with regio- or stereoselectivity. The cyclic transition state 29 with zinc replacing lithium then shows the way to the anti-aldol7 30. 

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... 

More complex products are obtained from cyclizations in which the oxidizable functionality and the alkene are present in the same molecule. y9-Keto esters have been used extensively for Mn(III)-based oxidative cyclizations and react with Mn(OAc)3 at room temperature or slightly above [4, 10, 11, 15], They may be cyclic or acyclic and may be a-unsubstituted or may contain an a-alkyl or chloro substituent. Cycloalkanones are formed if the unsaturated chain is attached to the ketone. y-Lactones are formed from allylic acetoacetates [10, 11]. Less acidic /3-keto amides have recently been used for the formation of lactams or cycloalkanones [37]. Malonic esters have also been widely used and form radicals at 60-80 °C. Cycloalkanes are formed if an unsaturated chain is attached to the a-position. y-Lactones are formed from allylic malonates [10, 11]. yff-Diketones have been used with some success for cyclizations to both alkenes and aromatic rings [10, 11]. Other acidic carbonyl compounds such as fi-keto acids, /3-keto sulfoxides, j8-keto sulfones, and P-nitro ketones have seen limited use [10, 11]. We have recently found that oxidative cyclizations of unsaturated ketones can be carried out in high yield in acetic acid at 80 °C if the ketone selectively enolizes to one side and the product cannot enolize... 

Surfaces with basic sites form enolates from both the aldehydes and ketones, leading to multiple aldol condensations and Michael additions. " Candidate molecules must be enolizable, i.e., contain an a-hydrogen atom. Aldol condensation / Michael addition products cover the range from a,p-unsaturated aldehydes, saturated aldehydes, hydrogenated products (alcohols), and the heavier aromatics resulting from multiple condensations. The presence of coordina-... 

This reaction was first reported by Haddadin and Issodorides in 1965. It is the preparation of quinoxaline-1,4-dioxides from the cycloaddition between benzofuroxan (i.e., benzofu-razan A -oxide) and dienes, a.y -unsaturated ketones, enamines, or enolates. Unfortunately, this reaction is not named after the authors who discovered it instead it is known as the Beirut reaction after the city in which the inventors carried out is the initial work. In most cases, ketones," /3-diketones, j8-ketoesters, )8-ketonitrile, LS-dinitrile, and/8-ketoamides all are suitable for this reaction, and the corresponding enolates can be easily prepared in the presence of a weak base such as triethylamine. In addition, even phenolic enolates from phenol, resorcinol, hydroquinone, or benzoquinone undergo a similar dehydrative condensation with benzofuroxan under mild conditions (e.g., Na0H/H20, H2O, MeOH/RNH2, Si02/MeCN at room temperature), to give phenazine iV,iV -dioxide derivatives. ... 

Proton abstraction from a,jS-unsaturated ketones occurs preferentially from the y-carbon atom to afford the more stable enolate ... 

In the mid 1960s, Issidorides and Haddadin addressed some of the limitations in substitution met in earlier reported procedures by developing a synthesis of heteroaromatic A/ oxides that, upon reduction, afford heteroaromatic compounds like phenazine. The Beirut reaction, named after its origin from the capital of Lebanon, involves condensation of benzofurazan oxide (benzo[1,2,5]oxadiazole-1-oxide) and, e.g., enamines, dienes, aldehydes, a,/ -unsaturated ketones, or enolates to form heterocycles... 

This new methodology is quite general and can be applied to the magnesium complexes of 1,2-dimethylenecyclopentane, 1,2-dimethylenecyclohep-tane, and 2-methyl-3-phenyl-l,3-butadiene. Likewise, other carboxylic esters, such as butyl and ethyl benzoates, can also be used to make various fused carbocyclic enols or p,y-unsaturated ketone products. Significantly, the overall synthetic process to form fused carbocyclic enols from the corresponding l,2-bis(methylene)cycloalkanes represents a formal [4+1] annulation. 

The reductive generation of specific lithium enolates from cyclic ajS-unsaturated ketones can be extended to acyclic analogues however, much polymethylation was observed on alkylation with methyl iodide in the latter cases. This undesirable side-reaction was ascribed to the effect of the conjugate base of the proton donor used in the reduction step, it being minimized by use of triphenylcarbinol as proton donor. 

Potassium hydroxide in acetonitrile solution with dicyclohexyl-18-crown-6 gives good yields of aj8-unsaturated nitriles from a variety of aldehydes and ketones, including benzophenone. One consequence of the rate enhancement of the [3,3] sigmatropic rearrangement of certain enolates reported last year by Evans is a new route to prenylated quinones (Scheme 14). A development in the synthesis of olefins by the boron mediated cross-coupling reaction is the use of the boronic... 

Trapping of the initially formed aluminium enolate from a,/8-unsaturated ketones and diethylaluminium cyanide, with chlorotrimethylsilane-pyridine yields the corresponding silylenol ethers (35), which can be alkylated or phenyl-sulphenylated (Scheme 22). ... 

Miscellaneous Reactions.—a-Alkoxylated a-lithioacetates may be alkylated,may react with ketones (the products from which cyclize to f3-lactones, themselves precursors of enol ethers by CO2 elimination" ), and may be condensed with lactones, as applied in a synthesis of natural product derivatives.The trianion derived from PhCH(0H)C02H is. C-alkylated but only in mediocre yield.The anions PhSCHCO and PhSCHC02Me react efficiently with electrophiles however, the former adds 1,2 to a, 8-unsaturated ketones, whereas the latter adds 1,4- ... 

Carbonylation of enol triflates derived from ketones and aldehydes affords Q,/)-unsaturated esters[332]. Steroidal esters are produced via their aryl and enol triflates[328]. The enol triflate in 477 is more reactive than the aryl tritlate and the carbonylation proceeds stepwise. First, carbonylation of the enol triflate affords the amide 478 and then the ester 479 is obtained in DMSO using dppp[333]. 

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