Enolates metal derivatives

Mono and Di-iubstitution Derivatives. The enolic sodium derivative of ethyl acetoacetate (E) is prepared by mixing ethanolic solutions of the ester and of sodium ethoxide. It should not be prepared by the direct action of metallic sodium on the ester, as the reaction is slow and the nascent hydrogen evolved reduces some of the ester to ethyl p4iydroxy- butyrate, CH3CH(OH)CHjCOOEt. 

Lithium ester enolate addition to imines has been used for the construction of optically active p-lactams, e.g. 64 and the lithium enolates have been found to be superior to other metal derivatives for both yields and diastereoselectivity in some cases <00H(53)1479>. Immobilized lithium ester enolates have been utilized for the first time <00OL907> and soluble polymer supported imines were used to obtain N-unsubstituted azetidin-2-ones under mild conditions <00CEJ193>. Both lithium and titanium enolates have been employed to obtain cholesterol absorption inhibitors <99TA4841>. Lithium ynolates 65 add to imines to provide P-lactams in good to excellent yield <00TL5943>. 

It is only since the early 1980s that significant progress has been made with aldol reactions. This chapter introduces some of the most important developments on the addition of metallic enolates and the more important of the related allylic metal derivatives to carbonyl compounds. These processes are depicted as paths A and B in Scheme 3-1. 

The preferential -configuration of the enol esters, derived from p-dicarbonyl compounds under phase-transfer conditions, contrasts with the formation of the Z-enol esters when the reaction is carried out by classical procedures using alkali metal alkoxides. In the latter case, the U form of the intermediate enolate anion is stabilized by chelation with the alkali metal cation, thereby promoting the exclusive formation of the Z-enol ester (9) (Scheme 3.5), whereas the formation of the ion-pair with the quaternary ammonium cation allows the carbanion to adopt the thermodynamically more stable sickle or W forms, (7) and (8), which lead to the E-enol esters (10) [54],... 

Ketone and ester enolates have historically proven problematic as nucleophiles for the transition metal-catalyzed allylic alkylation reaction, which can be attributed, at least in part, to their less stabilized and more basic nature. In Hght of these limitations, Tsuji demonstrated the first rhodium-catalyzed allylic alkylation reaction using the trimethly-silyl enol ether derived from cyclohexanone, albeit in modest yield (Eq. 4) [9]. Matsuda and co-workers also examined rhodium-catalyzed allylic alkylation, using trimethylsilyl enol ethers with a wide range of aUyhc carbonates [22]. However, this study was problematic as exemplified by the poor regio- and diastereocontrol, which clearly delineates the limitations in terms of the synthetic utihty of this particular reaction. 

Recently, a reductive magnesium insertion into a carbon-iodine bond of a / -iodo-a-ketoester has been described. The preparation of the iodomagnesium enolate 17 derived from an a-ketoester is the first preparation of such metallic species in this series. It was obtained from the reaction between the /1-iodo-a-ketoester precursor 16 and magnesium. In this case, the form of the metal is critical and magnesium powder with a large surface area is necessary (equation 6). 

Felhnann and Dubois have described the structure of the enolate 29 derived from the reaction of f-butyl acetate with (MeO)2Mg. The NMR spectrum reveals two O-metallated species, which should be symmetric enolates as proposed by Pinkus and Wu for the bromomagnesium enolate of methyhnesityl ketone (metal is tricoordinated). ... 

The Michael reaction is the conjugate addition of a soft enolate, commonly derived from a P-dicarbonyl compound 24, to an acceptor-activated alkene such as enone 41a, resulting in a 1,5-dioxo constituted product 42 (Scheme 8.14) [52]. Traditionally, these reactions are catalyzed by Bronsted bases such as tertiary amines and alkali metal alkoxides and hydroxides. However, the strongly basic conditions are often a limiting factor since they can cause undesirable side- and subsequent reactions, such as aldol cyclizations and retro-Claisen-type decompositions. To address this issue, acid- [53] and metal-catalyzed [54] Michael reactions have been developed in order to carry out the reactions under milder conditions. 

The corresponding disconnection is of the newly formed C-C bond 8a. The synthons are the acyl cation and a nucleophilic carbon species that might be a metal derivative RM (chapter 13) but will generally be an enolate in the next 10 chapters. And that is how carbonyl compounds are nucleophilic. 

The addition of an alkaline earth metal enolate A to a carbonyl compound is always an exer-gonic process irrespective of whether the enolate is derived from a ketone, an ester, or an amide and whether the carbonyl compound is an aldehyde or a ketone (Figure 13.44, top). One of the reasons for this exergonicity hes in the fact that the alkaline earth metal ion is part of a chelate in the alkoxide B of the aldol addition product. The driving forces for the additions of alkaline earth metal enolates of esters and amides to carbonyl compounds are further increased because the aldol adducts B are resonance-stabilized, whereas the enolates are not. 

The same principles determine bond formation in the complexes formed by the )5-diketones. The ability of diketones to form metallic derivatives is determined by the extent of enolization, e,g. 

We found that the stereoisomeric lithium (94) or sodium (95) enolates showed precisely the same stereoisomerism. Benzoylation of the enolates (XI) and (XII) gave the appropriate stereoisomeric benzoates. Hence, the enolates are not subject to steric isomerization under these conditions. Consequently, no C-metallic derivative of the ketone species is involved, otherwise it would function as an intermediate, allowing the stereoisomeric enolates to isomerize to an equilibrated mixture. Indeed, if a tetramethyl-ammonium salt whose cation cannot form any covalent bond with oxygen is... 

In this manner, both C- and 0-metallo derivatives of keto-enol systems were shown not to be in tautomeric ketone enolate equilibrium (in benzene), thus differing from ketones and enols themselves where ketone enol equilibria exist. Metal enolates, however, are transformed by substitution to the derivatives of the ketone species, while our C-mercury derivatives of ketones or aldehydes have been shown to produce the enol compounds. A conventional scheme (in which ketones, not their metallic derivatives, are shown) thus becomes somewhat unsatisfactory ... 

This reaction was suggested to proceed by alcohol interchange involving the vinyl alcohol formed by enolization of the acetaldehyde. Naturally, the instability of vinylic alcohols relative to tautomeric aldehydes or ketones precluded synthesis of their metal derivatives for a very long time. 

One ingenious and elegant improvement in the standard synthetic procedure for the preparation of alkynes was introduced in 1989 with the use of dimethyl l-diazo-2-oxopropyIphosphonate. - This valuable and efficient reagent is prepared in a single step by reaction of the a-metallated derivative of dimethyl 2-oxopropylphosphonate with tosyl azide. It was observed that the sodium enolate prepared from NaH in 0,1 b,/ I HL solution gives superior results (80-96%) to f-BuOK in... 

It has been proposed that some aldolases function by a similar mechanism (5). In these cases metal ion complexes of sugars may act as electrophiles that react with enolate carbanions derived from the other reaction partner (Scheme 3). Alternatively, the metal ion may stabilize the incipient enolate. 

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