Metal enolates formation

Conjugate reduction by the transition metal-hydride (TM - H) accompanied by transition metal enolate formation... 

As first demonstrated by Stork,the metal enolate formed by metal-ammoni reduction of a conjugated enone or a ketol acetate can be alkylated in liquic ammonia. The reductive alkylation reaction is synthetically useful since ii permits alkylation of a ketone at the a-position other than the one at whicf thermodynamically controlled enolate salt formation occurs. Direct methyl-ation of 5a-androstan-17-ol-3-one occurs at C-2 whereas reductive methyl-... 

In the Michael addition of achiral enolates and achiral Michael acceptors the basic general problem of simple diastereoselection (see Section D.1.5.1.3.2.), as described in Section 1.5.2.3.2. is applicable. Thus, the intermolecular 1,4-addition of achiral metal enolates to enones, a.jS-unsat-urated esters, and thioamides, results in the formation of racemic syn-1,2 and/or anti-3,4 adducts. 

GL 4] [R 5] [P 5] The rate of the fluorination of y0-keto esters is usually correlated with the enol concentration or the rate of enol formation as this species is actually fluorinated [15, 16]. For the fluorination of ethyl 2-chloroacetoacetate in a micro reactor, much higher yields were found as expected from such relationships and as compared with conventional batch processing which has only low conversion. Obviously, the fluorinated metal surface of the micro channel promotes the enol formation. 

C - C bond formation involving the transition metal enolate... 

With conjugated enone substrates, the alkoxymetallation leads to the formation of a metal enolate that can undergo a facile protonation to accomplish the hydroalkoxylation. Following this mechanism, various /3-alkoxyketones were obtained in good yields by the addition of primary and secondary alcohols to methyl vinyl ketone under cationic Pd(n) catalysis.443 Similarly, [Rh(COD)(OMe)]2 was found to catalyze the hydroalkoxylation of both methyl vinyl ketone and phenyl vinyl ketone (Equation (121)).444... 

Sodium borohydride (160) was found to serve as a hydrogen donor in the asymmetric reduction of the presence of an a,pi-unsaturated ester or amide 162 catalyzed by a cobalt-Semicorrin 161 complex, which gave the corresponding saturated carbonyl compound 163 with 94-97% ee [93]. The [i-hydrogen in the products was confirmed to come from sodium borohydride, indicating the formation of a metal enolate intermediate via conjugate addition of cobalt-hydride species (Scheme 2.17). 

Stoichiometric, irreversible formation of enolates from ketones or aldehydes is usually performed by addition of the carbonyl compound to a cold solution of LDA. Additives and the solvent can strongly influence the rate of enolate formation [23]. The use of organolithium compounds as bases for enolate formation is usually not a good idea, because these reagents will add to ketones quickly, even at low temperatures. Slightly less electrophilic carbonyl compounds, for example some methyl esters [75], can, however, be deprotonated by BuLi if the reactants are mixed at low temperatures (typically -78 °C), at which more metalation than addition is usually observed. A powerful lithiating reagent, which can sometimes be used to deproto-nate ketones at low temperatures, is tBuLi [76],... 

In some instances, for example the reactions involving complexes 7 and 8, the metal-chiral ligand complex alone does not suffice for good performance and addition of external base in either catalytic or (over)stoichiometric quantity, or even trimethylsilyl triflate, is required [13, 14]. Apparently, in Scheme 6, although the metal center(s) is (are) fundamental for a well-ordered transition state and for acceptor activation, the external base is required for deprotonation leading to formation of a transient metal enolate. 

In a general sense, the Reformatsky reaction can be taken as subsuming all enolate formations by oxidative addition of a metal or a low-valent metal salt into a carbon-halogen bond activated by a vicinal carbonyl group, followed by reaction of the enolates thus formed with an appropriate electrophile (Scheme 14.1).1-3 The insertion of metallic zinc into a-haloesters is the historically first and still most widely used form of this process,4 to which this chapter is confined. It is the mode of enolate formation that distinguishes the Reformatsky reaction from other fields of metal enolate chemistry. 

In Figure 13.1, the enolate structures are shown with the charge on the heteroatom and with the heteroatom in association with a metal ion. The metal ion stems from the reagent used in the enolate formation. In the majority of the reactions in Chapter 13, the enolate is generated by deprotonation of C,H acids. The commonly employed bases contain the metal ions Li , Na , or K . Therefore, in Chapter 13, we will consider the chemistry of lithium, sodium, and potassium enolates. 

Alkaline earth metal amides have a unique place in enolate chemistry in light of the preceding discussion. Yet, amides without steric demand—from NaNH2 to LiNEt2— also are not suitable for enolate formations, since their nucleophilicities exceed their basicities. On the other hand, the amides LTMP, LDA, and LiHMDS (structures in Figure 4.17) are so bulky that they can never act as nucleophiles and always deprotonate C,H acids to the respective enolates. 

Over the past 30 years, the widespread use of Sml2 in organic synthesis has brought the chemistry of Sm(III) enolates to the fore as many processes using the reagent involve the formation and reaction of these organometallic species. Although Sm(III) enolates can be exploited as nucleophiles in a number of reactions, their reactivity is still poorly understood and they appear to behave differently to more conventional metal enolates for example, there are few... 

Arene ruthenium complexes are used frequently in metal-mediated organic synthesis for a wide range of reactions.5 For the purposes of our studies we have focused attention mainly on enol formate synthesis as a representative reaction for comparing the activity of 2 with its non-supported analogue 5. As with the supported cobalt complex, we find that attachment of 5 to a polymer support has little effect in its catalytic activity with a range of enol formates being prepared in high yield. 

Phenylethynylcopper and phenacyl bromide afford intractable tars upon long reflux in DMF. However, at higher temperatures ( 240°C) a-haloketones can be converted in one step to furan derivatives [Eqs. (68a), (68b)] uncyclized acetylenic ketones are not isolated. The cycliza-tion is catalyzed by copper(I) through the copper-coordinated enol 128). Reaction of a,a -dibromoketones with an excess of a diorganocuprate is a new method for the a-alkylation of a ketone 231a). Only the monoalkyl derivative is isolated. The evidence points to the formation of a cyclopropanone intermediate which reacts with more of the cuprate to give an a-alkylated metal enolate. 

The fluorination of carbonyl compounds is facilitated by the formation of a metal enolate prior to fluorination. The fluorination of metal enolates has been successfully achieved using a wide variety of N-F reagents, e.g. A-fluorosulfonamidcs, chiral /V-fluorocamphorsul-tam." A-fluorooxathiazinone dioxides," iV-fluoroperfluoroalkylsulfonamides." 1-fluoropyridinium trifluoromethanesulfonates, " and l-alkyl-4-fluoro-1,4-dia7-oniabicyclo[2.2.2]octane salts" (see Table 8). 

Metal enolates can be fluorinated successfully with perchloryl fluoride, e.g. formation of 4,"" but due to the aggressive nature of perchloryl fluoride its applications are limited " (caulion see Vol.ElOa, p265ff). Alternatively, fluorination can be performed by acetyl hypofluorite... 

Strontium enolate chemistry is almost nonexistent barium enolate chemistry is rare radium enolate chemistry is unknown. Allyl chlorides react with barium to form the corresponding organometallics, which in turn react with o ,/ -unsaturated ketones to form the metal enolate . These enolates may also be formed in situ by the reaction of a-chloroketones with barium metal in the presence of an aldehyde, resulting in addition products. These reactions and the enthalpies of formation of the precursor a-haloketones and enones are seemingly ideal candidates for calorimetric investigation. 

Three main types of redox reactions of keto compounds leading to the formation of metal enolates have been reported (i) two-electron reduction of diketones or a,(f-unsaturated ketones or esters (equation 1), (ii) oxidative addition reactions (equation 2) and (iii) threefold deprotonation of diketoamines followed by a two-electron oxidation of the trianion by the metal (equation 3). 

Cleavage of thf by LiR occurs with formation of ethylene and the metal enolate of acetaldehyde (ethenolate), the simplest enolate anion. For example, Li(OCH=CH2) results from the reaction of LiR (R = n-Bu , t-Bu ) with thf and it has been used in the synthesis of other metal enolato complexes. 

IV. C-C BOND FORMATION BY MICHAEL ADDITION OF METAL ENOLATES A. Introduction... 

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