Metal enolates

Alkali alkaline earth metal enolates tend to be aggregates- complicates stereo selection models. 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

Enolate Initiators. In principle, ester enolate anions should represent the ideal initiators for anionic polymeri2ation of alkyl methacrylates. Although general procedures have been developed for the preparation of a variety of alkaU metal enolate salts, many of these compounds are unstable except at low temperatures (67,102,103). Usehil initiating systems for acrylate polymeri2ation have been prepared from complexes of ester enolates with alkak metal alkoxides (104,105). 

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-... 

Table 2. Reaction of (S)-3-Ben2yloxy-2-fluoro-2-methyl-propionaldehyde with Various Metal Enolates [d]...

Addition Reactions of Metal Enolates of Non-stabilized Esters, Amides, and Ketones to Epoxides... 

In spite of their intrinsic synthetic potential, addition reactions of metal enolates of non-stabilized esters, amides, and ketones to epoxides are not widely used in the synthesis of complex molecules. Following the seminal work of Danishefsky [64], who introduced the use of Et2AlCl as an efficient catalyst for the reaction, Taylor obtained valuable spiro lactones through the addition reaction of the lithium eno-late of tert-butyl acetate to spiro-epoxides, upon treatment of the corresponding y-... 

A direct application of the ring-opening reaction of an epoxide by a metal enolate amide for the synthesis of a complex molecule can be found in the synthesis of the trisubstituted cyclopentane core of brefeldin A (Scheme 8.35) [68a]. For this purpose, treatment of epoxy amide 137 with excess KH in THF gave a smooth cyclization to amide 138, which was subsequently converted into the natural product. No base/solvent combination that would effect cyclization of the corresponding aldehyde or ester could be found. 

The classical aldol addition, which is usually run in protic solvents, is reversible. Most modern aldol methodologies, however, rely on highly reactive preformed metal enolates, whereby proton donors are rigorously excluded. As a consequence, the majority of recent stereoselective aldol additions are performed under kinetic control. Despite this, reversibility and, as a consequence, an equilibration of yrn-aldolates to a t/-aldolates by retro-aldol addition, should not be excluded a priori. 

The complexation of achiral metal enolates by chiral additives, e.g., solvents or complexing agents could, in principle, lead to reagent-induced stereoselectivity. In an early investigation, the Reformatsky reaction of ethyl bromoacetate was performed in the presence of the bidentate ligand (—)-sparteine20. The enantioselectivity of this reaction varies over a wide range and depends on the carbonyl Compound, as shown with bcnzaldehyde and acetophenone. 

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. 

With a sufficiently active donor, the separate generation of metal enolates is not required. Thus, 1,4-addition may be mediated by stoichiometric or catalytic amounts of base. 

The intramolecular Michael addition of an achiral metal enolate is similarly subject to simple diastereoselection. 

C02-Bridged bimetallic zirconocene complexes have been formed from 1 and metallocarboxylic acids [229]. Reachon of 1 with metal enolates Cp(CO)3WCHR COX (X = OEt, Me, Ph) gives Cp(CO)3WCH(R )CH(R)OZrCp2(Cl). The structure for R = H and R = Me was solved by an X-ray analysis and the chemical reactivity of these organometallic products have been studied [230]. 

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

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

Cp 2Sm(jU-H)]2, (188), affords very high-molecular-weight PMMA with very low polydispersities (typically < 1.05).453-456 At — 95 °C the polymer formed is highly syndiotactic (95% rr triad). Isolation and X-ray analysis of (189), the 1 2 complex of (188) and MMA, provides strong support for the participation of a metal-enolate as the active site. (189) behaves in an identical manner to the hydride precursor, converting 100 equivalents MMA to polymer with Mn= 11,000 and Mw/Mn= 1.03.457 The successful structural characterization of (189) provides support for intermediates proposed earlier.458,459... 

In view of the extensive and fruitful results described above, redox reactions of small ring compounds provide a variety of versatile synthetic methods. In particular, transition metal-induced redox reactions play an important role in this area. Transition metal intermediates such as metallacycles, carbene complexes, 71-allyl complexes, transition metal enolates are involved, allowing further transformations, for example, insertion of olefins and carbon monoxide. Two-electron- and one-electron-mediated transformations are complementary to each other although the latter radical reactions have been less thoroughly investigated. 

In the general context of donor/acceptor formulation, the carbonyl derivatives (especially ketones) are utilized as electron acceptors in a wide variety of reactions such as additions with Grignard reagents, alkyl metals, enolates (aldol condensation), hydroxide (Cannizzaro reaction), alkoxides (Meerwein-Pondorff-Verley reduction), thiolates, phenolates, etc. reduction to alcohols with lithium aluminum hydride, sodium borohydride, trialkyltin hydrides, etc. and cyloadditions with electron-rich olefins (Paterno-Buchi reaction), acetylenes, and dienes.46... 

Carreira and Kruger reported facile transmetallation of silicon enolates to other soft metal enolates including Gu derivatives.499 They reasoned that the use of soft metal fluoride complexes enabled silyl metal transmetallation with catalytic use of a soft metal source. The concept is illustrated in Scheme 103. Normal Lewis acid-catalyzed reactions of silicon enolates with aldehydes proceed via activation of aldehydes by carbonyl oxygen coordination to Lewis acids, as shown in the upper equation of Scheme 103. A key step for catalytic turnover is the desilyation of 233 by the... 

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... 

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. 

In general, the aldol reaction of an aldehyde with metal enolate creates two new chiral centers in the product molecule, and this may lead to four possible stereoisomers 2a, 2b, 2c, and 2d (Scheme 3-2 and Fig. 3-1). 

One of the key features of such stereocontrolled aldol reactions is the predictability of the absolute stereochemistry of the enantiomers (or diastereo-mers) that will be formed as the major products. The preferred intermediate for an archetypal aldol reaction, proceeding by way of a metal enolate, can be tracked using the Zimmerman Traxler transition state and the results from the different variations of the aldol reaction can be interpreted from similar reasoning, and hence predictions made for analogous reactions1129]. 

---