Transition metal enolates

Traditionally, aldol reactions were carried out under protic conditions, such that the enolate was formed reversibly (see Volume 2, Chapter 1.5). An added measure of control is possible if one uses a sufficiently strong base that the enolate may be quantitatively formed prior to addition of the electrophile. The renaissance that has occurred in the aldol reaction in the last two decades has been mainly due to the development of methods for the formation and use of preformed enolates. The simplest enolates to prepare are those associated with lithium and magnesium, and there now exists a considerable literature documenting certain aspects of lithium and magnesium enolate aldol chemistry. This chapter summarizes the aldol chemistry of preformed enolates of these Group I and Group II metals. Other chapters in this volume deal with boron enolates, zinc enolates, transition metal enolates and the related chemistry of silyl and stannyl enol ethers. 

In recent years this simple picture has been completely transformed and it is now recognized that the alkali metals have a rich and extremely varied coordination chemistry which frequently transcends even that of the transition metals. The efflorescence is due to several factors such as the emerging molecular chemistry of lithium in particular, the imaginative use of bulky ligands, the burgeoning numbers of metal amides, alkoxides, enolates and organometallic compounds, and the exploitation of multidentate... 

Due to mechanistic requirements, most of these enzymes are quite specific for the nucleophilic component, which most often is dihydroxyacetone phosphate (DHAP, 3-hydroxy-2-ox-opropyl phosphate) or pyruvate (2-oxopropanoate), while they allow a reasonable variation of the electrophile, which usually is an aldehyde. Activation of the donor substrate by stereospecific deprotonation is either achieved via imine/enamine formation (type 1 aldolases) or via transition metal ion induced enolization (type 2 aldolases mostly Zn2 )2. The approach of the aldol acceptor occurs stereospecifically following an overall retention mechanism, while facial differentiation of the aldehyde is responsible for the relative stereoselectivity. 

Divalent transition metal 3-keto-enolate complexes as Lewis acids. D. P. Graddon, Coord. Chem. Rev., 1969, 4,1-28(117). 

Graddon, D. P. (1968). Divalent transition metal j8-ketone-enolate complexes as Lewis acids. Coordination Chemistry Reviews, 4, 1-28. 

On the other hand, the enantioselective 1,4-addition of carbanions such as enolates to linear enones is an interesting challenge, since relatively few efficient methods exist for these transformations. The Michael reaction of p-dicarbonyl compounds with a,p-unsaturated ketones can be catalysed by a number of transition-metal compounds. The asymmetric version of this reaction has been performed using chiral diol, diamine, and diphosphine ligands. In the past few years, bidentate and polydentate thioethers have begun to be considered as chiral ligands for this reaction. As an example, Christoffers et al. have developed the synthesis of several S/O-bidentate and S/O/S-tridentate thioether... 

Other transition-metals have also been used. For example, Trost183 reported that heating a 1 1 mixture of 1-octene and 1-octyne in DMF-water (3 1) at 100°C with a ruthenium complex for 2 h generated a 1 1 mixture of two products corresponding to the addition of the alkene to the acetylene (Eq. 3.47). The presence of a normally reactive enolate does not interfere with the reaction. 

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

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

Transition metals 172 a-bonded to cyclopropanes, substituted on the a-carbon with a halogen atom, are interesting intermediates for cyclopropylidene complexes 173 or allene ones 174 [88]. The former complexes are also supposed to be precursors of the above-mentioned nickel enolates. (Scheme 65)... 

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. 

Ketones are resistant to oxidation by dioxygen in aqueous solutions at T= 300-350 K. Transition metal ions and complexes catalyze their oxidation under mild conditions. The detailed kinetic study of butanone-2 oxidation catalyzed by ferric, cupric, and manganese complexes proved the important role of ketone enolization and one-electron transfer reactions with metal ions in the catalytic oxidation of ketones [190-194],... 

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

The isomerization of allylic alcohols provides an enol (or enolate) intermediate, which tautomerizes to afford the saturated carbonyl compound (Equation (8)). The isomerization of allylic alcohols to saturated carbonyl compounds is a useful synthetic process with high atom economy, which eliminates conventional two-step sequential oxidation and reduction.25,26 A catalytic one-step transformation, which is equivalent to an internal reduction/oxidation process, is a conceptually attractive strategy due to easy access to allylic alcohols.27-29 A variety of transition metal complexes have been employed for the isomerization of allylic alcohols, as shown below. 

With an electrophilic transition metal complex, it is believed that the hydration of an alkyne occurs through a trans-addition of water to an 72-alkyne metal complex (Scheme 15, path A),380 although the m-pathway via hydroxymetallation has also been proposed (path B).381,382 However, distinguishing between the two pathways is difficult due to the rapid keto-enol tautomerization that renders isolation of the initial water adduct challenging. 

Perhaps the most elusive variant of the aldol reaction involves the addition of metallo-aldehyde enolates to ketones. A single stoichiometric variant of this transformation is known [29]. As aldolization is driven by chelation, intramolecular addition to afford a robust transition metal aldolate should bias the enolate-aldolate equilibria toward the latter [30, 31]. Indeed, upon exposure to basic hydrogenation conditions, keto-enal substrates provide the corresponding cycloal-dol products, though competitive 1,4-reduction is observed (Scheme 22.7) [24 d]. 

Ferraris et al.108 demonstrated an asymmetric Mannich-type reaction using chiral late-transition metal phosphine complexes as the catalyst. As shown in Scheme 3-59, the enantioselective addition of enol silyl ether to a-imino esters proceeds at —80°C, providing the product with moderate yield but very high enantioselectivity (over 99%). 

Transition metal-catalyzed reactions of ct-diazocarbonyl compounds proceed via electrophilic Fischer-type carbene complexes. Consequently, when cr-diazoketone 341 was treated, at room temperature, with catalytic amounts of [ RhiOAcbh, it gave the formation of a single NH insertion product, which was assigned to the enol stmcture 342. At room temperature, in both solid state and in solution, 342 tautomerizes to give the expected 1-oxoperhydropyr-rolo[l,2-c]oxazole derivative 343 (Scheme 50) <1997TA2001>. 

One more example of metal ion catalysis will be considered briefly. In a now classic paper, Cox (1974) showed that the enolization of 2-acetylpyri-dine (but not 4-acetylpyridine) is catalysed by divalent transition metal ions. Proton abstraction by acetate ions is strongly accelerated by Zn2+, Ni2+ and Cu2+ ions and the transition state stabilization by these ions roughly parallels their abilities to bind to the substrate (Table A6.5). The three metal ions are significantly superior to the proton as electrophilic catalysts, no doubt because they can chelate to both the pyridine nitrogen and the... 

This preparation illustrates an efficient two-step process for the transformation of a cycloalkenone to the corresponding a-substituted derivative. The first step involves the installation of an a-iodo substituent by a process thought to involve nucleophilic addition of pyridine, iodine capture of the resulting enolate, and pyridine-promoted elimination of pyridine.5 The resulting vinyl iodides are superior to other vinyl halides as participants in a variety of transition-metal catalyzed coupling reactions, illustrated here by the Suzuki coupling with an arylboronic acid. Other coupling partners that... 

On the other hand, the use of [Rh(CO)2Cl]2 as a catalyst results in ring opening of the siloxycyclopropanes 13 to the silyl enol ethers 14 with high stereoselectivity [10]. The 2-siloxyrhodacyclobutane 15a is proposed to undergo j8-elimination to give jr-allylrhodium 16a followed by reductive elimination to the silyl enol ether 14a. 1-Trimethylsiloxybicyclo[n.l.0]alkanes serve as / -metallo-carbonyl compounds via desilylation with a variety of transition metals [11]. The palladium-catalyzed reaction of the siloxycyclopropanes 17 under carbon monoxide in chloroform provides a route to the 4-keto pimelates 18. In the presence of aryl triflates, the 1,4-dicarbonyl compounds 19 are... 

As will be discussed more thoroughly in Section 3.2.5, transition metal carbene complexes can mediate olefin metathesis. Because heteroatom-substituted carbene complexes are usually less reactive towards olefins than the corresponding nonheteroatom-substituted complexes, it is, e.g., possible to use enol ethers to terminate living polymerization or other types of metathesis reaction catalyzed by a non-heteroatom-substituted carbene complex. Olefin metathesis can also be used to prepare new heteroatom-substituted carbene complexes (Figure 2.15, Table 2.11). 

Various transition metals have been used in redox processes. For example, tandem sequences of cyclization have been initiated from malonate enolates by electron-transfer-induced oxidation with ferricenium ion Cp2pe+ (51) followed by cyclization and either radical or cationic termination (Scheme 41). ° Titanium, in the form of Cp2TiPh, has been used to initiate reductive radical cyclizations to give y- and 5-cyano esters in a 5- or 6-exo manner, respectively (Scheme 42). The Ti(III) reagent coordinates both to the C=0 and CN groups and cyclization proceeds irreversibly without formation of iminyl radical intermediates.The oxidation of benzylic and allylic alcohols in a two-phase system in the presence of r-butyl hydroperoxide, a copper catalyst, and a phase-transfer catalyst has been examined. The reactions were shown to proceed via a heterolytic mechanism however, the oxidations of related active methylene compounds (without the alcohol functionality) were determined to be free-radical processes. 

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

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