Aluminum enolates, reactivity

A notable effect ol rra/i.v comdination has tilso been observed for the aniitnic pttlymeriziition of methacryloni-trile (22) initiated from a living polymer ctf methyl methacrylate (21, R = Me) with an aluminum enolate reactive end (32 ), in which the chain grttwth is promoted by the trails coordination of pyridine, to afford a narrow MWD block copolymer (42)- Ott the other hand, in the absence of axially ccatrdinating pyridine under otherwise identical conditions as described, no block copolymerization of 22 from 32 takes place. 

Transmetalation of lithium enolate 1 a (M = Li ) by treatment with tin(II) chloride at — 42 °C generates the tin enolate that reacts with prostereogenic aldehydes at — 78 °C to preferentially produce the opposite aldol diastereomer 3. Diastereoselectivities of this process may be as high as 97 3. This reaction appears to require less exacting conditions since similar results are obtained if one or two equivalents of tin(ll) chloride arc used. The somewhat less reactive tin enolate requires a temperature of —42 C for the reaction to proceed at an acceptable rate. The steric requirements of the tin chloride counterion are probably less than those of the diethyla-luminum ion (vide supra), which has led to the suggestion26 44 that the chair-like transition state I is preferentially adopted26 44. This is consistent with the observed diastereoselective production of aldol product 3, which is of opposite configuration at the / -carbon to the major product obtained from aluminum enolates. 

Scheme 9 outlines the synthesis of a prostanoid intermediate (99) that relies on an intermolecular Nozaki process. It is important to note that unlike the intramolecular case described above, the intermolecular version of this protocol requires an aldehyde as the electrophilic trap however, it is interesting to note that there have been no reports of the addition of Lewis acid activated ketones (presumably, as a preformed complex which would be added via cannula at low temperature) to the preformed aluminum enolate. Finally, in this example, the conversion of enone (96) to adduct (98) is promoted by the less reactive dimethylaluminum phenyl thiolate and not the corresponding ate complex. 

Enolates are undoubtedly the most versatile intermediates for C-C, C-N, C-O bond-forming reactions [36]. Continuous progress has been made not only in fundamental operations involving these anionic species but also during the synthesis of complex natural products. Compared with metal enolates with counter cations of, e.g., B, Si, Li, Na, K, Mg, Ti, Sn, Cu, etc., aluminum enolates have found fewer apphcations, probably because no particular advantages over the other metals have been perceptible. There are, however, still intriguing aspects of novel reactivity and selectivity in the formation and reaction of aluminum enolates. Specifically, very recent development have highhghted pre-formation of Lewis acid-carbonyl complexes by use of bulky aluminum compounds as precursors of aluminum enolates the behavior of these complexes is unprecedented. 

Anionic polymerization of methacrylates involves enolate intermediates of diverse molecular weight. These distinctive enolates are readily formed via a number of consecutive conjugate addition steps. As discussed in Section 6.1, control of reactivity and selectivity of enolates should directly reflect the stereoselective synthesis of poly(methyl methacrylate)s (PMMA). Thus it is advisable to compare the nature of aluminum enolates involved in bimolecular and polymolecular reactions. 

Living anionic polymerization can also be used to produce well-controlled block copolymers. For PMMA, the best procedures need temperatures below O C and are therefore unlikely to be commercially attractive. Hiey are, furthermore, largely unsuccessful for the controlled polymerization of acrylates, which are far too reactive. The use of tetraalkyl ammonium ate complexes, in conjunction with an appropriate aluminum catalyst, solved fhis problem [225]. The function of the ammonium counterion is to promote dissociation of the complex ion to form the reactive ate complex of the aluminum enolate of the ester (Scheme 6.176). Thus, polymerization was initiated by the lithium enolate of isobutylate in the presence of the ate complex of Me3Al-R3NCl. A controlled block copolymer (PMMA-block-... 

Reactivity of Aluminum Enolates and Application in Organic Synthesis. 293... 

As an alternative to lithium enolates. silyl enolates or ketene acetals may be used in a complementary route to pentanedioates. The reaction requires Lewis acid catalysis, for example aluminum trifluoromethanesulfonate (modest diastereoselectivity with unsaturated esters)72 74 antimony(V) chloride/tin(II) trifluoromethanesulfonate (predominant formation of anti-adducts with the more reactive a,/5-unsaturated thioesters)75 montmorillonite clay (modest to good yields but poor diastereoselectivity with unsaturated esters)76 or high pressure77. 

The reductive coupling of carbonyl compounds with formation of C-C double bonds was developed in the early seventies and is now known as McMurry reaction [38, 39]. The active metal in these reactions is titanium in a low-valent oxidation state. The reactive Ti species is usually generated from Ti(IV) or Ti(III) substrates by reduction with Zn, a Zn-Cu couple, or lithium aluminum hydride. A broad variety of dicarbonyl compounds can be cyclized by means of this reaction, unfunctionalized cycloalkenes can be synthesized from diketones, enolethers from ketone-ester substrates, enamines from ketone-amide substrates [40-42], Cycloalkanones can be synthesized from external keto esters (X = OR ) by subsequent hydrolysis of the primary formed enol ethers (Scheme 9). 

Inoue et al. have developed photochemical carboxylation of ketones by the virtue of photo-enhanced nucleophilic reactivities of aluminum porphyrin complexes. Treatment of [(TPP)AlNEt2l with aromatic ketones produces the corresponding porphinatoaluminum enolate products,... 

Complementary to the acylation of enolate anions is the acid-catalyzed acylation of the corresponding enols, where the regiochemistry of acylation can vary from that observed in base-catalyzed reactions. Although the reaction has been studied extensively in simple systems, it has not been widely used in the synthesis of complex molecules. The catalysts most frequently employed are boron trifluoride, aluminum chloride and some proton acids, and acid anhydrides are the most frequently used acylating agents. Reaction is thought to involve electrophilic attack on the enol of the ketone by a Lewis acid complex of the anhydride (Scheme 58). In the presence of a proton acid, the enol ester is probably the reactive nucleophile. In either case, the first formed 1,3-dicarbonyl compound is converted into its borofluoride complex, which may be decomposed to give the 3-d>ketone, sometimes isolated as its copper complex. 

The transmetallation of alkali enolates 164 (M = Li, Na, K) with metal salts (M Y L, ) is a general method for the preparation of a large variety of enolates 165, provided that is less electropositive than M. It is particularly suitable for such enolates 165 whose reactivity and/or selectivity is tuned by additional ligands L. Thus, a variety of magnesium, boron, aluminum, siUcon, tin, titanium, zirconium, and zinc enolates become readily available (Scheme 2.48) [2c,d]. Usually, the configuration of the enolates is maintained during the transmetallation, but cis-tmns isomerization in the transmetallated enolates occur occasionally. Individual examples will be discussed with their applications in asymmetric syntheses. 

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