Transition metal enolates aldol reaction

Bergman and Heathcock have demonstrated fhat fhe Rh(I)-catalyzed aldol reaction, originally reported by Matsuda et al, [87], proceeds via Rh(l) enolates 25 and aldolates 26 (Scheme 10.25) [88]. This type of transition metal-catalyzed aldol reaction has been used for asymmetric synthesis using readily accessible chiral phosphines (vide infra). 

Aldol reactions of silyl enolates are promoted by a catalytic amount of transition metals through transmetallation generating transition metal enolates. In 1995, Shibasaki and Sodeoka reported an enantioselective aldol reaction of enol silyl ethers to aldehydes using a Pd-BINAP complex in wet DMF. Later, this finding was extended to a catalytic enantioselective Mannich-type reaction to a-imino esters by Sodeoka s group [Eq. (13.21)]. Detailed mechanistic studies revealed that the binuclear p-hydroxo complex 34 is the active catalyst, and the reaction proceeds through a palladium enolate. The transmetallation step would be facilitated by the hydroxo ligand transfer onto the silicon atom of enol silyl ethers ... 

The most smdied O-bonded transition metal enolates are titanium enolates . The reason for their success has beeu recognized in the fact that titanium enolates show an enhanced stereochemical control in C—C bond-forming reactions over simple lithium enolates and the possibility of incorporating chiral ligands at the titanium centre, a possibility which has lead to enantioselective aldol reactions with excellent enantiomeric excess. Moreover, titanium euolates have been used in oxidation reactions with remarkable diastereoselectivity. 

For a comprehensive review, see Paterson, I. The Aldol Reaction Transition Metal Enolates ,... 

Paterson, I. The Aldol Reaction Transition Metal Enolates. in Comp. Org. Synth, (eds. Trost, B. M.,Fleming, I.), 1, 301-319 (Pergamon Press, Oxford, 1991). 

Advances in the development of metal-catalyzed Mukaiyama aldol addition reactions have primarily relied on a mechanistic construct in which the role of the Lewis acidic metal complex is to activate the electrophilic partner towards addition by the enol silane. Alternate mechanisms that rely on metallation of enol silane to generate reactive enolates also serve as an important construct for the design of new catalytic aldol addition processes. In pioneering studies, Bergman and Heathcock documented that transition-metal enolates add to aldehydes and that the resulting metallated adducts undergo silylation by the enol silane leading to catalyst turnover. 

Cyclic cobalt-acyl complexes can be deprotonated, and subsequent reaction of these enolates with aldehydes gives predominantly the anti/threo product (Scheme 63). Rhenium-acyl complexes can be deprotonated in the same manner. These lithium enolates can be alkylated or can react with [M(CO)5(OTf)] (M = Re, Mn) to give the corresponding enolates (Scheme Many transition metal enolates of type (21) or (22) are known, - but only a few have shown normal enolate behavior , e.g. aldol reaction, reaction with alkyl halides, etc. Particularly useful examples have been developed by Molander. In a process analogous to the Reformatsky reaction, an a-bromo ester may be reduced with Smia to provide excellent yields of condensation products (Scheme 65) which are generated through intermediacy of a samarium(III) enolate. ... 

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. 

The aldol reactions of titanium enolates have been the best studied of all the transition metal enol-ates."- In many cases they show higher stereoselectivity and chemoselectivity in their reactions than lithium enolates and are easily prepared using inexpensive reagents. They also promote high levels of diastereofacial selectivity in reactions of chiral reactants. The Lewis acidity of the titanium metal center can be easily manipulated by variation of the ligands (chloro, alkoxy, amino, cyclopentadienyl, etc.) attached to titanium, which leads to enhanced selectivity in appropriate cases. Moreover, the incorporation of chiral ligands on titanium makes possible efficient enantioselective aldol reactions. 

A number of methods have been developed to bring about the directed aldol reaction between two different carbonyl compounds to give a mixed-aldol product. Most of them proceed from the preformed enolate or silyl enol ether of one of the components. With enolates, a number of metal counterions have been used and the best results have been obtained with lithium or boron enolates, although zinc or transition-metal enolates have found widespread use. For example, the aldol reaction of acetone with acetaldehyde under basic aqueous conditions is inefficient... 

Condensation Reactions. Traditionally, intermolecular aldol condensation reactions have been performed under equilibrating conditions using weaker bases than r-BuOK in protic solvents. Since the mid-1970s, new methodology has focused on directed aldol condensations which involve the use of preformed Lithium and (jroup 2 enolates, (Troup 13 enolates, and transition metal enolates. Although examples of the use of f-BuOK in intramolecular aldol condensations are limited, complex diketones... 

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