Transition metal complexes aldol reaction

Transition metal catalyzed aldol reactions are attractive methods due to their high catalytic activity, privileged chelation effects of controlling stereoselectivity, and mild or neutral reaction conditions. Except group 5-7, most of transition metals have been shown as efficient catalyst in homogeneous aldol reactions with variants of substrates. Thus and correspondingly, the catalytic aldol reactions will be emphasized herein with representative transition metal based complexes in group 4 and 8-11. 

After the initial two reports of Rh- and Co-catalyzed reductive aldol couplings, further studies did not appear in the literature until the late 1990s. Beyond 1998, several stereoselective and enantioselective reductive aldol reactions were developed, which are catalyzed by a remarkably diverse range of metal complexes, including those based upon Pd, Cu, Ir, and In. In this chapter, transition metal-catalyzed aldol, Michael, and Mannich reactions that proceed via transition metal hydride-promoted conjugate reduction are reviewed. 

The reaction of alkenes (and alkynes) with synthesis gas (CO + H2) to produce aldehydes, catalyzed by a number of transition metal complexes, is most often referred to as a hydroformylation reaction or the oxo process. The discovery was made using a cobalt catalyst, and although rhodium-based catalysts have received increased attention because of their increased selectivity under mild reaction conditions, cobalt is still the most used catalyst on an industrial basis. The most industrially important hydrocarbonylation reaction is the synthesis of n-butanal from propene (equation 3). Some of the butanal is hydrogenated to butanol, but most is converted to 2-ethylhexanol via aldol and hydrogenation sequences. 

The (5)-tryptophan-derived oxazaborolidenes utilized in this aldol study have been previously examined by Corey as effective catalysts for enantioselective Diels-Alder cycloaddition reactions [6]. Corey has documented unique physical properties of the complex and has proposed that the electron-rich indole participates in stabilizing a donor-acceptor interaction with the metal-bound polarized aldehyde. More recently, Corey has formulated a model exemplified by 7 in which binding by the aldehyde to the metal is rigidified through the formation of a hydrogen-bond between the polarized formyl C-H and an oxyanionic ligand [7], The model illustrates the sophisticated design elements that can be incorporated into the preparation of transition-metal complexes that lead to exquisite control in aldehyde enantiofacial differentiation. 

Since the middle of the 198O s remarkable progress has been achieved in the development of asymmetric aldol reactions of silyl enolates. In the beginning of this evolution, chiral auxiliary-controlled reactions were extensively studied for this challenging subject [106]. As new efficient catalysts and catalytic systems for the aldol reactions were developed, much attention focused on catalytic enantiocontrol using chiral Lewis acids and transition metal complexes. Thus, a number of chiral catalysts realizing high levels of enantioselectivity have been reported in the last decade. 

In 1986, Reetz et al. reported that chiral Lewis acids (B, Al, and ll) promoted the aldol reaction of KSA with low to good enantioselectivity [115]. The following year they also introduced asymmetric aldol reaction under catalysis by a chiral rhodium complex [116]. Since these pioneering works asymmetric aldol reactions of silyl enolates using chiral Lewis acids and transition metal complexes have been recognized as one of the most important subjects in modern organic synthesis and intensively studied by many synthetic organic chemists. 

ALDOL REACTIONS CATALYZED BY TRANSITION METAL COMPLEXES [1063]... 

Prior chapters have covered the use of transition metals in asymmetric hydrogenations ( 6.2 and 7.1), hydroborations ( 7.3), hydrosilylations and hydro-cyanations ( 6.3, 6.4, 7.4 and 7.5), cyclopropanations ( 7.19), aldol reactions ( 6.11), allylations of carbanions ( 5.3.2), and some sigmatropic rearrangements ( 10.3). This chapter covers other reactions catalyzed by transition metal complexes including coupling of organometallic reagents with vinyl, aryl or allyl derivatives, Heck reactions allylamine isomerizations, some allylation reactions, car-bene insertions into C-H bonds and Pauson-Khand reactions. 

Metal Free Transition metal catalysts are highly effective for C—H bond activation. However, transition metal complexes are not only expensive, but also difficult to remove from the reaction products, resulting in toxicity concerns. DDQ is a well-known oxidant in organic chemistry [33]. For many years, it has been used for the oxidation of alcohols to ketones and aromatization. The first intermolecular C—C bond formation was realized by DDQ-mediated Mukaiyama-type aldol reactions [34], The reactions of electron-rich benzyl ethers and silyl enol ethers afforded 3-alkoxy-3-phenylpropionyl derivatives at ambient temperature with moderate to excellent yields (Equation 11.12). 

ALDOL REACTIONS OF METAL ENOLATES OF ACYL-TRANSITION METAL COMPLEXES... 

Quite a number of transition-metal complexes are capable of isomerizing allyUc alcohols into transition-metal-enol complexes through an internal redox process. Those can then be trapped in situ with aldehydes in an aldol reaction. Motherwell and coworkers developed a RhClIPPhjIj-catalyzed domino isomerization-aldol reaction of secondary allyl alcohols, which gave rise to a mixture of syn- and owti-aldol products, with only small amounts of the regioisomeric aldol product occasionally being formed (Scheme 8.25) [42]. 

For the more important coupling reaction of silyl enol ethers, the Mukaiyama Aldol reaction, electron transfer reactions of silyl enol ethers have to be taken into account. As commonly used catalysts, transition metal complexes can be deactivated by electron transfer reduction, leading to a significant change in Lewis acidity as has been shown by Bosnich and co-workers. ° Setsune et al. reported another connection... 

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