Aldol condensations metal complexes

Mukiayama aldol reactions between silyl enol ethers and various carbonyl containing compounds is yet another reaction whose stereochemical outcome can be influenced by the presence of bis(oxazoline)-metal complexes. Evans has carried out a great deal of the work in this area. In 1996, Evans and coworkers reported the copper(II)- and zinc(II)-py-box (la-c) catalyzed aldol condensation between benzyloxyacetaldehyde 146 and the trimethylsilyl enol ether [(l-ferf-butylthio)vinyl]oxy trimethylsilane I47. b82,85 Complete conversion to aldol adduct 148 was achieved with enantiomeric excesses up to 96% [using copper(II) triflate]. The use of zinc as the coordination metal led to consistently lower selectivities and longer reaction times, as shown in Table 9.25 (Eig. 9.46). 

One of the first reactions reported on the activation of the a C—H bond was the aldol condensation reaction of glycine, coordinated to Cu11, with acetaldehyde to yield threonine.72 The reaction, which is base catalyzed, proceeds under far milder conditions than for free glycine. Similar reactions have been reported with other metal ions and aldehydes again the postulated intermediate is a carbanion.69 70 By using resolved Co111 complexes, e.g. A-(+)-[Co(en)2(GlyO)]2+, some stereoselectivity can be obtained in the threonine product.73... 

Metal template syntheses of complexes incorporating the p-amino imine fragment have been introduced by Curtis as a result of his discovery that tris(l,2-diaminoethane)nickel(II) perchlorate reacted slowly with acetone to yield the macrocyclic complexes (40) and (41) (equation 8).81-83 In this macrocyclic structure the bridging group is diacetone amine imine, arising from the aldol condensation of two acetone molecules. This reaction is widely general, in the same way that the aldol reaction is, and can be applied to many types of amine complexes. The subject has been reviewed in detail with respect to macrocyclic complexes by Curtis.84... 

Very recently, Belokon and North have extended the use of square planar metal-salen complexes as asymmetric phase-transfer catalysts to the Darzens condensation. These authors first studied the uncatalyzed addition of amides 43a-c to aldehydes under heterogeneous (solid base in organic solvent) reaction conditions, as shown in Scheme 8.19 [47]. It was found that the relative configuration of the epoxyamides 44a,b could be controlled by choice of the appropriate leaving group within substrate 43a-c, base and solvent. Thus, the use of chloro-amide 43a with sodium hydroxide in DCM gave predominantly or exclusively the trans-epoxide 44a this was consistent with the reaction proceeding via a thermodynamically controlled aldol condensation... 

Roasting cocoa beans results in the production of volatile and non-volatile compounds which contribute to the total flavor complex. 5-Methyl-2-phenyl-2-hexenal, which exhibited a deep bitter persistant cocoa note, was reported in the volatile fraction (53). It was postulated to be the result of aldol condensation of phenylacetaldehyde and isovaleraldehyde with the subsequent loss of water. The two aldehydes were the principal products of Strecker degradation products of phenylalanine and leucine, respectively. Non-volatiles contained diketopiperazines (dipeptide anhydride) which interact with theobromine and develop the typical bitterness of cocoa (54). Theobromine has a relatively stable metallic bitterness, but cocoa bitterness is rapidly noticed and disappears quickly. 

The gas phase acid-catalyzed synthesis of pyridines from formaldehyde, ammonia and an alkanal is a complex reaction sequence, comprising at least two aldol condensations, an imine formation, a cyclization and a dehydrogenation (9). With acetaldehyde as the alkanal, a mixture of pyridine and picolines (methylpyridines) is formed. In comparison with amorphous catalysts, zeolites display superior performance, particularly those with MFI or BEA topology. Because formation of higher alkylpyridines is impeded in the shape-selective environment, the lifetime of zeolites is much improved in comparison with that of amorphous materials. Moreover, the catalytic performance can be enhanced by doping the structure with metals such as Pb, Co or Tl, which assist in the dehydrogenation. 

The first attempt to imprint a metal complex with a reaction intermediate coordinated to the metal center was reported by Mosbach and coworkers [51], A Co monomer coordinated with dibenzoylmethane, which is as an intermediate for the aldol condensation of acetophenone and benzaldehyde, was tethered to a styrene-DVB copolymer matrix. After, the template, dibenzoylmethane was removed from the polymer, the resulting molecularly imprinted cavity had a shape similar to the template due to the interaction of the template with the polymerized styrene-DVB monomers through n-n stacking and van der Waals interactions. The rate of aldol condensation of adamantyl methyl ketone and 9-acetylanthracene was lower than the rate of condensation with acetophenone, indicating some degree of increased substrate selectivity. This is the first known formation of a C-C bond using a molecularly imprinted catalytic material. 

A remarkable example of the cooperation of different active sites in a polyfunctional catalyst is the one-step synthesis of 2-ethylhexanol, including a combined hydroformylation, aldol condensation, and hydrogenation process [17]. The catalyst in this case is a carbonyl-phosphine-rhodium complex immobilized on to polystyrene carrying amino groups close to the metal center. Another multistep catalytic process is the cyclooligomerization of butadiene combined with a subsequent hydroformylation or hydrogenation step [24, 25] using a styrene polymer on to which a rhodium-phosphine and a nickel-phosphine complex are anchored (cf Section 3.1.5). 

An interesting metal effect was observed in the aldol condensations of the enolate derived from the iron acetyl complex (r)"-C HdFe(CO)(PPhd(COMe) with aldehydes [56,57]. Although the lithium enolate did not show any selectivity, the corresponding aluminum enolate by transmetalation with Et.AlCl exhibited exceptionally high diastereoselectivity (>99% de). The resultant P-hydroxy acyl complexes are transformed to P-hydroxy acids on decomplexation with Br.. 

Transition-metal complexes bearing chiral ligands catalyze an asymmetric aldol condensation of isocyanoacetates with aldehydes to afford a mixture of cis- and /rons-4,5-disubstituted-4,5-dihydrooxazoles (188) in high optical purity (Equation (27)). Both gold and silver ferrocenylphos-phine complexes are effective <94TL2713>. 

Proline is a stable, nontoxic, cyclic, secondary pyrrolidine-based amino acid with an increased pK value. Thus, proline is a chiral bidentate compound that can form catalytically active metal complexes (Melchiorre et al. 2008). Bidentate means that proline has not only one tooth but also a second one to bite and react. The greatest difference to other amino acids is a Lewis-base type catalysis that facilitates iminium and enamine-based reactions. It is especially noteworthy that cross-aldol condensations of unprotected glycoladehyde and racemic glyceralde-hyde in the presence of catalytic amounts of the Zn-(proline)2 gave a mixture of pentoses and hexoses (Kofoed et al. 2004). Again, proline seems to play the decisive role. The conditions are prebiotic the reaction proceeded in water for seven days at room temperature. It is remarkable that the pentose products contained ribose (34%), lyxose (32%), arabinose (21%), and xylose (12%) and that all are stable under the conditions. Thus, the diastereomeric and enantiomeric selection observed support the idea that amino acids have been the source of chirality for prebiotic sugar synthesis. 

Propionylcyclopentadienyliron carbonyl complexes 1.151 (R = MeCH2) form enolates whose aldol condensations are highly selective. Depending on the associated metal, either anti (aluminum) or syn (copper) aldols are predominantly formed at -100°C. The absolute configuration of these aldols depends upon that of the starting complex [408, 522] (Figure 6.87). 

Aldol condensation between campholenic aldehyde (6.72) and an aldehyde or a ketone (6.73) produces an unsaturated derivative (6.74). It should be noted that this material contains an -double bond. The reason for this lies in the mechanism of the aldol condensation as described in Figure 6.4 and associated text. The carbonyl group of (6.74) can be reduced to the corresponding alcohol by, for example, a complex metal hydride such as lithium aluminium hydride or sodium boro-hydride. This produces the sandalwood material (6.75). Three typical examples are shown at the bottom of Figure 6.18. The first, (6.76), is known under various trade names such as Bangalol (Quest) and is... 

Aliphatic nitro compounds cannot as a rule be prepared in the same way as the aromatic nitro compounds. The more rapid oxidation of aliphatic hydrocarbons by nitric acid is the main interfering factor, so that conditions must be chosen which minimize oxidation and promote nitration. The oxidation reactions are of such complexity in these cases that no attempt will be made to formulate them. Only a summary of the conditions favoring nitration will be given. The use of a solvent such as ether for carrying out the reaction is often successful. Also dilute nitric acid has been used, and alkyl (generally ethyl) nitrate. In the Friedel-Crafts reaction with ethyl nitrate, aluminium chloride is used as catalyst. In aliphatic nitrations with ethyl nitrate, alkalis such as metal alkoxides (NaOC Hs) are found to be best. The use of alkalis brings out the similarity of this reaction to aldol condensations which are also favored by alkalis. An example of aliphatic nitration, in comparison with an aromatic one may be given ... 

---