Aldol cross

Allysine then reacts with other side chain aldehyde or amino groups to form cross-linkages. For example, two allysine residues react to form an aldol cross-linked product ... 

Intramolecular aldol, crossed aldol, and the related Knoevenagel condensations involve similar mechanisms. 

The attractiveness of this enzyme resides in its potential to catalyze self-aldol, cross-aldol, and cascade aldol reactions (for a review, see Ref. 87). DERA generally presents a stereoselectivity toward the aldehyde acceptor and catalyzes often the conversion of only one enantiomer. However, it often requires the presence of phosphorylated aldehyde acceptors. The most recent efforts were thus focused on directed evolution of the enzyme in view to improve the scope toward unphosphorylated substrates. DeSantis et al., in particular, performed some saturation site-directed mutagenesis in view to improve the reactivity for the unnatural D-glyceraldehyde substrate 37 for the synthesis of 2-deoxy-D-ribose 38. They reached a 2.5-fold improvement in DERA activity toward the unphosphorylated aldehyde with the mutant S238D (Scheme 28.18). 

Aldol cross coupling Aldehyde or Nonenolizable Acid or base p-Hydroxyaldehyde Product usually... 

The base-catalyzed reaction of acetaldehyde with excess formaldehyde [50-00-0] is the commercial route to pentaerythritol [115-77-5]. The aldol condensation of three moles of formaldehyde with one mole of acetaldehyde is foUowed by a crossed Cannizzaro reaction between pentaerythrose, the intermediate product, and formaldehyde to give pentaerythritol (57). The process proceeds to completion without isolation of the intermediate. Pentaerythrose [3818-32-4] has also been made by condensing acetaldehyde and formaldehyde at 45°C using magnesium oxide as a catalyst (58). The vapor-phase reaction of acetaldehyde and formaldehyde at 475°C over a catalyst composed of lanthanum oxide on siHca gel gives acrolein [107-02-8] (59). 

Pentaerythritol is produced by reaction of formaldehyde [50-00-0] and acetaldehyde [75-07-0] in the presence of a basic catalyst, generally an alkah or alkaline-earth hydroxide. Reaction proceeds by aldol addition to the carbon adjacent to the hydroxyl on the acetaldehyde. The pentaerythrose [3818-32-4] so produced is converted to pentaerythritol by a crossed Cannizzaro reaction using formaldehyde. All reaction steps are reversible except the last, which allows completion of the reaction and high yield industrial production. 

AldolRea.ctlons, In the same way, hydroxybenzaldehydes react readily with aldehydes and ketones to form a,P-unsaturated carbonyl compounds in the Claisen-Schmidt or crossed-aldol condensation (60). 

Butyraldehyde undergoes stereoselective crossed aldol addition with diethyl ketone [96-22-0] ia the presence of a staimous triflate catalyst (14) to give a predominantiy erythro product (3). Other stereoselective crossed aldol reactions of //-butyraldehyde have been reported (15). 

Trimethylolpropane (TMP), the reduced crossed aldol condensation product of //-butyraldehyde and formaldehyde, competes in many of the same markets as glycerol (qv) and pentaerythritol. The largest market for TMP is as a precursor in unsaturated polyester resins, short-oil alkyds, and urethanes for surface coatings (see Alkyd resins). 

Methyl amyl ketone, derived from the crossed aldol condensation of -butyraldehyde and acetone, is used predominandy as a high soHds coatings solvent. It is also employed as a replacement for the very toxic 2-ethoxyethyl acetate [111 -15-9J. 

The principal markets for neopentyl glycol (NPG), the hydrogenated, crossed aldol condensation product of isobutyraldehyde and formaldehyde, are in water-borne and alkyd-surface coatings. 

Stannous triflate is an efficient catalyst for aldol-type condensations [ 23, 124, 125 Under conditions of kinetic control, it provides excellent diastereo-selectivity in various cross-aldol reactions (equation 61)... 

FIGURE 6.21 Collagen fibers are stabilized and strengthened by Lys-Lys cross-links. Aldehyde moieties formed by lysyl oxidase react in a spontaneous nonenzymatic aldol reaction. 

A different situation is found in the case of crossed aldol reactions, which are also called Claisen-Schmidt reactions. Here the problem arises, that generally a mixture of products might be obtained. 

From a mixture of two different aldehydes, each with a-hydrogens, four different aldols can be formed—two aldols from reaction of molecules of the same aldehyde -I- two crossed aldol products not even considering possible stereoisomers (see below). By taking into account the unsaturated carbonyl compounds which could be formed by dehydration from the aldols, eight different reaction products might be obtained, thus indicating that the aldol reaction may have preparative limitations. 

If only one of the two aldehydes has an a-hydrogen, only two aldols can be formed and numerous examples have been reported, where the crossed aldol reaction is the major pathway. For two different ketones, similar considerations do apply in addition to the unfavorable equilibrium mentioned above, which is why such reactions are seldom attempted. 

A two-step sequence of nitrile oxide-olehn cycloaddition and reduction of the resulting A -isoxazolines offers a unique and attractive alternative to the classical aldol reaction and its many variants (2J). The procedure bypasses traditional problems, including enolate equilibrium and cross condensation (20). 

An analogous reaction has been carried out using malononitrile and different products derived by a Cross-Aldol reaction of acetone (Scheme 32). The cyclic furanimide 91 was then reacted under microwave irradiation in the presence of NaOEt with a second molecule of malononitrile to give the furanone 92 [66]. The NLO chromophore 93 was prepared using this procedure. 

The raw materials are usually mutually contaminated to about 5 %. Thus, DSC can be ruled out. The compounds are made by aldol condensations and cross Canizzaro reactions between acetaldehyde and formaldehyde. An elegant method of distinguishing between the two raw materials takes advantage of the 10 fold solubility difference between the two in methanol and water. 

The reaction can be stopped at this point, but more often a second mole of formaldehyde is permitted to reduce the newly formed aldol to a 1,3-diol, in a crossed Cannizzaro reaction (19-60). If the aldehyde or ketone has several a-hydrogens, they can all be replaced. An important use of the reaction is to prepare pentaerythritol from acetaldehyde ... 

---