Aldehyde, bound

A solid-phase version of the palladium-catalyzed carbonyl allylation of aldehydes by allylic alcohol has been described. Thus, allylation of resin-bound aldehyde (P = Merrifield resin) with allylic alcohols (e.g., MeCH=CHCH2OH) in the presence of SnCl2 afforded the homoal-lylic alcohols under different solvent conditions, in DMSO and aqueous DMSO respectively (Eq. 8.45).102... 

Reductive amination of an aldehyde with excess primary amine, using a support-bound borohy-dride, provides the desired secondary amine contaminated with the primary amine precursor. Covalent capture of the primary amine with a support-bound aldehyde provides the pure secondary amine. Treatment with excess isocyanate yields the final urea product, which is purified by reaction with a support-bound amine to remove unreacted isocyanate. For the full potential of this method to be realized, further development of support-bound reagents and scavengers for most of the important chemical transformations will be necessary. Al-... 

The essential features of the catalytic cycle are summarized in Figure 12.6. After binding of NAD+ the water molecule is displaced from the zinc atom by the incoming alcohol substrate. Deprotonation of the coordinated alcohol yields a zinc alkoxide intermediate, which then undergoes hydride transfer to NAD+ to give the zinc-bound aldehyde and NADH. A water molecule then displaces the aldehyde to regenerate the original catalytic zinc centre, and finally NADH is released to complete the catalytic cycle. 

The essential features of the catalytic cycle (see Figure 10) involve the binding of NAD, the displacement of the water molecule by alcohol, the deprotonation of the coordinated alcohol to give a zinc alkoxide intermediate, the hydride transfer from the alkoxide to NAD to give a zinc-bound aldehyde, the displacement of the aldehyde by water and the release of NADH. The principal role of the zinc in the dehydrogenation reaction is, therefore, to promote deprotonation of the alcohol and thereby enhance hydride transfer... 

Schwartz (1972) also noted the detection of about 70 glycerol-l-alkyl ethers in milk fat. Saturated ethers, both odd and even from C-10 through C-18, were found, with traces of ethers up to C-25 present. Fifty-five unsaturated ethers were separated, but only the A-9, A-9, 12, and A-9, 12,15 compounds were tentatively identified. In addition, Schwartz isolated over 50 bound aldehydes probably derived from the glycerol-l-alkenyl ethers (phosphorus free). 

Duin, H. van. 1958. Investigation into the carbonyl compounds in butter. III. Phosphatide-bound aldehydes. Neth. Milk Dairy J. 12, 90-95. 

Carboxylates and other negatively charged functional groups can be detected by treatment with a positively charged dye, such as malachite green [71]. Polystyrene-bound aldehydes can be visualized by treatment with 4-methoxybenzaldehyde under acidic conditions [72]. Quantification of resin-bound carbonyl compounds has been achieved by conversion into dansyl hydrazones [73],... 

Illustrative examples of cleavage reactions of /V-arylbenzylaminc derivatives are listed in Table 3.25. Aromatic amines can be immobilized as /V-bcnzylanilincs by reductive amination of resin-bound aldehydes or by nucleophilic substitution of resin-bound benzyl halides (Chapter 10). The attachment of the amino group of 5-aminoin-doles to 2-chlorotrityl chloride resin has been reported [486]. Anilines have also been linked to resin-bound dihydropyran as aminals [487]. 

Resin-bound aldehydes and ketones have been used as linkers for 1,2- and 1,3-diols (Entries 4-6, Table 3.33). Cleavage of acetal-based linkers is usually effected by acid-catalyzed transacetalization or by hydrolysis. 

Polystyrene-bound benzaldehydes can be smoothly olefinated with benzyl- or cin-namylphosphonium salts in DMF or THF using sodium methoxide as a base (Entry 1, Table 5.5 [64-67]). Alkylphosphonium salts, however, only react with resin-bound aldehydes upon deprotonation with stronger bases, such as butyllithium [30,68-70]. The more acidic acceptor-substituted phosphonium salts, on the other hand, even react with resin-bound aldehydes and ketones upon treatment with tertiary amines, DBU, sodium ethoxide, or lithium hydroxide [71-75], but stronger bases are also used occasionally [76]. 

Table 5.5. Wittig olefination of support-bound aldehydes and ketones.

One problem that may be encountered with this type of reaction is related to the fact that in solid-phase synthesis reagents generally have to be used in excess. This can occasionally lead to side reactions, ff, for instance, a resin-bound aldehyde is condensed under basic conditions with excess ketone, the resulting enone might undergo Michael addition with an additional equivalent of ketone (Figure 5.10). For some of these enones, the Wittig reaction may represent a superior synthetic method [75]. 

Figure 5.10. Double condensation of resin-bound aldehydes with 1,3-diketones [108],...

Support-bound aldehydes or ketones can be reduced to alcohols under mild reaction conditions that are compatible with most supports and linkers. Typical reducing agents are sodium borohydride or diisobutylaluminum hydride, which can penetrate cross-linked polystyrene provided that a solvent with sufficient swelling ability is... 

Thiol esters RC(0)SR are stronger acylating agents than simple alkyl esters, and have been prepared on solid phase mainly as synthetic intermediates. The preparation of thiol esters as intermediates for the synthesis of support-bound thiols is discussed in Section 8.1. Further examples of the preparation of thiol esters on insoluble supports include the aldol addition of ketene thioacetals to polystyrene-bound aldehydes... 

The reaction of support-bound aldehydes with trimethylsulfonium halides in the presence of a strong base allows non-oxidative access to oxiranes (Entry 5, Table... 

Retrosynthetic analysis of the oxazolidinone pharmacophore 1 shown in Fig. 3 revealed that the oxazolidinone aminomethyl group could serve as an attachment site to the solid support during the elaboration of a suitably substituted scaffold. We envisioned amine scaffold 2 could be readily coupled to a resin-bound aldehyde. Attachment of two points of diversity via derivatization of the solid-supported secondary amine 3 with a variety... 

Several variants of the Wittig olefination reaction have been adapted to solid phase (Fig. 8). Williard et al. [43] prepared a series of stilbenes using the Homer-Emmons reaction on resin-bound aldehydes. A route to either substituted or unsubstituted unsatu-... 

The Namiki pathway, involving cleavage of the Schiff base, forming protein-bound aldehydes and glycolaldehyde and glyoxal.402... 

Indium-mediated Barbier-type coupling between carbonyl compounds and allyl halides has been revealed to proceed effectively in diverse reaction media. Even under solvent-free conditions, allylation works well, although no reaction is observed with benzyl bromide and a-halo carbonyl compounds.59 Various aldehydes react with allyl bromide mediated by indium in liquid carbon dioxide to give homoallylic alcohols (Scheme 1). In contrast to the corresponding neat allylation, the liquid C02-mediated reaction can allylate solid aldehydes successfully.60 Indium-mediated allylations of carbonyl compounds with allyl bromide proceed in room temperature ionic liquids. In [bmim][BF4] and [bmim][PF6] (bmin l-butyl-3-methylimidazolium), the desired homoallylic alcohols are formed with good levels of conversion.61 Homoallyllic alcohols are also prepared by the reaction of resin-bound aldehydes (Equation (l)).62... 

Volatile aldehydes, including 1-hexanal, may be primarily responsible for the beany odor of soybean (10, 13, 14). They are present even in defatted soybean flour. Recently, Chiba et al. (15) have deodorized soybean flour by treatment with aldehyde dehydrogenase from bovine liver. Deodorization was a result of converting aldehydes to acids, e.g., 1-hexanal to caproic acid. They postulated that both free and bound aldehydes can act as substrates for this dehydrogenase. Consequently, enzymatic treatment resulted in a product without beany odor. 

Figure 6.9 SP chemical assessment for the tetrahydroquinoline library LI from resin-bound aldehydes 6.1, 6.2.

Aldehyde-tannin and aldehyde-anthocyanin condensation reactions result in polymer formation (Figure 1). These polymers may be responsible for haze formation in wine and the polymers may eventually precipitate out of solution (26). The polymerized tannins have different flavor properties than the monomeric starting units (21-29) and formation of anthocyanin polymers affects wine color. In addition, these reactions may result in a reduction of aldehyde flavors in the wine. These condensation reactions are discussed more fully in other chapters of this volume. The formation of strong covalent bonds between the aldehyde and the tannin or anthocyanin makes recovery of the bound aldehydes difficult. 

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