Hydroxy aldehydes formation

Another reaction that is characteristic of a-hydroxy aldehydes or ketones, which has been found of value for the characterisation of sugars, is the formation of osazones with phenylhydrazine. This reagent reacts with either an aldose... 

Aldol condensation (Sections 18 9-18 10) When an aldol ad dition IS carried out so that the 3 hydroxy aldehyde or ke tone dehydrates under the conditions of its formation the product IS described as ansing by an aldol condensation... 

Nitro alcohols form salts upon mild treatment with alkahes. Acidification causes separation of the nitro group as N2O from the parent compound, and results in the formation of carbonyl alcohols, ie, hydroxy aldehydes, from primary nitro alcohols and ketols from secondary nitro alcohols. 

A reaction of great synthetic value for carbon-carbon bond formation. Nucleophilic addition of an enolate ion to a carbonyl group, followed by dehydration of the p-hydroxy aldehyde, yields an a,p-unsaturated aldehyde. 

The addition of the a-carbon of an enolizable aldehyde or ketone 1 to the carbonyl group of a second aldehyde or ketone 2 is called the aldol reaction It is a versatile method for the formation of carbon-carbon bonds, and is frequently used in organic chemistry. The initial reaction product is a /3-hydroxy aldehyde (aldol) or /3-hydroxy ketone (ketol) 3. A subsequent dehydration step can follow, to yield an o ,/3-unsaturated carbonyl compound 4. In that case the entire process is also called aldol condensation. 

The intramolecular cyclization of diketo-enals and keto-enals was accomplished by the combination of a cationic Rh complex and fn(2-furyl)phos-phine (2 - Fur3P). The corresponding bicyclic hydroxy-aldehydes were produced in good to excellent yields, as demonstrated by the formation of 74,76 and 78 (Scheme 22) [36]. 

An a-hydroxy aldehyde will be oxidized relatively rapidly if another hydroxyl group in a position 7 or 5 to the carbonyl permits formation of a pseudoglycol structure by cyclic hemiacetalization. ... 

Rats exposed to a fteptone-containing atmosphere excreted a variety of metabolites resulting from oxidative pathways [176]. The major metabolites were isomeric mono-alcohols and ketones, but small amounts of 2-ethyl-5-methyl-2,3-dihydrofuran (11.171, R = Et, R = Me, Fig. 11.22,a) and 5-ethyl-2-methyl-2,3-dihydrofuran (11.171, R = Me, R = Et) were also detected. These metabolites are believed to arise from 6-hydroxyheptan-3-one (11.170, R = Et, R = Me) and 5-hydroxyheptan-2-one (11.170, R = Me, R = Et). The postulated mechanism of formation of 2,3-dihydrofurans involves their equilibrium with the corresponding linear y-hydroxy ketones, as shown in Fig. 11.22,a. Such a reaction has been documented for linear y-hydroxy aldehydes [177],... 

In the condensation of /3-hydroxy aldehydes 303 with A -sulfonyl aliphatic aldimines 304 (which could also be prepared in situ from the aliphatic aldehyde and A -sulfinyl /i-toluenesulfonamide), 2,5,6-trisubstituted 3,6-dihydro-277-1,3-oxazines 306 were formed as single /ra r-stereoisomers (Scheme 57). No oxazine formation was observed in the... 

Reaction XXXVI. Condensation of Carbon Tetrachloride with Phenols and simultaneous Hydrolysis (Tiemann-Reimer). (B., 10, 2185.)—This reaction is closely analogous to that of the formation of hydroxy-aldehydes by means of chloroform and caustic alkali (see p. 104). A mixture of a phenol, carbon tetrachloride and caustic soda or caustic potash solution is boiled. Condensation occurs, chiefly in the para-position, but small amounts of the ortho-acids are also formed. The product, after the excess of carbon tetrachloride has been removed, is saturated with carbon dioxide and the unchanged phenol extracted with ether. The hydroxy acids are then precipitated by acidification with hydrochloric acid. 

The addition of hydrogen cyanide to a carbonyl group results in the formation of an a-hydroxy nitrile, a so-called cyanohydrin (A, Scheme 6.1) [1]. Compounds of this type have in many instances served as intermediates in the synthesis of, e.g., a-hydroxy acids B, a-hydroxy aldehydes C, fS-amino alcohols D, or a-hydroxy ketones E (Scheme 6.1) [1], In all these secondary transformations of the cyanohydrins A, the stereocenter originally introduced by HCN addition is preserved. Consequently, the catalytic asymmetric addition of HCN to aldehydes and ketones is a synthetically very valuable transformation. Besides addition of HCN, this chapter also covers the addition of trimethylsilyl cyanide and cyanoformate to car-... 

The hydroxynitrile lyase (HNL) class of enzymes, also referred to as oxynitrilases, consists of enzymes that catalyze the formation of chiral cyanohydrins by the stereospecific addition of hydrogen cyanide (HCN) to aldehydes and ketones (Scheme 19.36).275 279 These chiral cyanohydrins are versatile synthons, which can be further modified to prepare chiral a-hydroxy acids, a-hydroxy aldehydes and ketones, acyloins, vicinal diols, ethanolamines, and a- and P-amino acids, to name a few.280 Both (R)- and (.S )-selective HNLs have been isolated, usually from plant sources, where their natural substrates play a role in defense mechanisms of the plant through the release of HCN. In addition to there being HNLs with different stereo-preferences, two different classifications have been defined, based on whether the HNL contains a flavin adenine dinucleotide (FAD) co-factor. 

The effect of proximal groups on the diastereoselectivity in the addition of allylindium to a carbonyl group has been extensively surveyed.153 When a- and /3-hydroxy aldehydes are subjected to the allylation, excellent diastereocontrol is realized, syn- 1,2-Diol and anti- 1,3-diol products are formed, respectively, at accelerated rates (Tables 1 and 2). Protection of the free hydroxy group results in the alternative formation of 1,2-anti products. High stereoselectivities have been observed for indium-promoted allylations of a- and /3-hydroxy aldehydes in aqueous media, implying that a chelate control still operates even in water.72,73,154-158... 

Indium-promoted addition of (Z)-2-(bromomethyl)-2-butenoate to ct-protected hydroxy aldehydes in water results in the selective formation of diastereomer 37 of the possible four stereoisomers 36-39 via the Felkin-Anh transition state (Scheme 40).170... 

The aldehyde substrates may be used as racemic mixtures in many cases, as the aldolase catalyzed reactions can concomitantly accomplish kinetic resolution. For example, when DHAP was combined with d- and L-glyceraldehyde in the presence of FDP aldolase, the reaction proceeded 20 times faster with the D-enantiomer. Fuc 1-P aldolase and Rha 1-P aldolase show kinetic preferences (greater than 19/1) for the L-enantiomer of 2-hydroxy-aldehydes. Alternatively, these reactions may be allowed to equilibrate to the more thermodynamically favored products. This thermodynamic approach is particularly useful when the aldol products can cyclize to the pyranose form. Since the reaction is reversible under thermodynamic conditions, the product with the fewest 1,3-diaxial interactions will predominate. This was demonstrated in the formation of 5-deoxy-5-methyl-fructose-l-phosphate as a minor product (Scheme 5.5).20a 25 The major product, which is thermodynamically more stable, arises from the kinetically less reaction acceptor. 

A new method for the ortho hydroxylation of aromatic aldehydes via orr/io-lithiated aromatic atninoal-koxides has recently been reported by Einhom et al Formation of the aminoalkoxide serves two purposes. Firstly, the aldehyde group is protected and, secondly, the aminoalkoxide directs lithiation to the ortho position. Oxidation of the lithio species was effected by either MoOPH or molecular oxygen, albeit in poor yield. Alternatively, a two-step, one-pot condensation of the lithio intermediate with tributyl borate followed by oxidation with hydrogen peroxide gave the orr/io-hydroxy aldehydes (24) in slightly better yields (Scheme 9). 

A recent application of the furan-carbonyl photocycloaddition involved the synthesis of the mycotoxin asteltoxin (147)." Scheme 16 shows the synthetic procedure that began with the photoaddition of 3,4-dimethylfuran and p-benzyloxypropanal to furnish photoaldol (148), which was epoxidized with MCPBA to afford the functionalized product (149) in 50% overall yield. Hydrolysis (THF, 3N HCl) provided the monocyclic hemiacetal which was protected as its hydrazone (150). Chelation-controlled addition of ethylmagnesium bromide to the latent a-hydroxy aldehyde (150) and acetonide formation produced compound (151), which was transformed through routine operations to aldehyde (152). Chelation-controlled addition of the lithium salt of pentadienyl sulfoxide (153) followed by double 2,3-sigma-tropic rearrangement provided (154) as a 3 1 mixture of isomers (Scheme 17). Acid-catalyzed cyclization of (154) (CSA/CH2CI2) gave the bicyclic acetal (155), which was transformed in several steps to ( )-asteltoxin (147). ... 

A simultaneous reduction-oxidation sequence of hydroxy carbonyl substrates in the Meerwein-Ponndorf-Verley reduction can be accomplished by use of a catalytic amount of (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylaluminum) (8) [33], This is an efficient hydride transfer from the sec-alcohol moiety to the remote carbonyl group and, because of its insensitivity to other functionalities, should find vast potential in the synthesis of complex polyfunctional molecules, including natural and unnatural products. Thus, treatment of hydroxy aldehyde 18 with 8 (5 mol%) in CH2CI2 at 21 °C for 12 h resulted in formation of hydroxy ketone 19 in 78 % yield. As expected, the use of 25 mol% 8 enhanced the rate and the chemical yield was increased to 92 %. A similar tendency was observed with the cyclohexanone derivative. It should be noted that the present reduction-oxidation sequence is highly chemoselective, and can be utilized in the presence of other functionalities such as esters, amides, rert-alco-hols, nitriles and nitro compounds, as depicted in Sch. 10. 

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