A-Hydroxyaldehyde

C=N, C=S, C=C, and N N containing substrates. Thus oxa2oles, imidazoles, thiazoles, p rrroles, and 1,2,4-triazoles have been prepared, respectively. Furthermore, p-tolylsulfonylmethyl isocyanide has found use in a one-step conversion of ketones into cyan-idea and in a two-step synthesis of a-hydroxyaldehydes from ketones. ... 

Patemo-Biichi reaction between 2-methylfuran 31 and an a-hydroxyaldehyde 30 to form the core oxetane. Two of the three stereocenters set in the electrocyclization appear in the final product while the third is selectively reversed with anomeric assistance. 

The (racemic) tmns disulfoxide of 1,3-dithiolane 59 is readily deprotonated at C2 by lithium hexamethyldisilazide, and the resulting anion reacts with aldehydes at -78°C with moderate to excellent diastereoselectivity to give mainly the products 60, although subsequent cleavage of these to give the a-hydroxyaldehydes was not described (97JOC1139). 

Dithioacetal monoxide anions react with carbonyl compounds in a similar way affording the corresponding a-hydroxy aldehyde dithioacetal oxides 428. Ogura and Tsuchihashi, who performed this reaction for the first time using the anion of methyl methylthiomethyl sulphoxide 324, obtained in this way a series of a-hydroxyaldehydes 429504 (equation 257). 

Hydroperoxides, as optically active oxidizing agents 289-291 Hydrosulphonylation 172 /J-Hydroxyacids 619 a-Hydroxyaldehydes, synthesis of 330 a-Hydroxyalkyl acrylates, chiral 329 j -Hydroxycarboxylic esters, chiral 329 3-Hydroxycycloalkenes, synthesis of 313 Hydroxycyclopentenones, synthesis of 310 -Hydroxyesters 619 synthesis of 616 Hydroxyketones 619, 636 Hydroxymethylation 767 a-Hydroxysulphones, synthesis of 176 / -Hydroxysulphones 638, 639 reactions of 637, 944 electrochemical 1036 synthesis of 636 y-Hydroxysulphones 627 synthesis of 783... 

Figure 10.17 Kinetic enantiopreference of class II DHAP aldolases useful for racemic resolution of a-hydroxyaldehydes.

A more synthetically reliable version of this reaction involves epoxidation of silyl enol ethers. Epoxidation of the silyl enol ethers followed by aqueous workup gives a-hydroxyketones and a-hydroxyaldehydes.144... 

Normally, the addition of C-nucleophiles to chiral a-alkoxyaldehydes in organic solvents is opposite to Cram s rule (Scheme 8.15). The anti-Cram selectivity has been rationalized on the basis of chelation control.142 The same anti preference was observed in the reactions of a-alkoxyaldehydes with allyl bromide/indium in water.143 However, for the allylation of a-hydroxyaldehydes with allyl bromide/indium, the syn isomer is the major product. The syn selectivity can be as high as 10 1 syn anti) in the reaction of arabinose. It is argued that in this case, the allylindium intermediate coordinates with both the hydroxy and the carbonyl function leading to the syn adduct. 

On the basis of the electrochemical oxidation of silyl-substituted ethers, a general and iterative route to optically active polyols has been developed (Scheme 20) [51]. The key intermediates of this iterative process are jS-hydroxy-a-methoxysilanes, a protected form of a-hydroxyaldehydes. The electrochemical... 

An identical compound is formed from benzil by the action of phenylhydrazine, and from benzaldehyde phenylhydrazone by autoxida-tion (Busch). The formation of osazones from a-hydroxyketones (and a-hydroxyaldehydes) will be discussed later (p. 298). 

After protection, the a-hydroxy esters can be reduced by DIBAL-H into O-protected a-hydroxyaldehydes that are very useful synthetic intermediates (e.g., leukotrienes,7-9 ionophore antibiotics,10 insect pheremones,11 etc.). The secondary hydroxyl group of the a-hydroxy esters may also be substituted with inversion of configuration after activation as triflates of nosylates (p-nitrobenzenesulfonates) to give a-alkyl esters12 ora-amino esters.13... 

The metabolite but-3-ene-l,2-diol (10.104, Fig. 10.24) is of particular interest since further oxidation by alcohol dehydrogenase yields reactive products such as a,)3-unsaturated ketones [166] [167], Dehydrogenation of the primary alcoholic group to the a-hydroxyaldehyde followed by fast rearrange-... 

Acharya SA and Manning JM (1983) Reaction of glycolaldehyde with proteins latent crosslinking potential of a-hydroxyaldehydes. Proc Natl Acad Sci USA 80, 3590-3594. 

The starting material is an O-protected a-hydroxyaldehyde which is submitted to an (E)- or (Z)-selective olefination. After O-deprotection, the allylic alcohol is rearranged to the y.d-un-saturaled ethyl ester with >99% chirality transfer. 

The diamine (99) was applied 117) to the synthesis of chiral a-hydroxyaldehydes. Thus, treatment of the aminal (100), prepared from the chiral diamine (99) and phenylglyoxal, with the Grignard reagent affords the hydroxyaminal, which in turn was hydrolyzed to yield a-alkyl-a-hydroxyphenylacetaldehyde (101). The chiral auxiliary was recovered ll7). 

Mukaiyama et al. developed a rather general and versatile method for the preparation of optically active a-hydroxyaldehydes by using the diamine (99) as chiral adjuvant. Thus, one Grignard reagent (R MgX) is reacted with the aminal (102) of methyl glyoxylate. In the next step a second kind of Grignard reagent (R2-MgX) is diastereoselectively added to the ketoaminal, and the desired chiral a-hydroxy-aldehyde (103) is obtained by hydrolysis 117-1I8). 

Scheme 2.2.2.1 Principal reactions of transketolase. Ketose donor substrates include xylulose 5-phosphate (upper left) or hydroxypyruvate (lower left). Acceptor substrates are a-hydroxyaldehydes. A C2 unit ( activated glycolaldehyde ) is transferred to the acceptor substrate via a ThDP-bound a, 3-dihydroxyethyl group thereby forming a novel ketose of 3S,4R...

A convenient asymmetric synthesis of a-hydroxyaldehydes begins with the addition of a Grignard reagent to the methoxycarbonyl aminal (238) prepared from methyl hydroxy-methoxyacetate and diamine (236) (79CL705). Treatment of the derived keto aminal (239) with a second Grignard reagent and hydrolysis of the resulting hydroxy aminal (240) yields the optically active a-hydroxyaldehyde (241). Enantiomeric excesses vary between 78 and... 

Fig. 11. Schematic representations for substrate binding by the FruA from rabbit muscle to rationalize the origin of enantioselectivity observed with a-hydroxyaldehydes carrying a distant carboxylate function...

The studies revealed a rather broad acceptor tolerance in that the natural acceptor aldehyde(s) can be considerably varied among phosphorylated as well as unphosphorylated a-hydroxyaldehydes 140 which are both converted at comparable rates (Table 7). 

Very often, when the treatment of a 1,4- or a 1,5-diol with PDC leads to the initial formation of a hydroxyaldehyde that can equilibrate with a cyclic hemiacetal, the latter is further oxidized to a lactone.168... 

An uneventful oxidation to a dialdehyde happens regardless of the intermediacy of a hydroxyaldehyde, that would be expected to equilibrate with a substantial proportion of hemiacetal. ... 

The oxidation of the primary alcohol yields a hydroxyaldehyde that equilibrates with a lactol, which is further oxidized to a 8-lactone. 

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