A-Hydroxyaldehydes synthesis

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... 

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. ... 

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). 

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... 

Weber [61,62] has developed in the context of prebiotic chemistry an original pathway for a-aminothioester synthesis [180], which can start from hydroxyaldehydes 30 intermediates in the formose reaction (a likely prebiotic pathway to carbohydrates). Obviously, thioesters themselves are not observed as products because of their fast hydrolysis in the medium, but they could be converted into peptide bonds in the presence of amino acids or peptide free amino groups, and into mixed anhydride with phosphoric acid in the presence of inorganic phosphate. The reaction involves two key-steps the condensation of ammonia and of the mercaptan on a-keto aldehyde 31... 

This is a simple example for a macrolide synthesis from an to-hydroxyaldehyde andylideH. 

The method has been applied to the diastereoselective synthesis of naturally occurring compounds such as frontalin (84-100% ee) and(—)-malyngolide (95% ee). On the other hand, diastereoselective alkylation of chiral formylaminal with Grignard reagents and the subsequent hydrolysis afford optically active S-a-hydroxyaldehydes with moderate stereoselectivity (60% ee). ... 

Karrer, P. Hydroxycarbonyl compounds. I. A new synthesis of hydroxyaldehydes. Helv. Chim. Acta 1919, 2, 89-94. 

Baker s yeast offers the synthetic chemist an enzymatic method for the asymmetric reduction of p-keto esters, a-hydroxyaldehydes and ketones, and p-diketones. Reviews (a) Rene Csuk, R. Glaenzer, B. 1. Chem. Rev. 1991, 91, 49-97. (b) Servi, S. Synthesis, 1990, 1-25. 

Recently, some extensive research has been devoted to exploring a diastereo-selective and enantioselective route for the synthesis of a-hydroxyaldehydes or a-hydroxyketones because they are important building blocks for the construction of complex natural products and biologically active molecules [91]. In parallel with the transition-metal-catalyzed asymmetric nitroso-aldol reaction [92], much interest has also been expressed towards the proline-catalyzed direct asymmetric a-aminoxylation of aldehydes or ketones for the synthesis of optically active a-hydroxyladehydes and a-hydroxyketones [93]. Wang [94] and Huang [95] independently reported an L-proline-catalyzed asymmetric a-aminoxylation reaction in ionic liquids, whereby it was found tliat aldehydes and ketones could undergo... 

The reduction of 2-acyl- 1,3-oxathianes such as 3.96 (X = S) or of 2-acyl-3-oxa-N-benzylpiperidines 3.96 (X = NCH2Ph) can also take place with or without chelation control [El, EFl, EH2, KEl, KF4]. In cases of chelation control, the oxygen atom of the heterocycle participates in the chelation process (Figure 3.32). When the reaction is carried out with Li(5-Bu)3BH in the presence of Lil as an additive, the reduction occurs under chelation control. However, when using two equivalents of DIBAH, each of them coordinates to a one basic site, and no chelation takes place. The use of these chiral auxiliaries allows the synthesis of nonracemic a-hydroxyaldehydes or a-hydroxyesters with a high enantiomeric excess [NNl, S3]. 

The diamine (R=Ph) was also applied to the synthesis of optically active a-hydroxyaldehydes. Treatment of the aminal, prepared from the chiral diamine and phenylglyoxal, with Grignard... 

Synthesis of carbinols and (Scheme 9) is entirely analogous to the syntheses described earlier. However cleavage in the case of and was carried out by mecuis of N-chloro-succinimide (NCS) - silver nitrate (25). This cleavage produces not only the chiral a-hydroxyaldehydes in good yields but also returns the hydroxythiol chiral adjuvcuit in form of the pair of diastereomeric sultines (Lithiimi aluminum hydride reduction... 

Experiments presently in progress suggest that the mono-tosylate precursors of the terticiry alcohols can alternatively be converted, by base, to primcury-tertiary epoxides which in t im may be opened at the primary site by a variety of nucleophiles, thus greatly amplifying the opportunities for synthesis of compounds bearing chiral tertiary carbinol moieties. It has also proved possible (23, 30) to oxidize the a-hydroxyaldehydes to a-hydroxy-esters which, in turn, may be saponified to a-hydroxyacids. 

Figure 9 a-hydroxyaldehyde used in the solid phase synthesis of i// [CH(OH)CH2NH] isosteres [148]. 

Ester synthesis. Use of this reagent permits the formal oxidation, of a-hydroxyaldehydes and y-ketoaldehydes to the corresponding esters. ... 

Guanti established [4] that the LAH reduction of a-tolylthio-p-ketosulfoxides, prepared by direct acylation of the lithio-anion of optically pure (S)-(+)-p-tolyl p-tolylthiomethyl sufoxide was highly diastereoselective, yielding diastereoisomeric product alcohols in ratios up to >99 1 (4a 4b) (Scheme 4.3) [5]. The p-hydroxysulfoxide products (4a) and (4b) can be considered as protected a-hydroxyaldehydes indeed, the synthesis of enantiomerically pure (R)-(-)-a-methoxyphenylacetaldehyde (5) (and its (S )-(+) antipode) was demonstrated through application of a previously established procedure [6]. 

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