Aldehyde hemiacetals, from esters

The formation of side product ester 10 in oxidation of diol 5 (Table 3.1, entry 4) can be explained with the intermediacy of aldehyde as well. Upon generation of aldehyde 11 from 5, intermolecular nucleophilic attack of the carbonyl group by the free hydroxyl group produced hemiacetal 12, oxidation of which led to carboxylic ester 10 (Scheme 3.2). Formation of similar by-products during oxidation of primary hydroxyl groups in carbohydrates has been observed previously. ... 

The most widely used reagent for partial reduction of esters and lactones at the present time is diisobutylaluminum hydride (DiBAlH).83 By use of a controlled amount of the reagent at low temperature, partial reduction can be reliably achieved. The selectivity results from the relative stability of the hemiacetal intermediate that is formed. The aldehyde is not liberated until the hydrolytic workup and is therefore not... 

Primary alcohols 121 undergo an efficient oxidative dimerization by [IrCl(coe)2]2 under air, without any solvent, to form esters 122 in fair to good yields (Equation 10.30) [54]. The reaction is initiated by the in situ generation of an Ir-hydride complex via hydrogen transfer from alcohols to afford aldehydes, followed by the dehydrogenation of hemiacetals derived from alcohols and aldehydes by action of the Ir-complex to afford esters. 

Formation of ester and aldehyde is thus explained since the latter is produced in an acidic environment by decomposition of a hemiacetal such as that produced in Reaction 5. The formation of carbonyl groups from peroxides by nucleophilic displacement has been discussed by Waters (25) and by Kharasch (14). Production of the corresponding... 

Chemoselective reduction of methyl ester 7 to aldehyde 2 is possible with DIB AH. The metallatcd hemiacetal that results from addition of DIBAII to the carbonyl group of ail ester usually decomposes rapidly in polar solvents like THF to an intermediate aldehyde This then competes with the ester and, as a result of its higher clcctrophilicity. js reduced by DIBAH to an alcohol. However, ester 7 bears a methoxymethyl residue in its a-position, which stabilizes the metallated hemiacetal by chelate formation. Chelate complex 22 is protolytically cleaved by way of the hemiacetal only in the course of aqueous workup, so in this case the DIBAH reaction produces only aldehyde 2, not the alcohol (see also Chapter 3), DIBAH, THF, -78 C 100. ... 

The base is important because it removes the proton from the alcohol as it attacks the carbonyl group. A base commonly used for this is pyridine. If tbe electrophile had been an aldehyde or a ketone, we would have got an unstable hemiacetal, which would collapse back to starting materials by eliminating the alcohol. With an acyl chloride, the alkoxide intermediate we get is also unstable. It collapses again by an elimination reaction, this time losing chloride ion, and forming the ester. 

The stereoselective allylation of aldehydes was reported to proceed with allyltrifluorosilanes in the presence of (S)-proline. The reaction involves pentacoordinate silicate intermediates. Optical yields up to 30% are achieved in the copper-catalyzed ally lie ace-toxylation of cyclohexene with (S)-proline as a chiral ligand. The intramolecular asymmetric palladium-catalyzed allylation of aldehydes, including allylating functionality in the molecules, via chiral enamines prepared from (5)-proline esters has been reported (eq 15). The most promising result was reached with the (S)-proline allyl ester derivative (36). Upon treatment with Tetrakis(triphenylphosphine)palladium(0) and PPh3 in THF, the chiral enamine (36) undergoes an intramolecular allylation to afford an a-allyl hemiacetal (37). After an oxidation step the optically active lactones (38) with up to 84% ee were isolated in high chemical yields. The same authors have also reported sucessful palladium-catalyzed asymmetric allylations of chiral allylic (S)-proline ester enamines" and amides with enantiomeric excesses up to 100%. 

Since aldehydes are, in general, more electroactive than the corresponding acids or esters, alcohols can be obtained according to a sole four-electron step. If, on the contrary, the hemiacetal transient is fairly stable, the aldehyde may be isolated from the solution or be continuously trapped as soon as it is formed in the catholyte. 

Masamune has also completed a synthesis of tylonide hemiacetal (291) based on the creative use of enantioselective aldol condensations, as shown in Scheme 2.26. The aldol condensation of 328, derived from (/f)-hexahydromandelic acid and prop anal, was found to be >100 1 diastereoselective, affording the 2,3 syn compound 329 in 97% yield. Transformation to the p,7-unsaturated ester 330 occurred via selenoxide elimination and periodate cleavage followed by esterification. Formation of the silyl ether, reduction, and protection of the ester followed by ozonolysis of the terminal olefin gave the diol-protected aldehyde 331. The C-11 to C-15 segment 332 was then completed via chain elongation and a subsequent reduction-oxidation sequence in 34% overall yield from 330. 

Primary alcohols are more reluctant to undergo oxidation to aldehydes under solventless conditions. Typically, esters with small quantities of carboxyhc acids are observed under these conditions. It has been proposed that esters derive from the oxidation of the corresponding hemiacetal, rather than from the esterification of the carboxylic acid (Scheme 12.9). This proposal is based on the observation... 

Oxidation Reactions. Hypoiodite intermediates may be generated from the reaction of simple alcohols with NIS. When conducted under photochemical irradiation, the products of Barton-type or fragmentation reactions of alkoxyl radical intermediates may be obtained. Aldehydes are oxidized to methyl esters via hemiacetal intermediates by reaction with NIS in methanol at rt. However, such conditions are not effective for the oxidation of simple alcohols. The combination of NIS and Tetrabutylammonium Iodide in dichloromethane has been developed for the oxidation of a variety of alcohols to the corresponding carbonyl corrpounds (eq 8). This reagent system is most widely used for the oxidation of lactols to lactones, in which near-quantitative yields are generally obtained under mild conditions (eq 9). ... 

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