Hydroxy aldehydes from alkenes

In a study by Wicha directed to the synthesis of prostaglandins from the Corey lactone, the use of BFs-EtaO to catalyze the addition of the lithium sulfone anion (470) to aldehydes was demonstrated (equation 109). The use of Lewis acid catalysis results in significantly improved yields for the addition component of the Julia coupling. In this example, the addition of either the lithium or the magnesium sulfone anion proceeded in low yield. With the addition of BF3-Et20, the p-hydroxy sulfone can either be isolated, or directly converted to an alkene in one pot. This sequence was originally developed to deal with the specific problem of a-hydroxy aldehydes, and the difficulty of sulfone anion addition to these adducts. Other problems with addition of the sulfone adduct may be amenable to this solution as well. 

C-Glycosidation of enol silane 279 to lactol acetate 278, prepared from 277 in two steps, furiushed ynone 280 as a single isomer. Reduction of the ketone with L-selectride furnished alcohol 270 with poor selectivity, but the minor isomer can be converted into the desired isomer via the Mitsunobu protocol Dihydroxylation of the terminal alkene, reduction of alkyne, and oxidative cleavage of the resulting triol gave the intermediate hydroxy aldehyde, which was spontaneously transformed into macrolactol 281 as a single diastereomer. 

Other Methods.— The palladium-catalysed oxidation of terminal olefins to methyl ketones is very efficient using 30% hydrogen peroxide in acetic acid or t-butyl alcohol. The method offers advantages in that conversions are usually high, aldehyde production is very low, and the method requires only very low concentrations of palladium [20—40p.p.m, as palladium(li) acetate], fi-Hydroxy-o-nitrophenylselenides, or their O-acyl derivatives, on oxidation with hydrogen peroxide undergo elimination to form ketones or enol esters [equation (10)]. The starting materials can be prepared easily from alkenes via their epoxides. 

Ozonolysis of double bonds as a route to ketones and aldehydes is well known. Thiourea may be used for the reduction of the ozonide to afford aldehydes from suitable alkenes. Electrolytic reduction of ozonization products from the oxidation of trisubstituted cyclic alkenes in acetic acid offers a route to hydroxy-ketones. a-Alkoxy-peroxides, from ozonolysis in alcoholic solution, are stable... 

The 4-hydroxy-1-alkene (homoallylic alcohol) 81 is oxidized to the hetni-acetal 82 of the aldehyde by the participation of the OH group when there is a substituent at C3. In the absence of the substituent, a ketone is obtained. The hemiacetal is converted into butyrolactone 83[117], When Pd nitro complex is used as a catalyst in /-BuOH under oxygen, acetals are obtained from homoallylic alcohols even in the absence of a substituent at C-3[l 18], /-Allylamine is oxidized to the acetal 84 of the aldehyde selectively by participation of the amino group[l 19],... 

The olefin metathesis of 3-hydroxy-4-vinyl-l,2,5-thiadiazole 112 and a McMurry coupling reaction (Ti3+ under reductive conditions) of the aldehyde 114 were both unsuccessful <2004TL5441>. An alternative approach via a Wittig reaction was successful. With the use of the mild heterogenous oxidant 4-acetylamino-2,2,6,6-tetramethyl-piperidine-l-oxoammonium perfluoroborate (Bobbitt s reagent), the alcohol 113 was converted into the aldehyde 114. The phosphonium salt 115 also obtained from the alcohol 113 was treated with the aldehyde 114 to give the symmetrical alkene 116 (Scheme 16) <2004TL5441>. 

Bis [(trifluoromethyl)thio] acetaldehyde (83a) has been prepared from an enam-ine precursor (84), although refluxing in aqueous ethanolic HCl is required to effect this reaction.The aldehyde is less stable than its enol tautomer (83b), and many reactions typical of aldehydes fail. For example, addition of aqueous silver nitrate immediately yields the silver salt of (83b), rather than giving precipitation of (elemental) silver. The (trifluoromethyl)thio substituent has pseudohalogenic character and, together with the hydroxy group, stabilizes the alkene tautomer in the manner of a push-pull alkene. The enol-aldehyde equilibrium mixture in acetonitrile shows an apparent of 2.6 when titrated with aqueous hydroxide. 

The alkenes 149 and 150 are easily cleaved by ozonolysis either directly or after protection of the hydroxy gronp. Depending on the workup conditions of the ozonolysis, either diols 151 or 0-protected aldehydes 152 can be obtained. The C2 symmetric ketone 153 dr 75 25) is available from another addition of the dilithium reagent 148 (R = Ph)... 

Optically active aldehydes are available in abundance from amino and hydroxy acids or from carbohydrates, thereby providing a great variety of optically active nitrile oxides via the corresponding oximes. Unfortunately, sufficient 1,4- or 1,3-asymmetric induction in cycloaddition to 1-alkenes or 1,2-disubstituted alkenes has still not been achieved. This represents an interesting problem that will surely be tackled in the years to come. On the other hand, cycloadditions with achiral olefins lead to 1 1 mixtures of diastereoisomers, that on separation furnish pure enantiomers with two or more stereocenters. This process is, of course, related to the separation of racemic mixtures, also leading to both enantiomers with 50% maximum yield for each. There has been a number of applications of this principle in synthesis. Chiral nitrile oxides are stereochemicaUy neutral, and consequently 1,2-induction from achiral alkenes can fully be exploited (see Table 6.10). 

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