Of a-hydroxy aldehydes

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... 

Intramolecular cyclization of a hydroxy aldehyde forms a hemiacetal with a new stereogenic center, so that an equal amount of two enantiomers results. 

Osazone formation is not limited to carbohydrates, but is typical of a-hydroxy aldehydes and a-hydroxy ketones in general (e.g., benzoin, C5H5CHOHCOC6H5). 

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. 

Extension of this work to the synthesis of a-hydroxy aldehydes with substituents other than phenyl a an be carried out by using the methyl ester (79 Scheme 7) as precursor. Grignard additions afiord a vair-iety of ketoaminals (80) in good yield aldehydes (R = H) are available via diisobutylaluminum hydriide reaction. A second Grignard addition, followed by hydrolysis, generates a-hydroxy aldehydes (82) in... 

The asymmetric synthesis of a-hydroxy aldehydes was investigated by treating the derived keto aminal with Grignard reagents. The aminal 10a, which is easily prepared... 

Carbanions of type (2) or (4) react readily with ketones to give mercaptals of a-hydroxy aldehydes and a-hydroxy ketones, respectively ... 

Pummerer rearrangement (5,3-4). The Pummerer rearrangement of P-hydroxy sulfoxides to derivatives of a-hydroxy aldehydes has been extended to the rearrangement of 3-keto sulfoxides. Thus rearrangement of (1) with acetic anhydride-sodium acetate in toluene under reflux gives the S-aryl thioester (2) in 74% yield. The ester is hydrolyzed by base to mandelic acid (3). In the absence of sodium acetate the normal product of the Pummerer rearrangement... 

Resolution by transesterification. A procedure for the large-scale preparation of (15,25)-tran -2-methoxycyclohexanol, which is a key intermediate for the synthesis of tricyclic 3-lactam antibiotics, has been worked out." Monoprotected 1,2-diols and acetals of a-hydroxy aldehydes afford chiral acetates hy the lipase-catalyzed transesterification. a-Ketols are also resolved. Dimethyl /nejo-2,5-dibromoadipate is readily desymmetrized by the transesterification protocol, permitting the synthesis of chiral cA-2,5-disubstituted pyrrolidines. ... 

Other recent reports on the synthesis of a-hydroxy aldehydes using Pummerer chemistry can be found in the synthesis of analogues of mannostatin A and in the synthesis of nelfinavir 38, as described by Raghavan et al. fScheme 20.91. ... 

Lithio-l,3-dithianes add to the carbonyl group of aldehydes and ketones to provide mercaptal derivatives of a-hydroxy aldehydes or ketones (equation 55). The yields are normally quite high. Reaction with a,j8-unsaturated ketones has been observed to give only 1,2-addition however, Seebach and Lietz have reported 1,4-addition to occur in reactions with a,]8-unsaturated nitro derivatives (equation 56). In the case... 

Mukaiyama has extended the use of the chiral ligand (63) to the synthesis of a-hydroxy-aldehydes of desired configuration (Scheme 56). ... 

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