Phenylacetaldehyde, enol acidity

An additional indication of the mildness of the cyclization is provided by the synthesis of the chiral tetrahydroisoquinoline-3-carboxylic acid (294) (72HCA15) in the presence of hydrogen and palladium-on-charcoal the jV-methyl derivative was obtained. Acetaldehyde gave a mixture of diastereoisomers in which the cis isomer (295) predominated (95 5). Unstable aldehydes can sometimes be generated in situ, as when the phenylglycidate (296) replaces the much less stable phenylacetaldehyde (66T(S8)129) acetals, enol ethers and chloromethyl methyl ethers have also been used. The mild conditions also allow the isolation of 4-hydroxytetrahydroisoquinolines (297) (75H(3)311). A review is available listing syntheses of 4-oxytetrahydroisoquinolines (73AHC(15)99). 

Isomeric enols have different acidity. The more stable (El-enol of phenylacetaldehyde (53) was found to be more acidic (pAla ) than its less stable (pAIe) stereoisomeric (Z)-enol. This was presumably due to the less sterically demanding ( )-enol or ( l-enolate being better solvated in water than the corresponding (Z)-stereoisomers. Increasing the... 

A related reagent (186) is prepared in three steps from (5)-atrolactic acid. The lithium enolate of (186) reacts with phenylacetaldehyde to give two aldols in a ratio of 94 6 (Scheme 12). [The full relative stereochemistry of aldols (187) and (188) was not rigorously determined, but may be deduced from the stereochemistry of (190). It is surprising that the lithium enolate of (186) has a diastereofacial preference that is opposite that of the related ketone (181).] Compound (186) has been used in a synthesis of the Prelog-Djerassi lactonic acid (191), as shown in Scheme 12. Reagents related to (181) and (186) have been used as their boron enolates for other synthetic purposes (see Chapter 1.7, this volume). 

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