Unit 7.2 Carbonyl Compounds and Carboxylic Acids

The carbonyl bases constitute another important class of weak bases that present interesting possibilities for investigation of structural effects. In solution, experiments with these compounds are subject to severe difficulties. The result is a serious lack of agreement among different investigators about pAa. Arnett and co-workers point out that pKa values reported for acetophenone cover a range of over four units ( — 3.65 to —7.99), while those for acetone span seven units (-0.2 to -7.2).102 In view of these uncertainties, it is impossible to say whether aldehydes, ketones, or carboxylic acids are the most basic in solution. Gas-phase data are available for some of these substances. 

Various [l- C]carboxylic acids have been prepared by carboxylation of carbanions stabilized by -I or -M substituents. The examples in Figure 5.7 have been selected here as prototypes, since they are of strategic interest. Deprotonation of diethyl methylphos-phonate (18 with n-BuLi followed by [ CJcarboxylation and esterification with diazoethane provided triethyl phosphonoll- Clacetate (19) in an overall radiochemical yield of 62%. Compound 19 has been widely exploited for chain extensions by a labeled two-carbon unit via its alkenylation reaction with carbonyl compounds (Homer-Wadsworth-Emmons reaction). Similarly, reaction of alkyl halides, tosylates or carbonyl compounds with LiC = CH or LiC=CH H2NCH2CH2NH2 followed by deprotonation and [ C]carboxylation of the resulting terminal alkynes has been used as a strategic tool for the incorporation of a labeled three-carbon unit, as exemphfied in a steroid platform (20 to 21). This chemistry provides outcomes complementary to those using [ C2]acetylene (Chapter 8, Section 5.1). Finally, the [ CJcarboxylation of lithiated dimethylsulfide provided an alkylthio[l- C]acetic acid 22 and thence a functionalized 2-alkylthio[l- C]ethyl derivative 23 useful, in this case, for elaboration into e.p. 

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