Terminal Alkynes into Carboxylic Acids

CONVERSION OF TERMINAL ALKYNES INTO CARBOXYLIC ACIDS 

Terminal alkynes can be converted by a process of hydrosilylation followed by oxidative cleavage into carboxylic acids (10). An alternative basic cleavage yields the corresponding aldehydes. 

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Aromatic and furan rings are smoothly converted into carboxylic acids (Eqs. (7.10) and (7.11)) [23], Terminal alkynes undergo a similar oxidative cleavage to afford carboxylic acids, while internal alkynes are converted into diketones (Eq. (7.12)) [24, 25],... 

The reaction was of general applicability not only internal but also terminal alkynes reacted in the same way, e.g. 1-hexyne was converted into hexanoic acid (58%) and 2-ethynylthiophene to 2-thienylacetic acid (54%). By contrast, heating terminal alkynes in chloroform with HTI afforded alkynyl or alkenyl phenyliodonium salts the former in refluxing methanol rearranged to methyl carboxylates [11],... 

A novel catalytic reaction of 3-iodothiophene-2-carboxylic acid with terminal alkynes leading to 4-alkynylthieno[2,3- ]-pyran-7-ones has been described <2006TL83>. This extension of the Sonogashira coupling occurs under Pd-Cu-catalysis (Equation 28). The reaction seems to proceed through an initial Sonogashira pathway to 3-( 1 -alkynyl)thiophene-2-carboxylic acid, which then reacts with a Pd(ll) species formed by insertion of a Pd(0) complex into the C-H bond of the second molecule of alkyne. Both Pd- and Cu-catalysts played cmcial roles, since the reaction failed if either was omitted. 

Alkenyldialkylboranes undergo simple protonolysis of the alkenyl group on treatment with hydrochloric acid, but other alkenyldialkylboranes rearrange under these conditions. This problem does not arise on protonolysis with a carboxylic acid, and hydroboration with a dialkylborane followed by protonolysis with a carboxylic acid is therefore of general utility for conversion of alkynes into alkenes. Internal alkynes cleanly give (Z)-alkenes (Scheme 12, Section 3.10.7.1). The process can also be used for stereospecific production of ( )-1-deuterio-1-alkenes from terminal alkynes (equation 57). Tritiated alkenes have been prepared similarly. ... 

A further example of an indirect electrooxidation of alkynes is their transformation into 1,2-diones when catalytic amounts of RUO4 are generated anodically from Ru02 in a two-phase system (CCU-saturated aqueous NaCl solution). Overoxidation to carboxylic acids is a minor reaction for disubstituted acetylenes, but terminal triple bonds are cleaved... 

This concept was refined by the research group of Li, who employed the thiol-yne reaction instead of the olefin cross-metathesis reaction as key step [60]. In this case, the carboxylic acid component served as anchor, whereby terminal alkynes were introduced by the remaining components (5-hexyn-l-al and propargyl isocyanoacetamide). Interestingly, thiol-yne addition of 3-mercaptopropionic acid to the pendant alkynes enabled not only the incorporation of further carboxylic acids, but also resulted in additional branching. Therefore, the second generation dendrimer, synthesized in three steps, exhibited 16 peripheral triple bonds. Moreover, this concept offers the opportunity to introduce structural diversity into the dendrimer architecture because the use of only one alkyne-functionalized compound in the Passerini-3CR still results in branching due to the thiol-yne reaction. Here, a structural sequence of employed phenylacetaldehyde and 2-nitrobenzaldehyde was demonstrated. 

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. 

H2O Ozonolysis When treated with these reagents, an alkyne undergoes oxidative cleavage of the C C bond. Internal alkynes are converted into two carboxylic acids, while terminal alkynes are converted into a carboxylic acid and carbon dioxide. 

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