Divergent pathway for the solid-phase conversion of aromatic acetylenes to carboxylic acids, α-ketocarboxylic acids, and methyl ketones
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
An efficient divergent pathway for the selective and quantitative solid-phase conversion of aromatic acetylenes to the corresponding carboxylic acids, α-keto-carboxylic acids, and methyl ketones is presented. A range of aromatic trimethylsilyl-protected acetylene building blocks was synthesized in excellent yields using a Sonogashira cross-coupling protocol and used in solid-phase synthesis on PEGA resin. Dependent on the selection of conditions, the same solid-supported alkyne could be quantitatively converted to an aromatic carboxylic acid, an aromatic α-ketocarboxylic acid, or an aromatic methyl ketone. The conversion to carboxylic acid involved an OsO4/NaIO 4/HMTA-mediated oxidative cleavage of the silyl-deprotected alkyne to provide the aromatic carboxylate in excellent yield. The α-ketocarboxylic acids were obtained by direct treatment of the trimethylsilyl-protected alkyne with OsO4/NMO/HMTA, while the ketones were obtained by simple acid-mediated hydration of the alkyne using aqueous TFA. In general, all products were obtained in excellent purities, typically above 90%. In addition, it was shown mat the alkyne-containing building blocks could easily be incorporated into resin-bound peptides and after chemoselective conversion of the alkyne the new functional groups could be used for further derivatization into peptidomimetic compounds.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Combinatorial Chemistry |
Vol/bind | 10 |
Udgave nummer | 4 |
Sider (fra-til) | 546-556 |
Antal sider | 11 |
ISSN | 1520-4766 |
DOI | |
Status | Udgivet - jul. 2008 |
Eksternt udgivet | Ja |
ID: 321826933