Regioselectivity of Larock indole synthesis using functionalized alkynes
Kumi Sugino1, Hiroshi Yoshimura, Toshio Nishikawa
1Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Japan.
The Larock indole synthesis, a palladium-catalyzed reaction, showed low to moderate regioselectivity when using specific functional groups on acetylene. These groups, including esters and protected amines, did not provide significant directing effects in this important organic synthesis.
Area of Science:
- Organic Chemistry
- Catalysis
- Synthetic Methodology
Background:
- The Larock indole synthesis is a valuable method for constructing indole rings, a common motif in pharmaceuticals.
- Controlling regioselectivity is crucial for efficient synthesis and avoiding unwanted isomers.
Purpose of the Study:
- To investigate the regioselectivity of the Larock indole synthesis using functionalized acetylenes.
- To evaluate the directing effects of ester and Boc-protected amine groups at the homopropargylic position, as well as glucose moieties.
Main Methods:
- Palladium-catalyzed heteroannulation reaction between o-iodoaniline and variously substituted internal acetylenes.
- Synthesis of acetylenes bearing ester, Boc-protected amine, and glucose substituents.
- Analysis of reaction products to determine regioselectivity.
Main Results:
- Low to moderate regioselectivities were observed across all tested substrates.
- The presence of ester and Boc-protected amine groups did not significantly enhance regioselectivity.
- Glucose-substituted acetylenes also yielded limited regiocontrol.
Conclusions:
- The functional groups investigated (ester, Boc-amine, glucose) exhibit poor directing effects in the Larock indole synthesis.
- Further development of directing groups or alternative synthetic strategies may be needed for improved regioselectivity in complex indole synthesis.
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