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Abstract α‐Amino nitriles are versatile structural motifs in a variety of biologically active compounds and pharmaceuticals and they serve as valuable building blocks in synthesis. The preparation of α‐ and β‐functionalized α‐amino nitriles from readily available scaffolds, however, remains challenging. Herein is reported a novel dual catalytic photoredox/copper‐catalyzed chemo‐ and regioselective radical carbocyanation of 2‐azadienes to access functionalized α‐amino nitriles by using redox‐active esters (RAEs) and trimethylsilyl cyanide. This cascade process employs a broad scope of RAEs and provides the corresponding α‐amino nitrile building blocks in 50–95 % yields (51 examples, regioselectivity >95 : 5). The products were transformed into prized α‐amino nitriles and α‐amino acids. Mechanistic studies suggest a radical cascade coupling process.
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Synthesis of Non‐canonical Tryptophan Variants via Rh‐catalyzed C–H Functionalization of Anilines
Tryptophan and its non‐canonical variants play critical roles in pharmaceutical molecules and enzymes. Facile access to this privileged class of amino acids from readily available building blocks remains a long‐standing challenge. Here, we report a regioselective synthesis of non‐canonical tryptophans bearing C4‐C7 substituents via Rh‐catalyzed annulation between structurally diverse tert‐butyloxycarbonyl (Boc)‐protected anilines and alkynyl chlorides readily prepared from amino acid building blocks. This transformation harnesses Boc‐directed C–H metalation and demetalation to afford a wide range of C2‐unsubstituted indole products in a redox‐neutral fashion. This umpolung approach compared to the classic Larock indole synthesis offers a novel mechanism for heteroarene annulation and will be useful for the synthesis of natural products and drug molecules containing non‐canonical tryptophan residues in a highly regioselective manner.
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- Award ID(s):
- 1847932
- PAR ID:
- 10552455
- Publisher / Repository:
- Angewandte Chemie International Edition
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1002/anie.202414998
