- Award ID(s):
- 2154593
- PAR ID:
- 10534991
- Publisher / Repository:
- ACS
- Date Published:
- Journal Name:
- Organic Letters
- Volume:
- 25
- Issue:
- 39
- ISSN:
- 1523-7060
- Page Range / eLocation ID:
- 7132 to 7136
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract Functionalized indoles are recurrent motifs in bioactive natural products and pharmaceuticals. While transition metal‐catalyzed carbene transfer has provided an attractive route to afford C3‐functionalized indoles, these protocols are viable only in the presence of N‐protected indoles, owing to competition from the more facile N−H insertion reaction. Herein, a biocatalytic strategy for enabling the direct C−H functionalization of unprotected indoles is reported. Engineered variants of myoglobin provide efficient biocatalysts for this reaction, which has no precedents in the biological world, enabling the transformation of a broad range of indoles in the presence of ethyl α‐diazoacetate to give the corresponding C3‐functionalized derivatives in high conversion yields and excellent chemoselectivity. This strategy could be exploited to develop a concise chemoenzymatic route to afford the nonsteroidal anti‐inflammatory drug indomethacin.
-
more » « less
Abstract Indole is one of the most important heterocycles in organic synthesis, natural products, and drug discovery. Recently, tremendous advances in the selective functionalization of indoles have been reported. Although the most important advances have been powered by transition metal catalysis, exceedingly useful methods in the absence of transition metals have also been reported. In this review, we provide an overview of functionalization reactions of indoles that have been published in the last years with a focus on the most recent advances, aims, and future trends. The review is organized by the positional selectivity and type of methods used for functionalization. In particular, we discuss major advances in transition‐metal‐catalyzed C−H functionalization at the classical C2/C3 positions, transition‐metal‐catalyzed C−H functionalization at the remote C4/C7 positions, transition‐metal‐catalyzed cross‐coupling, and transition‐metal‐free functionalization.
magnified image -
more » « less
Abstract Functionalized indoles are recurrent motifs in bioactive natural products and pharmaceuticals. While transition metal‐catalyzed carbene transfer has provided an attractive route to afford C3‐functionalized indoles, these protocols are viable only in the presence of N‐protected indoles, owing to competition from the more facile N−H insertion reaction. Herein, a biocatalytic strategy for enabling the direct C−H functionalization of unprotected indoles is reported. Engineered variants of myoglobin provide efficient biocatalysts for this reaction, which has no precedents in the biological world, enabling the transformation of a broad range of indoles in the presence of ethyl α‐diazoacetate to give the corresponding C3‐functionalized derivatives in high conversion yields and excellent chemoselectivity. This strategy could be exploited to develop a concise chemoenzymatic route to afford the nonsteroidal anti‐inflammatory drug indomethacin.
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acs.orglett.3c02609
