A Diels–Alder reaction‐based strategy for the synthesis of indoles and related heterocycles is reported. An intramolecular cycloaddition of alkyne‐tethered 3‐aminopyrones gives 4‐substituted indolines in good yield and with complete regioselectivity. Additional substitution is readily tolerated in the transformation, allowing synthesis of complex and non‐canonical substitution patterns. Oxidative conditions give the corresponding indoles. The strategy also allows the synthesis of carbazoles. The method was showcased in a formal synthesis of lysergic acid.
A regiodivergent Truce–Smiles rearrangement: a strategy for the synthesis of arylated indoles promoted by KN(SiMe 3 ) 2
The first highly regioselective tandem indole formation/Truce–Smiles rearrangement controlled by choice of ligands for K+is presented. Use of N,N-diethylethylenediamine gives 2,3-disubstituted indoles whereas 18-crown-6 gives benzhydryl indoles.
more »
« less
- Award ID(s):
- 2154593
- PAR ID:
- 10534986
- Publisher / Repository:
- The Royal Society of Chemistry
- Date Published:
- Journal Name:
- Organic Chemistry Frontiers
- Volume:
- 10
- Issue:
- 20
- ISSN:
- 2052-4129
- Page Range / eLocation ID:
- 5265 to 5273
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract -
A Rh( i )-catalyzed trideuteromethylation of heteroarenes with inexpensive and readily available deuterated acetic acid (CD 3 CO 2 D) with the aid of a N -containing directing groups is developed. The oxidant-free reaction is applicable to a wide range of heteroarene substrates, including 2-pyridones, indoles, aryl rings, pyrroles and carbazoles. It allows installation of CD 3 groups under straightforward reaction conditions. It is expected that the salient and practical features of this trideuteromethylation protocol will be of use to academic and industrial researchers.more » « less
-
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 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 A unified approach to mono- and disubstituted N–H indoles is described by means of oxidative cyclization of 2-alkenyl anilines, which are prepared by cross-coupling of the corresponding o-bromoanilines. This procedure is operationally expedient and tolerant of common functional groups to allow regiospecific installation of the alkyl and aryl substituents.
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D3QO01105D
