DOI: 10.1002/chem.201903916
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Organic Synthesis
Synthesis of N-Alkyl and N-H-Carbazoles through SNAr-Based
Aminations of Dibenzothiophene Dioxides
Abstract: Alkyl amines have become available for the syn-
thesis of diverse N-alkyl carbazoles through twofold SNAr
aminations of dibenzothiophene dioxides by using alkali
metal bases. Of particular importance is the choice of
counter cations on alkali metal bases, that is, i) the use of
Li base for the efficient intermolecular reaction and ii) the
sequential addition of heavier alkali metal bases (Na, K, or
Cs) to promote intramolecular cyclization in a one-pot
manner. This protocol also enables the cascade synthesis
of N-H-carbazoles by using 2-phenylethylamine by remov-
al of the 2-phenethyl group from N-(2-phenethyl) carba-
zoles in a single operation.
Scheme 1. Syntheses of N-alkyl carbazoles.
Carbazoles represent an important class of nitrogen-containing
heteroaromatics in the field of medicinal and material scien-
ces.[1,2] Of particular interest is N-alkyl carbazoles which possess
potent bioactivities[3] and unique photophysical and electro-
chemical properties.[4] The syntheses of N-alkyl carbazoles gen-
erally rely on the nucleophilic substitution reaction of N-H-car-
bazoles with alkyl halides by the SN2 pathway (Scheme 1,
path A).[5] However, the process is sensitive to the steric hin-
drance of alkyl halides, primary and activated secondary alkyl
halides being only applicable to the reaction.[6] Another ap-
proach is the transition-metal-catalyzed double N-arylation of
primary amines with 2,2’-di(pseudo)halobiaryls (path B), which
typically requires a precious palladium catalyst.[7] In addition,
the benzannulation of N-alkyl indoles with various four-carbon
synthons, such as two molecules of alkynes, has proven to be
a successful strategy to give N-alkyl carbazoles (path C)[8,9]
while installable N-alkyl chains are not diverse. The oxidative
resents a transformation of a heteroaromatic skeleton to an-
other ring system through the partial disassembly of the start-
ing aromatic core.[12–14] Particularly, we have developed the
transition-metal-free transformation of dibenzothiophenes into
N-aryl carbazoles through twofold SNAr reactions of dibenzo-
thiophene dioxides[15] with anilines in the presence of
KN(SiMe3)2, the potassium cation of which played a key role to
promote SNAr aminations (Scheme 2).[13b] However, the reaction
of dibenzothiophene dioxides with alkyl amines by using
KN(SiMe3)2 was sluggish. We thus investigated the effect of
Brønsted bases in more detail to achieve the efficient synthesis
of N-alkyl carbazoles from dibenzothiophene dioxides and alkyl
amines.
cyclization of N,N-diarylalkylamines (path D) or 2-alkylamino-
[10,11]
biaryls (path E) has also been developed
while these
methods suffer from the poor regioselectivity in the case of
multisubstituted aromatic substrates. Therefore, the develop-
ment of novel methods for the synthesis of diverse N-alkyl car-
bazoles is still desirable.
Recently, we have been interested in ‘aromatic metamorpho-
sis’ of heteroatom-containing aromatic compounds, which rep-
Scheme 2. Our previous transformation of dibenzothiophenes into carba-
zoles and its limitation.
[a] Dr. A. Kaga, Dr. K. Nogi, Prof. Dr. H. Yorimitsu
Department of Chemistry, Graduate School of Science
Kyoto University, Sakyo-ku, Kyoto 606-8502 (Japan)
We commenced our studies with the reaction of dibenzo-
thiophene dioxide (1a) with n-hexylamine (2a) in 1,4-dioxane
at 1008C (Table 1). Extensive screening of Brønsted bases re-
vealed that the use of KN(SiMe3)2 or NaN(SiMe3)2 resulted in
poor yields of desired carbazole 3aa along with a complex
Supporting information and the ORCID identification number(s) for the
author(s) of this article can be found under:
Chem. Eur. J. 2019, 25, 1 – 6
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