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. 2018 Aug 3;83(15):7939-7949.
doi: 10.1021/acs.joc.8b00812. Epub 2018 Jun 25.

Synthesis of [3a,7a]-Dihydroindoles by a Tandem Arene Cyclopropanation/3,5-Sigmatropic Rearrangement Reaction

Sidney M Wilkerson-Hill  1 , Brandon E Haines  1 , Djamaladdin G Musaev  1 , Huw M L Davies  1
Affiliations

Synthesis of [3a,7a]-Dihydroindoles by a Tandem Arene Cyclopropanation/3,5-Sigmatropic Rearrangement Reaction

Sidney M Wilkerson-Hill et al. J Org Chem. .

Abstract

Donor/acceptor carbenes provide a powerful platform for building molecular complexity, but the majority of their reactions have been limited to aryl and vinyl donor groups. We found that a N-containing donor/acceptor carbene precursor, 4-phthalimido- N-methanesulfonyl-1,2,3-triazole, reacts with unactivated arenes resulting in a mixture of [3+2]-cycloadducts, [3a,7a]-dihydroindoles, and formal C-H functionalization products in up to 82% yield upon heating. We also demonstrate that the formal C-H functionalization products arise from ring-opening of the [3+2]-cycloadducts. Computational studies suggest that the formal cycloaddition process takes places through a tandem arene cyclopropanation/6π electrocyclization/6π electrocyclic ring-opening/3,5-sigmatropic rearrangement reaction, which also accounts for the distinctive regioselectivity of the formal cycloaddition reaction.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Representative examples of N-sulfonyltriazoles participating in dearomatization reactions. N-phthalimidotriazole (1) undergoes thermal cyclopropanation reactions (Davies, 2012) and dearomatization reactions (this work).
Figure 2:
Figure 2:
a) Products are obtained as a separable mixture of the [3+2] cycloadduct 4 and C–H insertion products 5 favoring the isomer indicated unless otherwise stated. The isolated yield of only the dihydroindole product(s) given. The 1H NMR yield of cycloadduct 4 determined from the crude reaction mixture is given in parenthesis. See the Supporting Information for combined isolated amounts of both 4 and 5 b) Conditions 50.0 mg (0.171 mmol) triazole 1a, 4 equiv arene 3, 0.50 M at 70 °C in CHCl3 for 90 min. c) Mixtures of dihydroindole regioisomers are inseparable by column chromatography d) Performed with 1.00 mmol triazole 1b e) No ring-opened isomers (5) were detected by 1H NMR analysis.
Figure 3:
Figure 3:
a Products are obtained as a mixture of the [3+2]-cycloadducts 7 and 8 and C–H insertion products 9 favoring the compound indicated. Combined isolated yield in parenthesis. 1,2-DCE = 1,2-dichloroethane. See the Supporting Information for details.
Figure 4.
Figure 4.
Conversion of dihydroindole 4a to arene 5a thermally in CD3CN (green), in C6D6 (blue) and CDCl3 (red). The reaction in C6D6 is markedly slower.
Scheme 1.
Scheme 1.
Proposed mechanism for the synthesis of dihydroindoles from triazole 1a and rationalization of dihydroindole regioselectivity from sigmatropic rearrangements. Energetically preferred pathway shown in blue. Transition state energies are calculated relative to endo-C and are given in parenthesis as ΔG/ΔH at 343 K. See the supporting information for details. RXN = reaction, RAR = rearrangement, Rot = rotation, TS = transition state.
See this image and copyright information in PMC

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