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2
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33750600956
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note
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A search for the indole core in the WDI database retrieved more than 3700 hits. See also ref. 12a.
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see also ref. 7b
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This list is not exhaustive. For example, since the completion of this work, a one-pot synthesis of indoles via enamines has been reported, see: Barluenga, J.; Fernandez, M. A.; Aznar, F.; Valdes, C. Chem. Eur. J. 2005, 11, 2276; see also ref. 7b.
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and references cited therein
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For a very comprehensive overview of the challenges posed by the synthesis of 7-substituted indoles, see: (a) Ezquerra, J.; Pedregal, C.; Lamas, C.; Barluenga, J.; Perez, M.; Garcia-Martin, M. A.; Gonzales, J. M. J. Org. Chem. 1996, 61, 5804; and references cited therein.
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(b) Rodriguez, A. L.; Koradin, C.; Dohle, W.; Knochel, P. Angew. Chem. Int. Ed. 2000, 39, 2488; and references cited therein.
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It is possible to functionalise the 3-position in situ, but it needs concomitant substitution at the 2-position: (a) Arcadi, A.; Cacchi, S.; Marinelli, F. Tetrahedron Lett. 1992, 33, 3915.
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33750600955
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note
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The synthesis of the 7-substituted indoles will be described with ethyl or n-propyl at the 3-position. The synthetic routes described in this paper are applicable to both substituents.
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For a review on iodination of aryl compounds, see: Merkushev, E. B. Synthesis 1988, 923.
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Bis(pyridine)iodonium(I) tetrafluoroborate is also efficient for high-yielding selective iodination of aniline; see ref. 12a and: (a) Barluenga, J.; Gonzalez, J. M.; Garcia-Martin, M. A.; Campos, P. J.; Asensio, G. J. Org. Chem. 1993, 58, 2058.
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45
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33750576285
-
-
note
-
An NOE experiment proved that the stereochemistry of the exocyclic double bond is as shown in Scheme 7.
-
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46
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0000486622
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See also ref. 17b
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33750591724
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note
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See references 133d and 136a-e cited in ref. 7b.
-
-
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49
-
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33750588200
-
-
note
-
Compounds 28a and 28b are drawn as acids for convenience, but are isolated as trimers. See ref. 20a.
-
-
-
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50
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0023889587
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Sulfonamide: (a) Krolski, M. E.; Renaldo, A. F.; Rudisill, D. E.; Stille, J. K. J. Org. Chem. 1988, 53, 1170.
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54
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85083276516
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The synthesis of indoles from 2-halogenated anilines and a (2-alkoxyvinyl)boronic ester, followed by hydrolysis and in situ cyclisation has also been described. However, the synthesis of the (2-alkoxyvinyl)boronic ester requires two steps and we felt this route would not offer significant advantages compared to the others (see below): Satoh, M.; Miyaura, N.; Suzuki, A. Synthesis 1987, 373.
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55
-
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33750586086
-
-
note
-
The structure of 30 was assigned by an NOE experiment.
-
-
-
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56
-
-
33750578288
-
-
note
-
We ensured that we were able to reproduce Larock's results on 2-iodoaniline. Under the same conditions, methyl 4-amino-3-iodo-benzoate gave a 94:6 mixture of isomers. Within this set of examples, the selectivity appears related to the electron deficiency of the aromatic ring.
-
-
-
-
57
-
-
33750594485
-
-
note
-
We did not attempt to increase the yield of the ring formation by using substituents more stable than trimethylsilyl to the reaction conditions, since the yield obtained was adequate for our purposes.
-
-
-
-
58
-
-
33750578137
-
-
note
-
Removal of the trifluoroacetamido group proved easier for 25 (deprotection takes 45 minutes at room temperature) than for 14 (deprotection not complete after two days under similar conditions).
-
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