- Iron-Catalyzed Reductive Cyclization by Hydromagnesiation: A Modular Strategy Towards N-Heterocycles
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A reductive cyclization to prepare a variety of N-heterocycles, through the use of ortho-vinylanilides, is reported. The reaction is catalyzed by an inexpensive and bench-stable iron complex and generally occurs at ambient temperature. The transformation likely proceeds through hydromagnesiation of the vinyl group, and trapping of the in situ generated benzylic anion by an intramolecular electrophile to form the heterocycle. This iron-catalyzed strategy was shown to be broadly applicable and was utilized in the synthesis of substituted indoles, oxindoles and tetrahydrobenzoazepinoindolone derivatives. Mechanistic studies indicated that the reversibility of the hydride transfer step depends on the reactivity of the tethered electrophile. The synthetic utility of our approach was further demonstrated by the formal synthesis of a reported bioactive compound and a family of natural products.
- Larin, Egor M.,Lautens, Mark,Loup, Joachim
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p. 22345 - 22351
(2021/09/09)
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- Indole synthesis by controlled carbolithiation of o-aminostyrenes
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An effective synthesis of the functionalized indole ring system has been developed from substituted o-aminostyrene starting material. Our methodology involves a novel cascade reaction sequence of alkyllithium addition to the styrene double bond and subsequent trapping of the intermediate organolithium with a suitable electrophile, followed by an in situ ring closure and dehydration to generate the indole ring. This new reaction sequence allows for the introduction of molecular diversity at all positions on the indole scaffold. The procedure was shown to be successful with a range of both C and N substituents on the o-aminostyrenes. The reaction sequence was tolerant to the reactivity range of alkyllithiums such as tert-, sec-, and n-butyllithium. The electrophiles used were DMF, which generated indole products with C-2 unsubstituted, and nitriles, which incorporated the nitrile substituent at C-2. The o-aminostyrene starting materials were generated by a Pd-catalyzed cross-coupling reaction of a vinyl boronic acid equivalent with the readily available substituted o-bromoanilines.
- Kessler, Albane,Coleman, Claire M.,Charoenying, Patchanee,O'Shea, Donal F.
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p. 7836 - 7846
(2007/10/03)
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- New organolithium addition methodology to diversely functionalized indoles
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A novel synthetic approach to diversely functionalized indoles is described. Boc-protected ortho-aminostyrenes undergo an alkyllithium addition reaction, thereby generating a lithiated intermediate, which upon reaction with specific electrophiles sets up
- Coleman, Claire M.,O'Shea, Donal F.
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p. 4054 - 4055
(2007/10/03)
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