Synthesis of Novel Polycyclic Indolyldiamines

Cutri, Sabrina; Diez, Anna; Bonin, Martine; Micouin, Laurent; Husson, Henri‐Philippe

doi:10.1021/ol047408b

Cited by 15 publications

(6 citation statements)

References 18 publications

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“…Finally, the use of indole aminals as starting materials for intra-or inter-molecular additions of nucleophiles has been studied more in details by Diez, Bonin and co-workers. 20 Our method using aminocyclopropanes as acyl iminium precursors complements well the existing approaches, as it proceeds under mild conditions and does not require strong Lewis acids or reducing agents. Furthermore, both the C3 and the N1 cyclization products can be obtained in high yields in a single step just by changing the reaction conditions.…”

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confidence: 89%

Cyclization of Aminocyclopropanes in Indole Alkaloids Synthesis

Simone¹,

Waser²

2011

Synlett

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Abstract:The regioselective and diastereoselective cyclization of acyliminium intermediates generated from aminocyclopropanes on unprotected indole is presented. The recent results obtained in our group are compared with previous intermolecular reactions with aminocyclopropanes as well as with other cyclization methods involving iminium ions and unprotected indoles. A first speculative analysis of possible reaction mechanisms allows rationalizing the observed selectivity. The high potential of the method for the synthesis of natural alkaloids is demonstrated in the formal synthesis of aspidospermidine and the total synthesis of goniomitine.Key words: Alkaloids, Cyclization, Indoles, Iminium, Aminocyclopropanes Cyclization and cycloaddition reactions are important tools in organic chemistry to access the complex polyclic core of natural products. 1 Both concerted pericyclic processes or reactions involving reactive intermediates can be envisaged. The former has the advantage of a low activation barrier, which allows mild conditions. It is limited usually to substrates containing correctly aligned orbital systems (DielsAlder, electrocyclic cyclization, sigmatropic rearrangements). The use of reactive intermediates such as carbocations or radicals opens further pathways for cyclization. To make them accessible under mild conditions, the introduction of destabilizing elements in the starting material is an important strategy. Cyclopropanes are well-suited for this task, due to their high strain energy (26-29 Kcal/mol). Especially donor-acceptor substituted cyclopropanes are easily opened under mild conditions to form reactive zwitterionic intermediates. 2 They can be considered as homologous equivalents of olefins in diverse annulation and cyclization reactions. After the pioneering work of Stork, Danishefsky and Corey in the 1970's, 3 progress in reactions involving activated cyclopropanes was slow. An important exception is represented by the work of Wenkert and Reissig. 4 In the last 10 years, the potential of cyclopropanes in catalysis has been increasingly recognized, either in Lewis or Brønsted acid mediated [3+2] cycloadditions, or in ring-opening reactions with nucleophiles or electrophiles (Scheme 1). 5 The introduction of cyclopropanes into classical substrates used in pericyclic reactions can lead to unprecedented reactivity. For example, it is well known that the Cope rearrangement of divinylcyclopropanes proceeds much faster than in the absence of the strained ring. 6 The Nazarov cyclization is another important pericyclic reaction. 7 Catalytic and asymmetric versions of the reaction were developed in the course of the last 20 years. 8 Substitution of a double bond by a cyclopropane in divinyl ketones leads to the formal homo-Nazarov cyclization. Despite its promising potential for the synthesis of cyclohexenones, the homo-Nazarov cyclization has been only scarcely studied and the strong conditions needed have limited its applicability. 9Scheme 1 Reactivity of activated cyclopropanes.In 2009, we demo...

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confidence: 89%

Cyclization of Aminocyclopropanes in Indole Alkaloids Synthesis

Simone¹,

Waser²

2011

Synlett

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“…Thus,`bridged' THPI 39 is formed in a small yield from aminal 40 already when applied to silica gel. 43 The optically active group R used for the diastereoselective synthesis of the aminal 40 can be removed by hydrogenation.…”

Section: Syntheses Based On Substituted Indoles To Form a Tetrahydropmentioning

confidence: 99%

The synthesis and physiological activity of 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles

Ivashchenko¹,

Mitkin²,

Кадиева³

et al. 2010

Russ. Chem. Rev.

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“…In this case the diethoxymethyl group also plays the role of a one-carbon building block, taking part in the formation both of tetrahydro-γ-carboline and of the isomeric tetrahydropyrimido[1,6-a]indole, which can also serve as precursor for the production of tetrahydro-γ-carboline according to the following scheme [92] A synthetic equivalent of the carbonyl compound for the Pictet-Spengler condensation can be not only an acetal fragment at the nitrogen atom of indole (as in the previous example) but also an aminal fragment in the side chain. Here, however, the yield of the bridged γ-carboline derivative 32 is low on account of the chemoselective transformation of the respective bicyclic aminal [93]. During the reduction of compound 33 by the action of LiAlH 4 , accompanied by rearrangement, a 5-unsubstituted structure analogous with compound 32 is formed as a single diastereomer [93].…”

Section: Syntheses With the Formation Of The C(1)-c(9b) Bondsmentioning

confidence: 99%

“…Here, however, the yield of the bridged γ-carboline derivative 32 is low on account of the chemoselective transformation of the respective bicyclic aminal [93]. During the reduction of compound 33 by the action of LiAlH 4 , accompanied by rearrangement, a 5-unsubstituted structure analogous with compound 32 is formed as a single diastereomer [93]. 2-(Bromoacetyl)indole can be transformed into the tetrahydro-γ-carboline 34 through a stage involving the formation of a pyridinium salt followed by reductive cyclization with lithium aluminum hydride [94].…”

Section: Syntheses With the Formation Of The C(1)-c(9b) Bondsmentioning

confidence: 99%