Efficient synthesis of 2,6-dioxo-1,2,3,4,5,6-hexahydroindoles based on the synthesis and reactions of (2,4-dioxocyclohex-1-yl)acetic acid derivatives

Juma, Benard; Adeel, Muhammad; Villinger, Alexander; Langer, Peter

doi:10.1016/j.tetlet.2008.02.027

Cited by 6 publications

(2 citation statements)

References 18 publications

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“…The derivatization of N,N′-dibenzylbimorpholine provided quaternary bimorpholinium salts used as chiral phase transfer alkylation catalysts. Juma reported the preparation of acetal-protected (2,4-dioxocyclohex-1-yl)acetic acid derivatives by the allylation of dilithiated 1,3cyclohexane-1,3-diones, the protection of carbonyl groups, and the oxidation of the alkene precursor [12]. Polyacetals (and ketals) and polymers containing acetal bonds in the main chain or pendant chains have also been reported as an essential class of degradable polymers that can be considered for biomedical applications with orthopedic purposes and CH2CH2 groups linked to the methyl group of each butyl fragment but also to the diastereotopic hydrogen atoms of the CH2 group in the ethyl fragment attached directly to the hemiacetalic carbon, which, concerning 5, undergo a high-field shift due to an inductive effect.…”

Section: Introductionmentioning

confidence: 99%

Butyl (2,2-Dibutoxybutanoyl)-ʟ-Tryptophanate

Quiroga,

Coy-Barrera

2024

Molbank

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The multicomponent reaction between ʟ-tryptophan 1, 2-oxobutanoic acid 2, and 1-butanol in the presence of SiMe3Cl was studied using microwave irradiation conditions. The main product was identified as an unreported acetal-containing compound, namely, butyl (2,2-dibutoxybutanoyl)-ʟ-tryptophanate (3), yielding 89%. NMR experiments demonstrated that the adjacent methylene protons of the acetal group appeared as two signals exhibiting their behavior as diastereotopic protons. DFT/B3LYP calculations revealed an asymmetric molecular structure with specific angles, leading to an explanation of the NMR results. The calculated chemical shifts showed slight differences with the experimental values and suggested magnetic anisotropy and inductive deprotection around the methylene hydrogen atoms in the acetal location. The reaction mechanism was proposed in which SiMe3Cl plays a crucial role by promoting water removal through key steps.

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Section: Introductionmentioning

confidence: 99%

Butyl (2,2-Dibutoxybutanoyl)-ʟ-Tryptophanate

Quiroga,

Coy-Barrera

2024

Molbank

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“…The carbonyl group of III was expected to be a useful tool for the synthesis of Erythrina-type natural products and their non-natural analogues. It was planned to prepare the required starting material IV from (2,4-dioxocyclohex-1-yl)acetic acid which, therefore, represents an important key intermediate of the present study.Recently, we have reported [7] preliminary results related to the synthesis of (2,4-dioxocyclohex-1-yl)acetic amides, such as IV. Their cyclization, in the presence of catalytic amounts of para-toluenesulfonic acid (PTSA), resulted in the formation of 2,6-dioxo-1,2,3,4,5,6-hexahydroindoles rather than the expected Erythrina-type spiro compounds.…”

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confidence: 99%

Synthesis of 2,6‐Dioxo‐1,2,3,4,5,6‐hexahydroindoles by Acid‐ Catalyzed Cyclization of Acetal‐Protected (2,4‐Dioxocyclohex‐1‐yl)acetamides and their Transformation into 5,8,9,10‐Tetrahydro‐6H‐indolo[2,1‐a]isoquinolin‐9‐ones

et al. 2009

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Acetal-protected (2,4-dioxocyclohex-1-yl)-acetic acids were prepared by allylation of dilithiated 1,3-cyclohexane-1,3-diones, protection of the carbonyl groups and oxidation of the alkene moiety. Their reaction with amines afforded the corresponding amides which were transformed, by acid-catalyzed cyclization, into various 2,6-dioxo-1,2,3,4,5,6-hexahydroindoles. The reaction of the latter with triflic acid resulted in the formation of novel 5,8,9,10-tetrahy-Keywords: alkaloids; amides; C À C bond formation; cyclization; nitrogen heterocycles IntroductionErythrina alkaloids occur in various tropical and subtropical plants [1] and show a wide range of interesting biological properties.[2] This includes, for example, curare-like, hypotensive, sedative, anticonvulsive, and CNS-depressive activity.[3] Erythrina alkaloids have been prepared, for example, using photochemical [2 + 2] cycloadditions or Diels-Alder reactions as the key steps.[4] An important strategy for the synthesis of Erythrina alkaloids relies on the acid-catalyzed domino reaction of (2-oxocyclohex-1-yl)acetic amides. [4][5][6] This transformation proceeds by acid-catalyzed cyclization of the amide to give an N-(2-arylethyl)-2-oxo-1,2,3,4,5,6-hexahydroindole which is transformed in situ into the Erythrina-type spirocyclic product by a Pictet-Spengler reaction. For example, spirocycle I has been directly prepared from the amide II under various conditions (use of acids or Lewis acids) (Scheme 1). Despite its utility, the preparative scope of this reaction is very narrow and its success strongly depends on the structure of the substrate (substitution pattern of the aryl group, length of the linker between the aryl group and the nitrogen atom, etc.). This is a severe limitation because the synthesis of specific target molecules heavily relies on functional group transformations of the spiro compounds obtained by the domino process. FULL PAPERSTo address this problem, we planned to prepare the unknown Erythrina derivative III, which contains an additional carbonyl group, from the corresponding amide IV (Scheme 1). The carbonyl group of III was expected to be a useful tool for the synthesis of Erythrina-type natural products and their non-natural analogues. It was planned to prepare the required starting material IV from (2,4-dioxocyclohex-1-yl)acetic acid which, therefore, represents an important key intermediate of the present study.Recently, we have reported [7] preliminary results related to the synthesis of (2,4-dioxocyclohex-1-yl)acetic amides, such as IV. Their cyclization, in the presence of catalytic amounts of para-toluenesulfonic acid (PTSA), resulted in the formation of 2,6-dioxo-1,2,3,4,5,6-hexahydroindoles rather than the expected Erythrina-type spiro compounds. Herein, we report a full account of the preparative scope of this methodology which provides, to the best of our knowledge, the as yet most general approach to 2,6-dioxo-1,2,3,4,5,6-hexahydroindoles.

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ChemInform Abstract: Efficient Synthesis of 2,6‐Dioxo‐1,2,3,4,5,6‐hexahydroindoles Based on the Synthesis and Reactions of (2,4‐Dioxocyclohex‐1‐yl)acetic Acid Derivatives.

et al. 2008

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Indole derivatives R 0140Efficient Synthesis of 2,6-Dioxo-1,2,3,4,5,6-hexahydroindoles Based on the Synthesis and Reactions of (2,4-Dioxocyclohex-1-yl)acetic Acid Derivatives. -The approach to hexahydroindoles (V), important intermediates for alkaloid synthesis is based on the selective oxidation of the protected dione (II). -(JUMA, B.; ADEEL, M.; VILLINGER, A.; LANGER*, P.; Tetrahedron Lett. 49 (2008) 14, 2272-2274; Inst. Chem., Univ. Rostock, D-18059 Rostock, Germany; Eng.) -Mais 29-112

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Efficient synthesis of 2,6-dioxo-1,2,3,4,5,6-hexahydroindoles based on the synthesis and reactions of (2,4-dioxocyclohex-1-yl)acetic acid derivatives

Cited by 6 publications

References 18 publications

Butyl (2,2-Dibutoxybutanoyl)-ʟ-Tryptophanate

Butyl (2,2-Dibutoxybutanoyl)-ʟ-Tryptophanate

Synthesis of 2,6‐Dioxo‐1,2,3,4,5,6‐hexahydroindoles by Acid‐ Catalyzed Cyclization of Acetal‐Protected (2,4‐Dioxocyclohex‐1‐yl)acetamides and their Transformation into 5,8,9,10‐Tetrahydro‐6H‐indolo[2,1‐a]isoquinolin‐9‐ones

ChemInform Abstract: Efficient Synthesis of 2,6‐Dioxo‐1,2,3,4,5,6‐hexahydroindoles Based on the Synthesis and Reactions of (2,4‐Dioxocyclohex‐1‐yl)acetic Acid Derivatives.

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