Syntheses of aza-analogous iso-ergoline scaffolds using carbene mediated C–H insertion

Krogsgaard‐Larsen, Niels; Begtrup, Mikael; Frydenvang, Karla; Kehler, Jan

doi:10.1016/j.tet.2010.09.023

Cited by 7 publications

(5 citation statements)

References 16 publications

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“…However, 12a proved to be unstable at room temperature and we therefore screened several different protecting groups starting from the corresponding N ‐protected 4‐bromoindole . The tosyl‐ and benzyl‐protected indoles 9b and 9c , respectively, failed to undergo the one‐pot Friedel–Crafts/Michael addition sequence.…”

Section: Resultsmentioning

confidence: 99%

Application of a One‐Pot Friedel–Crafts Alkylation/Michael Addition Methodology to the Asymmetric Synthesis of Ergoline Derivatives

et al. 2017

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Herein, we report a short and facile stereoselective route to ergoline derivatives. The key steps are a one‐pot Friedel–Crafts alkylation/Michael addition sequence which, in the absence of chiral ligands, affords the trans‐trans‐stereoisomer in 44 % yield as a racemate. Screening of a range of chiral bisoxazoline ligands allowed this sequence to proceed in 42–55 % yields (six examples), with up to 99 % ee. This approach allows for the first time, substitution at the C4‐position and the introduction of 3 chiral centres in one pot. An interesting, base‐mediated conversion of the trans‐trans‐stereoisomer to the cis‐cis‐stereoisomer was discovered and both stereoisomers were characterized by X‐ray crystallography.

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Section: Resultsmentioning

confidence: 99%

Application of a One‐Pot Friedel–Crafts Alkylation/Michael Addition Methodology to the Asymmetric Synthesis of Ergoline Derivatives

et al. 2017

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“…The chemistry leading from 4-bromoindole 1 to compound 15 and 28 followed a previously developed protocol (Scheme 1). 14 Tetracycle 15 was readily alkylated or benzylated selectively at the secondary amine. The syntheses of the derivatives 16−27 were only performed in small scale and purified by preparative LC−MS with the n-propyl analogue being the exception for full characterization purposes.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Carbamate-protected piperazino indoles 7 and 8 are readily available from protection of commercially available 4-piperazinoindole, however, the disbursement of the compound prompted an alternative synthetic route. The chemistry leading from 4-bromoindole 1 to compound 15 and 28 followed a previously developed protocol (Scheme ) . Tetracycle 15 was readily alkylated or benzylated selectively at the secondary amine.…”

Section: Results and Discussionmentioning

confidence: 99%

Novel Aza-analogous Ergoline Derived Scaffolds as Potent Serotonin 5-HT₆ and Dopamine D₂ Receptor Ligands.

et al. 2014

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By introducing distal substituents on a tetracyclic scaffold resembling the ergoline structure, two series of analogues were achieved exhibiting subnanomolar receptor binding affinities for the dopamine D2 and serotonin 5-HT6 receptor subtype, respectively. While the 5-HT6 ligands were antagonists, the D2 ligands displayed intrinsic activities ranging from full agonism to partial agonism with low intrinsic activity. These structures could potentially be interesting for treatment of neurological diseases such as schizophrenia, Parkinson's disease, and cognitive deficits.

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“…However, the analogous metal-free version employing o-aminobenzaldehyde derivatives leading to indolines has been recently documented. [11] We are currently evaluating the scope of this transitionmetal-free heterocyclization as a new entry to the benzofuran scaffold, and the results will be reported in due course. Scheme…”

Section: Resultsmentioning

confidence: 99%

Straightforward Reductive Esterification of Carbonyl Compounds with Carboxylic Acids through Tosylhydrazone Intermediates

et al. 2012

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The reaction of carboxylic acids with tosylhydrazones in basic media gives rise to the corresponding esters through an O–H insertion reaction in the in situ generated diazo compound. The process is operationally very simple, catalyst free, and very general with regard to the structure of both coupling partners. In particular, the esterification can be accomplished by employing tosylhydrazones derived from enolizable carbonyl compounds. Considering the ready availability of tosylhydrazones from carbonyl compounds, this reaction can be visualized as a reductive esterification of carbonyl compounds.

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Syntheses of aza-analogous iso-ergoline scaffolds using carbene mediated C–H insertion

Cited by 7 publications

References 16 publications

Application of a One‐Pot Friedel–Crafts Alkylation/Michael Addition Methodology to the Asymmetric Synthesis of Ergoline Derivatives

Application of a One‐Pot Friedel–Crafts Alkylation/Michael Addition Methodology to the Asymmetric Synthesis of Ergoline Derivatives

Novel Aza-analogous Ergoline Derived Scaffolds as Potent Serotonin 5-HT₆ and Dopamine D₂ Receptor Ligands.

Straightforward Reductive Esterification of Carbonyl Compounds with Carboxylic Acids through Tosylhydrazone Intermediates

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Syntheses of aza-analogous iso-ergoline scaffolds using carbene mediated C–H insertion

Cited by 7 publications

References 16 publications

Application of a One‐Pot Friedel–Crafts Alkylation/Michael Addition Methodology to the Asymmetric Synthesis of Ergoline Derivatives

Application of a One‐Pot Friedel–Crafts Alkylation/Michael Addition Methodology to the Asymmetric Synthesis of Ergoline Derivatives

Novel Aza-analogous Ergoline Derived Scaffolds as Potent Serotonin 5-HT6 and Dopamine D2 Receptor Ligands.

Straightforward Reductive Esterification of Carbonyl Compounds with Carboxylic Acids through Tosylhydrazone Intermediates

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Novel Aza-analogous Ergoline Derived Scaffolds as Potent Serotonin 5-HT₆ and Dopamine D₂ Receptor Ligands.