New Access to 2,3-Disubstituted Quinolines through Cyclization of <i>o</i>-Alkynylisocyanobenzenes

Suginome, Michinori; Fukuda, Takeshi; Ito, Yoshihiko

doi:10.1021/ol991133w

Cited by 89 publications

(33 citation statements)

References 10 publications

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“…We have demonstrated the synthetic utility of imidoyl radicals, generated by addition of a tin radical to isocyanides, for the synthesis of indoles. It should be noted that various nucleophiles can also be added to isocyanides to give imidoyl anion species, which then cyclize to proximal unsaturated C‐C bonds to furnish heterocycles 28. In contrast, the advantage of our protocol is that both 2‐stannyl and 2‐iodo indole intermediates could be used for the subsequent palladium‐mediated coupling reaction to install a variety of substituents.…”

Section: Resultsmentioning

confidence: 99%

Indole synthesis by radical cyclization of o‐alkenylphenyl isocyanides and its application to the total synthesis of natural products

Tokuyama

Fukuyama

2002

The Chemical Record

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Development of indole synthesis by tin-mediated radical cyclization of o-alkenylphenyl isocyanide is described. Upon heating o-alkenylphenyl isocyanide in the presence of tri-n-butyltin hydride and AIBN, 2-stannyl-3-substituted indole was formed via 5-exo-trig cyclization of the imidoyl radical intermediate. After acidic workup, 3-substituted indoles were isolated. For substrates bearing simple alkyl groups, a substantial amount of tetrahydroquinoline derivatives were generated through 6-endo-trig cyclization. This undesired cyclization was suppressed by using an excess amount (five equivalents based on o-alkenylphenyl isocyanide) of ethanethiol instead of tri-n-butyltin hydride. The 2-stannylindole intermediates proved to be a suitable substrate for Stille coupling, giving 2,3-disubstituted indoles in a one-pot procedure. In addition, the 2-stannylindole intermediates could be converted to 2-iodoindoles by treatment with iodine or N-iodosuccinimide. The 2-iodoindoles thus obtained served as good substrates for Heck reactions, Stille couplings, Suzuki couplings, and palladium-mediated carbonylations, to afford a variety of 2,3-disubstituted indoles. The utility of this protocol was demonstrated by application to synthetic studies on gelsemine and discorhabdin A, and the total synthesis of an aspidosperma alkaloid, (-)-vindoline.

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Section: Resultsmentioning

confidence: 99%

Indole synthesis by radical cyclization of o‐alkenylphenyl isocyanides and its application to the total synthesis of natural products

Tokuyama

Fukuyama

2002

The Chemical Record

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“…Die von Ito et al. beschriebene Reaktion von ortho ‐Alkinylphenylisocyaniden 171 mit Nucleophilen wie Alkoholen, Aminen oder dem Natriumenolat von Diethylmalonat bietet eine bequeme und effiziente Synthese von 2,3‐disubstituierten Chinolinen 172 (Tabelle 26, Reaktion a) 97. Die verwandte Diethylamin‐induzierte 6‐ endo ‐ dig ‐Cyclisierung von ortho ‐Isocyanobenzonitril 173 ergab in quantitativer Ausbeute 2‐Diethylaminochinazolin ( 174 ) (Tabelle 26, Reaktion b) 97.…”

Section: Additionen An Die Isocyanogruppe Mit Anschließender Cycliunclassified

Isocyanide in der Synthese von Stickstoff‐Heterocyclen

2010

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Isocyanide bewähren sich seit langem als unersetzliche Bausteine in der modernen organischen Chemie. Die einzigartigen Eigenschaften der Isocyanogruppe machen Isocyanide für die Synthese etlicher wichtiger Klassen von Stickstoff‐Heterocyclen wie Pyrrolen, Indolen oder Chinolinen besonders wertvoll. In letzter Zeit wurde eine ganze Reihe von Cocyclisierungen von Isocyaniden über Zwitterionen und radikalische Intermediate ebenso wie übergangsmetallkatalysierte Synthesen verschiedener Arten von Heterocyclen entwickelt. Methoden, die von Isocyaniden ausgehen, weisen oftmals deutliche Vorteile gegenüber alternativen Wegen auf, was oft der verbesserten Konvergenz und der Einfachheit solcher Verfahren sowie der großen Vielfalt einfach zugänglicher Isocyanide geschuldet ist. So finden Isocyanide auch in enantioselektiven Synthesen chiraler heterocyclischer Verbindungen einschließlich Naturstoffen Verwendung.

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“…Two further isomerization steps would convert 33 to triene 35 via intermediate 34 . A 6π‐azaelectrocyclization of 35 would then afford directly the 1,6‐dihydropyrimidine 17 (pathway c, Scheme ) …”

Section: Resultsmentioning

confidence: 99%

“…[42] Twof urther isomerization steps would convert 33 to triene 35 via intermediate 34.A6 p-azaelectrocyclization of 35 would then afford directly the 1,6-dihydropyrimidine 17 (pathway c, Scheme 6). [43,44] To differentiate pathways ba nd c, the reaction between 1a and 15 a leading to 17 a was re-examined in detail. Gratefully, we were able to isolate 1,4-dihydropyrimidine 31 a in 87 % yield by rapidly extracting the aqueous work-ups olution and confirmed that 31 a was readily isomerized to thermodynamically more stable form 17 a in the presence of aw eak base such as NaHCO 3 (Scheme 7).…”

Section: Scheme5results Of Control Experiments [A]mentioning

confidence: 99%

Switchable [3+2] and [4+2] Heteroannulation of Primary Propargylamines with Isonitriles to Imidazoles and 1,6‐Dihydropyrimidines: Catalyst Loading Enabled Reaction Divergence

Tong

Wang

et al. 2016

Chemistry A European J

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Isonitrile 1 due to its carbene-like reactivity serves generally as a one-carbon synthon in a diverse set of organic transformations. We report in this article that the isocyano group can also act as a polarized triple bond to undergo, as a two-atom synthon, heteroannulation with primary propargylamines 15. In addition, we serendipitously discovered that the reaction pathways can be modulated by simply changing the catalyst loading. In the presence of 0.1 equiv of Yb(OTf)3 or TfOH, the reaction between 1 and 15 afforded exclusively imidazoles 16 by a formal [3+2] cycloaddition. At a higher catalyst loading (Yb(OTf)3 (0.4 equiv) or TfOH (0.5 equiv)) under otherwise identical conditions, the same reaction furnished 1,6-dihydropyrimidines 17 in good to excellent yields by way of a formal [4+2] cycloaddition process. Mechanistic investigations indicated that both annulations went through an amidine intermediate resulting from the insertion of the isocyano group to the NH bond of the primary amine. Subsequent catalyst-loading-dependent 5-exo-dig or 6-endo-dig cyclization provided selectively the two heterocycles, respectively.

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New Access to 2,3-Disubstituted Quinolines through Cyclization of o-Alkynylisocyanobenzenes

Cited by 89 publications

References 10 publications

Indole synthesis by radical cyclization of o‐alkenylphenyl isocyanides and its application to the total synthesis of natural products

Indole synthesis by radical cyclization of o‐alkenylphenyl isocyanides and its application to the total synthesis of natural products

Isocyanide in der Synthese von Stickstoff‐Heterocyclen

Switchable [3+2] and [4+2] Heteroannulation of Primary Propargylamines with Isonitriles to Imidazoles and 1,6‐Dihydropyrimidines: Catalyst Loading Enabled Reaction Divergence

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