Dearomative Spirocyclization of Tryptamine-Derived Isocyanides via Iron-Catalyzed Carbene Transfer

Thomas R Roose; Finn McSorley; Bryan Groenhuijzen; Jordy M Saya; Bert U W Maes; Romano V A Orrù; Eelco Ruijter

doi:10.1021/acs.joc.3c02160

Dearomative Spirocyclization of Tryptamine-Derived Isocyanides via Iron-Catalyzed Carbene Transfer

Thomas R Roose, Finn McSorley, Bryan Groenhuijzen, Jordy M Saya, Bert U W Maes, Romano V A Orrù^*, Eelco Ruijter^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Tryptamine-derived isocyanides are valuable building blocks in the construction of spirocyclic indolenines and indolines via dearomatization of the indole moiety. We report the Bu N[Fe(CO) NO]-catalyzed carbene transfer of a-diazo esters to 3-(2-isocyanoethyl)indoles, leading to ketenimine intermediates that undergo spontaneous dearomative spirocyclization. The utility of this iron-catalyzed carbene transfer/spirocyclization cascade was demonstrated by its use as a key step in the formal total synthesis of monoterpenoid indole alkaloids (±)-aspidofractinine, (±)-limaspermidine, (±)-aspidospermidine, and (±)-17-demethoxy- -acetylcylindrocarine.

Original language	English
Pages (from-to)	17345-17355
Number of pages	11
Journal	Journal of Organic Chemistry
Volume	88
Issue number	24
DOIs	https://doi.org/10.1021/acs.joc.3c02160
Publication status	Published - 4 Dec 2023

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Cite this

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title = "Dearomative Spirocyclization of Tryptamine-Derived Isocyanides via Iron-Catalyzed Carbene Transfer",

abstract = "Tryptamine-derived isocyanides are valuable building blocks in the construction of spirocyclic indolenines and indolines via dearomatization of the indole moiety. We report the Bu N[Fe(CO) NO]-catalyzed carbene transfer of a-diazo esters to 3-(2-isocyanoethyl)indoles, leading to ketenimine intermediates that undergo spontaneous dearomative spirocyclization. The utility of this iron-catalyzed carbene transfer/spirocyclization cascade was demonstrated by its use as a key step in the formal total synthesis of monoterpenoid indole alkaloids (±)-aspidofractinine, (±)-limaspermidine, (±)-aspidospermidine, and (±)-17-demethoxy- -acetylcylindrocarine.",

author = "Roose, {Thomas R} and Finn McSorley and Bryan Groenhuijzen and Saya, {Jordy M} and Maes, {Bert U W} and Orr{\`u}, {Romano V A} and Eelco Ruijter",

year = "2023",

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doi = "10.1021/acs.joc.3c02160",

language = "English",

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journal = "Journal of Organic Chemistry",

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TY - JOUR

T1 - Dearomative Spirocyclization of Tryptamine-Derived Isocyanides via Iron-Catalyzed Carbene Transfer

AU - Roose, Thomas R

AU - McSorley, Finn

AU - Groenhuijzen, Bryan

AU - Saya, Jordy M

AU - Maes, Bert U W

AU - Orrù, Romano V A

AU - Ruijter, Eelco

PY - 2023/12/4

Y1 - 2023/12/4

N2 - Tryptamine-derived isocyanides are valuable building blocks in the construction of spirocyclic indolenines and indolines via dearomatization of the indole moiety. We report the Bu N[Fe(CO) NO]-catalyzed carbene transfer of a-diazo esters to 3-(2-isocyanoethyl)indoles, leading to ketenimine intermediates that undergo spontaneous dearomative spirocyclization. The utility of this iron-catalyzed carbene transfer/spirocyclization cascade was demonstrated by its use as a key step in the formal total synthesis of monoterpenoid indole alkaloids (±)-aspidofractinine, (±)-limaspermidine, (±)-aspidospermidine, and (±)-17-demethoxy- -acetylcylindrocarine.

AB - Tryptamine-derived isocyanides are valuable building blocks in the construction of spirocyclic indolenines and indolines via dearomatization of the indole moiety. We report the Bu N[Fe(CO) NO]-catalyzed carbene transfer of a-diazo esters to 3-(2-isocyanoethyl)indoles, leading to ketenimine intermediates that undergo spontaneous dearomative spirocyclization. The utility of this iron-catalyzed carbene transfer/spirocyclization cascade was demonstrated by its use as a key step in the formal total synthesis of monoterpenoid indole alkaloids (±)-aspidofractinine, (±)-limaspermidine, (±)-aspidospermidine, and (±)-17-demethoxy- -acetylcylindrocarine.

U2 - 10.1021/acs.joc.3c02160

DO - 10.1021/acs.joc.3c02160

M3 - Article

SN - 0022-3263

VL - 88

SP - 17345

EP - 17355

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 24

ER -