Katalytische Funktionalisierung von Indolen in einer neuen Dimension

Abstract

Vor 140 Jahren schlug Adolf von Baeyer die Struktur für eine heteroaromatische Verbindung vor, die die organische und medizinische Chemie nachhaltig veränderte: Indol. Nach mehr als einem Jahrhundert beeinflussen Indol selbst, ebenso wie natürliche Indolderivate, weitgehend die Entwicklung in der Synthesechemie. Vor allem die allgegenwärtige Präsenz des Indolrings in pharmazeutischen und agrochemischen Verbindungen sowie seine Verwendung in der Materialchemie sind ausschlaggebend für das anhaltende Interesse an der Entwicklung von neuen milden und effizienten Synthesestrategien für funktionalisierte Indolderivate. Dieser Aufsatz fasst die Fortschritte hinsichtlich der selektiven katalytischen Funktionalisierung von Indolen (durch C‐C‐Kupplung) aus den vergangenen vier Jahre zusammen.

Catalytic Asymmetric Inverse‐Electron‐Demand (IED) [4+2] Cycloaddition of Salicylaldimines: Preparation of Optically Active 4‐Aminobenzopyran Derivatives

“…[16] In the presence of phosphoric acid catalysts 8, 2-vinylindole 4 reacted selectively with N-aryl-A C H T U N G T R E N N U N G imines, affording exclusively the corresponding benzo- pyran derivatives 7 as the IED-aza-Diels-Alder-type products could never be detected.…”

Rapid Assembly of Functionalised Spirocyclic Indolines by Palladium‐Catalysed Dearomatising Diallylation of Indoles with Allyl Acetate

“…Whilst there is good precedent for the Pd-catalysed allylation of indoles with a range of allyl sources,14–18 and even for the dearomatising allylation of 3-substituted indoles with allyl carbonates, with allyl alcohols in combination with organoboranes15 or by rearrangement of N -alloc protected indoles,14, 19–22 the direct use of allyl acetate in such reactions has proved challenging to date 23. Although highly activated allylic esters containing two conjugated aromatic rings can be successfully used in Pd-catalysed allylation reactions,24 there is only a single report of the Pd-catalysed reaction of indole 1 a with allyl acetate 2 , and the reaction was reported to produce a relatively complex mixture of N and C allylated products 3 a – 6 a from which 3-allylindole 4 a was isolated in up to 54 % yield 23.…”

Fischer Indole Synthesis with Organozinc Reagents

“…Furthermore, unsymmetrical ketones result in regioisomeric mixtures of indoles. [7] Since organozinc reagents are readily available, inexpensive, and compatible with numerous functional groups, [9] we envisioned a new retrosynthetic pathway for the Fischer indole synthesis, in which the key intermediates 4 A and 4 B would not be obtained from 2 and 3, but rather from the reaction of readily available aryldiazonium salts of type 5 and functionalized alkylzinc reagents of type 6 (Scheme 1). [10,11] This approach proved to be very fruitful, since many functional groups such as ester, cyano, nitro, and keto groups are tolerated, and unexpectedly the issue of regioselectivity mentioned above is resolved.…”

“…[3] The classical Fischer indole synthesis [4] starting from aryl hydrazines [5,6] 2 and ketones 3 is still extensively used, although this method suffers from several drawbacks. [7,8] The highly acidic reaction conditions combined with moderate functional-group tolerance and the poor availability of aryl hydrazines 2 strongly limit this method. Furthermore, unsymmetrical ketones result in regioisomeric mixtures of indoles.…”