Ruthenium Hydride/Brønsted Acid-Catalyzed Tandem Isomerization/N-Acyliminium Cyclization Sequence for the Synthesis of Tetrahydro-β-carbolines

Casper Lykke Hansen, Janie Regitse Waël Clausen, Ragnhild Gaard Ohm, Erhad Ascic, Sebastian Thordal Le Quement, David Ackland Tanner, Thomas Eiland Nielsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

This paper describes an efficient tandem sequence for the synthesis of 1,2,3,4-tetrahydro-β-carbolines (THBCs) relying on a ruthenium hydride/Brønsted acid-
catalyzed isomerization of allylic amides to N-acyliminium ion intermediates which are trapped by a tethered indolenucleophile. The methodology provides not only a convenient “aldehyde-free” alternative to the classical Pictet−Spengler reaction but also attractive possibilities for total synthesis, including rapid generation of molecular complexity and formation of quaternary stereogenic centers. TBHCs can also be accessed by harnessing the Suzuki cross-coupling reaction to the isomerization/N-acyliminium cyclization sequence. Finally, diastereo- and enantioselective versions of the title reaction have been examined using substrate control (with dr >15: 1) and asymmetric catalysis (ee up to 57%), respectively
Original languageEnglish
JournalJournal of Organic Chemistry
Volume78
Pages (from-to)12545-12565
ISSN0022-3263
DOIs
Publication statusPublished - 2013

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