A concise Friedländer/Buchwald–Hartwig approach to the total synthesis of quindoline, a bioactive natural indoloquinoline alkaloid, and toward the unnatural 10-methylquindoline. (24th June 2019)

• Record Type: Journal Article
• Authors: Méndez, María V.; Simonetti, Sebastian O.; Kaufman, Teodoro S.; Bracca, Andrea B. J.
• Is Part Of: New journal of chemistry. Volume 43:Number 27(2019)
• Page Start: 10803
• Page End: 10813
• Publication Date: 2019-06-24
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c9nj01961h
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : Friedländer and Buchwald–Hartwig reactions were used to achieve an efficient total synthesis of quindoline and a new synthesis of the unnatural 10-methylquindoline. DFT calculations were employed to explain the outcome of a failed key transformation. Abstract : A new approach toward the synthesis of quindoline, a recognized indoloquinoline alkaloid, is reported. The sequence comprises the synthesis of 2-(2-nitrophenyl)quinoline through an optimized Friedländer condensation of 2-amino benzaldehyde with 2-nitroacetophenone, followed by the selective C-3 bromination of the quinoline moiety to direct the cyclization, reduction of the nitro group and a final Buchwald–Hartwig cyclization. In addition, quindoline was also converted to the unnatural 10-methylquindoline by reaction with dimethyl carbonate under DBU promotion. It was found that the non-directed reductive cyclization of 2-(2-nitrophenyl)quinoline results in indazolo[2, 3- a ]quinoline, instead of yielding quindoline. DFT calculations were employed to explain this reaction outcome; this finding suggested that the result of a previously reported total synthesis of quindoline should be revised.