(–)-Cytisine: Access to a stereochemically defined and functionally flexible piperidine scaffold

Worawat Niwetmarin, Hugo Rego Campello, Hazel A. Sparkes, Varinder Aggarwal, Tim Gallagher

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)
110 Downloads (Pure)

Abstract

N-Benzyl cytisine undergoes an efficient C(6)-N(7) cleavage via directed C(6) lithiation, borylation and oxidation to provide a “privileged” heterocyclic core unit comprising a highly functionalised, cis-3,5-disubstituted piperidine in enantiomerically pure form. The potential offered by this unit as a means to explore chemical space has been evaluated and methods have been defined (and illustrated) that allow for selective manipulation of N(1), C(3’), and the pyridone N. The pyridone core can also be diversified via bromination (at C(3’’) and C(5’’)) which is complementary to direct C-H activation based on Ir-catalyzed borylation to provide access to C(4’’). The use of a boronate-based 1,2-migration as an alternative trigger to mediate C(6)-N(7) cleavage of cytisine was evaluated but failed. However, the stability of the intermediate boronate opens a new pathway for the elaboration of cytisine itself using both Matteson homologation and Zweifel olefination.
Original languageEnglish
Number of pages10
JournalOrganic and Biomolecular Chemistry
Early online date23 Jul 2018
DOIs
Publication statusE-pub ahead of print - 23 Jul 2018

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