2. Academic Validation
  3. Development of a Continuous Flow Synthesis of 2-Substituted Azetines and 3-Substituted Azetidines by Using a Common Synthetic Precursor

Development of a Continuous Flow Synthesis of 2-Substituted Azetines and 3-Substituted Azetidines by Using a Common Synthetic Precursor

  • J Org Chem. 2021 Oct 15;86(20):13943-13954. doi: 10.1021/acs.joc.1c01297.
Marco Colella 1,  Pantaleo Musci 1,  Debora Cannillo 1,  Mauro Spennacchio 1,  Andrea Aramini 2,  Leonardo Degennaro 1,  Renzo Luisi 1
Affiliations

Affiliations

  • 1 FLAME-Lab, Flow Chemistry and Microreactor Technology Laboratory, Department of Pharmacy - Drug Sciences, University of Bari "A. Moro", Via E. Orabona 4, 70125 Bari, Italy.
  • 2 Department of Discovery, Dompé Farmaceutici S.p.A., Via Campo di Pile, L'Aquila 67100, Italy.
PMID: 34291947 DOI: 10.1021/acs.joc.1c01297
Abstract

The generation and functionalization, under continuous flow conditions, of two different lithiated four-membered aza-heterocycles is reported. N-Boc-3-iodoazetidine acts as a common synthetic platform for the genesis of C3-lithiated azetidine and C2-lithiated azetine depending on the lithiation agent. Flow technology enables easy handling of such lithiated intermediates at much higher temperatures compared to batch processing. Flow technology combined with cyclopentylmethyl ether as an environmentally responsible solvent allows us to address sustainability concerns.

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