Monocyclic Azetidines via a Visible-Light-Mediated Aza Paternò-Büchi Reaction of Ketone-Derived Sulfonylimines
The recent rise in popularity of azetidines in pharmaceutical chemistry has inspired the development of visible-light-mediated aza Paternò-Büchi reactions as direct transformations to form these desirable products. Despite these advancements, successful reports of accessing monocyclic azetidines from acyclic imines remain scarce. Here, we report a visible-light-mediated aza Paternò-Büchi reaction of acyclic ketone-derived sulfonylimines, which are previously unexplored substrates in this transformation, with activated alkenes (i.e., styrenes and dienes) to form 2,2-disubstituted monocyclic azetidines that can be further modified to reveal free <i>N</i>-<i>H</i> azetidines. Computational and experimental mechanistic studies reveal that in contrast to aldehyde-derived oximes, the use of ketone-derived sulfonylimines enables tuning of the reaction mechanism to favor initial formation of the <i>C-N</i> rather than <i>C-C</i> bond, thus enabling access to 2,2-disubstituted monocyclic azetidine scaffolds.
Authors
- Ka‐Ming Tong (ORCID: https://orcid.org/0000-0001-6675-652X)
- Eric A. Voight (ORCID: https://orcid.org/0000-0002-9542-5356)
- Gianmarco Terrones (ORCID: https://orcid.org/0000-0001-5360-165X)
- Benjamin D. Bergstrom (ORCID: https://orcid.org/0000-0003-2179-1334)
- Emily R. Wearing (ORCID: https://orcid.org/0000-0002-7482-3144)
- Corinna S. Schindler (ORCID: https://orcid.org/0000-0003-4968-8013)
- Heather Janine Kulik (ORCID: https://orcid.org/0000-0001-9342-0191)
- Julia C. Donovan (ORCID: https://orcid.org/0009-0007-0075-5584)
- Kaid C. Harper (ORCID: https://orcid.org/0000-0003-3894-4851)
- Michael O. Wolf (ORCID: https://orcid.org/0000-0003-3076-790X)
- Jéssica Toigo (ORCID: https://orcid.org/0000-0001-9420-460X)
- Dominique E. Blackmun (ORCID: https://orcid.org/0000-0002-7868-3572)
- Cody Ng (ORCID: https://orcid.org/0000-0001-8759-0821)
- Madeleine A. Gonley
Institutions
- University of British Columbia (CA)
- University of Michigan (US)
- AbbVie (United States) (US)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-06-17
- DOI
- https://doi.org/10.1021/jacs.5c04692
- Citations
- 11
- Primary Topic
- Synthesis and Catalytic Reactions
- Type
- article
- Field-Weighted Citation Impact
- 10.30
Funders
- University of Michigan
- Canada Research Chairs
- Natural Sciences and Engineering Research Council of Canada
- National Institute of General Medical Sciences
- Division of Chemistry