Synthesis of 3-Aminobenzisoxazoles Using an Electrophilic Aminating Reagent
Aminobenzisoxazoles are important scaffolds in medicinal chemistry. Traditionally, these heterocycles have been synthesized from 2-fluorobenzonitriles and N-protected hydroxylamines via the S<sub>N</sub>Ar reaction and subsequent cyclization. We have developed a novel, orthogonal method that utilizes 2-hydroxybenzonitriles with <i>O</i>-(diphenylphosphoryl)hydroxyl amine as an electrophilic nitrogen source. This approach inverts the traditional polarity (making the arene the nucleophile) and allows for mild reaction conditions, a broad substrate scope, and extension to a few other heterocycles.
Authors
- F. Wang
- Alexander Burtea
- G SMITH
- John Braganza (ORCID: https://orcid.org/0000-0002-6796-1645)
- Louise Bernier
- Khanh Tran
- Rebecca A. Gallego (ORCID: https://orcid.org/0000-0001-7893-9032)
- Madeline Berry
- Christiana S. Park
- Neal W. Sach (ORCID: https://orcid.org/0000-0002-9966-7459)
- Natalie Zachariou
- Gary M. Gallego (ORCID: https://orcid.org/0000-0002-5665-9416)
- Joyann S. Donaldson (ORCID: https://orcid.org/0000-0001-8873-0304)
- Jacob C. DeForest (ORCID: https://orcid.org/0000-0002-0316-6685)
- Stephanie Scales
- Raymond K. Twumasi (ORCID: https://orcid.org/0009-0008-1184-0087)
- Doris Chen
- Jacob W. Baer
- James L. Collins
Institutions
- Pfizer (United States) (US)
Publication Details
- Journal
- Organic Letters
- Published
- 2026-01-09
- DOI
- https://doi.org/10.1021/acs.orglett.5c05009
- Primary Topic
- Catalytic C–H Functionalization Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.00