One-Pot Synthesis of Diazirines and 15N2-Diazirines from Ketones, Aldehydes and Derivatives: Development and Mechanistic Insight

Quentin Ibert (1) , Madeleine Cauwel (2) , Thomas Glachet (1) , Tony Tite (2) , Patricia Le Nahenec-Martel (2) , Jean-François Lohier (1) , Pierre-Yves Renard (2) , Xavier Franck (2) , Vincent Reboul (1) , Cyrille Sabot (2)

1 LCMT - Laboratoire de chimie moléculaire et thioorganique
2 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

Broad scope one-pot diazirine synthesis strategies have been developed using two different oxidants depending on the nature of the starting material. In all cases, an inexpensive commercial solution of ammonia (NH 3) in methanol (MeOH) was employed, avoiding the difficult use of liquid ammonia. With aliphatic ketones, t-butyl hypochlorite (t-BuOCl) was found to be the best oxidant whereas it is preferable to use phenyliodine diacetate (PIDA) with aromatic ketones, aldehydes and imines. The nature of the imine-protecting group is essential and only t-butyl imine allowed the synthesis of 15 N 2-diazirine with complete 15 N incorporation, emphasizing a key transimination step in the reaction mechanism. These methods are operationally simple, and tolerant to most functional groups, providing diazirines with yields ranging from 20 to 99%.

Keywords: ammonia; t-BuOCl; PIDA; diaziridine; diazirine

Domains: Chemical Sciences; Organic chemistry

Quentin Ibert, Madeleine Cauwel, Thomas Glachet, Tony Tite, Patricia Le Nahenec-Martel, et al.. One-Pot Synthesis of Diazirines and 15N2-Diazirines from Ketones, Aldehydes and Derivatives: Development and Mechanistic Insight. Advanced Synthesis and Catalysis, 2021, 363, pp.4390-4398. ⟨10.1002/adsc.202100679⟩. ⟨hal-03331796⟩