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

Abstract

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 (NH3) 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 15N2‐diazirine with complete 15N incorporation, emphasizing a key trans‐imination 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%.

Regioselective Hydroamination of Unactivated Olefins with Diazirines as a Diversifiable Nitrogen Source

“…6C). While other methods exist for the conversion of ketones to diazirines, none are suitable for α,α,α-trifluoroacetophenone (44,49). Instead, we endeavored to devise a new route to 15 N-1 that used 15 NH3 as the lone source of isotopically labeled nitrogen (Fig.…”

Hypervalent iodine (III) reagents and ammonia as useful combination for highly chemoselective N-transfer to low-valent organosulfur compounds and amines

“…More recently Franck, Reboul, Sabot, and co-workers reported the transformation of aromatic aldehydes, imines and ketones into diazirines upon treatment with PIDA and a solution of ammonia in methanol. 29 This interesting methodology is limited mostly to electron poor aromatics, however the strategy allowed the preparation of diazirines carrying various functionalities, such as nitro (18ac,i), cyano (18d,j), ester (18e), acetyl (18f), trifluoromethyl (18g), and sulfide (18h) (Scheme 12, b). Better yields were generally observed using N-tosyl imines as substrates, and 15 N diazirines with complete 15 N incorporation could be efficiently prepared.…”

Synthesis of Sulfoximines and Sulfonimidamides Using Hypervalent Iodine Mediated NH Transfer

“…The reagent combination has been applied more broadly in processes involving N-transfer that may include other mechanistic steps. This includes the reaction with thiophenols to form sulfonimidates or sulfonamides [ 63 ], and the N-transfer to amines [ 64 ], N-transfer to form diazirines from amino acids [ 65 , 66 ], and for nitrogen extrusion in molecular editing processes [ 67 , 68 , 69 , 70 ].…”