Palladium‐Catalyzed N³‐Directed C−H Halogenation of N⁹‐Arylpurines and Azapurines

Abstract

A palladium‐catalyzed direct ortho‐halogenation of N9‐arylpurines was developed by using N‐halogenated succinimide (NBS/NCS/NIS) as the halogenation reagents. The current procedure offers a late‐stage strategy to generate N9‐(ortho‐haloaryl)purines in moderate to excellent yields. The protocol was applicable to the substrates with both electron‐rich and electron‐deficient substituents and only monohalogenated products were formed. Moreover, the purinyl N3‐atom was verified as the directing group to facilitate Pd‐catalyzed ortho‐C−H activation.

Microwave assisted regioselective halogenation of benzo[b][1,4]oxazin-2-onesviasp2C–H functionalization

“…During the past few decades, transition metal catalysed C–H activation and C–H functionalization has profoundly revolutionized the synthetic chemistry by providing sustainable tools for the construction of various C–C, C–O, C–N, C–S and C–X bonds. 19 These transformations do not require any pre-functionalization of substrates, making the method step and atom economical. 20 The coordinating group present in the heterocyclic compounds is commonly utilized to derive ortho -regioselectivity of C–H functionalization reactions.…”

“…Till date, numerous halogenating agents have been developed to overcome the toxicity, regioselectivity and handling difficulty imposed by typical halogenating agents such as elemental chlorine, bromine and iodine. 24 For instance, N -chloramines, 19 HOCl, 19 chlorinated cyclohexadiene, 19 N -bromodialkylamines, 25 ZrBr 4 , 26 KBr/oxone, 27 dioxane dibromide, 28 I 2 /KMnO 4 , 29 I 2 /H 2 O 2 , 30 etc. , are well known halogenating agents employed for the halogenation of aromatic compounds.…”

“…, are well known halogenating agents employed for the halogenation of aromatic compounds. Among these halogenating agents, N -halosuccinamides 19,27,31 are the reagent of choice owing to their low cost, commercial availability, ease of handling, high compatibility with transition metal catalysts and solubility of succinimide by-products in water. 32 To the best of our knowledge, transition-metal catalyzed halogenation of 3-phenyl-2 H -benzo[ b ][1,4]oxazine-2-ones is not reported so far.…”