Iridium-Catalyzed C–H Amination of Weinreb Amides: A Facile Pathway toward Anilines and Quinazolin-2,4-diones

Abstract

C–H amination of arenes directed by weakly coordinating Weinreb amides has been achieved with an iridium catalyst and 2,2,2-trichloroethoxycarbonyl (Troc) azide as an aminating agent, providing a robust method of producing synthetic useful ortho-TrocNH aryl Weinreb amides. Taking advantage of the reactivity of Weinreb amide and Troc groups in the amination products, selective hydrolysis was achieved as an attractive process for the synthesis of ortho-NH2 aryl Weinreb amides, which are the building blocks useful in the synthesis of bioactive compounds, and cascade aminocyclization with primary amines was successful and provided an efficient pathway for the construction of quinazolin-2,4-diones, which are present in various alkaloids and natural products.

Organic Azides: Versatile Synthons in Transition Metal‐Catalyzed C(sp2)−H Amination/Annulation for N‐Heterocycle Synthesis

“…Using the same aminating agent, the group of Lu further developed an iridium‐catalyzed C−H amination of Weinreb amides (Scheme 24). [32] A wide range of aryl and heteroaryl amides were compatible with this reaction, producing various ortho ‐TrocNH aryl Weinreb amides in high efficiency. Notably, the deprotection of Troc group results in ortho ‐NH 2 arylamides 91 and further aminocyclization of amination product 90 delivers quinazolin‐2,4‐dione derivatives 92 .…”

Synthesis of 3-(Pyridin-2-yl)quinazolin-2,4(1H,3H)-diones via Annulation of Anthranilic Esters with N-pyridyl Ureas

“…The biological significance causes the emergence of a number of methods for the synthesis of 3-substituted quinazoline-2,4diones, including (i) the treatment of 2-aminobenzamides with phosgene, (ii) the reaction of isatoic anhydride with amines or isocyanates, (iii) the condensation of 2-halobenzoates with monoalkylureas, (iv) Baeyer-Villiger oxidation of 4-iminoisatins, (v) the three-component catalytic condensation of 2-haloanilines with CO 2 and isocyanides (Scheme 1) [49,50]. Instead of phosgene, various phosgene surrogates can be used as a carbonylating agent, including phenylisocyanate [51] or Troc-group [52]. Recently, an alternative route for the synthesis of quinazoline-2,4-diones has been proposed, which consists of benzannulation strategy-the heteroaromatic condensed system is created by closing not the hetero-, but the carbocycle (Scheme 1, route vi) [53].…”

One-Pot Synthesis of Core Structure of Shewanelline C Using an Azidoindoline

“…The reported synthetic methods to quinazoline-2,4-diones necessarily require “nitrogen reagents”, such as amines (Scheme B-a), isocyanates (Scheme B-b), isocyanides (Scheme B-c), and urea (Scheme B-d) for the differentiation of two nitrogen atoms. The scope of these protocols depends on the availability of “nitrogen reagents” as the essential substrates.…”