Pd‐Catalyzed Amidation of Silyl Enol Ethers With CO and Azides via an Isocyanate Intermediate

Abstract

An efficient Pd-catalyzed amidation of silyl enol ethers to produce β-ketoamides has been developed using carbon monoxide and sulfonyl azides. The tandem reaction provides a simple and straightforward approach for the synthesis of β-ketoamides under mild conditions without any additive. The mechanistic studies indicate that the reaction undergoes via an in situ generated isocyanate intermediate.The β-ketoamides are one of the most useful and synthetic building blocks in organic chemistry, which have been used for the synthesis of fungicides, penicillins, organic dyes and other biologically compounds. [1] Furthermore, the β-ketoamide skeletons are widely found in pharmaceutical molecules, such as Lymecycline, Teriflunomide, etc (Scheme 1a). [2] Given the importance and wide utilization of β-ketoamides, several notable approaches have been developed to synthesize β-ketoamides, including aminolysis of β-ketoesters, [3] α-acylation of amides, [4] addition of enolates to isocyanates [5] etc. However, these traditional methods are limited to one or more of the following elements, narrow substrate ranges, harsh reaction conditions, or using unfriendly reagents. Therefore, the development of simple, straightforward, and efficient catalytic methods for the synthesis of β-ketoamides is still highly desirable.Isocyanates are particularly useful in organic synthesis. [6] As a highly reactive intermediate, isocyanate has been extensively utilized for the synthesis of various nitrogen-containing compounds, such as ureas, [7] oxazolidinones, [8] and lactams,. [9] It has also been widely used as amide precursors in organic synthesis. [10] However, the high reactivity of isocyanates makes[a] Y.

Pd/C-Catalyzed Carbonylative Amidation for the Synthesis of 2-Carboxamidocyclohexane-1,3-diones

“…Furthermore, they form the core structure of various drug molecules such as piroxicam and teriflunomide and are exemplified as a crucial functionality in a series of tetracycline-class drugs such as tetracycline, minocycline, oxycycline, doxycycline, sarecycline, eravacycline, and omadacycline (Scheme a) . Considering the intriguing structural features as well as widespread applications of β-ketoamides, various protocols have been developed for their synthesis. , However, despite the substantial progress realized in this arena, the synthesis of challenging 2-carboxamidocyclohexane-1,3-diones has remained underexplored. Only a few traditional approaches have been reported for their synthesis, involving reaction of the corresponding cyclohexane-1,3-dione with different metal cyanates, isocyanic acid, isocyanates, and urea or the treatment of sodio derivatives of cyclohexanedione with phosgene followed by ammonia .…”