Substituent-Controlled Selective Synthesis of N-Acyl 2-Aminothiazoles by Intramolecular Zwitterion-Mediated C–N Bond Cleavage

Abstract

The cleavage of C-N bonds is an interesting and challenging subject in modern organic synthesis. We have achieved the first zwitterion-controlled C-N bond cleavage in the MCR reaction among lithium alkynethiolates, bulky carbodiimides, and acid chlorides to construct N-acyl 2-aminothiazoles. This is a simple, highly efficient, and general method for the preparation of N-acyl 2-aminothiazoles with a broad range of substituents. The selective synthesis of N-acyl 2-aminothiazoles significantly depends on the steric hindrance of carbodiimides. The result is in striking contrast with our previous convergent reaction giving 5-acyl-2-iminothiazolines via 1,5-acyl migration. It is indeed interesting that the slight change of the substituents on the carbodiimides can completely switch the product structure. Experimental and theoretical results demonstrate the reason why the C-N bond cleavage in the present system is prior to the acyl migration. The intramolecular hydrogen relay via unprecedented Hofmann-type elimination is essential for this totally new zwitterion-controlled C-N bond cleavage.

Transition-Metal-Catalyzed Cleavage of C–N Single Bonds

“…Many papers on stoichiometric metal-promoted C–N bond cleavage have been published, − and we will not discuss them here because of the limited space. Since several excellent reviews have summarized transition-metal-free or transition-metal-catalyzed C–N bond cleavage in diazonium salts − and high-strained azaheterocycles, such as aziridines, , 2 H -azirines, , and four-membered-ring azaheterocycles, − only selected examples and recent works will be discussed.…”

Mechanistic Considerations of the Catalytic Guanylation Reaction of Amines with Carbodiimides for Guanidine Synthesis

“…Metal-catalyzed C–N bond formation by N–H bond activation to construct N-containing compounds is one of the most important chemical transformations in modern organic synthesis. − The catalytic guanylation reaction of amines with carbodiimides (hereafter denoted the CGAC reaction), which is also known as catalytic addition of an amine N–H bond to the CN double bond of carbodiimides (RNCNR′, which has been applied widely in organic synthesis − ) or hydroamination of carbodiimides, can be a straightforward and atom-economical route via C–N bond formation to prepare substituted guanidines (RNC­(NR′R″)­NHR). It is well-known that guanidine derivatives are an important class of N-containing compounds which may be utilized as building blocks in various drugs (Scheme ), natural products, agrochemicals, sweeteners, explosives, etc., as base catalysts in organic synthesis, and also as supporting ligands for various metal complexes. − Although this direct guanylation reaction of primary aliphatic amines with carbodiimides can be performed under rather harsh conditions without catalyst, the guanylation reaction of aromatic amines or secondary amines cannot be achieved without suitable catalysts, owing to their decreased nucleophilicity.…”

Recent Methodologies That Exploit Oxidative Addition of C–N Bonds to Transition Metals

“…The methods discussed are categorized according to the strategy employed: (A) C–N bond activation via quaternization of the nitrogen; (B) oxidative addition of neutral C–N bonds; (C) C–N bond activation using a directing group (DG); (D) C–N bond activation via strain release (Scheme ). There are many reports that detail stoichiometric metal-promoted C–N bond activation, − but these will not be discussed in this Perspective, which will instead focus on TM-catalyzed methodologies. Although outside the primary focus of this Perspective, there are a number of powerful strategies where C–N bonds are cleaved in the presence of a transition metal, but where an oxidative addition step is not involved; strategies of this type have been covered in a recent, comprehensive review .…”