Palladium-Catalyzed Amide Synthesis

Torisawa [17] developed an alternative oxidative amidation of aldehydes using palladium chloride (PdCl2)-xantphos complex as a catalyst. The use of hydrogen peroxide (H2O2)-urea complex as oxidant prevents the formation of imine from the carbinolamine intermediate and minimizes the level of benzoic acid side 

---

Palladium-catalyzed amidation was also used for the synthesis of ( )-de-methoxycarbonyldihydrogambirtannine as shown above (194). 

A palladium-catalyzed amidation of halo(hetero)aromatics substituted in the ortAo-position by a carbonyl function with a primary or secondary amine has been introduced as an alternative to the Friedlander condensation for the synthesis of naphthyridinones (and quinolinones) (Scheme 32) <2004OL2433>. 

Much later, an alternate synthesis of naphthyridinones and quinoli-nones was discovered. Palladium-catalyzed amidation of halo aromatic rings with an ortho carbonyl group with primary or secondary amides to from substituted naphthyridinones and quinolinones (Scheme 97) (04OL2433). 

Scheme 2.12 Palladium-catalyzed carbonylative synthesis of primary amides...

In 2006, Willis and co-workers reported a tandem palladium-catalyzed regioselective synthesis of 3-allqrlated 2,4-quinazolinediones via urea arylation-intramolecular ester amidation. o-Halo benzoates were reacted with monoallqrl ureas and gave the corresponding quinazolinedione products in good to excellent yields (Scheme 3.60). The reactions are... 

A.J. Rosenberg, J. Zhao, D. A. Clark, Synthesis of imidazo[4,5-fc]pyridines and imidazo[4,5-fc]pyrazines by palladium catalyzed amidation of 2-chloro-3-amino-heterocycles, Org. Lett. 14 (2012) 1761-1767. 

Scheme 8.15. Synthesis of Ketones, Esters, Carboxylic Acids, and Amides by Palladium-Catalyzed Carbonylation and Acylation... 

The palladium-catalyzed Heck carbonylation reaction is a powerful means of generating amides, esters, and carboxylic acids from aryl halides or pseudohalides [28]. The development of rapid, reliable, and convenient procedures for the introduction of carbonyl groups is important for the development of high throughput chemistry in general and high-speed microwave-mediated chemistry in particular. Unfortunately, the traditional method of introducing carbon monoxide into a reaction mixture via a balloon or gas tube is not practical because of the special requirements of microwave synthesis. 

The amidocarbonylation of aldehydes provides highly efficient access to N-acyl a-amino acid derivatives by the reaction of the ubiquitous and cheap starting materials aldehyde, amide, and carbon monoxide under transition metal-catalysis [1,2]. Wakamatsu serendipitously discovered this reaction when observing the formation of amino acid derivatives as by-products in the cobalt-catalyzed oxo reaction of acrylonitrile [3-5]. The reaction was further elaborated to an efficient cobalt- or palladium-catalyzed one-step synthesis of racemic N-acyl a-amino acids [6-8] (Scheme 1). Besides the range of direct applications, such as pharmaceuticals and detergents, racemic N-acetyl a-amino acids are important intermediates in the synthesis of enantiomeri-cally pure a-amino acids via enzymatic hydrolysis [9]. 

In a radically different approach, Alper has discovered that Me-DuPhos may be used in the synthesis of a-amino acids through a palladium-catalyzed double carbohydroamination whereby aryl iodides 74 can be converted to the corresponding arylglycine amides 75 in the presence of excess primary amine (Scheme 13.27).72... 

The synthesis of linker-head intermediate 16, illustrated in Scheme 3.2.5, began with Boc-tranexamic acid 15 [29] which, on amide coupling with Cbz-piperazine and EDC, again followed by palladium-catalyzed hydrogenation of the Cbz group as in the latter case, furnished derivative 16. 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

Synthesis of ester 83a and amide 83b was performed by palladium-catalyzed carbonylation starting from iodo lactone 98 to afford products in good yields (Scheme 13, Section 14.10.5.4) <2002JOC4565>. 

---