Amidocarbonylation, palladium-catalyzed

Scheme 6/1.85. Palladium-catalyzed amidocarbonylation of aromatic aldehydes.

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]. 

The relevance of the palladium-catalyzed amidocarbonylation for natural product synthesis has been demonstrated with the multi gram-scale preparation of the central amino acid of chloropeptin I ((S)-3,5-dichloro-4-hydroxyphenylglycine) as well as methionine and p-chlorophenyl alanine via the combination of amidocarbonylation and enzymatic hydrolysis (Table 4) [44]. 

Similarly, acylamino acids can be prepared with 100% atom utilization via palladium-catalyzed amidocarbonylation. " The method was used for the synthesis of a surfactant from sarcosine (Figure 9.8). 

Figure 9.8 Acylamino acids via palladium-catalyzed amidocarbonylation.

Since Wakamatsu serendipitously discovered amidocarbonylation while performing the cobalt-catalyzed hydroformyla-tion of olefins in 1971, this unique carbonylation reaction, affording a-amino acids directly from aldehydes, has been extensively studied.More recently, palladium-catalyzed processes have been developed to expand the scope of this reaction.The Pd-catalyzed amidocarbonylation has been applied to aldehydes,aryl halides, and imines. As a related reaction, lactamization " of aryl halides catalyzed by a rhodium complex has also been developed. 

The original amidocarbonylation reaction catalyzed by HCo(CO)4, generated in situ from Co2(CO)8, required very high pressures (>200 atm) of CO and H2, which made the scope of this process rather limited. However, the use of palladium catalysts for this process has substantially expanded the scope of the reaction. The Pd-catalyzed amidocarbonylation of aldehydes proceeds under CO pressure (60 atm) in the presence of water, a catalytic amount of acid, and a... 

AMIDOCARBONYLATION OF ALDEHYDES Table 2. Palladium-Catalyzed Ureidocarbonylation ... 

Carbonylation Reactions. A three-component palladium-catalyzed amidocarbonylation reaction provides IV-acylamino acids from aromatic and aliphatic aldehydes or acetals with amides under elevated CO pressure (60 bar) in the presence of PdBr2, PPhs, LiBr, an acid additive (typically H2SO4), and iV-methyl-2-pyrrolidone. Mechanistically, the palladium-catalyzed amidocarbonylation reaction is proposed to proceed through the in situ formation of an a-haloamide and Pd(0) species, which can undergo oxidative addition, followed by CO insertion, and lastly hydrolysis of the acyl palladium complex to afford the product and regenerate the catalyst (eq 45). 

Palladium-catalyzed amidocarbonylation of aldehyde amide mixtures was performed in ionic liquids to obtain N-acyl-a-amino acids [36]. It was found that strongly acidic ionic liquids such as [Rmim]HS04 (R= —(CH2)3S03H) act as powerful cocatalysts giving higher yields compared to traditionally added sulfuric acid. A subsequent biphasic approach was applied to the workup of catalytic batches and the catalyst-containing IL phase reused without further addition of palladium, phosphine, or cocatalyst. 

Amidocarbonylation is a recently developed, organometallic-catalyzed route to amino acid generation - particularly A(-acyl a-amino acids - using either aldehydes or alkenes as starting materials and synthesis gas as an integral building block. The two principal classes of reaction are illustrated in eqs. (1) and (2). Both syntheses offer the opportunity to introduce two functionalities, amido and carboxylate, simultaneously where an amide is the co-reactant. Homogeneous amidocarbonylation catalysts are typically cobalt carbonyl-based, or utilize transition-metal binary systems, e. g. cobalt-rhodium, cobalt-palladium, and cobalt-iron. 

The observation that palladium could also catalyze this process enhanced the scope of amidocarbonylation reactions.24 This method provided ready access to the arylglycine building block 39, from benzaldehyde 37 and amide 38, required for the synthesis of the chloropeptins 36 that have been shown to possess anti-HIV activity. 

An efficient three-component coupling reaction for the synthesis of Af-acyl-a-amino acids from aldehydes, amides, and carbon monoxide, namely, amidocarbonylation, was first described by Wakamatsu in 1971.Recently, amidocarbonylation has successfully been catalyzed by palladium (Scheme The reaction would proceed as follows. 

The platinum-catalyzed amidocarbonylation of aldehydes with amides and carbon monoxide was described. In contrast to precedent palladium catalysis, a remarkable ligand acceleration by phosphane was observed [161]. 

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