Ruthenium-Catalyzed Amide Synthesis

Metathesis of N-tosylated ene-amides and yne-amides has been less extensively investigated. An example of the RCM of ene-amides is a new indole synthesis developed by Nishida [79] metathesis precursor 96 (prepared by ruthenium-catalyzed isomerization of the corresponding allyl amide) is cy-clized to indole 97 in the presence of 56d (Eq. 13). 

A solid-phase synthesis of furo[3,2-3]pyran derivatives utilizing highly functionalized sugar templates has been reported <2003JOC9406>. After incorporation of alkenes within the sugar template, such as compound 95, the solid support is introduced via formation of the acid amide. This immobilized system then allows a ruthenium-catalyzed ring-closing metathesis that leads to the formation of the fused oxacycles. 

Ruthenium catalysts for hydroesterification are also known, but these catalysts typically operate by the addition of formates, rather than by the use of the combination of CO and alcohol. Nevertheless, some leading citations to this literature are provided here. In some cases, milder conditions have been developed with pyridylmethyl formates (Equation 17.36). These substrates were designed so that the pyridyl group would bind to the catalyst. -The synthesis of amides from olefins, CO, and amines is much less developed, and the most active catalyst for this process and for the addition of for-mamides to olefins is simply Ru3(C0)jj. Ruthenium-catalyzed hydroesterification with pyridylmethylformates has been used to prepare the lactone fragment of an HIV inte-grase inhibitor shown in Scheme 17.17. 

Zhang M, Imm S, Beller M et al (2011) Synthesis of alpha-amino acid amides ruthenium-catalyzed amination of alpha-hydroxy amides. Angew Chem Int Ed 50(47) 11197-11201... 

Kang B, Fu Z, Hong SH (2013) Ruthenium-catalyzed redox-neutral and single-step amide synthesis from alcohol and nitrile with complete atom economy. J Am Chem Soc 135(32) 11704-11707... 

The first example of the ruthenium-catalyzed synthesis of amides from alcohols and amines was reported by Murahashi et al. in 1991 [82aj. The contrast results were obtained from the RuH2(PPh3)4-catalyzed reaction of 5-aminopentanol. Thus, piperidine was obtained in 79% yield, while similar treatment in the presence of a hydrogen acceptor of l-phenyl-l-buten-3-one gave piperidone in 65% yield (Eq. (7.36)). Recently, Williams reported the intermolecular amidation reaction of benzyl alcohols with amines in the presence of [Ru(p-cymene)Cl2]2 and 3-methyl-2-butanone [82bj. 

Scheme 12 Ruthenium-catalyzed synthesis of lactams by intramolecular hydrolytic amidation...

Scheme 27 Ruthenium-catalyzed synthesis of amides from alcohols and nitriles...

Garcia-Alvarez R, Diaz-Alvarez AE, Crochet P, Cadiemo V (2013) Ruthenium-catalyzed one-pot synthesis of primary amides from aldehydes in water. RSC Adv 3 5889... 

Dam JH, Osztrovszky G, Nordstrpm LU, Madsen R (2010) Amide synthesis from alcohols and amines catalyzed by ruthenium V-heterocyclic carbene complexes. Chem Eur J 16 6820... 

Chen C, Zhang Y, Hongs H (2011) V-heterocyclic carbene based ruthenium-catalyzed direct amide synthesis from alcohols and secondary amines involvement of esters. J Org Chem... 

Development of new methods for the synthesis of cyclic amide compounds is important in view of medicinal chemistry. Scheme 11.12 indicates an example of ruthenium-catalyzed carbonylation of allenylamines with CO [15]. 

Cho D, Ko KC, Lee JY (2013) Catalytic mechanism for the ruthenium-complex-catalyzed synthesis of amides from alcohols and amines a DFT study. Organometallics 32 4571... 

Fig. 5 Possible catalytic cycle for the direct synthesis of amides from alcohols and amines, catalyzed by the PNN ruthenium pincer complex 5...

One of the standard methods for preparing enantiomerically pure compounds is the enantioselective hydrogenation of olefins, a,/3-unsaturated amino acids (esters, amides), a,/3-unsaturated carboxylic acid esters, enol esters, enamides, /3- and y-keto esters etc. catalyzed by chiral cationic rhodium, ruthenium and iridium complexes ". In isotope chemistry, it has only been exploited for the synthesis of e.p. natural and nonnatural H-, C-, C-, and F-labeled a-amino acids and small peptides from TV-protected a-(acylamino)acrylates or cinnamates and unsaturated peptides, respectively (Figure 11.9). This methodology has seen only hmited use, perhaps because of perceived radiation safety issues with the use of hydrogenation procedures on radioactive substrates. Also, versatile alternatives are available, including enantioselective metal hydride/tritide reductions, chiral auxiliary-controlled and biochemical procedures (see this chapter. Sections 11.2.2 and 11.3 and Chapter 12). 

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