Rhodium-catalyzed hydrogenation amino acid synthesis

Rate-determining step, hydroformylation, 163 Reactivity, enantiomers, 286 Recognition, enantiomers, 278 Reduction and oxidation, 5 Reductive coupling, dissolving metal, 288 Reductive elimination, 5, 111 Resolution. See Kinetic resolution Rhenium-carbene complexes, 288 Rhodium-catalyzed hydrogenation, 17, 352 amino acid synthesis, 18, 352 BINAP, 20... 

The first example of a combination of a metal-catalyzed substrate synthesis with a biotransformation conducted in a one-pot maimer proceeding according to Scheme 19.23 was reported by Hanefeld, Maschmeyer, Sheldon, and coworkers in 2006 [58]. In this pioneering work, enantioselective hydrogenation of methyl N-acetyl amino acrylate (72) with a heterogenized rhodium-diphosphane complex as catalyst gave the N-acetyl alanine (S)-73 with 100% conversion and 95% ee. This intermediate was then directly converted in situ after separation of the immobilized metal catalyst by means of an L-amino acylase (Scheme 19.23). This enzymatic resolution then led to the formation of the desired amino acid L-alanine (l-74 (S)-74) with 98% conversion and with an excellent enantiomeric excess of >98%. 

Kong, J.-R., Cho, C.-W., Krische, M. J. (2005). Hydrogen-mediated reductive coupling of conjugated alkynes with ethyl (Ai-sulfinyl)iminoacetates Synthesis of unnatural a-amino acids via rhodium-catalyzed C-C bond forming hydrogenation. Journal of the American Chemical Society, 127, 11269-11276. 

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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