Catalytic Hydrogenation of Chiral α-Amino and α-Hydroxy Esters at Room Temperature with Nishimura Catalyst without Racemization

Abstract

The hydrogenation of carboxylic acid derivatives at room temperature was investigated. With a mixed Rh/Pt oxide (Nishimura catalyst), low to medium activity was observed for various α‐amino and α‐hydroxy esters. At 100 bar hydrogen pressure and 10% catalysts loading, high yields of the desired amino alcohols and diols were obtained without racemization. The most suitable α‐substituents were NH2, NHR, and OH, whereas β‐NH2 were less effective. Usually, aromatic rings were also hydrogenated, but with the free bases of amino acids as substrates, some selectivity was observed. No reaction was found for α‐NR2, α‐OR, and unfunctionalized esters; acids and amides were also not reduced under these conditions. A working hypothesis for the mode of action of the catalyst is presented.

Enantioselective Heterogeneous Catalysis

“…Alkaloids (e.g., cinchonidine) α -hydroxy acids (e.g., (R, R)-tartaric acid) ketopantolactone [44], pyrrolidone-triones [45], α-ketoethers [46], α-diketones [47], and α,α,α-trifluoromethylketones [48]. The Ni/tartaric acid system is used for the hydrogenation of β-ketoesters and β-diketones [49,50].…”

Hydrogenation of 1,2-indanedione over heterogeneous cinchonidine-modified platinum catalysts

“…Kinetic resolution of the primary product has also been observed in the hydrogenation of other a-diketones, a-alkoxy ketones and some activated ketones [7,[15][16][17][18]. A common feature with all of these substrates, including the structurally rigid 2-hydroxycyclohexanone [15], 2-methoxycyclohexanone [17], and 2-fluorocyclohexanone [18a], is that the (S)-enantiomer is reacting faster thus increasing the enantiomeric excess of the remaining (R)-enantiomer.…”

Ketonok heterogén katalitikus enantioszelektív hidrogénezése cinkona alkaloidok jelenlétében

“…Hiszen az azonos metoxi és metil csoportok jelenlétének ellenére, az eredmények nem tendenciózusan változnak, hanem bizonyos esetekben jó szelektivitás érhető el, más esetekben igen gyenge [15,42,69,70]. Néhány olyan acetonszármazék esetében, ahol az elérhető szelektivitás gyenge, acetofenon analógjuk jó szelektivitással hidrogénezhető [42].…”

“…Cinkonidin jelenlétében a (S)2metoxiciklohexanon gyorsabban hidrogéneződik az (R) izomernél. Szilárd bázis hatására a 2metoxiciklohexanon izomerei gyorsan egymásba alakulnak, így a reakció végeredményben racém 2 metoxiciklohexanon kiindulási anyagból az (1R,2S)1hidroxi2metoxi ciklohexánt szolgáltat 80%nál nagyobb enantiomer felesleggel és 95%nál nagyobb termeléssel [70].…”