Synthesis of Substituted Mandelic Acid Derivatives via Enantioselective Hydrogenation: Homogeneous versus Heterogeneous Catalysis

Abstract

An extensive screening of both homogeneous and heterogeneous catalysts was carried out for the enantioselective hydrogenation of p-chlorophenylglyoxylic acid derivatives. For p-chlorophenylglyoxylic amides only homogeneous Rh-diphosphine complexes gave satisfactory results, ees up to 87% were observed for the cy-oxo-pronop ligand. For methyl p-chlorophenylglyoxylate both a homogeneous as well as a heterogeneous catalyst performed with ees > 90%. A Pt catalyst modified with cinchona derivatives achieved 93% ee for the (R)-and 87% ee for the (S)-methyl p-chloromandelate. A Ru-MeObiphep catalyst also reached 93% ee with TONs up to 4000 and TOFs up to 210 h À 1 . For all catalytic systems the effects of the metal, the nature of the chiral auxiliary and the solvent as well as of the reaction conditions were investigated. The homogeneous process was scaled up to the kg scale and the enantiomeric purity of the product was enhanced to > 99% ee by two recrystallizations of the free p-chlorophenylmandelic acid.

Effect of Microwave Irradiation on the Catalytic Activity of Palladium Supported Catalysts in the One-Step Isomerisation of Cinchona Alkaloids to Δ3,10-Isobases

“…This procedure was tested to find the optimal Literature data [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Oxidative cleavage [12][13][14][15] time for conversion of 1a or 2a to the isomers (Z/E)-3a or (Z/E)-4a. We monitored the ongoing conversion progress of substrates by taking micro-samples of the reaction mixture regularly, at 10-min intervals, which after extraction with diethyl ether in the presence of aqueous ammonia were analyzed by TLC (silica gel plates, methoxyethanol).…”

“…This paper described our work on influence of controlled microwave heating on activity of palladium solid supported (Pd/SS) catalysts in the heterogeneous isomerisation of four natural Cinchona alkaloids. We studied also possibility of analysis and isolation of the geometric isomers Z and E in Δ 3,10 -isomers, as they will be used as chiral ligands [7,8], catalysts and modifiers in asymmetric syntheses [9][10][11][12].…”

“…The Cinchona Δ 3,10 -isomers 3a,b and 4a,b (Scheme 1) were investigated as effective chiral modifiers of solid-supported metallic catalysts for enantioselective hydrogenation of activated ketones [9][10][11]. Δ 3,10 -Isobases were applied also as valuable intermediates for modification of the native structure [12] including the oxidative cleavage of the double bond [13][14][15][16].…”

Asymmetric transfer hydrogenation of ketones in aqueous solution catalyzed by rhodium(III) complexes with C2-symmetric fluorene-ligands containing chiral (1R,2R)-cyclohexane-1,2-diamine

“…This demand is due to strict government regulations that require evaluation of all the possible stereoisomers of a compound and commercialization of a chiral product only as a single enantiomer. 1 Among small chiral molecules, the chiral alcohols occupy an important place in the synthesis of pharmaceuticals, 2 cosmetic and food, 3 and agricultural chemicals. 4 Thus, the catalytic enantioselective reduction of prochiral ketones is one of the most practical ways to obtain pure chiral secondary alcohols.…”

Aktivált ketonok cinkona alkaloidokkal módosított heterogén katalitikus enantioszelektív hidrogénezése, folyamatos áramú rendszerben

“…Ezen vegyület család használata elméleti szempontból fontos sarokköve lett a reakció mechanisztikus feltárásának, ugyanis segített megérteni a sav-bázis típusú szubsztrát-módosító kölcsönhatást [77]. Az α-keto-amidok redukciója nem a legvonzóbb módszer királis alkoholok elıállítására az alacsony ee miatt [78], de a ciklusos imido-ketonok, úgymint a pirrolidin-2,3,5-trion, 91%-nál nagyobb enantiomer tisztaságú terméket produkál. Az α-diketonok nagy enantioszelektivitású hidrogénezıdésének oka egy kombinált enantioszelektív mechanizmusra eredeztethetı vissza.…”