Enantioselective hydrogenation of levulinic acid esters in the presence of the RuII-BINAP-HCl catalytic system

Abstract

The rate of hydrogenation of γ ketoesters MeCOCH 2 CH 2 COOR (R = Et, Pr i , Bu t ) in the presence of the chiral Ru II -BINAP catalyst (BINAP is 2,2´ bis(diphenylphosphino) 1,1´ binaphthyl) greatly increases upon the addition of 5-10 equivalents of HCl with respect to ruthenium. In the hydrogenation of ethyl levulinate, the optically active γ hydroxy ester ini tially formed would cyclize by ~95% to give γ valerolactone with optical purity of 98-99% ee. When the Ru(COD)(MA) 2 -BINAP-HCl catalytic system is used (COD is 1,5 cyclooctadiene, MA is 2 methylallyl), complete conversion of the ketoester (R = Et) in EtOH is attained in 5 h at 60 °C under an H 2 pressure of 60-70 atm.Key words: enantioselective catalytic hydrogenation, ruthenium(II), 2,2´ bis(diphenyl phosphino) 1,1´ binaphthyl (BINAP), esters of levulinic acid, esters of γ hydroxyvaleric acid, optically active γ valerolactone.The asymmetric catalytic hydrogenation of ketoesters is a highly efficient method for the preparation of opti cally active hydroxycarboxylic acids and their derivatives, valuable multi purpose building blocks. The asymmetric hydrogenation of α and β ketoesters catalyzed by chiral ruthenium(II) complexes has been studied rather compre hensively in recent years. 1-5 However, little is known about the asymmetric hydrogenation of γ ketoesters, which are much less reactive than α and β ketoesters. In the presence of the RuCl 2 (BINAP) catalyst (BINAP is 2,2´ bis(diphenylphosphino) 1,1´ binaphthyl), pre pared in situ from Ru(OAc) 2 (BINAP), 6 or the [RuCl 2 (BINAP)(DMF)] n , 7 [RuCl 2 (BINAP)] 2 NEt 3 , 8,9 [RuCl(p MeC 6 H 4 Pr i )(BINAP)]Cl, 10 and [Me 2 NH 2 ]{[RuCl(SEGPHOS)] 2 (µ Cl) 3 } 11 catalysts (SEGPHOS is 5,5´ bis(diphenylphosphino) 4,4´ bi(1,3 benzodioxolyl)), a high conversion of γ ketoesters com bined with a high hydrogenation enantioselectivity can be attained in 2 to 10 days at 30-65 °C and 50-100 atm H 2 .The purpose of this study is to search for a more effi cient catalytic system for the enantioselective hydrogena tion of γ ketoesters. Esters of levulinic acid (1a), com pounds 1b-d, were chosen as model substrates. They were hydrogenated (Scheme 1) in the presence of the Ru 1-Ru 4 catalytic systems (Tables 1 and 2).The plot shown in Fig. 1 indicates that in the presence of the Ru 1 catalytic system, containing only 2 equiv. of HCl (this amount of the acid is required for the formation of RuCl 2 (BINAP)), the conversion of ketoester 1b is less than 5% under the chosen hydrogenation conditions. When HCl is added up to 5 equiv. with respect to ru thenium, hydrogenation occurs much faster and gives γ hydroxy ester 2b, which would cyclize into lactone 3 bỹ 95% under the reaction conditions. Further increase in the amount of HCl induces a gradual increase in the conversion of ketoester, which reaches 100% for the ratio [HCl]/[Ru] = 10. This ratio was chosen as the standard one in the subsequent experiments. It is significant that the growth of the medium acidity does not influence the Scheme 1

The role of protic solvent in asymmetric hydrogenation of methyl levulinate in the presence of a ruthenium-containing catalyst

“…Catalytic hydrogenation of oxo ester 1 and analysis of the reaction products were carried out as described in the pre ceding paper. 1 Here the catalyst for the asymmetric hydrogena tion and deuteration of oxo ester 1 was prepared in situ without isolating the intermediate complex [((S) BINAP)RuCl 2 ].…”

Homogeneous Catalyzed Reactions of Levulinic Acid: To γ‐Valerolactone and Beyond

“…[28][29][30][31] In early pioneering studies Osakada et al, [32] showed the activation of C-O bonds of five membered cyclic anhydride, aldehydic and keto acids using two different ruthenium ( [10] demonstrated the use of an in situ generated Ru catalyst using a combination of Ru(acac) 3 and the strongly electron donating phosphine P n Bu 3 in the presence of NH 4 PF 6 for LA hydrogenation to GVL ( [33] reported the effect of the mondentate and chelating phosphines: trioctylphosphine (P n Oct 3 ), 1,4-diphenylphosphinobutane (DPPB) and triphos ( fig. 2) and various acidic additives for the transformation of LA.…”

“…[35,36,53,54] Ru and Ir phosphine complexes have provent ob ee ffective catalysts for CÀOb ond activation in carboxylic acids derivatives. [30][31][32][33] In early pioneering studies, Osakada et al [34] [10] demonstrated the use of an in situ-generated Ru catalyst using ac ombination of [Ru(acac) 3 ]( acac = acetylacetonate) and the strongly electron-donating phosphine PnBu 3 in the presence of NH 4 PF 6 for LA hydrogenation to GVL ( Table 1, entry 3). The reaction demonstrated quantitative conversion of LA to GVL.…”

“…In recent studies by Starodubtseva et al [30,50] the conversion of LA, EL ando ther levuinate esters to enantiopure lactones was investigated using Ru-BINAP catalysts prepared in situ and activated with HCl. LA could be converted to (S)-GVL in moderate yields of 66 %a nd with 98.5 % ee at 60 8Ca nd 60 bar H 2 in EtOH using ac atalyst system generated in situ from [Ru(Me-allyl) 2 (COD)] (COD = 1,5-cyclooctadiene);M e = methyl, (S)-BINAP and HCl.…”

Stereocontrolled approach to δ-amino acids by asymmetric hydrogenation of 5-acetylaminopent-4-enoic acid derivatives

“…12 Earlier, we have studied asymmetric catalytic hydro genation of prochiral substrates containing a keto group. [13][14][15][16] In the present work, we made an attempt to use similar approach to the synthesis of chiral δ amino acids starting from available δ keto acids. 5 Oxo 5 phenylpentanoic acid (1) has been chosen as the starting compound (Scheme 1), which gave rise to two model sub strates, viz., ω enamides 4 and 9.…”