Combined heterogeneous bio- and chemo-catalysis for dynamic kinetic resolution of (rac)-benzoin

Abstract

Dynamic kinetic resolution (DKR) of racemic starting material is a promising route to optically pure (S)-benzoin (2-hydroxy-1,2-di(phenyl)ethanone) and various symmetrical and unsymmetrical derivatives thereof. Here, this route was advanced towards technical scale synthesis using the basic (rac)-benzoin as model system. The reaction employed stereoselective transesterification of (S)-benzoin with lipase TL® from Pseudomonas stutzeri and racemization of (R)-benzoin with Metal-TUD-1, a metal-associated acidic meso-porous silicate, in pure organic solvent. Enzyme performance was improved by immobilization on Accurel MP1001 (yielding Acc-LipTL), and Zr-TUD-1 (Si/Zr = 25) was identified as most effective racemization catalyst. Compatibility in solvent and temperature dependency enabled performance in only one pot. DKR in toluene at 50 °C yielded conversions above 98% and an ee of >97% in only five hours. Stability of Acc-LipTL was further improved with polyethylene imine and the reaction system was then reused in five cycles, retaining a conversion of >99% and a product-ee of >98%. On a semi-preparative scale, the isolated yield of enantiopure (S)-benzoin butyrate was >98%. Thus, the system provides a good basis for synthesis of enantiopure benzoin, and potentially a broader range of aromatic α-hydroxy ketones

Dynamic Kinetic Resolution of Diarylmethanols with an Activated Lipoprotein Lipase

“…The yields ranged from 74-92% (entries [11][12][13][14][15][16][17][18][19][20][21]. The DKR reactions of 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 8 6 (carrying a TMS substituent) also required rather long times (60-72 h) to provide high enantiopurities (94-96% ee) with satisfactory yields (82-92%) (entries [22][23][24]. Overall, all the DKR reactions were successful and provided high enantiomeric excesses with satisfactory yields.…”

“…1 Over the past decade, the procedures employing an enzyme as the resolution catalyst and a metal (complex) as the racemization catalyst have been intensively explored for the efficient DKR. 2-6 Several useful procedures now are available for the DKR of alcohols, [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] amines, [23][24][25][26][27][28][29][30][31][32][33] and amino acids. [34][35][36][37][38] The wider applications of the DKR procedures, however, are limited by the low activity, narrow substrate specificity or modest enantioselectivity of enzyme employed.…”

Lipases: Valuable catalysts for dynamic kinetic resolutions

“…In fact, there are few examples of heterogeneous and immobilized racemization catalysts compatible with lipases (Akai et al, 2010;Egi et al, 2013;Han et al, 2010a;Långvik et al, 2010;Nieguth et al, 2014;Wieczorek et al, 2011). The development of these catalysts, which are in general reusable and more suitable for industrial applications, is still a challenge.…”

ChemInform Abstract: Heterogeneous Chemoenzymatic Catalyst Combinations for One‐Pot Dynamic Kinetic Resolution Applications

“…[62] The DKR of am odel hydroxyketone, benzoin, was recently reported by Ansorge-Schumacher and co-workers. [65] The enantiospecific kinetic resolution was accomplished by using an immobilized Lipase TL from Pseudomonas stutzeri.A dsorption of the enzyme on the porousp olypropylene resin Accurel MP1001s urface (35 m 2 g À1 according to BET method) was systematically characterized by measuringthe specific catalytic activity of the catalysts by varying the enzymec oncentration and pH of the buffer solution duringi mmobilization. Furthermore, racemization of (R)-benzoine was studied by incorporating different metals, Zr and W, in the mesoporous acidic silicate TUD-1.…”