Dynamic Enzymatic Kinetic Resolution of Methyl 2,3‐Dihydro‐1H‐indene‐1‐carboxylate

Abstract

A new reaction setup for kinetic enzymatic resolution was established and is demonstrated for the case of the hydrolase-catalysed conversion of methyl 2,3-dihydro-1H-indene-1-carboxylate (1) in conjunction with a base-catalysed racemisation. The system allows controlled racemisation, resulting in efficient dynamic kinetic resolution (DKR) of the title compound. Short reaction times and high enantio-

Biocatalytic Racemization Employing TeSADH: Substrate Scope and Organic Solvent Compatibility for Dynamic Kinetic Resolution

“…This approach applied here significantly reduced the hydrolysis, although results were still poor owing to the low racemization rate. As the μAq approach was not satisfactory, a biphasic migratory DKR system was tested, in which simultaneous racemization and kinetic resolution are separated between the phases, so that racemization takes place in the aqueous phase catalyzed by the ADH and the esterification occurs at the same time in the organic phase catalyzed by the lipase compartmentalized in a TeaBag . To eliminate any additional mass transfer barriers via the cell wall, we decided to apply a heat‐treated cell‐free extract (HT CFE) of TeSADH WIC and furthermore ethyl hexanoate as acyl donor (Scheme , Table ).…”

Indoline‐3‐Carboxylic Acid Derived Organocatalysts for the anti‐Mannich Reaction

“…In a previous study of structurally related methyl‐2,3‐dihydro‐1 H ‐indencarboxylate, conditions for an enzymatic kinetic resolution were determined, established and optimised 20. Therefore, we could adapt those findings and added the enzyme CAL‐B ( Candida antarctica lipase B) to a stirred solution of ester rac ‐ 19 in a potassium phosphate buffer (pH 8.0; 100 m M ).…”

“…In a previous study of structurally related methyl-2,3-dihydro-1H-indencarboxylate, conditions for an enzymatic kinetic resolution were determined, established and optimised. [20] Therefore, we could adapt those findings and added the enzyme CAL-B (Candida antarctica lipase B) to a stirred solution of ester rac-19 in a potassium phosphate buffer (pH 8.0; 100 mm). In contrast to our earlier results, we had to decrease the temperature of the reaction mixture to 0 8C because although the product (S)-12 was obtained in a respectable 95 % ee at room temperature, this was too low for our purpose (full data not shown).…”

“…Obtained data are full in agreement with those reported in literature. [29] [a] 20 Derivatisation of ester (R)-19: An analytical sample of (R)-19 (2 mL) was treated with trifluoroacetic acid anhydride (10 mL) in an Eppendorf vial and stirred vigorously at 30 8C on an Eppendorf Thermomix apparatus for 10 min. Aqueous saturated NaHCO 3 solution (500 mL) and n-heptane (300 mL) were added.…”

Synthesis of the 1-Monoester of 2-Ketoalkanedioic Acids, for Example, Octyl α-Ketoglutarate

“…Prepared from 1-octanol and 1 H -indene-3-carboxylic acid 14 11c (0.389 g, 2.4 mmol) by the procedure described for the preparation of 9 to give octyl 1 H -indene-3-carboxylate 12c (0.655 g, 99%) as a clear oil. 1 H NMR (300 MHz, CDCl 3 ): δ 8.10 (d, J = 7.6 Hz, 1H), 7.48 (d, J = 7.4 Hz, 1H), 7.47 (s, 1H), 7.38 (t, J = 7.4 Hz, 1H), 7.28 (dt, J = 7.4, 1.5 Hz, 1H), 4.34 (t, J = 6.7 Hz, 2H), 3.51 (s, 2H), 1.81 (pentet, J = 6.9 Hz, 2H), 1.55-1.25 (m, 10H), 0.94 (t, J = 7.0 Hz, 3H).…”