Scandium Triflate Catalyzed Transesterification of Carboxylic Esters

Abstract

The direct transesterification of carboxylic esters is efficiently catalyzed with Sc(OTf)₃ (10 mol%) in boiling alcoholic solvent. Methyl, ethyl, isopropyl, and allyl esters were prepared from a broad range of different substrates in high yields. The application of microwave irradiation led to significantly reduced reaction times.

Key words

carboxylic esters - catalysis - scandium - transesterification

References and Notes

• 1 Excellent review: Otera J. Esterification   Wiley-VCH; Weinheim: 2003. 
• Specialized reviews about transesterification:
• 2a Otera J. Chem. Rev.  1993,  93:  1449 
• 2b Grasa GA. Singh R. Nolan SP. Synthesis  2004,  971 
• 3 Seebach D. Hungerbühler E. Naef R. Schnurrenberger P. Weidmann B. Züger M. Synthesis  1982,  138 
• 4a Otera J. Yano T. Kawabata A. Nozaki H. Tetrahedron Lett.  1986,  27:  2383 
• 4b Otera J. Danoh N. Nozaki H. J. Org. Chem.  1991,  56:  5307 
• 5 Baumhof P. Mazitschek R. Giannis A. Angew. Chem. Int. Ed.  2001,  40:  4077 
• 6a Ishihara K. Kubota M. Kurihara H. Yamamoto H. J. Am. Chem. Soc.  1995,  117:  4413 
• 6b Ishihara K. Kubota M. Yamamoto H. Synlett  1996,  265 
• 7 Orita A. Nagano Y. Hirano J. Otera J. Synlett  2001,  637 
• 10 Excellent review about microwave-accelerated reactions: Kappe CO. Angew. Chem. Int. Ed.  2004,  43:  6250 ; Angew. Chem. 2004, 116, 6408

8

At room temperature no full conversion could be achieved even with 10 mol% catalyst and prolonged reaction times.

9

Typical Experimental Procedure.
A solution of the ester (1.00 mmol) in the respective alcohol (10 mL) was treated with 49.0 mg (0.10 mmol, 10 mol%) Sc(OTf)₃ and refluxed for the indicated reaction time. The reaction mixture was cooled to r.t. and filtered over a short plug of silica gel. All volatiles were evaporated in vacuo and the residue was purified by chromatography with mixtures of Et₂O and pentane. All esters prepared were characterized by NMR, IR, and MS and gave spectroscopic data matching the reported data. The ee values of the (S)-mandelate esters were determined by HPLC on a chiral OD-phase with hexane-i-PrOH = 90:10, flow rate 1.0 mL/min. The ee of (R)-methyl β-hydroxy butyrate was determined by ¹⁹F NMR analysis of the corresponding Mosher ester. For the micro-wave experiments a microwave reactor ‘microPREP A’ (MLS GmbH, Germany) with a single magnetron (max. 1200 W, pulsed irradiation, 2.45 GHz), terminal 320 controller, and easy CONTROL 06 software was used. An internal ATC-FO 300 fiberoptic sensor inserted into the reaction vessel was employed to measure the temperature inside the reaction mixture accurately and adjust the temperature to the set temperature automatically.