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Synthesis 2010(8): 1394-1397  
DOI: 10.1055/s-0029-1218636
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© Georg Thieme Verlag Stuttgart ˙ New York

A Concise Synthesis of (S)-2-(Fluorodiphenylmethyl)pyrrolidine: A Novel Organocatalyst for the Stereoselective Epoxidation of α,β-Unsaturated Aldehydes

Christof Sparr, Eva-Maria Tanzer, Julia Bachmann, Ryan Gilmour*
Laboratory for Organic Chemistry, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH) Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland
Fax: +41(44)6331235; e-Mail: ryan.gilmour@org.chem.ethz.ch;
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Publication History

Received 16 October 2009
Publication Date:
08 January 2010 (online)

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Abstract

A concise synthesis of (S)-2-(fluorodiphenylmethyl)pyrrolidine from cheap, commercially available starting materials is described. Pertinent features of this synthetic route include ease of synthesis, facile purification steps, and an operationally simple deoxy­fluorination step to install the C-F bond.

Key words

diethylaminosulfur trifluoride - fluorination - organocatalyst - proline - synthesis

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5

(S)-2-(Fluorodiphenylmethyl)pyrrolidine (1) (98% ee HPLC, 97%) (500 mg = 348.50 CHF) and its R-enantiomer (500 mg = 332.16 CHF) are available from Sigma-Aldrich.

9

For this analysis (R)-7 was prepared from d-proline following the procedure described in this manuscript. HPLC: Derivatisation with Ac2O (1.2 equiv) and DMAP (1.2 equiv) in CH2Cl2 at r.t. for 2 h. Removal of the solvent and purification by flash column chromatography (SiO2, EtOAc). HPLC on a Reprosil Chiral-OM, 5 µm column (1.0 mL/min, i-PrOH-n-hexane, 1:6): (S)-7 t R = 6.56 min and (R)-7 t R = 6.21 min.

12

Whilst the product is identical to known material,6 the yellow colouration may be removed by the following simple procedure to yield a clear, colourless oil: To the yellow oil (100 mg) was added HCl in MeOH (500 µL, 1.25 mol/L). The resulting suspension was filtered and the solid was washed with Et2O. The solid was dissolved in a mixture of EtOAc (5.0 mL) and NaOH (5.0 mL, 2.0 mol/L, pH >9). The layers were separated, the organic phase was washed with brine (5.0 mL), dried (Na2SO4) and concentrated in vacuo to give a colourless oil (98.5 mg).

13

Sigma Aldrich Specification Sheet (Product Number 552569, CAS Number 274674-23-6).