Download PDF
Synthesis 2003(11): 1693-1698
DOI: 10.1055/s-2003-40889
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioselective Addition of a Trifluoromethyl Anion to Aryl Ketones and Aldehydes

Stéphane Caron*, Nga M. Do, Patrice Arpin, Alexandre Larivée
Chemical Research and Development, Pfizer Global Research & Development, Groton MS-8118D-4002, CT 06340, USA
Fax: +1(860)7158584; e-Mail: stephane_caron@groton.pfizer.com;
Further Information

Publication History

Received 21 April 2003
Publication Date:
25 July 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

The identification and development of a catalyst for the enantioselective nucleophilic addition of a trifluoromethyl anion to a ketone is described. An easily prepared cinchonine-derived catalyst was used in amounts as low as 4 mol% to afford enantiomeric excess as high as 92%.

Key words

alkaloids - ketones - aldehydes - asymmetric catalysis - fluorine - nucleophilic additions - substituent effects

10

The enantiomeric excess was determined by evaluation of the corresponding diol (obtained by treating the silyl ether with TBAF followed by NaOH) by HPLC (Chiracel OD, 4.6 × 250 mm; 40 °C; 1.5 mL/min; 230 nm; hexanes-i-PrOH-TFA, 90:10:0.1). The absolute configuration was determined single crystal X-ray analysis of 4-bromobenzoate(6d).

11

The starting material was obtained by esterificaton of alcohol 3 with 3,4-dimethoxybenzoyl chloride (CH2Cl2, Et3N, DMAP, 100%) and Friedel-Crafts acylation (AcCl, TiCl4, CH2Cl2, 89%).

12

The enantiomeric excess was determined by evaluation of the corresponding tertiary alcohol (obtained by treating the silyl ether with TBAF) by HPLC (Chiracel OD, 4.6 × 250 mm; 40 °C; 1.5 mL/min; 230 nm; hexanes-i-PrOH-TFA, 80:20:0.2).

16

The absolute stereochemistry was not determined.