Enantioselective Alkylation of α-Fluoro-β-Keto Esters by Asymmetric Phase-Transfer Catalysis

Abstract

Highly enantioselective alkylation of tert-butyl α-fluoro-β-keto esters can be effected by the use of N-spiro chiral quaternary ammonium salt as chiral phase-transfer catalyst, as a complementary approach to the asymmetric fluorination of α-alkyl-β-keto esters.

phase-transfer catalysis - alkylations - asymmetric catalysis - esters - alkyl halides

References and Notes

For general reviews, see:

1a Mann J. Chem. Soc. Rev.  1987,  16:  381 

1b Welch JT. Tetrahedron  1987,  43:  3123 

1c Welch JT. Selective Fluorination   ACS Symposium Series 456:  American Chemical Society; Washington DC: 1991. 

1d Wilkinson JA. Chem. Rev.  1992,  92:  505 

1e Filler R. Kobayashi Y. Yagupolskii YL. Organofluorine Compounds in Medicinal Chemistry and Biological Applications   Elsevier; Amsterdam: 1993. 

1f Banks RE. Smart BE. Tatlow JC. Organofluorine Chemistry: Principles and Commercial Applications   Plenum Press; New York: 1994. 

1g Hudlicky M. Pavlath AE. Chemistry of Organic Fluorine Compounds II. A Critical Review   ACS Monograph 187:  American Chemical Society; Washington DC: 1995. 

1h Biomedical Frontiers of Fluorine Chemistry   Ojima I. McCarthy JR. Welch JT. American Chemical Society; Washington DC: 1996. 

1i Organofluorine Compounds. Chemistry and Applications   Hiyama T. Springer; New York: 2000. 

2a Bravo P. Resnati G. Tetrahedron: Asymmetry  1990,  1:  661 

2b Resnati G. Tetrahedron  1993,  49:  9385 

2c Hayashi T., Soloshonok V. A., Eds. Tetrahedron: Asymmetry  1994,  5:  955 

2d Iseki K. Tetrahedron  1998,  54:  13887 

2e Soloshonok VA. Enantiocontrolled Synthesis of Fluoro-Organic Compounds   Wiley; Chichester: 1999. 

2f Asymmetric Fluoroorganic Chemistry. Synthesis, Applications, and Future Directions   ACS Symposium Series 746:  Ramachandran PV. American Chemical Society; Washington DC: 2000. 

3a Ma J.-A. Cahard D. Chem. Rev.  2004,  104:  6119 

3b Pihko PM. Angew. Chem. Int. Ed.  2006,  45:  544 

3c Prakash GK. Beier SP. Angew. Chem. Int. Ed.  2006,  45:  2172 

3d Bobbio C. Gouverneur V. Org. Biomol. Chem.  2006,  4:  2065 

3e Shibata N. Ishimaru T. Nakamura S. Toru T. J. Fluorine Chem.  2007,  128:  469 

3f Brunet VA. O’Hagan D. Angew. Chem. Int. Ed.  2008,  47:  1179 ; and references cited therein

See also:

3g Hamashima Y. Yagi K. Takano H. Tamás L. Sodeoka M. J. Am. Chem. Soc.  2002,  124:  14530 

3h Kim DY. Park EJ. Org. Lett.  2002,  4:  545 

For recent reviews, see:

4a Hashimoto T. Maruoka K. Chem. Rev.  2007,  107:  5656 

4b Ooi T. Maruoka K. Angew. Chem. Int. Ed.  2007,  46:  4222 

4c Ooi T. Maruoka K. Aldrichimica Acta  2007,  40:  77 

4d Maruoka K. Ooi T. Kano T. Chem. Commun.  2007,  1487 

5a Ooi T. Takeuchi M. Kameda M. Maruoka K. J. Am. Chem. Soc.  2000,  122:  5228 

5b Ooi T. Kameda M. Tannai H. Maruoka K. Tetrahedron Lett.  2000,  41:  8339 

5c Ooi T. Takeuchi M. Maruoka K. Synthesis  2001,  1716 

5d Ooi T. Kameda M. Maruoka K. J. Am. Chem. Soc.  2003,  125:  5139 

5e Ooi T. Uematsu Y. Maruoka K. Tetrahedron Lett.  2004,  45:  1675 

5f Ooi T. Kameda M. Fujii J.-i. Maruoka K. Org. Lett.  2004,  6:  2397 

5g Jew S.-s. Lee Y.-J. Lee J. Kang MJ. Jeong B.-S. Lee J.-H. Yoo M.-S. Kim M.-J. Choi S.-h. Ku J.-M. Park H.-g. Angew. Chem. Int. Ed.  2004,  43:  2382 

5h Maeda K. Miller RA. Szumigala RH. Shafiee A. Karady S. Armstrong JD. Tetrahedron Lett.  2005,  46:  1545 

5i Lee Y.-J. Lee J. Kim M.-J. Jeong B.-S. Lee J.-H. Kim T.-S. Lee J. Ku J.-M. Jew S.-s. Park H.-g. Org. Lett.  2005,  7:  3207 

5j Kim T.-S. Lee Y.-J. Jeong B.-S. Park H.-g. Jew S.-s. J. Org. Chem.  2006,  71:  8276 

6a Ooi T. Miki T. Taniguchi M. Shiraishi M. Takeuchi M. Maruoka K. Angew. Chem. Int. Ed.  2003,  42:  3796 

6b Ooi T. Miki T. Maruoka K. Org. Lett.  2005,  7:  191 

6c Ooi T. Miki T. Fukumoto K. Maruoka K. Adv. Synth. Catal.  2006,  348:  1539 

7

Typical Procedure for the Catalytic Asymmetric Alkylation of tert -Butyl 2-Fluoro-3-oxo-3-phenyl-propanoate (2b) under Phase-Transfer Conditions To a solution of phase-transfer catalyst (S,S)-1 (0.001 mmol, 0.9 mg) and 2b (0.10 mmol, 23.6 mg) in mesitylene (2 mL) was added benzyl bromide (0.12 mmol, 14.0 µL), and the mixture was cooled to 0 ˚C. After adding 10% aq CsOH (0.3 mL, ca. 0.2 mmol) to this mixture, the reaction mixture was vigorously stirred until the completion of the reaction. The mixture was then poured into sat. aq NH₄Cl and extracted with EtOAc. The organic layer was dried over Na₂SO₄ and concentrated in vacuo. The residue was purified by column chromatography on SiO₂ to give tert-butyl 2-benzyl-2-fluoro-3-oxo-3-phenylpropanoate (3b) as a colorless oil [82% (26.8 mg), 85% ee]. Enantiomeric purity was determined by HPLC analysis [Daicel Chiralpak OD, hexane-2-PrOH (300:1), flow rate = 0.5 mL/min, 254 nm, t _R= 18.8 min(minor) and 21.7 min(major)]. ^¹H NMR (400 MHz, CDCl₃): δ = 7.99-8.02 (2 H, m, ArH), 7.53-7.58 (1 H, m, ArH), 7.41-7.44 (2 H, m, ArH), 7.25-7.30 (5 H, m, ArH), 3.46-3.68 (2 H, m, PhCH₂), 1.29 (9 H, s, t-Bu).