Phase-Transfer-Catalyzed Enantioselective Alkylation of α-Benzoyloxy-β-Keto Ester

Abstract

Highly enantioselective alkylation of tert-butyl 2-benzoyloxy-3-oxobutanoate could be realized by the use of N-spiro chiral quaternary ammonium salt as phase-transfer catalyst, as a complementary approach to the asymmetric hydroxylation of α-alkyl-β-keto esters.

Key words

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

References and Notes

• For general reviews, see:
• 1a Christoffers J. Baro A. Werner T. Adv. Synth. Catal.  2004,  346:  143 
• 1b Shibasaki M. Kanai M. Chem. Rev.  2008,  108:  2853 
• 2a Toullec PY. Bonaccorsi C. Mezzetti A. Togni A. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5810 
• 2b Bonaccorsi C. Althaus M. Becker C. Togni A. Mezzetti A. Pure Appl. Chem.  2006,  78:  391 
• 2c Acocella MR. Mancheno OG. Bella M. Jørgensen KA. J. Org. Chem.  2004,  69:  8165 
• 2d Ishimaru T. Shibata N. Nagai J. Nakamura S. Toru T. Kanemasa S. J. Am. Chem. Soc.  2006,  128:  16488 
• For recent reviews, see:
• 3a Hashimoto T. Maruoka K. Chem. Rev.  2007,  107:  5656 
• 3b Ooi T. Maruoka K. Angew. Chem. Int. Ed.  2007,  46:  4222 
• 3c Ooi T. Maruoka K. Aldrichimica Acta  2007,  40:  77 
• 3d Maruoka K. Ooi T. Kano T. Chem. Commun.  2007,  1487 
• 3e Maruoka K. Chimia  2007,  61:  263 
• 3f Maruoka K. Org. Process Res. Dev.  2008,  12:  679 
• 4 For the phase-transfer-catalyzed asymmetric hydroxylation of oxindoles by molecular oxygen, see: Sano D. Nagata K. Itoh T. Org. Lett.  2008,  10:  1593 
• 5a Ooi T. Miki T. Taniguchi M. Shiraishi M. Takeuchi M. Maruoka K. Angew. Chem. Int. Ed.  2003,  42:  3796 
• 5b Ooi T. Miki T. Maruoka K. Org. Lett.  2005,  7:  191 
• 5c Ooi T. Miki T. Fukumoto K. Maruoka K. Adv. Synth. Catal.  2006,  348:  1539 
• 6 Scheid G. Kuit W. Ruijter E. Orru RVA. Henke E. Bornsheuer U. Wessjohann LA. Eur. J. Org. Chem.  2004,  1063 

7

Typical Procedure for the Catalytic Asymmetric Alkylation of tert -Butyl 2-Benzoyloxy-3-oxobutanoate under Phase-Transfer Conditions
To a solution of phase-transfer catalyst (S,S)-1c (0.002 mmol, 2.2 mg) and 2a (0.20 mmol, 55.7 mg) in toluene (2 mL) was added benzyl bromide (0.24 mmol, 28.5 µL) and the mixture was cooled to -20 ˚C. After adding freshly powdered KOH (0.3 mmol, 19.8 mg) 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-benzoyloxy-2-benzyl-3-oxobutanoate as a colorless oil [91% (67.6 mg), 90% ee]. Enantiomeric purity was determined by HPLC analysis [(Daicel Chiralpak AD-H, hexane-2-PrOH (100:1), flow rate = 0.5 mL/min, t _R = 22.3 min(major) and 25.0 min(minor)].
^¹H NMR (400 MHz, CDCl₃): δ = 8.00 (2 H, d, J = 7.3 Hz, ArH), 7.61 (1 H, t, J = 7.6 Hz, ArH), 7.46 (2 H, app t, J = 7.8 Hz, ArH), 7.21-7.22 (3 H, m, ArH), 7.12 (2 H, m, ArH), 3.65 (2 H, s, PhCH₂), 2.25 (3 H, s, COCH₃), 1.40 (9 H, s, t-Bu). ^¹³C NMR (100 MHz, CDCl₃): δ = 202.2, 165.3, 165.2, 134.4, 133.5, 130.2, 129.8, 129.3, 128.5, 128.3, 127.1, 89.0, 83.4, 38.8, 27.6, 27.4. IR (neat): 2978, 2932, 1755, 1721, 1279, 1152, 1107, 1094, 1069, 1026 912, 845, 733, 700 cm^-¹. ESI-HRMS: m/z calcd for C₂₂H₂₄O₅: 391.1516 [M + Na]⁺; found: 391.1516 [M + Na]⁺. [α]_D ^²8 -46.5 (c 1.0, CHCl₃; 90% ee).