Proline-Catalyzed Asymmetric Direct Aldol Reaction Assisted by d-Camphorsulfonic Acid in Aqueous Media

Abstract

Asymmetric aldol reactions of aromatic aldehydes with various ketones catalyzed by l-proline with d-camphorsulfonic acid as co-catalyst have been developed in aqueous media. High reactivity and modest to excellent enantioselectivity has been achieved.

Keywords

asymmetric direct aldol reaction - co-catalyst - proline - camphorsulfonic acid - aqueous media

References

• 1a List B. Lerner RA. Barbas CF. J. Am. Chem. Soc.  2000,  122:  2395 
• 1b Sakthivel K. Notz W. Bui T. Barbas CF. J. Am. Chem. Soc.  2001,  123:  5260 
• 2a Ward DE. Jheengut V. Tetrahedron Lett.  2004,  45:  8347 
• 2b Notz W. List B. J. Am. Chem. Soc.  2000,  122:  7386 
• 2c List B. Tetrahedron  2002,  58:  5573 
• 2d Chandrasekhar S. Narsihmulu C. Reddy NR. Sultana SS. Tetrahedron Lett.  2004,  45:  4581 
• 2e Hayashi Y. Tsuboi W. Shoji M. Suzuki N. Tetrahedron Lett.  2004,  45:  4353 
• 2f Pan QB. Zou BL. Wang YJ. Ma DW. Org. Lett.  2004,  6:  1009 
• 2g Szollosi G. London G. Balaspiri L. Somlai C. Bartok M. Chirality  2004,  15:  90 
• 2h Liu HW. Peng LZ. Zhang T. Li YL. New J. Chem.  2004,  27:  1159 
• 2i Kotrusz P. Kmentova I. Gotov B. Toma S. Solcaniova E. Chem. Commun.  2002,  2510 
• 3a Notz W. Tanaka F. Barbas CF. Acc. Chem. Res.  2004,  37:  580 
• 3b Saito S. Yamamoto H. Acc. Chem. Res.  2004,  37:  570 
• 3c Nakadai M. Satio S. Yamamoto H. Tetrahedron  2002,  58:  8167 
• 3d Tang Z. Jiang F. Yu L.-T. Cui X. Gong L.-Z. Mi A.-Q. Jiang Y.-Z. Wu Y.-D. J. Am. Chem. Soc.  2003,  125:  5262 
• 3e Tang Z. Jiang F. Cui X. Gong LZ. Mi AQ. Jiang YZ. Wu YD. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5755 
• 3f Hayashi Y. Yamaguchi J. Hibino K. Sumiya T. Urushima T. Shoji M. Hashizume D. Koshino H. Adv. Synth. Catal.  2004,  346:  1435 
• 3g Berkessel A. Koch B. Lex J. Adv. Synth. Catal.  2004,  346:  1141 
• 3h Tang Z. Yang ZH. Cun LF. Gong LZ. Mi AQ. Jiang YZ. Org. Lett.  2004,  6:  2285 
• 4a Torii H. Nakadai M. Ishihara K. Saito S. Yamamoto H. Angew. Chem. Int. Ed.  2004,  43:  1983 
• 4b Hartikka A. Arvidsson PI. Tetrahedron: Asymmetry  2004,  15:  1831 
• 5 Mase N. Tanaka F. Barbas CF. Angew. Chem. Int. Ed.  2004,  43:  2420 
• 6 Córdova A. Notz W. Barbas CF. Chem. Commun.  2002,  3024 
• 7 Nyberg AI. Usano A. Pihko PM. Synlett  2004,  1891 
• 8 Peng Y.-Y. Ding Q.-P. Li Z. Wang PG. Cheng J.-P. Tetrahedron Lett.  2003,  44:  3871 
• 9 Wu Y.-S. Shao W.-Y. Zheng C.-Q. Huang Z.-L. Cai J. Deng Q.-Y. Helv. Chim. Acta  2004,  87:  1377 
• 10 Darbre T. Machuqueiro M. Chem. Commun.  2003,  1090 
• 11 Wu Y.-S. Cai J. Hu Z.-Y. Lin G.-X. Tetrahedron Lett.  2004,  45:  8949 
• 13 Mestres R. Green Chem.  2004,  6:  583 

12

Typical Procedure (Table [1] , entry 3): Anhyd acetone (2.0 mL, dried with K₂CO₃ before use) was added to p-nitro-benzaldehyde (75 mg, 0.5 mmol), followed by l-proline (20 mol%) and d-CSA (10 mol%) dissolved in water (0.5 mL). The resulting mixture was stirred at r.t. for 12 h. After treating the reaction mixture with saturated aq NaHCO₃ (5 mL), the aqueous layer was separated, and extracted with EtOAc three times. The combined organic extracts were washed with brine (5 mL), dried over anhyd Mg₂SO₄, and concentrated. The residue was purified by preparative thin layer chromatography (Silica gel plates GF254, hexane-EtOAc) to give the aldol product (76.3 mg). The anti/syn ratio is established by ¹H NMR; d = 4.83 ppm (J = 9.0 Hz) - CH of the anti-isomer; 5.42 ppm (J = 2.7 Hz) - CH of the syn-isomer (Table [4] , entry 1). The ee values were determined by HPLC, Daicel chiralpak AS-RH.