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Synlett 2006(20): 3443-3446  
DOI: 10.1055/s-2006-956474
LETTER
© Georg Thieme Verlag Stuttgart · New York

New Enantiopure N-Ferrocenylmethyl Azetidin-2-yl(diphenyl)methanol and Its Application in Catalytic Asymmetric Ethylation and Arylation of Arylaldehydes

Min-Can Wang*, Wen-Xian Zhao, Xiao-Dan Wang, Mao-Ping Song*
Department of Chemistry, Zhengzhou University, Zhengzhou, Henan 450052, P. R. of China
Fax: +86(371)67769024; e-Mail: wangmincan@zzu.edu.cn;
Further Information

Publication History

Received 1 September 2006
Publication Date:
08 December 2006 (online)

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Abstract

A novel, facile and practical approach to preparation of new enantiopure N-ferrocenylmethyl azetidin-2-yl(diphenyl)methanol has been developed. In the presence of a catalytic amount of the chiral N-ferrocenylmethyl azetidin-2-yl(diphenyl)methanol, the enantioselective ethylation and arylation of arylaldehydes afforded addition products with enantioselectivities of up to 98.4% ee and 95.7% ee, respectively.

Key words

asymmetric addition - diethylzinc - aryl boronic acids - ethylation - arylation

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Compound 6: mp 122.7-123.9 °C; [α]D 20 -27.2 (c = 0.32, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.87-2.09 (m, 1 H), 1.92-2.03 (m, 1 H), 2.81, 2.87 (dd, J = 13.2 Hz, 2 H), 2.89-2.93 (m, 1 H), 3.18 (t, J = 6.0 Hz, 1 H), 3.83-4.05 (m, 9 H), 4.27 (t, J = 7.2 Hz, 1 H), 5.20 (s, 1 H), 7.18-7.61 (m, 10 H). MS (ESI): m/z [M + H]+ calcd for C27H27FeNO: 438; found: 438.

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Enantioselective Addition of Diethylzinc to Benzaldehyde: A solution of diethylzinc (1 M in n-hexane, 1.1 mL) was added to a solution of a chiral catalyst 6 (0.015 mmol, 3 mol%) in anhyd toluene under a nitrogen atmosphere. The mixture was cooled to 0 °C, and stirred for 30 min. Freshly distilled benzaldehyde (0.05 mL, 0.5 mmol) was added to the mixture. The resulting mixture was stirred for 10 h at 0-5 °C and was allowed to warm to the r.t., and stirring was continued for another 38 h at the same temperature. The reaction was quenched by the addition of sat. aq NH4Cl (4 mL). The mixture was extracted with Et2O (3 × 8 mL). The combined organic layers were washed with brine, dried over anhyd Na2SO4 and evaporated under reduced pressure. Purification of the residue by the preparative silica gel TLC plate (hexane-EtOAc = 4:1) afforded the (S)-1-phenyl-1-propanol. The ee was determined by HPLC analyses using a chiral column (a Chiralcel OD); hexane-i-PrOH = 100:2, flow rate: 0.6 mL/min, t R(R) = 19.6 min, t R(S) = 23.8 min.

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Asymmetric Arylation of Arylaldehydes Catalyzed by 6; General Procedure: A dried Schlenk tube containing toluene (2 mL), aryl boronic acid (122 mg, 1 mmol), and diethylzinc (3 mmol, 1.0 M solution in hexanes) was heated at 60 °C for 12 h. After the mixture was cooled to r.t., the chiral amino alcohol ligand 6 (43.7 mg, 0.1 mmol) was added. The mixture was stirred for another 15 min. It was cooled to -20 °C, and the aldehyde (1 mmol) was subsequently added under nitrogen atmosphere. After 48 h at -20 °C, the reaction was quenched by the addition of sat. aq NH4Cl (8 mL). The mixture was extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were washed with brine, dried over anhyd Na2SO4 and evaporated under reduced pressure. Purification of the residue by the preparative silica gel TLC plate (hexane-EtOAc) afforded the pure diarylmethanol. The ee was determined by HPLC analyses using a chiral column: Chiralcel OB, Chiralcel OD or Chiralpak AD.