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Synlett 2006(7): 1085-1089  
DOI: 10.1055/s-2006-939724
LETTER
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Cyanosilylation of Aldehydes Catalyzed by Novel Chiral Tetraaza-Titanium Complexes

Yanling Liua, Xiaohua Liua, Junguo Xina, Xiaoming Feng*a,b
a Key Laboratory of Green Chemistry & Technology (Sichuan University), Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China
Fax: +86(28)85418249; e-Mail: xmfeng@scu.edu.cn;
b State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
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Publication History

Received 11 January 2006
Publication Date:
24 April 2006 (online)

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Abstract

The asymmetric addition of trimethylsilyl cyanide ­(TMSCN) to a range of aldehydes was efficiently catalyzed by a novel, easily prepared C 2-symmetric chiral tetraaza-Ti(IV) complex in high yields with up to 92% ee under mild conditions. A negative nonlinear effect between the ee of the ligand and the ee of the ­product was observed.

Key words

C 2-symmetric chiral tetraaza ligand - cyanosilylation - aldehydes - enantioselectivity - organotitanium

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General Procedure for the Preparation of C 2 -Symmetric Tetraaza Ligands.
Step 1: To a solution of S-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (3.467 g, 12.5 mmol) in CH2Cl2 was added Et3N (2.1 mL, 15 mmol) and isobutyl isobutyl chlorocarbonate (1.8 mL, 13.75 mmol) at 0 °C under stirring. After 20 min, (1R,2R)-1,2-diphenyl-ethane-1,2-diamine (1.061 g, 5 mmol) was added. It was warmed to r.t. and stirred for 10 h. The mixture was washed with 1 M KHSO4, sat. NaHCO3 and brine, dried over anhyd MgSO4 and concentrated. The residue was used for the next step directly.
Step 2: To a solution of the residue in CH2Cl2 (20 mL) was added TFA (12.5 mL) and stirred for 5 h. Then the solution was concentrated in vacuo, and H2O (25 mL) was added. The pH of the mixture was brought into the range of 11-12 by the addition of 2 M NaOH. The aqueous phase was extracted with CH2Cl2. The CH2Cl2 extracts were pooled, washed with brine, dried over anhyd MgSO4 and evaporated in vacuo. The crude product was purified by recrystallization to afford C 2-symmetric tetraaza ligands 2d as a white solid (2.388 g, 90% yield).

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The following are the physical, NMR and HRMS data of 2d: mp 200.0-201.1 °C; [α]D 25 -86.3 (c 1.62, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 8.09 (2 H, s), 6.95-7.26 (18 H, m), 5.31 (2 H, m), 3.88 (2 H, m), 3.48 (4 H, m), 2.74-3.07 (4 H, m), 2.3 (2 H, m) ppm. 13C NMR (100 MHz, CDCl3): δ = 30.5, 47.1, 56.3, 58.8, 125.6, 126.2, 126.4, 127.6, 127.7, 128.5, 129.2, 133.7, 135.4, 138.7, 173.2 ppm. HRMS (ESI): m/z calcd for C34H34N4O2 531.2755 [M + H]+; found: 531.2760 [M + H]+.

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General Procedure for Asymmetric Cyanosilylation of Aldehydes. To a solution of 2d (19.9 mg, 0.0375 mmol) and p-nitro-benzoic acid (3.1 mg, 0.0186 mmol) in CH2Cl2 (0.4 mL) was added Ti(Oi-Pr)4 (1 M in toluene, 75 µL, 0.075 mmol) and CH2Cl2 (0.5 mL) at r.t., then the mixture was stirred at 35 °C for 1 h under N2 atmosphere. To this solution, aldehyde (0.25 mmol), TMSCN (70 µL, 0.525 mmol) and CH2Cl2 (0.1 mL) were added, in that order, at 0 °C under an N2 atmosphere. After the aldehyde was completely converted (monitored by TLC, 14-36 h), the crude product was purified by column chromatography to give the corresponding cyanohydrin trimethylsilyl ether as colorless oil. After conversion into the acetate, the ee value was determined.

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Physical, NMR and HRMS data of 1a: mp 140.5-141.3 °C; [α]D 25 -73.3° (c 1.86, CH2Cl2). 1H NMR (600 MHz, CDCl3): δ = 8.37 (s, 2 H), 7.06-7.12 (m, 6 H), 7.00-7.02 (m, 4 H), 5.14 (m, 2 H), 3.63 (m, 2 H), 2.93 (m, 2 H), 2.86 (m, 2 H), 2.23 (s, 2 H), 2.07 (m, 2 H), 1.76 (m, 2 H), 1.63 (m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 26.0, 30.6, 47.2, 58.1, 60.5, 127.4, 127.5, 128.2, 139.0, 174.5 ppm. HRMS (ESI): m/z calcd for C24H30N4O2: 407.2442 [M + H]+; found: 407.2456 [M + H]+.

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Only 16-24% ee was obtained for aliphatic aldehydes.