Download PDF
Synlett 2008(6): 857-860  
DOI: 10.1055/s-2008-1042913
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Novel Chiral H′4-NOBIN Schiff Base for Hetero-Diels-Alder Reaction of Danishefsky’s Diene with Aldehydes

Xinsheng Li*a,b, Xiangyan Mengb, Hong Sua, Xiaohua Wub, Dongcheng Xua,b
a Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces, Institute of Physical Chemistry, Zhejiang Normal University, Jinhua 321004, P. R. of China
Fax: +86(579)82282610; e-Mail: sky33@zjnu.cn;
b Department of Chemistry and Life Science, Zhejiang Normal University, Jinhua 321004, P. R. of China
Further Information

Publication History

Received 26 October 2007
Publication Date:
11 March 2008 (online)

    Permissions and Reprints All articles of this category

Abstract

Novel chiral H′4-NOBIN was synthesized in 66% yield through partial hydrogenation of 2-amino-2′-hydroxy-1,1′-binaphthyl, and the structure was proved via X-ray analysis of its salicyl­aldehyde Schiff base, which was tested in the enantioselective titanium-catalyzed hetero-Diels-Alder reaction of Danishefsky’s diene with aldehydes. The reaction provided dihydropyranone in moderate to high yield (up to 99%) and enantioselectivities (up to 84.5% ee).

Key words

asymmetric catalysis - Schiff bases - Diels-Alder reactions - heterocycles - titanium

9

Synthesis of ( S )-5′,6′,7′,8′-tetrahydro-2-amino-2′-hydroxy-1,1′-binaphthyl ( S )-5
(S)-NOBIN (0.57 g, 2 mmol), 5% Pd/C (0.21 g), and EtOH (15 mL) were placed into a 100 mL autoclave and stirred under 80 bar hydrogen pressure at 80 °C for 10 h. The reaction mixture was cooled to r.t., the catalyst was filtered off, and washed with THF (2 × 10 mL). The combined filtrates were concentrated in vacuum to give a mixture of 3 and 5, which was submitted to column chromatographic separation on silica gel with hexane-EtOAc (9:1) as eluent to afford (S)-5 (382 mg, 66% yield) as a foam solid with >99.5% ee [HPLC on an AD-H column with hexane-i-PrOH (90:10) as eluent, 1 mL min-1, t R = 13.88 (R) min, t R = 22.73 min (S)]; mp 113-115 °C; [α]D 20 -59 (c 1, THF). 1H NMR (400 MHz, CDCl3): δ = 1.60-1.63 (m, 2 H), 1.70-1.74 (m, 2 H), 2.13-2.18 (m, 1 H), 2.21-2.26 (m, 1 H), 2.77-2.80 (m, 2 H), 3.76 (s, 2 H), 4.59 (s, 1 H), 6.80 (d, 1 H, J = 8.4 Hz), 7.09-7.17 (m, 3 H), 7.26-7.30 (m, 2 H), 7.74 (d, 2 H, J = 8.4 Hz). 13C NMR (100 MHz, CDCl3): δ = 23.0, 23.1, 26.8, 29.3, 110.3, 112.8, 117.9, 120.5, 122.6, 127.2, 128.2, 128.3, 129.8, 130.1, 130.4, 133.5, 137.7, 142.7, 151.4. IR (KBr): 3447, 3376, 3052, 2926, 1619, 1471 cm-1. Anal. Calcd for C20H19NO: C, 83.01; H, 6.62; N, 4.84. Found: C, 82.94; H, 6.68; N, 4.80.

10

Synthesis of Ligand ( S )-7
Compound (S)-5 (285 mg, 0.1 mmol) and salicylaldehyde (122 mg, 0.12 mmol) were stirred in toluene (20 mL) and the mixture was heated to reflux for 16 h. The solvent was removed in vacuo and the product was isolated by flash chromatography on silica gel (316 mg, 80.3% yield); mp 166-168 °C, [α]D 20 -118 (c 0.2, THF). 1H NMR (400 MHz, CDCl3): δ = 1.54-1.58 (m, 2 H), 1.67-1.70 (m, 2 H), 1.99-2.10 (m, 1 H), 2.14-2.17 (m, 1 H), 2.76-2.81 (m, 2 H), 4.27 (s, 1 H), 6.84-6.89 (m, 3 H), 7.11-7.13 (m, 1 H), 7.27-7.32 (m, 3 H), 7.48-7.52 (m, 2 H), 7.59-7.61 (m, 1 H), 8.01-8.03 (m, 1 H), 8.51-8.53 (m, 1 H), 8.73 (s, 1 H), 12.3 (s, 1 H). 13C NMR (100 MHz, CDCl3): δ = 22.9, 23.0, 23.1, 27.4, 29.3, 112.7, 117.2, 117.4, 118.8, 119.3, 122.1, 125.7, 126.3, 127.2, 127.5, 128.2, 129.7, 130.2, 130.3, 132.3, 132.7, 132.9, 133.1, 136.4, 143.9, 150.6, 161.3, 162.1. IR (KBr): 3381, 3053, 2928, 1610, 1569 cm-1. Anal. Calcd for C27H23NO2: C, 82.42; H, 5.89; N, 3.56. Found: C, 82.39; H, 5.88; N, 3.58.

11

Crystallographic data (excluding structure factors) for the structures in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 658558 [(R)-7]. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033 or e-mail: deposit@ccdc.cam.ac.uk.].

13

General Procedure for Catalytic Enantioselctive Hetero-Diels-Alder Reaction
A mixture of (S)-Schiff Base (19.7 mg, 0.05 mmol), Ti(Oi-Pr)4 in toluene (0.25 M, 0.1 mL, 0.025 mmol) and activated powdered 4 Å MS (40 mg) in toluene (1 mL) was stirred for 2 h at 50 °C. The red solution was cooled to r.t. and naproxen (5.8 mg, 0.025 mmol), aldehyde (0.25 mmol), and Danishefsky’s diene (60 µL, 0.3 mmol) were added sequentially. The mixture was stirred for 12 h at r.t. before quenched with TFA (0.2 mL). After stirring for additional 30 min, the mixture was neutralized with sat. NaHCO3 (3 mL). After filtration through a plug of Celite, the organic layer was separated and the aqueous layer was extracted with EtOAc (3 × 5 mL). The combined organic layers were dried over anhyd Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc-hexane, 1:4) to give the products for 1H NMR and HPLC analysis.