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Synlett 2009(15): 2524-2528  
DOI: 10.1055/s-0029-1217823
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Chiral Acid-Catalyzed Asymmetric Nazarov Reaction: Nucleophilic Construction of a Quaternary Asymmetric Center at the α-Position of the Keto Function

Kentaro Yajia, Mitsuru Shindo*b
a Interdisciplinary Graduate School of Engineering Sciences, Kyushu University, Kasuga-koen, Kasuga 816-8580, Japan
b Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga-koen, Kasuga 816-8580, Japan
Fax: +81(92)5837875; e-Mail: shindo@cm.kyushu-u.ac.jp;
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Publication History

Received 11 June 2009
Publication Date:
17 August 2009 (online)

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Abstract

A chiral Lewis acid catalyzed enantioselective Nazarov reaction affording α-alkoxy cyclopentenones has been developed. This is the first example for construction of an asymmetric quaternary center by using the monodentate coordinated divinyl ketones via the interrupted Nazarov reaction, which involves a nucleophilic attack of an alcohol on the α-position of the keto function.

Key words

asymmetric catalysis - asymmetric synthesis - electrocyclic reactions - ketones - Lewis acids

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Representative Experimental Procedure for the Catalytic Asymmetric Nazarov Reaction
A solution of Sc(OTf)3 (9.8 mg, 0.02 mmol), pybox-Ph (8, 8.1 mg, 0.022 mmol) in dry CH2Cl2 (0.4 mL) was stirred for 3 h. Then, Et3N (2.0 µL, 0.014 mmol) and the (E)-β-alkoxy divinyl ketone (23, 54 mg, 0.2 mmol) in dry CH2Cl2 (0.4 mL) were added. The mixture was stirred at r.t. for 4 h, quenched with sat. aq NaHCO3, and extracted with CH2Cl2. The organic extract was washed with sat. aq NaHCO3 and brine, dried over MgSO4, filtered, and concentrated in vacuo. The residual oil was purified over silica gel column chromatography (hexane-EtOAc, 80:20) to afford the
α-alkoxy cyclopentenone (20).
Compound 20 [R¹ = Ph(CH2)2, R² = i-Pr]: ¹H NMR (600 MHz, CDCl3): δ = 1.07 (d, J = 6.6 Hz, 3 H), 1.10 (d, J = 6.0 Hz, 3 H), 1.26 (s, 3 H), 1.57 (s, 3 H), 2.40 (d, J = 18.0 Hz, 1 H), 2.64-2.78 (m, 3 H), 2.85 (t, J = 7.2 Hz, 2 H), 3.66 (quint, J = 6.0 Hz, 1 H), 7.16-7.29 (m, 5 H). ¹³C NMR (150 MHz, CDCl3): δ = 7.89, 23.2, 24.2, 24.7, 32.6, 33.0, 44.0, 66.8, 78.7, 126.4, 128.2, 128.5, 134.6, 140.3, 168.8, 208.5. IR (neat): 1706, 1643, 1082 cm-¹. MS (EI): m/z = 229 [M+ - CH(CH3)2]. HRMS-FAB: m/z calcd for C18H25O2 [M+ + H]: 273.1856; found: 273.1855. [α]D -6.7 (c 0.3, CHCl3, 80% ee). The enantiomeric purity of 20 [R¹ = Ph(CH2)2, R² =
i-Pr] was determined by HPLC analysis [Chiralpak OJ-H, hexane-i-PrOH (90:10), 1.0 mL/min, 254 nm] in comparison with authentic racemic material.