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DOI: 10.1055/s-0029-1217823
Chiral Acid-Catalyzed Asymmetric Nazarov Reaction: Nucleophilic Construction of a Quaternary Asymmetric Center at the α-Position of the Keto Function
Publikationsverlauf
Publikationsdatum:
17. August 2009 (online)

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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References and Notes
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.