194
Z. E. D. Cele et al. / Tetrahedron: Asymmetry 24 (2013) 191–195
complex compared to Mg(OTf)2.27 The reaction shown in Scheme 2,
proceeded smoothly in excellent yield and with moderate ee using
L2-Cu(OTf)2 complex at 0.2 mol % catalyst loading to hinder the
Mukaiyama aldol reaction.
at room temperature for 30 min. The reaction mixture was cooled
to 0 °C and dimethyl malonate (0.12 mmol, 14 L) was added, after
l
which the reaction mixture was stirred at 0 °C for 8 h while being
monitored by TLC. The solvents were evaporated under reduced
pressure and the residue was purified through column chromatog-
raphy (hexane/ethyl acetate = 4:1) to afford the pure conjugated
product as a yellow oil in 95% yield. The enantioselectivity was
determined by chiral HPLC (Chiralpak IA, hexane/i-PrOH = 80/10,
flow rate 1.0 mL/min, k = 254 nm).
OH
OMe
O
L2
(0.2 mol%)
Cu(OTf)2 (0.2 mol%)
OMe
Ph
∗
H
+
Ph
CH2Cl2, 30 °C
4Å M.S., 2 h
O
O
4.4. Typical procedure for the catalytic asymmetric hetero-ene
reaction of glyoxal with 2-methoxypropene
6
8
7
yield = 95%, ee = 77%
A mixture of 100 lL (0.002 mmol) of catalyst solution (0.002 M
Scheme 2. Catalytic asymmetric hetero ene reaction of glyoxal with 2-
Cu(OTf)2-L2 in CH2Cl2), phenylglyoxal (0.1 mmol), and 3 Å MS
(50 mg) was stirred at 30 °C for 30 min. Then, 2-methoxypropene
(1.25 equiv) was added at room temperature under nitrogen. The
reaction mixture was then allowed to reflux for 2 h while being
monitored by TLC and was directly purified by column chromatog-
raphy on silica gel (ethyl acetate/hexane = 1:10). The pure ene
product was obtained in 90% yield as a colorless liquid. The enanti-
oselectivity was determined by chiral HPLC using a DAICEL CHI-
RALCEL AS-H column, 2-propanol/n-hexane = 10/80, flow
rate = 0.8 mL/min, k = 254 nm.
methoxypropene.
3. Conclusion
We have demonstrated the use of C2-symmetric TIQ-N0N-diox-
ides as efficient ligands for C–C bond forming reactions. High yields
(up to 95%), moderate enantioselectivities (up to 89% ee), a broad
range of substrates, and mild reaction conditions demonstrate
the potential of this catalytic system for other asymmetric trans-
formations. The choice of solvent also played an important role
in the selectivity of these reactions with dichloromethane being
the most efficient for all three of the C–C bond forming reactions
reported herein. The Michael addition reaction of ketoesters with
cyclohexane1,3-dione (Tables 1 and 2) and malonate (Table 3) re-
quired 2 and 5 mol % catalytic loading, respectively, to achieve the
best results. The benchmark hetero-ene reaction proceeded
smoothly with relatively low catalyst loading (0.2 mol %) allowing
us to avoid the Mukaiyama product. A comparative study of our
TIQ-N0N-dioxide with Fengfs bis N-oxide ligands demonstrated
complementarity in their behavior, however our system did not
achieve equivalent yields and selectivities. Further studies of the
application of this catalyst to other reactions are currently ongoing
in our laboratory.
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A solution of ligand L2 (3.8 mg, 0.005 mmol), Y(OTf)3 (2.68 mg,
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0.10 mmol) in anhydrous dichloromethane (0.2 mL) was stirred
c
a