1688
H. Li et al. / Tetrahedron Letters 49 (2008) 1686–1689
Table 3
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126.
Asymmetric addition of phenylacetylene to aldehydes promoted by ligand
3aa,b
O
H
OH
Ligand 3a
Et2Zn
+
Ph
R
R
H
Ph
Entry
R
Yieldc (%)
eed (%)
1
2
3
4
5
6
7
8
9
Ph
99
99
92
99
88
96
84
99
93
75
99
65
95
84
92
90
90
89
83
89
81
88
85
84
88
84
89
54
o-Me–Ph
m-Me–Ph
p-Cl–Ph
m-MeO–Ph
p-MeO–Ph
o-F–Ph
m-F–Ph
p-F–Ph
10
11
12
13
14
a
m-CF3-Ph
p-CF3-Ph
3,5-2Cl–Ph
1-Naphthyl
Cyclohexyl
Phenylacetylene/Et2Zn/aldehyde/ligand = 2.0:2.0:1:0.1; 1 mL toluene,
rt, 16 h.
b
All reactions were performed under argon and at room temperature.
Isolated yield.
The ee values were determined by HPLC on a Chiracel OD-H column.
c
d
Under the optimized reaction conditions (Table 2, entry
11), ligand 3a was successfully employed to catalyze the
asymmetric addition of phenylacetylene to aldehydes. As
can be seen from the summarized results (Table 3), this
method was highly efficient for all of aromatic aldehydes
studied; the propargylic alcohols were obtained with 81–
92% ee and up to 99% yield (Table 3, entries 1–13). More-
over, 54% ee for cyclohexanecarboxaldehyde was provided
(Table 3, entry 14).
In summary, a class of new chiral Tf-based SAA ligands
has been conveniently synthesized from commercially
available starting materials in two simple steps. Tf-based
SAA 3a is a highly enantioselective and extensively practi-
cal ligand for the enantioselective alkynylation of aromatic
aldehydes in the absence of Ti(O–iPr)4 at room tempera-
ture. Comparing our Ts-based SAA for this reaction of
up to 84% ee,9b it provides a more effective practical
method to produce chiral propargyl alcohols. Studies are
currently underway to apply these ligands to other enantio-
selective catalytic reactions.
10. Pritchett, S.; Gantzel, P.; Walsh, P. J. Organometallics 1997, 16, 5130.
11. Typical procedure for the preparation of Tf-based sulfamide-amine
alcohols (3a): The aziridines were synthesized according to the
literature.13 Triflic anhydride (3.6 mL, 22 mmol) was added dropwise
over 1 h to a solution of (R)-phenylglycinol (1.37 g, 10 mmol) and
triethylamine (2.8 mL, 20 mmol) in dry dichloromethane (40 mL)
under argon at ꢀ78°C, then the mixture was kept at ꢀ30 °C
overnight. The reaction mixture was washed twice with chilled
(0 °C) 0.1 M HCl and twice with chilled saturated aqueous Na2CO3.
The organic phase was dried (MgSO4). Without purification, the
solution was added dropwise to a solution of (ꢀ)-ephedrine (1.65 g,
8 mmol) in acetonitrile at 0 °C. The resulting mixture was stirred
overnight at room temperature followed by 3 days at 40 °C, and the
acetonitrile was evaporated. The residue was purified by column
chromatography to give the pure ligand 3a: white solid, 42% yield;
Acknowledgement
Financial support from the National Basic Research Pro-
gram of China (2003CB114402) is gratefully acknowledged.
27
mp: 141–142 °C; ½aꢁD ꢀ42.26 (c 1.7, CHCl3); 1H NMR (CDCl3): d
0.61 (d, J = 6.4 Hz, 3H), 2.21 (s, 3H), 3.06 (dd, J = 6.4 and 12.8 Hz,
1H), 3.34 (dd, J = 4.8 and 9.6 Hz, 1H), 3.42–3.47 (m, 1H), 3.67 (dd,
J = 4.8 and 10.0 Hz, 1H), 3.96 (s, 2H), 4.57 (d, J = 6.0 Hz, 1H), 7.08–
7.10 (m, 2H), 7.24–7.40 (m, 8H); 13C NMR (CDCl3): d 11.48, 36.10,
44.90, 57.48, 66.82, 76.82, 119.91 (q, JCF = 320 Hz), 126.61, 128.02,
128.37, 128.61, 128.82, 137.16, 142.72; HRMS Calculated for
C19H24N2O3F3S [M+H]+ 417.1460, found: 417.1466.
References and notes
1. (a) Catalytic Asymmetric Synthesis; Ojima, I., Ed., 2nd ed.; Wiley:
New York, 2000; (b) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H.
Comprehensive Asymmetric Catalysis; Springer: Heidelberg, 1999.