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H. Yu, H. Koshima / Tetrahedron Letters 44 (2003) 9209–9211
Table 1. Asymmetric alkylation of N-diphenylmethylene glycine t-butyl ester (1) on solid supportsa
Entry
RBr
Product
Condition
Method
Yieldb (%)
Eec (%)
Config.d
Support
Time (min)
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2b
2c
2a
2a
2a
2b
2c
3a
3a
3a
3a
3b
3c
3a
3a
3a
3b
3c
Kaolin
Mont-K10
Al2O3
Kaolin
Kaolin
Kaolin
Kaolin
Mont-K10
Al2O3
A
A
A
Ae
A
A
B
B
B
B
B
60
60
60
300
46
30
7
8
5
4
4
95
93
92
93
92
91
68
58
82
79
67
79
75
75
83
78
72
34
32
44
34
58
S
S
S
S
S
S
S
S
S
S
S
9
10
11
Al2O3
Al2O3
a Support loaded with KOH.7
b Isolated yield.
c The ee was determined by HPLC analysis using a chiral column (Chiralcel OD) with hexane/2-propanol as solvent.
d The absolute configuration was assigned by the HPLC retention times of both enantiomers determined previously.2,3b
e Reaction at −20°C. Others at room temperature.
In comparison, we made reexamination of usual liquid–
liquid PTC reaction according to the literature proce-
dure.3b The reaction of 1 (0.34 mmol) with 2a (0.38 mmol)
in the presence of catalyst 4 (0.034 mmol) in toluene (3
mL) and 50% KOH (0.7 mL) at room temperature gave
almost comparable results of 90% yield and 86% ee, but
required quite a long reaction time of 18 h for completion.
Acknowledgements
We are grateful to the Kurata Memorial Hitachi Science
and Technology Foundation for financial support.
Yields and enantioselectivities of products among kaolin,
montmorillonite K-10 and alumina were compared in the
reaction of 1 with 2a, a slightly better result was obtained
using kaolin (entries 1–3). Lowering the reaction temper-
atureto−20°Cslightlyincreasedtheenantioselectivitybut
prolonged the reaction time for 5 h (entry 4). With our
optimized reaction conditions in hand, other aralkyl
bromides 2b and 2c afforded similar good results (entries
5 and 6). These results showed that structural differences
among the three solid supports scarcely affected the
activity and enantioselectivity. Namely, the role of solid
supports for the rate enhancement is thought to be the
smooth and homogeneous dispersion of reactants and
products on the large surfaces by the help of CH2Cl2 as
a carrier. The supports could be recycled three times
without losing their activity by washing with CH2Cl2 and
evaporating all CH2Cl2 after the reaction.
References
1. (a) O’Donell, M. J. Aldrichim. Acta 2001, 34, 3–15; (b)
Najera, C. Synlett 2002, 1388–1403.
2. O’Donnell, M. J.; Bennett, W. D.; Wu, S. J. Am. Chem.
Soc. 1989, 111, 2353–2355.
3. (a) O’Donnell, M. J.; Wu, S.; Hoffman, C. Tetrahedron
1994, 50, 4507–4518; (b) Lygo, B.; Wainwright,
P. G. Tetrahedron Lett. 1997, 38, 8595–8598; (c) Corey,
E. J.; Xu, F.; Noe, M. C. J. Am. Chem. Soc. 1997,
119, 12414–12415; (d) Matsumoto, T.; Shioiri, T. Tetra-
hedron 1996, 52, 5961–5970; (e) Shibuguchi, T.; Fukuta,
Y.; Akachi, Y.; Sekine, A.; Ohshima, T.; Shibasaki, M.
Tetrahedron Lett. 2002, 43, 9539–9543; (f) Ooi, T.;
Kameda, M.; Maruoka, K. J. Am. Chem. Soc. 2003, 125,
5139–5151.
4. Ooi, T.; Tayama, E.; Doda, K.; Takeuchi, M.; Maruoka,
K. Synlett 2000, 1500–1502.
Finally, in order to attain further acceleration of the
reaction, microwave irradiation was applied for the
alkylation using the solid supports (Method B8b). The
reactions were dramatically accelerated and completed
within several minutes but unfortunately resulted in the
considerable decrease of enantioselectivities (entries 7–
11).
5. Okino, T.; Takemoto, Y. Org. Lett. 2001, 3, 1515–1517.
6. Varma, R. S. Tetrahedron 2002, 58, 1235–1255.
7. Support/KOH was prepared as follow: Support (alumina,
montmorillonite K-10 or kaolin clay) (3 g) was added to 4
mL of 25% KOH solution, and the mixture was sonicated
for a period of 4 h. The water was removed under reduced
pressure. The resultant solids were irradiated with
microwave for 15 min and ground to a powder.
In summary, we have discovered and explored that the
rapid asymmetric alkylation of glycine imine esters using
commercial available and low cost solid supports. The
reaction involves simple operations without any aqueous
work-up, mild conditions and provides high yields and
good enantioselectivities.
8. Typical procedure: (a) Method A: A solution of catalyst 4
(0.005 mmol), N-diphenylmethylene glycine t-butyl ester
(1) (0.05 mmol) and 2a (0.06 mmol) in CH2Cl2 (0.2 mL)
was dispersed on kaolin/KOH (0.5 g, 51 equiv. KOH to 1)
and the mixtures was stood on at room temperature for
appropriate time. After completion of the reaction (moni-