Y.-S. Hon, Y.-C. Wong / Tetrahedron Letters 46 (2005) 1365–1368
1367
1
,4-silyl
O
TBS
O
DBU-H
TBS
O
TBS
O
migration
R=PhCH2-
O
PhCH O
2
PhCH O
2
β
RO
O
8d
TBS
8e
α
H
H-DBU
OTBS
8
c
H
O
R=Ph-
β-elimination
O
R=PhCH - 8c
PhO
2
O
R=Ph- 9c
9g H
H-DBU
9c
H
PhOH 9f
Scheme 2.
ranged product 5e. Presumably, the a-proton acidity of
the alkyl-substituted aldehyde 5b is not strong enough to
be removed by Et N. Therefore, a stronger base such as
DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) is required,
and a-silyloxy ketone 5e was obtained in 71% yield (en-
try 2). The results of entries 1 and 2 imply that the ten-
dency of the a-deprotonation for the a-silyloxy aldehyde
tries 16 and 17) groups were comparable with tert-butyl-
dimethylsilyl group (entries 1–5). When the migratory
group was hydrogen, the rearranged products 21e and
22e were formed only in modest yields (entries 18 and
19).
3
In summary, the ozonolysis of substituted-allyl silyl
ethers or -allyl esters followed by treatment with bases
is a-substituent-dependent. Et N is good for a-aryl sub-
3
stituent and DBU is good for a-alkyl substituent. Once
deprotonation occurs, the subsequent 1,4-silyl migration
should be a facile process because no more a-silyloxy
aldehyde 5b was observed from the reaction. Increasing
the steric hindrance of the a-substituent of a-silyloxy
aldehydes also gave the rearranged products in high
yields (entries 3 and 4). However, for the tert-butyl
substituted aldehyde 7b, it needed to heat the reaction
mixture in CH Cl under refluxing for 60 h to give the
or Ph P afforded the corresponding a-silyloxy aldehydes
or a-acyloxy aldehydes intermediates, which could be
converted to the corresponding a-silyloxy ketones or
3
a-acyloxy ketones in good yields by base (Et N or
3
DBU) in the same flask. The reaction via a novel ene–
diol rearrangement is proposed. In addition, the trialkyl-
silyl, acetyl, trimethylacetyl, and benzoyl are suitable
groups for the 1,4-migration in the present synthesis.
Efforts to exploit this methodology in organic synthesis
are currently underway in our laboratory.
2
2
tert-butyldimethylsilyloxy ketone 7e in good yield (entry
).
4
Both the b-elimination and 1,4-silyl migration should be
the possible processes for the a-alkoxymethyl-substi-
tuted a-silyloxy aldehyde intermediates 8c and 9c, gener-
ated from the deprotonation of aldehydes 8b and 9b,
respectively (Scheme 2). We found that only 1,4-silyl
migration occurred for the a-benzyloxymethyl-substi-
tuted aldehyde 8c to give a-silyloxy ketone 8e in 84%
yield (entry 5). For the reaction of a-phenoxymethyl-
substituted aldehyde 9c, however, we isolated the phenol
Acknowledgements
We are grateful to the National Science Council,
National Chung Cheng University and Academia Sinica
for the financial support. We thank Professor Pi-Tai
Chou, Department of Chemistry, National Taiwan
University, for the theoretical calculation.
(
9f) resulted from the b-elimination (entry 6). The results
References and notes
of entries 5 and 6 indicate that any moiety with leaving
aptitude better than phenoxide can not be applied to the
1. (a) Hon, Y. S.; Lin, S. W.; Chen, Y. J. Synth. Commun.
1993, 23, 1543–1553; (b) Hon, Y. S.; Lin, S. W.; Lu, L.;
Chen, Y. J. Tetrahedron 1995, 51, 5019–5034.
1
,4-silyl migration purpose as shown in Scheme 2.
2
. (a) Hon, Y. S.; Lu, L. Tetrahedron Lett. 1993, 34, 5309–
The high yield of the aldehyde derived from terminal
alkene is crucial to the success of the present study. In
some cases, if the yield of the aldehyde from the ozonide
by base treatment (i.e. Conditions A and B in Table 1)
5312; (b) Hon, Y. S.; Yan, J. L. Tetrahedron Lett. 1993, 34,
6591–6594; (c) Hon, Y. S.; Yan, J. L. Tetrahedron Lett.
1994, 35, 1743–1746; (d) Hon, Y. S.; Lu, L. Tetrahedron
1995, 51, 7937–7942; (e) Hon, Y. S.; Yan, J. L. Tetrahedron
was not satisfactory, Ph P usually was an alternative re-
3
1997, 53, 5217–5232; (f) Hon, Y. S.; Yan, J. L. Tetrahedron
998, 54, 8525–8542; (g) Hon, Y. S.; Lu, L.; Chang, R. C.;
agent (i.e. conditions C and D) for this purpose. The
ozonolysis of a-(tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)
allyl silyl ether 10 followed by sequential treatment with
1
Lin, S. W.; Sun, P. P.; Lee, C. F. Tetrahedron 2000, 56,
9269–9279; (h) Hon, Y. S.; Wu, K. C. Tetrahedron 2003, 59,
493–498.
Ph P and DBU gave the rearranged product 10e in 56%
3
3
. Hon, Y. S.; Chang, C. P.; Wong, Y. C. Tetrahedron Lett.
2
yield. Even though in the presence of DBU, the reten-
tion of the C-4 configuration of the ribose ring of com-
004, 45, 3313–3315.
8
4. The typical procedure of this study is described as follows.
A two-necked flask fitted with a glass tube to admit ozone,
a CaCl2 drying tube and a magnetic stirring bar was
pound 10e was observed (entry 7). The success of this
reaction may open a new entry for the chain elongation
of the carbohydrates.
2 2
charged with terminal alkene 4 (1 mmol) in CH Cl (5 mL).
The flask was cooled to À78 °C and ozone was bubbled
through the solution. When the solution turned blue, ozone
addition was stopped. Nitrogen was passed through the
solution until the blue color was discharged. To the resulted
As for the aptitude of the migratory group in the ene–
diol rearrangement, we found that the acetyl (entries
8
–12), trimethylacetyl (entries 13–15) and benzoyl (en-