J. Hefner, P. Langer / Tetrahedron Letters 49 (2008) 4470–4472
4471
Me3SiO
OH O
OSiMe3
OMe
OH O
1) TiCl4
(2 equiv.)
OH O
H2
OMe
Me
OMe
1a
OMe
Pd/C
4Å MS
Me
Cl
+
(10 mol%)
Cl
Me
O
O
OH
OBn
CH2Cl2
MeOH
Cl
MeO
_
OMe
78
20 ºC
3g
4 (68%)
Me
TiCl4
O
3a (48%)
2) HCl (10%)
OH O
NaH (2.3 equiv.),
TBAI (cat.)
DMF
2a
Me3SiOH
HCl (10%)
OMe
Me
O
Me3SiO
O
Cl4Ti
MeO
5 (62%)
O
OMe
Scheme 3. Synthesis of tetrahydrobenzopyran 5.
Me
Me
Cl
OMe
tetrahydrobenzopyran 5 by debenzylation and subsequent Wil-
liamson reaction (Scheme 3). A number of related products were
successfully prepared.
A
D
1a
TiCl4
In conclusion, we have reported the first substrate-directed
domino ‘[3+3] cyclization/homo-Michael’ reaction of 1,3-bis(tri-
methylsilyloxy)-1,3-butadienes with 1,1-diacylcyclopropanes.
These reactions provide a convenient approach to highly function-
alized phenols, which are not readily available by other methods.
The regioselectivity can be explained by the Lewis acid-directing
effect of the alkoxy groups of the substrates. We believe that the
strategy outlined herein can be applied also to other annulation
reactions of 1,3-bis(silyl enol ethers).
Me3SiCl
2 Cl3TiOH
Cl3TiOH
O
Me3SiO
Me3SiO
O
O
OMe
OTiCl3
Me
+
O
OMe
TiCl4
Cl3Ti
MeO
O
Cl3Ti
MeO
Cl _
Me
C
B
Acknowledgment
Scheme 1. Possible mechanism of the formation of 3a.
Financial support by the State of Mecklenburg-Vorpommern is
gratefully acknowledged.
Me3SiO OSiMe3
OH O
R1
References and notes
R2
R1
TiX4
R2
1a-f
(2 equiv.)
1. Römpp Lexikon Naturstoffe; Steglich, W., Fugmann, B., Lang-Fugmann, S., Eds.;
Thieme: Stuttgart, 1997.
2. (a) Langer, P.; Bose, G. Angew. Chem., Int. Ed. 2003, 42, 4033; (b) Bose, G.;
Nguyen, V. T. H.; Ullah, E.; Lahiri, S.; Görls, H.; Langer, P. J. Org. Chem. 2004, 69,
9128.
3. For a review of [3+3] cyclizations, see: Feist, H.; Langer, P. Synthesis 2007, 327.
4. For a review of 1,3-bis(silyl enol ethers), see: Langer, P. Synthesis 2002, 441.
5. For reviews of chelation control in Lewis acid-mediated reactions, see: (a)
Yamamoto, H. Lewis Acid Chemistry; Oxford University Press: Oxford, 1999; (b)
Mahrwald, R. Chem. Rev. 1999, 99, 1095; (c) Santelli, M.; Pons, J. M. Lewis Acids
and Selectivity in Organic Synthesis; CRC Press: Boca Raton, 1996; (d)
Shambayati, S.; Schreiber, S. L. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 1, pp 283–324.
6. Chelation control has been reported for the [4+3] annulation reaction of
benzyloxy-substituted 1,4-dicarbonyl compounds with bis(silyl enol ethers):
Molander, G. A.; Eastwood, P. R. J. Org. Chem. 1996, 61, 1910.
+
R3
O
O
4Å MS
CH2Cl2
OR4
R4O
X
R3
_
78
20 ºC
3a-s
2a-d
Scheme 2. Synthesis of 3a–s.
Table 1
Products and yields
1
2
3
R1
R2
R3
R4
X
Yielda (%)
a
b
c
d
a
a
c
e
a
a
c
f
d
a
a
e
d
a
a
a
a
a
a
b
b
b
b
c
c
c
c
c
d
d
d
d
a
b
c
d
f
H
H
Me
Me
H
OMe
OEt
OMe
Et
OMe
OMe
OMe
OMe
OMe
OMe
OMe
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
Me
Me
Me
Me
Me
Bn
Bn
Bn
Bn
Me
Me
Me
Me
Me
Bn
Bn
Bn
Bn
Cl
Cl
Cl
Cl
Br
Cl
Cl
Cl
Br
Cl
Cl
Cl
Cl
Br
Cl
Cl
Cl
Br
44
38
30
30
46
40
44
41
79
63
48
33
36
49
40
64
33
52
7. Bruce, W. F.; Coover, H. W. J. Am. Chem. Soc. 1944, 66, 2092.
8. Typical procedure for the synthesis of diacylcyclopropanes 2a–d: To a DMSO
solution (100 mL) of methoxyacetylacetone (5.00 g, 38.5 mmol) and potassium
carbonate (15.90 g, 115.5 mmol) was added 1,2-dibromoethane (9.40 g,
50.0 mmol) dropwise. The mixture was stirred at 20 °C for 24 h. The mixture
was poured into water (400 mL), and the mixture was extracted with diethyl
ether (3 Â 100 mL). The combined organic layers were washed with water and
with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Vacuum
destillation (bp = 46 °C, 0.15 mbar) afforded 2a (2.41 g, 40%) as a yellowish oil.
1H NMR (300 MHz, CDCl3): d = 1.44 (m, 2H, CH2), 1.51 (m, 2H, CH2), 2.10 (s, 3H,
CH3), 3.38 (s, 3H, OCH3), 4.31 (s, 2H, CH2). 13C NMR (75.5 MHz, CDCl3): d = 17.4
(CH2), 26.3 (CH3), 41.0 (C), 59.1 (OCH3), 77.1 (CH2OCH3), 202.9, 203.6 (CO).
9. (a) Chan, T.-H.; Brownbridge, P. J. Am. Chem. Soc. 1980, 102, 3534; (b)
Brownbridge, P.; Chan, T.-H.; Brook, M. A.; Kang, G. J. Can. J. Chem. 1983, 61,
688.
10. Typical procedure for the synthesis of phenols 3a–s. To a CH2Cl2 solution (100 mL)
of 2a (156 mg, 1.0 mmol) and 1a (391 mg, 1.5 mmol) in the presence of
molecular sieves (4 Å, 1.00 g) was added TiCl4 (0.22 mL, 2.0 mmol) dropwise at
À78 °C under an argon atmosphere. The solution was allowed to warm to 20 °C
over 18 h with stirring and subsequently filtered. The filtrate was poured into
hydrochloric acid (10%, 100 mL) and the mixture was extracted with CH2Cl2
g
h
i
H
Me
Et
H
j
k
l
H
Me
H
Me
H
H
Et
Me
H
Ph
Ph
m
n
o
p
q
r
Et
Ph
OMe
OMe
OMe
Et
Ph
Ph
Ph
Ph
s
OMe
Ph
a
Yields of isolated products.