Table 2. Thermal and Lewis Acid Promoted Intramolecual Diels-Alder Cycloadditions of Trienes 7 and 10
product
yield (%)
a
ratiob
entry substrate
R
reaction conditions
products
c
1
2
3
4
5
6
7
8
7a
7b
7b
7b
7c
7c
7d
7d
-H
(1) 180 °C, 24 h; (2) TBAF, THF, 60 °C, 1.5 h
75
81
0
3a:4a
3b:4b
<1:20
1:1
c
-CO2Me
-CO2Me
-CO2Me
-CHO
-CHO
-COMe
-COMe
(1) 140 °C, 20 h; (2) TBAF, THF, 60 °C, 1.5 h
d
MeAlCl2, -78 to 23 °C, 16 h
e
SnCl4, -78 to 23 °C, 16 h
0
c
2.5:1f
(1) 100 °C, 20 h; (2) TBAF, THF, 12 h
60
55
85
75
3c:4c
3c:4c
3d:4d
3d:4d
d
f
(1) MeAlCl2, -78 to -20 °C, 3 h; (2) TBAF, THF, 12 h
>20:1
c
(1) 100 °C, 20 h; (2) TBAF, THF, 60 °C, 1.5 h
2:1
94:6
d
(1) MeAlCl2, CH2Cl2, -78 to -20 °C, 3 h;
(
2) TBAF, THF, 60 °C, 1.5 h
c
9
0
1
2
3
4
5
6
7
7e
-CH(-OCH2CH2O-) (1) 160 °C, 36 h; (2) TBAF, THF, 60 °C, 1.5 h
74
65
92
0
3e:4e
5a:6a
5b:6b
<1:20
1.25:1
>20:1
c
1
1
1
1
1
1
1
1
10a
10b
10b
10b
10c
10c
10d
10d
-H
(1) 190 °C, 72 h; (2) TBAF, THF, 60 °C, 1.5 h
c
-CO2Me
-CO2Me
-CO2Me
-CHO
-CHO
-COMe
-COMe
(1) 140 °C, 20 h; (2) TBAF, THF, 60 °C, 1.5 h
d
MeAlCl2, -78 to 23 °C, 16 h
e
SnCl4, -78 to 23 °C, 16 h
0
c
f
(1) 120 °C, 24 h; (2) TBAF, THF, 12 h
57
55
93
60
5c:6c
5c:6c
5d:6d
5d:6d
>20:1
>20:1
d
f
(1) MeAlCl2, -78 to -20 °C, 6 h; (2) TBAF, THF, 12 h
c
(1) 120 °C, 24 h; (2) TBAF, THF, 60 °C, 1.5 h
97:3
>20:1
d
(1) MeAlCl2, -78 to 0 °C, 6 h;
(
2) TBAF, THF, 60 °C, 1.5 h
c
18
10e
-CH(-OCH2CH2O-) (1) 190 °C, 72 h; (2) TBAF, THF, 60 °C, 1.5 h
57
5e:6e
1.8:1
a
b
1
Combined yield of products after purification by silica gel chromatography. Product ratios determined by H NMR analysis of crude reaction mixtures
prior to protiodesilylation. 0.03-0.05 M PhMe solution in a sealed tube. 0.01 M solution in CH2Cl2 with 1.0 equiv of MeAlCl2. e 0.01 M solution in
c
d
f
CH2Cl2 with 0.2 equiv of SnCl4. Ca. 10% epimerization R to the aldehyde ocurred during protiodesilation and chromatography. Stereostructures were
1
assigned by H NOESY and J data (see the Supporting Information).
Results of the intramolecular Diels-Alder reactions of
trienes 7 and 10 are summarized in Table 2. Thermal
cycloadditions were performed at the indicated reaction tem-
peratures in toluene (0.03 to 0.05 M) in a sealed tube. Lewis
(0.01 M). A solution of the Lewis acid was added via syringe
to the solution of triene at -78 °C, then the solution was
warmed to the final reaction temperature. In both cases, the
crude cycloadducts were immediately subjected to protio-
desilylation by treatment with TBAF (typically in THF at
2 2
acid promoted cycloadditions were carried out in CH Cl
19
6
0 °C) to aid in product isolation and purification. Stereo-
(12) (a) Vanderwal, C. D.; Vosburg, D. A.; Weiler, S.; Sorensen, E. J.
1
chemistry of the cycloadducts was assigned by using H
NOSEY and J data (see the Supporting Information).
The thermal cyclization of unactivated triene 7a gave cis-
fused cycloadduct 4a with g20:1 selectivity (entry 1). This
result suggests that the siloxacyclopentene unit destabilizes
the trans-fused transition state B, since it is known that
thermal cycloadditions of conformationally unconstrained,
unactivated nonatrienes provide the cis-fused cyloadducts
Org. Lett. 1999, 1, 645. (b) Armstrong, A.; Goldberg, F. W.; Sandham, D.
A. Tetrahedron Lett. 2001, 42, 4585. (c) Vanderwal, C. D.; Vosburg, D.
A.; Sorensen, E. J. Org. Lett. 2001, 3, 4307. (d) Clarke, P. A.; Davie, R.
L.; Peace, S. Tetrahedron Lett. 2002, 43, 2753. (e) Suzuki, T.; Nakada, M.
Tetrahedron Lett. 2002, 43, 3263. (f) Methot, J. L.; Roush, W. R. Org.
Lett. 2003, 5, 4223. (g) Suzuki, T.; Tanaka, N.; Matsumura, T.; Hosoya,
Y.; Nakada, M. Tetrahedron Lett. 2006, 47, 1593.
(
13) (a) Vosburg, D. A.; Vanderwal, C. D.; Sorensen, E. J. J. Am. Chem.
Soc. 2002, 124, 4552. (b) Evans, D. A.; Starr, J. T. Angew. Chem., Int. Ed.
002, 41, 1787. (c) Vanderwal, C. D.; Vosburg, D. A.; Weiler, S.; Sorensen,
E. J. J. Am. Chem. Soc. 2003, 125, 5393.
14) (a) Zacuto, M. J.; O’Malley, S. J.; Leighton, J. L. J. Am. Chem.
Soc. 2002, 124, 7890. (b) Clark, T. B.; Woerpel, K. A. J. Am. Chem. Soc.
2
2
0
with ca. 2-3:1 selectivity.
(
The high intrinsic selectivity preference for the cis-ring
fusion exhibited in the IMDA reaction of 7a proved difficult
to overcome, as thermal cycloaddition of terminally activated
trienes 7b-d proved to be unselective (entries 2, 5, and 7).
Thermal IMDA reactions of trienes analogous to 7b-d but
lacking the siloxacyclopentane unit generally display useful
2
004, 126, 9522. (c) Miller, R. L.; Maifeld, S. V.; Lee, D. Org. Lett. 2004,
6
, 2773. (d) Trost, B. M.; Ball, Z. T.; Laemmerhold, K. M. J. Am. Chem.
Soc. 2005, 127, 10028. (e) Maifeld, S. V.; Lee, D. Org. Lett. 2005, 7, 4995.
(
15) Tidwell, T. T. Org. React. 1990, 39, 297.
(16) (a) Grubbs, R. H. Tetrahedron 2004, 60, 7117. (b) Thiel, O. R. In
Transition Metals for Organic Synthesis, 2nd ed.; Beller, M., Bolm, C.,
Eds.; Wiley-VCH Verlag: Weinheim, Germany, 2004; Vol. 1, p 321. (c)
Connon, S. J.; Blechert, S. Angew. Chem., Int. Ed. 2003, 42, 1900.
(
17) Cossy, J.; BouzBouz, S.; Hoveyda, A. H. J. Organomet. Chem. 2001,
6
24, 327.
(19) The siloxacyclopentane units of some of the IMDA cycloadducts
proved unstable to silica gel chromatography.
(20) (a) Oppolzer, W.; Fehr, C.; Warneke, J. HelV. Chim. Acta 1977,
60, 48. (b) Lin, Y.-T.; Houk, K. N. Tetrahedron Lett. 1985, 26, 2269.
(
18) Product yields in the absence of benzoquinone were typically <65%.
For the use of quinones in metathesis see: Hong, S. H.; Sanders, D. P.;
Lee, C. W.; Grubbs, R. H. J. Am. Chem. Soc. 2005, 127, 17160.
Org. Lett., Vol. 9, No. 11, 2007
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