Preparation of siloxacyclopentene containing 1,3-dienes and their Diels-Alder reactions

Article abstract of DOI:10.1016/j.tetlet.2007.08.133

A number of enynyloxy dimethyl and diisopropyl silanes have been prepared and converted into siloxacyclopentene containing 1,3-dienes via intramolecular hydrosilylation of the alkyne functional group. Diels-Alder reactions of these dienes are reported.

Full text of DOI:10.1016/j.tetlet.2007.08.133

Tetrahedron Letters 48 (2007) 7853–7856
Preparation of siloxacyclopentene containing 1,3-dienes
and their Diels–Alder reactions
Ramakrishna R. Pidaparthi and Mark E. Welker*
Department of Chemistry, Wake Forest University, PO Box 7486, Winston-Salem, NC 27109, USA
Received 6 August 2007; revised 30 August 2007; accepted 30 August 2007
Available online 5 September 2007
Abstract—A number of enynyloxy dimethyl and diisopropyl silanes have been prepared and converted into siloxacyclopentene con-
taining 1,3-dienes via intramolecular hydrosilylation of the alkyne functional group. Diels–Alder reactions of these dienes are
reported.
ꢀ 2007 Elsevier Ltd. All rights reserved.
We have embarked on a synthetic program aimed at the
synthesis of stable 2-boron and 2-silicon substituted 1,3-
dienes and investigation of their reaction chemistry.1,2
Earlier this year, we reported the simple preparation
of 2-triethoxysilyl-1,3-butadiene and its conversion into
2-silatrane and 2-biscatecholsiloxy substituted 1,3-
dienes. Those new siloxy substituted dienes proved to
be remarkably reactive in Diels–Alder cycloadditon
reactions, and the Diels–Alder cycloadducts could be
used in Hiyama cross coupling reactions.2 Reports of
the preparation and use of 2-trialkoxysilyl-1,3-dienes
are extremely rare. We found a report of 2-trimethoxy-
silyl- and 2-triethoxysilyl-1,3-butadiene in 1984,3 and
then a report of the polymerization of these materials
in 1989.4
1,3-diene unit via a condensation/metathesis strategy
using alkenyl alcohols and alkynyl silanes.10 No Diels–
Alder or cross coupling reactions of these substrates
were reported. Earlier this year Halvorsen and Roush
reported using this procedure to make siloxacyclopent-
enes containing pendant dienophiles and demonstrated
that they could be used in intramolecular Diels–Alder
reactions, which were followed by protiodesilylation.11
We had simultaneously been using a combination of
the Tamao–Ito5 and Lee protocols12 to make siloxa-
cyclopentenes, which could participate in intermolecular
Diels–Alder reactions. Here, we report our preliminary
results in this area.
We first prepared several enynyl silanes (Scheme 1) in
excellent yields from pentenyne and tried to convert
them into siloxacyclopentene containing 1,3-dienes (4)
using Lee’s alkynylation–hydrosilylation sequence.12
Unfortunately, we recovered enynyl silanes (1–3) from
these reactions. We then switched to the preparation
of siloxy substituted enynes (7a, 7c–e) (prepared from
methylbutenyne (5a) and cyclohexenylethyne (5b) via
condensation with carbonyl compounds followed by
Denmark’s protocol),13 and converted them into siloxa-
cyclopentenes (8a, 8e, 10a, 10e) using Lee’s KOtBu
catalyzed trans-hydrosilylation protocol12 (Scheme 2).
Diisopropylsilyloxy substituted enynes (7a, 7c–e) could
be isolated and characterized prior to conversion to
siloxacyclopentenes (8a, 8e).
In 1988, Tamao, Ito, and co-workers reported the intra-
molecular hydrosilylation of the alkyne moiety of homo-
propargyl alcohols to make siloxacyclopentanes
containing exocyclic alkenes.5 Other routes to siloxa-
cycle containing species, which have been used in cross
coupling chemistry, have also been reported previ-
ously.6–8 In 2004, Clark and Woerpel reported the reac-
tion of a ‘tBu2Si’ source with a protected enynol to
produce a siloxacyclopentene containing a silicon substi-
tuent at the 1 position of a 1,3-diene moiety.9 This diene
reacted with N-phenylmaleimide in a Diels–Alder reac-
tion. Also in 2004, Lee and co-workers reported the
synthesis of a number of siloxacyles that are part of a
Dimethylsiloxy substituted enynes (9a, 9e) were gener-
ated in situ by using the Tamo–Ito protocol5 and then
converted into siloxacyclopentenes (10a, 10e), which
*
Corresponding author. Tel.: +1 336 758 5758; fax: +1 336 758
4321; e-mail: welker@wfu.edu
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.08.133

7854
R. R. Pidaparthi, M. E. Welker / Tetrahedron Letters 48 (2007) 7853–7856
O
H
H
n
1. BuLi
R1
R2
H
R1
10 mol% KOtBu
2. R1R2Si(H)Cl
Si
×
Si
H
THF
R2
O
4
1: R1, R2 = Me (94%)
2: R1 = Ph, R2 = Me (96%)
3: R1, R2 = iPr (89%)
Scheme 1. Synthesis of enynylsilanes (1–3).
a, b
c
d
H
OH
OSi(H)iPr2
R1
Si
R1
O
R2
7a-e
R2
5a-b
6a-f
8a,8e
H
OSi(H)iPr2
OH
Si
5a
6a (73%)
6b (94%)
7a (90%)
O
8a (72%)
11
OH
OH
OSi(H)iPr2
OSi(H)iPr2
10
12
13
5b
Ph
9
7c (74%)
7d (96%)
8
3
H
2
Si
4
O
6
7
5
1
6c (33%)
6d (63%)
8e (75%)
12
H
11
Si
OH
10
6
8
5
4
O
2
7
1
3
9
7e (53%)
OH
OH
6e (93%)
6f (97%)
Ph
Scheme 2. Synthesis of diisopropylsilyloxy substituted enynes (7a–e) and siloxacyclopentene containing 1,3-dienes (8a, 8e). Reagents and conditions:
(a) (i) THF, ꢀ78 ꢁC; (ii) nBuLi; (iii) ꢀ78 ꢁC ! 0 ꢁC, 1 h; (b) (i) 0 ꢁC ! ꢀ78 ꢁC; (ii) aldehyde/ketone; (iii) ꢀ78 ꢁC ! rt, overnight; (c) (i) hexanes, 0 ꢁC;
i
(ii) DMAP, NEt3; (iii) Pr2Si(H)Cl in hex, 10 min; (iv) 0 ꢁC rt, overnight; (d) (i) THF; (ii) water bath; (iii) KOtBu in THF; (iv) rt, 1 h.
were isolated and characterized (Scheme 3). All dienes
are stable for weeks at 25 ꢁC in the presence of air and
can be purified by chromatography on silica gel. Repre-
sentative experimental procedures for the preparation of

R. R. Pidaparthi, M. E. Welker / Tetrahedron Letters 48 (2007) 7853–7856
7855
b
a
H
OSi(H)Me2
OH
Si
O
6a, 6e
9a, 9e
10a,10e
9
5
8
7
3
H
4
H
2
Si
Si
O
O
6
1
10e (71%)
10a (70%)
Scheme 3. Synthesis (Tandem) of dimethylsiloxacyclopentene containing 1,3-dienes (10a, 10e). Reagents and conditions: (a) (i) water bath;
(ii) (Me2SiH)2NH (neat); (iii) rt, overnight; (b) (i) THF; (ii) water bath; (iii) KOtBu in THF; (iv) rt, 1 h.
O
O
O
H
H
H
H
THF, 90 °C
+
H
N Ph
H
N Ph
R
+
N
Ph
H
24 - 36 h
R
R
Si
Si
Si
R
O
R
O
O
R
O
O
O
8a, 10a
11a (Exo)
11b, 12 (Endo)
R = iPr (8a)
= Me (10a)
11a (40%)
11b (46%)
12 (88%)
----
Scheme 4. Intermolecular Diels–Alder reactions of diene-8a and 10a with N-phenylmaleimide.
all diene types reported are included in the reference sec-
tion.15–17
H
O
H
12
4
5
6
N7
5a
8a
16
i
3
8
With these dienes in hand, we have performed several
Diels–Alder reactions. Methyl substituted dienes 8a
and 10a both react completely with N-phenylmaleimide
after 24–36 h at 90 ꢁC (Scheme 4). The dimethylsiloxy
13
Pr
11
8b
9
Si
15
14
H
2
O
10
H
H
O
1
Endo adduct (11b) in C6D6 (other protons were not shown for clarity)
substituted diene (10a) provides endo adduct (12),
whereas the more bulky diisopropyl siloxy diene 8a pro-
vides exo and endo cycloadducts (11a and 11b, respec-
tively) in almost equal proportions. This outcome can
be rationalized by unfavorable steric interactions
between the N-phenyl and the isopropyl groups in the
electronically favored endo transition state. Cycloh-
exenyl substituted dienes 8e and 10e proved much less
reactive in thermal Diels–Alder reactions and only
started to show traces of Diels–Alder cycloadducts after
40–50 h of heating at 90 ꢁC. Halvorsen and Roush
found that siloxacyclopentene constrained nonatrienes
participated in thermal Diels–Alder reactions with little
stereoselectivity, whereas these substrates participated in
Lewis acid catalyzed intramolecular Diels–Alder reac-
tions through endo transition states to produce perhydro-
indene cycloadducts with high stereoselectivity.11 They
found that siloxacyclopentene constrained decatrienes
participated in thermal or Lewis acid-catalyzed cyclo-
additions through endo transition states to produce
octahydronaphthalenes with high stereoselectivity.
Scheme 5. Cycloadduct stereochemistry.
HMQC, and HMBC to make all the 1H assignments fol-
lowed by NOESY to assign stereochemistry. In the cis
isomers that arise from the endo transition states (11b,
12), one of the diastereotopic H5 protons exhibits
NOE to both H8a and H8b, whereas the other H5 does
not exhibit NOE to either of those protons (Scheme 5).
In summary, we have prepared a new diisopropylsiloxa-
cyclopentene containing 1,3-dienes via a simple three-step
procedure from enynes. We have prepared a new dimeth-
ylsililoxacyclopentene containing 1,3-dienes via a one
pot, two-step sequence from enynols. These dienes partic-
ipate in Diels–Alder reactions with a higher preference for
the production of trans cycloadducts from the sterically
more bulky diisopropylsiloxy substituted dienes.
Acknowledgements
The stereochemistry of the Diels–Alder cycloadducts 11
and 12 were assigned using a combination of COSY,
We thank the National Science Foundation for their
support of this work (CHE-0450722) and the NMR

7856
R. R. Pidaparthi, M. E. Welker / Tetrahedron Letters 48 (2007) 7853–7856
(3 · 5 mL) solution over a period of 10 min. After the
addition, the water bath was removed and stirring
continued for 1 h at room temperature. The reaction
mixture was diluted with Et2O (20 mL), followed by
quenching with satd NH4Cl (50 mL). The organic layer
was separated and the aqueous layer was extracted with
Et2O (3 · 20 mL). The combined organics were washed
with satd NaCl solution (50 mL) and dried over MgSO4.
After the removal of volatiles, the crude product was
purified by flash chromatography yielding 8e as a color-
less, clear liquid; Rf 0.45 (hexanes/Et2O, 15:2). The
isolated compound was found to have an impurity of
about ꢁ20% with a similar Rf value, hence the compound
was further purified by using a chromatotron (2.0 mm
silica gel) (0.537 g, 2.144 mmol, 75%). 1H NMR
(300 MHz, CDCl3) d 6.56 (s, 1H, H-4), 5.57 (s, 1H, H-
9), 4.61 (s, 2H, H-5), 2.17–2.26 (m, 2H, H-13), 2.03–2.16
(m, 2H, H-10), 1.64–1.75 (m, 2H, H-12), 1.52–1.64 (m, 2H,
H-11), 1.06–1.20 (m, 2H, H-6), 1.04 (d, J = 6.6 Hz, 6H, H-
7), 0.98 (d, J = 6.8 Hz, 6H, H-7); 13C NMR (300 MHz,
CDCl3) d 140.3 (C-3), 138.0 (C-4), 135.7 (C-8), 128.9 (C-
9), 72.8 (C-5), 26.2 (C-13), 26.0 (C-10), 22.8 (C-12), 22.4
(C-11), 17.4 (C-7), 17.1 (C-7), 13.4 (C-6); HRMS: (M+H)+
calcd for C15H27OSi, 251.1831; found, 251.1828.
instrumentation used to characterize the compounds re-
ported here. The Duke University Center for Mass Spec-
trometry and Mass Spectrometry Facility at UNC-CH
performed high-resolution mass spectral analysis. We
thank Dr. Marcus W. Wright for NMR assistance.
References and notes
1. De, S.; Welker, M. E. Org. Lett. 2005, 7, 2481.
2. Pidaparthi, R. R.; Welker, M. E.; Day, C. S.; Wright, M.
W. Org. Lett. 2007, 9, 1623.
3. Takenaka, K.; Hattori, T.; Hirao, A.; Nakahama, S.
Macromolecules 1989, 22, 1563.
4. Sato, F.; Uchiyama, H.; Samaddar, A. K. Chem. Ind.
1984, 20, 743.
5. Tamao, K.; Maeda, K.; Tanaka, T.; Ito, Y. Tetrahedron
Lett. 1988, 29, 6955.
6. Zacuto, M. J.; O’Mallaey, S. J.; Leighton, J. L. J. Am.
Chem. Soc. 2002, 124, 7890.
7. Trost, B. M.; Ball, Z. T.; Laemmerhold, K. M. J. Am.
Chem. Soc. 2005, 127, 10028.
8. Kim, Y. J.; Lee, D. Org. Lett. 2006, 8, 5219.
9. Clark, T. B.; Woerpel, K. A. J. Am. Chem. Soc. 2004, 126,
9522.
10. Miller, R. L.; Maifeld, S. V.; Lee, D. Org. Lett. 2004, 6,
2773.
17. Representative procedure for the synthesis (tandem) of
dimethylsiloxacyclodiene (10a): Alkenynol (6a) (1.792 g,
18.64 mmol) was taken into a 50 mL, round-bottomed
flask kept in a water bath under N2. After the slow
addition of 1,1,3,3-tetramethyldisilazane (1.504 g, 11.28
mmol) over ꢁ5 min using a syringe, the water bath
(23 ꢁC) was removed and stirring continued overnight at
room temperature. Then the volatiles were removed by
rotovap (30 ꢁC, 20 mm) and the crude reaction mixture
was dissolved in THF (10 mL), and the flask was cooled in
a water bath at ambient temperature. The flask was
purged with N2 for 2 min, then KOtBu (0.217 g,
1.934 mmol) was added in THF (3 · 5 mL) solution over
a period of 10 min. After the addition, the water bath was
removed and stirring continued for 1 h at room temper-
ature. The reaction mixture was diluted with Et2O
(20 mL), followed by quenching with satd NH4Cl
(50 mL). The organic layer was separated and the aqueous
layer was extracted with Et2O (3 · 20 mL). The combined
organics were washed with satd NaCl solution (50 mL),
dried over MgSO4 and the volatiles were removed by
rotovap. A brown colored crude reaction mixture was
produced, which upon purification by column chroma-
tography yielded 10a as a clear colorless oil (2.014 g,
11. Roush, W. R.; Halvorsen, G. T. Org. Lett. 2007, 9, 2243.
12. Maifeld, S. V.; Lee, D. Org. Lett. 2005, 7, 4995.
13. Denmark, S. E.; Pan, W. T. Org. Lett. 2001, 3, 61.
14. Hurley, A. L.; Welker, M. E.; Day, C. S. J. Organomet.
Chem. 2000, 598, 150.
15. Typical procedure for the synthesis of siloxyenynes (7e).
Alkenynol (6e)14 (1.236 g, 12.86 mmol), triethylamine
(1.30 g, 12.85 mmol), dimethylaminopyridine (0.152 g,
1.267 mmol), and diisopropylchlorosilane (1.918 g, 12.73
mmol) were used to yield compound 7e (1.680 g,
6.71 mmol, 53%) as a colorless, clear oily substance after
purification by flash chromatography: Rf 0.85 (hexanes/
Et2O, 4:1); 1H NMR (500 MHz, CDCl3) d 6.08 (h,
J = 1.8 Hz, 1H, H-5), 4.48 (s, 2H, H-1), 4.20 (s, 1H, H-
10), 1.98–2.17 (m, 4H, H6-9), 1.49–1.71 (m, 4H, H6-9),
0.96–1.12 (m, 14H, H-11, 12). 13C NMR (300 MHz,
CDCl3) d 134.8 (C-5), 120.3 (C-4), 87.1 (C-2/3), 84.4 (C-2/
3), 54.3 (C-1), 29.0 (C6-9), 25.6 (C6-9), 22.2 (C6-9), 21.5
(C6-9), 17.3 (C-12), 17.2 (C-12), 12.3 (C-11); HRMS:
(M+Na)+ calcd for C15H26NaOSi, 273.1651; found,
273.1639.
1
13.05 mmol, 70%): Rf 0.68 (pentane/Et2O, 3:1); H NMR
(500 MHz, CDCl3) d 6.60 (as, 1H, H-4), 4.99 (s, 1H, H-80),
4.82 (s, 1H, H-800), 4.66 (s, 2H, H-5), 1.93 (s, 3H, H-9),
0.33 (as, 6H, H-6); 13C NMR (300 MHz, CDCl3) d 142.2
(C-3), 141.3 (C-7), 141.2 (C-4), 115.7 (C-8), 71.9 (C-5),
20.4 (C-9), 0.45 (C-6); HRMS: (M+) calcd for C8H14OSi,
154.0814; found, 154.0813.
16. General procedure for diisopropylsiloxacyclodiene synthesis
(8e).
(3-Cyclohexenylprop-2-ynyloxy)diisopropylsilane
(7e) (0.715 g, 2.854 mmol) was taken into a 50 mL,
round-bottomed flask kept in a water bath at ambient
temperature. The flask was purged with N2 for 2 min, then
10 mol % KOtBu (0.037 g, 0.330 mmol) was added in THF