Radical addition to (2,3-epoxy-4-pentenyloxy)trialkylsilanes yielding α,β-unsaturated aldehydes via carbon-carbon bond cleavage

Article abstract of DOI:10.1055/s-2002-22718

Treatment of (2,3-epoxy-4-pentenyloxy)trialkylsilane with radical precursors such as triphenylgermane and α-halo carbonyl compounds in the presence of Et₃B yields α,β-unsaturated aldehydes. The reaction involves β-scission of a secondary alkoxy radical that releases a siloxymethyl radical.

Full text of DOI:10.1055/s-2002-22718

LETTER
569
Radical Addition to (2,3-Epoxy-4-pentenyloxy)trialkylsilanes Yielding
, -Unsaturated Aldehydes via Carbon-carbon Bond Cleavage
Radical
Additi
h
on to
(
2,3-E
p
i
oxy-4
n
o
)
trialkylsila
n
b
es u Tanaka, Tomoaki Nakamura, Hideki Yorimitsu, Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Fax +81(75)7534863; E-mail: oshima@fm1.kuic.kyoto-u.ac.jp
Received 1 February 2002
O
Abstract: Treatment of (2,3-epoxy-4-pentenyloxy)trialkylsilane
R
R1
OH
R2
with radical precursors such as triphenylgermane and -halo carbo-
nyl compounds in the presence of Et3B yields , -unsaturated alde-
hydes. The reaction involves -scission of a secondary alkoxy
radical that releases a siloxymethyl radical.
O
Et3B
O
1
+
Ph3Ge
R
Ph3GeH
2
R
3
Key words: radical reactions , -unsaturated aldehydes, carbon-
carbon bond cleavage, vinyloxirane, germanium compounds
OSi-t-BuMe2
O
Et3B
O
1a
Ph3Ge
+
H
Ph3GeH
4
Recently, we reported that radical addition of triphe-
nylgermane to vinyloxiranes 1 afforded the corresponding
ring opening products, 4-triphenylgermyl-2-buten-1-ol
derivatives 2, and that the allylic alcohols proved to be
good precursors of 4-vinyltetrahydro-2-furanones 3
(Scheme 1).1 During the course of this study, our interest
turned to the synthesis of santolinolide A.2 t-Butyldimeth-
yl(2,3-epoxy-4-pentenyloxy)silane (1a) seemed a promis-
ing precursor because it was anticipated that the reaction
of 1a with triphenylgermane would furnish allylic alcohol
2a. However, contrary to our expectations, similar
treatment1a of 1a (0.45 mmol) with triphenylgermane
(0.30 mmol) in the presence of triethylborane3 at ambient
temperature furnished , -unsaturated aldehyde 4 in 44%
yield instead of 2a. Here we wish to report the study of the
unusual formation of , -unsaturated aldehyde with con-
comitant loss of the siloxymethyl group.
O
OH
O
Ph3Ge
OSi-t-BuMe2
2a
Santolinolide A
Scheme 1
action of triphenylgermane with 1e yielded a trace of the
desired product (entry 4). Tri(2-furyl)germane5 was the
choice of a reagent when 1e was used as a radical acceptor
(entry 5). Benzenethiol was so reactive that 4-phenylthio-
substituted 2-butenals were obtained in high yields (en-
tries 6 and 7). The reactions of alkyl halides with these vi-
nyloxiranes provided the corresponding unsaturated
aldehydes in unsatisfactory yields (entries 8–16). The
alkyl groups were introduced at the 4 positions of the
enals. Reaction of diethyl bromomalonate (entries 15 and
16) was more efficient than that of 1-iodooctane. As
shown in Table 2, the reaction with 1a usually yielded E
isomers selectively, except for entries 8 and 10.
Reaction conditions were initially examined to optimize
yields of enal 4 (Table 1). Elevated temperatures resulted
in better yields (entries 2 and 3). Addition of triethylbo-
rane to a mixture of triphenylgermane and 1b in boiling
benzene afforded the desired aldehyde in 70% yield. The
reaction proceeded faster in toluene at reflux (2 h, 71%
yield, entry 4). The siloxy moiety of 1 was essential to
achieve satisfactory results. Benzyl 2,3-epoxy-4-pentenyl
ether (1c) was converted to 4 in 41% yield. Moreover,
treatment of benzoyl ester 1d gave rise to the formation of
allylic alcohol 5 as a major product in addition to 4.
The addition of triphenylgermane to vinyloxirane, t-butyl-
diphenyl(2,3-epoxy-4-pentenyloxy)silane (1f), was per-
formed to obtain mechanistic information through careful
analysis of the product distribution (Scheme 2). The reac-
tion afforded 0.18 mmol of enal 4 with concomitant pro-
The reaction of various radical precursors with 1a and me-
thyl-substituted 1e was investigated in benzene.4 The re-
sults are summarized in Table 2. A tris(trimethylsilyl)silyl
group was similarly introduced to yield 4-silyl-2-butenal
(entry 2). On the other hand, the reaction of tributyltin hy-
dride led to recovery of the starting material (entry 3). Re-
duction of
a similar amount of t-butyldiphenyl-
methoxysilane (9, 0.20 mmol). Moreover, aldehydes 10
and 11 that bear the t-butyldiphenylsiloxy groups were
isolated. The formation of 10 and 11 clearly indicates that
the siloxymethyl radical would exist as a key intermediate
(vide infra).
Synlett 2002, No. 4, 29 03 2002. Article Identifier:
1437-2096,E;2002,0,04,0569,0572,ftx,en;Y00802ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

570
S. Tanaka et al.
LETTER
Table 1 Optimization of Reaction Conditionsa
Entry
1
R
Et3B (mmol)
0.30
Time (h)
Solvent
hexane
Temp (°C)
Yield (%)
1
2
3
4
5
6
1a
1a
1b
1b
1c
1d
t-BuMe2Si
t-BuMe2Si
Ph2MeSi
Ph2MeSi
PhCH2
9
25
80
44
57
70
71
41
18c
0.30b
0.45
4.5
7.5
2
benzene
benzene
toluene
benzene
benzene
80
0.30
112
80
0.40
8.5
9
PhCO
0.48
80
a Triphenylgermane (0.30 mmol), 1 (0.45 mmol), and benzene (3 mL) were used.
b AIBN was used.
c Allylic alcohol 5 was obtained in 30% yield.
AIBN
OSi-t-BuPh2
+
Ph3GeH
The plausible mechanism is depicted in Scheme 3. A rad-
ical 12, derived by the action of the initiator, adds to 1f to
afford 13. Rapid ring opening led to oxygen-centered rad-
ical 14. -Scission of the alkoxy radical 14 generates , -
unsaturated aldehyde 4 and radical 15 that the siloxy
group stabilizes. The siloxymethyl radical abstracts hy-
drogen (or halogen) to form methoxysilane 9 (or halo-
methoxysilane 9 ) and 12. The radical chain thereby
continues. By-product 10 or 11 was formed when the
siloxymethyl radical 15 adds to 1f or 4, respectively.
O
benzene, reflux
(0.30 mmol)
1f (0.45 mmol)
Ph2t-BuSiO
O
O
H
Ph3Ge
Ph3Ge
H
4 (0.18 mmol)
10 (0.05 mmol)
O
Ph2t-BuSiOMe
Ph2t-BuSiO
H
9 (0.20 mmol)
Scheme 2
11 (0.07 mmol)
R
OSi
O
1f
13
R–H
or
R–X
O
R
12
R
OSi
14
CH3OSi
9
or
O
CH2OSi
XCH OSi
9 '
2
R
H
15
4
R–H or R–X
1f
O
SiO
+
15
O
SiO
H
R–H
10
R
11
H
Scheme 3
Synlett 2002, No. 4, 569–572 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Radical Addition to (2,3-Epoxy-4-pentenyloxy)trialkylsilanes
571
Table 2 Addition of Various Radical Precursorsa
Entry
1
1
R–H or R–X
Ph3GeH
(TMS)3SiH
n-Bu3SnH
Ph3GeH
Fu3GeHb
PhSH
Et3B (mmol)
0.20
Time (h)
3.5
10
Yield (%)
65
E/Z
1a
1a
1a
1e
1e
1a
1e
1a
1e
1a
1e
1a
1e
1a
1a
1e
> 95/5
> 95/5
–
2
0.20
60
3
0.20
8
N.R.
trace
89
4
0.40
3.5
1
–
5
0.10
65/35
> 95/5
78/22
43/57
58/42
75/25
72/28
> 95/5
90/10
> 95/5
> 95/5
> 95/5
6
0.10
5
70
7
PhSH
0.20
2.5
5.5
8.5
11
93
8
n-C8H17I
n-C8H17I
6c
0.30
22
9
0.40
27
10
11
12
13
14
15
16
0.20
21
6c
0.40
7
53
7d
0.30
7.5
3
28
7d
0.30
25
ICH2CN
8e
0.30
7.5
1.5
5.5
29
0.10
53
8e
0.20
42
a R-H or R-X (0.30 mmol), 1 (0.45 mmol), and benzene (3 mL) were used.
b Fu3GeH = Tri(2-furyl)germane.
c 6 = benzyl iodoacetate.
d 7 = N,N-dimethyl-2-iodoacetamide.
e 8 = diethyl bromomalonate.
Finally, the utility of the product 4 was investigated In summary, radical addition to (2,3-epoxy-4-penteny-
(Scheme 4). Treatment of 4 with (E)-1-dodecenyllithium loxy)trialkylsilanes afforded , -unsaturated aldehydes
in ether afforded dienyl alcohol 16 in 75% yield. The al- instead of the expected allylic alcohols. This reaction in-
lylic alcohol 16 was converted to conjugated triene 17 in volves -scission of secondary alkoxy radical after the
95% yield by the action of BF3 OEt2.6,7 Compound 4 thus ring opening of the oxirane. The siloxymethyl radical is a
behaves as a butadienyl cation equivalent.
suitable leaving group in the present reaction. Synthesis of
, -unsaturated aldehyde via an oxiranylcarbinyl radical
is rare,8 whereas preparation of alcohol, ether, and ketone
are rather common and frequently used in organic synthe-
sis.9,10
Li
O
n-C10H21
Ph3Ge
Ph3Ge
H
–78 °C, ether
4
OH
BF3•Et2O
Acknowledgement
n-C10H21
–78 °C, CH2Cl2
16
This work was supported by Grant-in Aid for Scientific Research
(Nos. 09450341 and 10208208) from the Ministry of Education,
Science, Sports and Culture, Government of Japan. T. N. and H. Y.
thank the JSPS Research Fellowship for Young Scientists.
n-C10H21
4 =
17
Scheme 4
Synlett 2002, No. 4, 569–572 ISSN 0936-5214 © Thieme Stuttgart · New York

572
S. Tanaka et al.
LETTER
Jpn. 2001, 74, 747; excellent reactivity of tri(2-
References
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(4) Experimental Procedure: Triphenylgermane (90 mg, 0.30
mmol) and t-butyldimethyl(2,3-epoxy-4-pentenyloxy)silane
(1a, 0.10 g, 0.45 mmol) were placed in a 50 mL reaction
flask. The mixture was set under argon with a toy ballon, and
benzene (3 mL) was introduced. A hexane solution of
triethylborane (1.0 M, 0.20 mL, 0.20 mmol) was added to the
reaction flask with stirring. The whole mixture was heated at
reflux for 3.5 h. TLC analysis indicated the completion of
the reaction. (In the case of the other radical precursors,
when the reaction did not finish, an additional triethylborane
was added and stirring continued at reflux.) Evaporation of
the solvent and following silica gel column purication with
hexane/AcOEt = 10/1 as an eluent provided 4-
(8) Release of acyl groups was observed in the literatures. The
fragmentation is less efficient and the yields of aldehydes
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fragmentation, see: (a) Robertson, J.; Burrows, J.
Tetrahedron Lett. 1994, 35, 3777. (b) Murphy, J. A.;
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(10) As far as radical addition to vinyloxirane as an initial step is
concerned, synthesis of alcohol was reported: (a) Kim, S.;
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(b) Dang, H.-S.; Roberts, B. P. Tetrahedron Lett. 1992, 33,
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triphenylgermyl-2-butenal (75 mg, 0.20 mmol, 65%). (E)-4-
Triphenylgermyl-2-butenal(4): IR(neat): 2924, 2855,
1682, 1462, 1377, 1092, 741, 700 cm–1; 1H NMR (CDCl3):
= 2.79 (d, J = 9.0 Hz, 2 H), 6.00 (dd, J = 15.3, 8.1 Hz, 1 H),
6.93 (dt, J = 15.0, 9.0 Hz, 1 H), 7.36–7.47 (m, 15 H), 9.30 (d,
J = 8.4 Hz, 1 H); 13C NMR (CDCl3): = 22.60, 128.58,
128.65, 129.65, 132.44, 134.80, 157.20, 193.43. Calcd for
C22H20GeO: 374.0730. Found: 374.0735.
(5) Tri(2-furyl)germane was prepared according to the
literature: (a) Nakamura, T.; Yorimitsu, H.; Shinokubo, H.;
Oshima, K. Synlett 1999, 1415. (b) Nakamura, T.;
Yorimitsu, H.; Shinokubo, H.; Oshima, K. Bull. Chem. Soc.
Synlett 2002, No. 4, 569–572 ISSN 0936-5214 © Thieme Stuttgart · New York