Ring-opening iodo- and bromosilation of lactones for the formation of silyl haloalkanoates

Article abstract of DOI:10.1021/jo011153n

Ring-opening halosilation of lactones with two types of reagents, Et₃SiH/MeI(PdCl₂) (1a) and Et₃SiH/AllylBr(PdCl₂) (1b), was studied. Cyclic esters such as γ-butyrolactones, δ-valerolactone, and 6-hexanolide reacted with 1 equiv of 1a,b to give triethylsilyl ω-iodo- and ω-bromoalkanoates in good yields. Reaction of an acyclic ester, methyl benzoate, with 1a afforded triethylsilyl benzoate. O-Silyl-protected amino acids could be obtained by amination of the halosilation products, triethylsilyl ω-bromoalkanoates.

Full text of DOI:10.1021/jo011153n

J . Org. Chem. 2002, 67, 3927-3929
3927
fording siloxyethyl enol ethers,8 while the reaction of
acyclic esters produces trimethylsilyl alkanoates with the
liberation of iodoalkanes.4
Rin g-Op en in g Iod o- a n d Br om osila tion of
La cton es for th e F or m a tion of Silyl
Ha loa lk a n oa tes
To extend more the utility of these reagents, we
examined the reactions of cyclic esters. In this paper, we
describe the ring-opening halosilation of five- to seven-
membered lactones with the reagent R′3SiH/RX (PdCl2),
which produces triethylsilyl ω-haloalkanoates in good
yields. The products thus obtained may be potentially
useful starting material for O-silyl-protected amino acids.
Table 1 summarizes the results of ring-opening iodo-
and bromosilation of lactones with the use of reagents
Et3SiH/MeI(PdCl2) (1a ) and Et3SiH/AllylBr(PdCl2) (1b).
Thus, when γ-butyrolactone was treated with 1 equiv of
Et3SiH and 1.7 equiv of MeI in the presence of a catalytic
amount of PdCl2 (reagent 1a ), triethylsilyl 4-iodobu-
tanoate (2a ) was obtained in 68% isolated yield. In this
reaction, a small amount of a hydrosilation product,
triethylsilyl butanoate, was detected by GC/MS analysis,
although γ-butyrolactone did not react with Et3SiH alone,
in the presence of the PdCl2 catalyst. When AllylBr was
used (reagent 1b) instead of MeI in 1a , bromosilation of
γ-butyrolactone occurred to give triethylsilyl 4-bromobu-
tanoate (2b) in 74% yield. No hydrosilation product was
found to be formed in this reaction. Previously, we
reported that the reagent consisting of a mixture of Me3-
SiNEt2/2RX (RX ) MeI, AllylBr) reacts readily with cyclic
ethers to give halosilation products. However, interaction
of γ-butyrolactone with this reagent, Me3SiNEt2/2RX,
gave no ring-opened product, but the starting lactone was
recovered unchanged.
The present method could be applied also to ring-
opening iodo- and bromosilation of six- and seven-
membered lactones as shown in Table 1. Heating a
mixture of δ-valerolactone and 1a at 80-90 °C for 5 h
gave triethylsilyl 5-iodopentanoate (3a ) in 88% yield as
the sole volatile product. Bromosilation of δ-valerolactone
with 1b gave triethylsilyl 5-bromopentanoate (3b) in 79%
yield. 6-Hexanolide also underwent halosilation with 1a
and 1b to give triethylsilyl 6-iodohexanoate (4a ) and
triethylsilyl 6-bromohexanoate (4b), respectively, in good
yields.
Similar iodosilation of γ-valerolactone with 1a pro-
ceeded again smoothly to afford triethylsilyl 4-iodopen-
tanoate (5a ) in 87% yield. In contrast, the reaction of
γ-valerolactone with 1b gave a mixture of the starting
lactone and bromotriethylsilane, without any formation
of bromosilation products. The reaction of γ-ethyl-γ-
butyrolactone with 1a produced a 1:1 isomeric mixture
of triethylsilyl 4-iodohexanoate (6a ) and triethylsilyl
5-iodohexanoate (6a ′) in 60% combined yield, while
similar reaction of δ-methyl-δ-valerolactone gave 6a ′ as
the sole product. A likely mechanism for the formation
of 6a ′ from γ-ethyl-γ-butyrolactone is given in Scheme
1. Interaction of the starting γ-lactone with PdCl2 leads
to isomerization to δ-lactone via a Pd(II)-coordinated
unsaturated intermediate, and thus, 6a ′ is formed com-
petitively.9 Similar ring-opening isomerization of lactones
Arihiro Iwata, J oji Ohshita, Heqing Tang, and
Atsutaka Kunai*
Department of Applied Chemistry, Graduate School of
Engineering, Hiroshima University, Higashi-Hiroshima
739-8527, J apan
Yasushi Yamamoto and Chinami Matui
Silicone-Electronic Materials Research Center, Shin-Etsu
Chemical Co., Ltd., 1-10 Hitomi, Matsuida, Gunma
379-0224, J apan
akunai@hiroshima-u.ac.jp
Received December 19, 2001
Abstr a ct: Ring-opening halosilation of lactones with two
types of reagents, Et3SiH/MeI(PdCl2) (1a ) and Et3SiH/
AllylBr(PdCl2) (1b), was studied. Cyclic esters such as
γ-butyrolactones, δ-valerolactone, and 6-hexanolide reacted
with 1 equiv of 1a ,b to give triethylsilyl ω-iodo- and
ω-bromoalkanoates in good yields. Reaction of an acyclic
ester, methyl benzoate, with 1a afforded triethylsilyl ben-
zoate. O-Silyl-protected amino acids could be obtained by
amination of the halosilation products, triethylsilyl ω-bro-
moalkanoates.
Iodo- and bromosilanes play an important role in
synthetic organic chemistry.1 However, iodo- and bro-
mosilanes have a strong tendency to undergo hydrolytic
cleavage of silicon-halogen bonds even with atmospheric
moisture giving silanols, unless the silicon center is
protected with sterically bulky substituent(s),2 and there-
fore, iodo- and bromosilanes must be handled with special
care, compared with chloro- and fluorosilanes.
Recently, we found two types of reagents that can be
used conveniently as the synthetic equivalents of iodo-
and bromosilanes. One involves a 1:2 mixture of diethyl-
aminotrimethylsilane and methyl iodide or allyl bromide
(Me3SiNEt2/2RX, RX ) MeI, AllylBr),3-5 while the other
comprises 1:1 mixtures of hydrosilanes with methyl
iodide or allyl bromide and a catalytic amount of pal-
ladium dichloride (R′3SiH/RX(PdCl2), R′3 ) Et3, PhMe2,
Ph2Me, RX ) MeI, AllylBr).6 Both types of the reagents
react readily with cyclic ethers, such as tetrahydrofuran
and tetrahydropyran, giving ring-opening halosilation
products, R-halo-ω-siloxyalkanes.7 With the reagent Me3-
SiNEt2/RI, the dioxolane rings of cycloalkanone ethylene
acetals also undergo the ring-opening halosilation af-
* To whom correspondence should be addressed.
(1) Larson, G. L. In The Chemistry of Organic Silicon Compounds;
Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1989; Part 1, Chapter
11.
(2) Walsh, R. In The Chemistry of Organic Silicon Compounds;
Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1989; Part 1, Chapter
5.
(3) Yamamoto, Y.; Shimizu, H.; Matui, C.; Chinda, M. Main Group
Chem. 1996, 1, 409.
(4) Yamamoto, Y.; Shimizu, H.; Hamada, Y. J . Organomet. Chem.
1996, 509, 119.
(5) Yamamoto, Y.; Matui, C. Organometallics 1997, 16, 2204.
(6) Kunai, A.; Sakurai, T.; Toyoda, E.; Ishikawa, M. Organometallics
1994, 13, 3233.
(7) Ohshita, J .; Iwata, A.; Kanetani, F.; Kunai, A.; Yamamoto, Y.;
Matui, C. J . Org. Chem. 1999, 64, 8024.
(8) Ohshita, J .; Iwata, A.; Tang, H.-q.; Yamamoto, Y.; Matui, C.;
Kunai, A. C. Chem. Lett. 2001, 740.
10.1021/jo011153n CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/26/2002

3928 J . Org. Chem., Vol. 67, No. 11, 2002
Ta ble 1. Rin g-Op en in g Ha losila tion of La cton e w ith Rea gen t 1 a t 80-90 °Ca
Notes
a
Reactions were carried out without solvent, using 1a (Et3SiH/MeI(PdCl2)), 1a ′ (Et3SiH/MeI(Pd(acac)2/dppe)), and 1b (Et3SiH/
AllylBr(PdCl2)). At room temperature. c The reaction mixture was further treated with 1 equiv of Et3SiH for 5 h.
b
Sch em e 1
volatile product in a higher yield (82%). In a separate
experiment, Et3SiI reacted with γ-ethyl-γ-butyrolactone
to give 6a in 68% yield, without the formation of 6a ′.
These facts seem to indicate that Et3SiI is concerned as
the active species in the present reaction with reagent
1a ′. However, it is uncertain whether the increased yield
(82%) of 6a with the used of 1a ′, compared to the use of
Et3SiI alone (68%), arises partially from the formation
of a homogeneous complex of Pd(L2) and iodosilane, as
suggested previously.7 γ-Phenyl-γ-butyrolactone did not
react with 1a nor 1b at 80-90 °C, although iodo- and
bromotriethylsilane were found to be formed. Carrying
out the reactions at higher temperature (100-110 °C) led
to the formation of complex mixtures, from which no
major products were isolated.
in the presence of a PdCl2 catalyst has been reported
previously.10 In contrast to this, when Pd(acac)2/dppe was
used (reagent 1a ′) as the catalyst, iodosilation of γ-ethyl-
γ-butyrolactone occurred selectively to give 6a as the sole
(9) However, the fact that no isomerization products would be
observed in the reactions of γ-valerolactone and δ-methyl-δ-valerolac-
tone with reagent 1a indicates that such isomerization seems unfavor-
able when the lactones have a methyl group as the substituent,
probably because a less stable terminal double bond is involved in the
intermediate.
Attempted iodosilation of unsaturated lactones, such
as R-angelicalactone and 2-furanone with 1a was unsuc-
(10) Noels, A. F.; Herman, J . J .; Teyssie, P. J . Org. Chem. 1976, 15,
2527.

Notes
J . Org. Chem., Vol. 67, No. 11, 2002 3929
Sch em e 2
Exp er im en ta l Section
Reactions were carried out under an atmosphere of dry argon.
Representative procedures for the reactions of lactones and
methyl benzoate with reagent 1a and amination of the halosi-
lation products are as follows.
Rea ction of γ-Bu tyr ola cton e w ith 1a . A mixture of tri-
ethylsilane (1.85 g, 15.9 mmol), γ-butyrolactone (1.35 g, 15.7
mmol), methyl iodide (3.86 g, 27.2 mmol), and palladium chloride
(25 mg, 0.14 mmol) was stirred at room temperature for 5 h.
After evaporation of excess methyl iodide, the reaction mixture
was fractionally distilled under reduced pressure to give trieth-
ylsilyl 4-iodobutanoate (2a , 3.48 g, 10.6 mmol, 68%).
cessful and gave complex mixtures. The reaction of
phthalide with 1a gave a 26/74 mixture of triethylsilyl
o-(iodomethyl)benzoate (7a ) and triethylsilyl o-methyl-
benzoate (7a ′). Presumably, the reduction of an iodo-
methyl unit in the initial product 7a took place under
the reaction conditions to give 7a ′. In fact, when the
reaction mixture was further treated with 1 equiv of
triethylsilane for 5 h, 7a ′ was obtained as the sole product
in 85% yield. Treating methyl benzoate with 1a for 18 h
at 80-90 °C, followed by distillation of the primary
reaction mixture under reduced pressure, afforded tri-
ethylsilyl benzoate (8a ) in 76% yield. Dealkylation of
methyl benzoate with iodotrimethylsilane or a mixture
of Me3SiNEt2/2MeI has been previously reported.4,11
Data for 2a : bp 75-76 °C (1 mmHg); IR (neat) 1716 cm-1
;
1H NMR (δ in CDCl3) 3.23 (t, J ) 6.8 Hz, 2H), 2.46 (t, J ) 7.1
Hz, 2H), 2.15-2.06 (m, 2H), 0.96 (t, J ) 7.9 Hz, 9H), 0.76 (q, J
) 7.9 Hz, 6H); 13C NMR (δ in CDCl3) 172.72, 36.24, 28.64, 6.46,
5.59, 4.47; MS m/z 299 (M+ - Et), 201 (M+ - I). Anal. Calcd for
C10H21IO2Si: C, 36.59; H, 6.45. Found: C, 36.35; H, 6.45.
Rea ction of Meth yl Ben zoa te w ith 1a . A mixture of
triethylsilane (3.01 g, 25.9 mmol), methyl benzoate (3.40 g, 25.0
mmol), methyl iodide (5.40 g, 38.0 mmol), and palladium chloride
(18 mg, 0.10 mmol) was stirred at 80-90 °C for 18 h. After
evaporation of excess methyl iodide, the reaction mixture was
fractionally distilled under reduced pressure to give triethylsilyl
benzoate (8a , 4.51 g, 19.1 mmol, 76%).
Data for 8a : bp 64-65 °C (1 mmHg); IR (neat) 1703 cm-1
;
1H NMR (δ in CDCl3) 8.05 (d, J ) 7.5 Hz, 2H), 7.55 (t, J ) 7.5
Hz, 1H), 7.43 (t, J ) 7.5 Hz, 2H), 1.04 (t, J ) 7.7 Hz, 9H), 0.88
(q, J ) 7.7 Hz, 6H); 13C NMR (δ in CDCl3) 166.56, 132.85, 131.38,
To demonstrate the synthetic utility of the halosilation
products, we examined conversion of C-halogen bonds to
C-N bonds (Scheme 2). Thus, treatment of 3b with 2
equiv of diethylamine or dibutylamine led to triethylsilyl
5-diethylamimopentanoate (3c) and triethylsilyl 5-dibu-
tylamimopentanoate (3d ) as O-silyl-protected δ-amino
acids, in 71% and 84% yield, respectively. Similar treat-
ment of 2b and 4b with these amines afforded the
respective O-silylated amino acids 2c,d and 4c,d in 78%,
72%, 73%, and 74% yields.
130.12, 128.26, 6.55, 4.63; MS m/z 221 (M+ - Me), 207 (M+
-
Et). Anal. Calcd for C13H20O2Si: C, 66.05; H, 8.53. Found: C,
66.15; H, 8.55.
Rea ction of 3b w ith Et2NH. A mixture of triethylsilyl
5-bromopentanoate (3b, 1.83 g, 6.20 mmol) and diethylamine
(1.11 g, 14.8 mmol) was stirred at 60 °C for 5 h. The reaction
mixture was fractionally distilled by a Kugelrohr distillation
apparatus to give triethylsilyl 5-diethylaminopentanoate (3c,
1.27 g, 4.43 mmol, 71%).
Data for 3c: bp 120-125 °C (1 mmHg, oven temp); IR (neat)
In conclusion, we investigated ring-opening iodo- and
bromosilation of lactones with reagents 1a ,b. γ-Butyro-
lactone, δ-valerolactone, and 6-hexanolide reacted with
1 equiv of 1a ,b to give triethylsilyl ω-haloalkanoates in
good yields. The reactions of methyl-substituted γ- and
δ-lactones with 1a also produced iodosilation products.
The reaction of γ-ethyl-γ-butyrolactone with 1a produced
iodosilation products as a mixture of the structural
isomers, arising from initial isomerization, while treat-
ment with 1a ′ produced the expected product. Treatment
of methyl benzoate with 1a afforded triethylsilyl ben-
zoate. It was demonstrated that halosilation products can
be converted to O-silyl-protected amino acids by the
reaction with secondary amines.
1
1715 cm-1; H NMR (δ in CDCl3) 2.50 (q, J ) 7.0 Hz, 4H), 2.41
(t, J ) 7.3 Hz, 2H), 2.32 (t, J ) 7.2 Hz, 2H), 1.62-1.55 (m, 2H),
1.50-1.45 (m, 2H), 0.99 (t, J ) 7.0 Hz, 6H), 0.95 (t, J ) 7.8 Hz,
9H), 0.74 (q, J ) 7.9 Hz, 6H); 13C NMR (δ in CDCl3) 174.12,
52.43, 46.83, 35.72, 26.41, 23.22, 11.62, 6.46, 4.47; MS m/z 287
(M+), 258 (M+ - Et), 215 (M+ - NEt2), 156 (M+ - OSiEt3). Anal.
Calcd for C15H33NO2Si: C, 62.66; H, 11.57; N, 4.87. Found: C,
62.33; H, 11.96; N, 4.77.
Ack n ow led gm en t. We thank Sankyo Kasei Co.
Ltd., Tokuyama Corp., and Sumitomo Electric Industry
for financial support.
Su p p or tin g In for m a tion Ava ila ble: Detailed experi-
mental procedures and spectral and analytical data for the
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
(11) J ung, M. E.; Lyster, M. A. J . Am. Chem. Soc. 1977, 99, 968.
J O011153N