Addition of organozinc species to cyclic 1,3-diene monoepoxide

Article abstract of DOI:10.1021/ol017279o

(equation presented) The reaction of organozinc reagents (ZnEt₂, ZnPh₂) with cyclic 1,3-diene monoepoxides in the presence of CF₃COOH gave the cis-addition products. Lewis acids such as (CF₃CO₂)₂

Full text of DOI:10.1021/ol017279o

ORGANIC
LETTERS
2
002
Vol. 4, No. 6
05-907
Addition of Organozinc Species to
Cyclic 1,3-Diene Monoepoxide
9
Song Xue,* Yali Li, Kaizhen Han, Wen Yin, Meng Wang, and Qingxiang Guo
Department of Chemistry, UniVersity of Science and Technology of China,
Hefei, 230026, P. R. China
xuesong@ustc.edu.cn
Received December 20, 2001
ABSTRACT
The reaction of organozinc reagents (ZnEt
products. Lewis acids such as (CF CO Zn and ZnCl
stereoselectivity.
2
, ZnPh
2
) with cyclic 1,3-diene monoepoxides in the presence of CF
3
COOH gave the cis-addition
3
2
)
2
2
mediated the nucleophilic addition of ZnEt to cyclooctadiene monoepoxide with high
2
Vinylic epoxides are valuable synthetic building blocks, and
their reactions have been extensively investigated. The
with six-, seven-, and eight-membered 1,3-diene mono-
epoxide. The ratio of cis/trans-1,2-addition was up to
1
9
addition of organometallic reagents to vinylic epoxides is a
72/28 when 3,4-epoxycyclohexene reacted in ether at room
temperature. R-C-Glycosides were also synthesized by the
syn addition of aluminum or boron reagents to glycal
2
fundamental preparation of allylic and homoallylic alcohols.
3
4
5
Grignard reagents, allylstannanes, and alkyllithiums gener-
6
10
ally provide 1,2-addition products, and copper reagents and
copper-catalyzed organozinc reagents yield 1,4-addition
epoxides. We now wish to report a stereoselective addition
7
of organozinc species to cyclic 1,3-diene monoepoxides.
Our investigation started with 1,3-cyclooctadiene mono-
epoxide 1c as a substrate. The active organozinc species
products. Mixtures of regio- and/or stereoisomers are often
obtained in favor of a trans relationship between the hydroxy
group and the substitutent. In contrast, the syn addition of
carbon nucleophiles toward epoxide has received less atten-
tion.8
XZnR could be generated by reaction of ZnR (R ) Et, Ph)
2
with acids (HX). When a solution of organozinc CF CO -
3
2
ZnEt and substrate 1c in CH Cl was stirred at 0 °C for 2 h,
2
2
Recently, Zaidlewicz and Krzeminski reported that 1,2-
syn addition was favored in the reaction of allyldiethylborane
(9) They found a novel rearrangement reaction to occur in the reaction
of allyldiethylborane with 5- membered rings. Zaidlewicz, M.; Krzeminski,
M. P. Org. Lett. 2000, 2, 3897.
(
1) (a) Trost, B. M.; McEachern, E. J.; Toste, F. D. J. Am. Chem. Soc.
(10) Rainier, J. D.; Cox, J. M. Org. Lett. 2000, 2, 2707.
1
998, 120, 12702. (b) Johannes, C. W.; Visser, M. S.; Weatherhead, G. S.;
(11) Addition of CF3COOZnEt to 1c. To a solution of ZnEt2 (1 M in
n-hexane, 1.2 mL, 1.2 mmol) in 2 mL of CH2Cl2 at 0 °C was added CF3-
COOH (92 µL, 1.2 mmol) very slowly via syringe under N2. After 30 min
of stirring, a solution of 1c (124 mg, 1.0 mmol) in CH2Cl2 (1 mL) was
added. The mixture was stirred for 2 h at 0 °C and then quenched with
saturated aqueous NH4Cl. The mixture was extracted with Et2O (3 × 10
mL), washed with brine, dried (Na2SO4), and concentrated. Column
chromatography afforded 102 mg (66%) of homoallylic alcohol cis-2c. GC-
MS analysis of the crude reaction mixture revealed three peaks: 1c (8%),
3-cycloocten-1-one of the rearrangement product from epoxide (19%), and
cis-2c (73%).
Hoveyda, A. H. J. Am. Chem. Soc. 1998, 120, 8340. (c) Caldwell, C. G.;
Derguini, F.; Bigge, C. F.; Chen, A. H.; Hu, S.; Wang, J.; Sastry, L.;
Nakanishi, K. J. Org. Chem. 1993, 58, 3533. (d) Tueting, D. R.; Echavarren,
A. M. and Stille, J. K. Tetrahedron 1989, 45, 979.
(
2) Gorzynski-Smith, J. Synthesis 1984, 629.
(3) (a) S o¨ derberg, B. C.; Austin, L. R.; Davis, C. A.; Nystr o¨ m, J. E.;
Vagborg. J.O. Tetrahedron 1994, 50, 61. (b) Bloodworth, A. J.; Curtis, R.
J.; Spencer, M. D.; Tallant, N. A. Tetrahedron 1993, 49, 2729.
(
(
(
4) Naruta, Y.; Maruyama, K. Chem. Lett. 1987, 963.
5) Wieland, D. M.; Johnson, C. R. J. Am. Chem. Soc. 1971, 93, 3047.
6) (a) Marshall, J. A. Chem. ReV. 1989, 89, 1503. (b) Marshall, J. A.;
(12) The stereochemistry of cis-2c was assigned from a similarity of its
NMR spectrum to that of the known cis-2-allyl-3-cycloocten-1-ol in ref 9.
(13) Crystal data of cis-2c: C10H18O, crystal system, tetragonal; a )
Crute, T. D., III; Hsi, J. D. J. Org. Chem. 1992, 57, 115.
(7) (a) Lipshutz, B. H.; Woo, K.; Gross, T.; Buzard, D. J.; Tirado, R.
3
Synlett 1997, 477. (b) Badalassi, F.; Crotti, P.; Macchia, F.; Pineschi, M.;
Arnold, A.; Feringa, B. L. Tetrahedron Lett. 1998, 39, 7795.
22.583(2) Å, b ) 22.583(2) Å, c ) 7.6273(9) Å, V ) 3889.9(7) Å ; space
-1
group, I4(1)/a; Z ) 16; F(000) ) 1376; µ ) 0.065 mm ; full matrix least-
2
(8) Trost, B. M.; Molander, G. A. J. Am. Chem. Soc. 1981, 103, 5969.
squares refinement on F ; residuals, R ) 0.042, wR2 ) 0.0826.
1
0.1021/ol017279o CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/26/2002

only 1,2-addition product cis-2c was obtained with 66% yield
type of cis-1,2-addition with 56% and 63% yield, respec-
tively. These results obtained show that ZnEt is an effective
nuclephile to cyclic 1,3-diene monoepoxide in the presence
11
(Table 1). The relative stereochemistry between the hydroxy
2
1
4
3
of CF COOH. The byproducts of these reactions were the
Table 1. Addition of ZnEt
Acids
2
to Epoxides in the Presence of
rearrangement products of monoepoxides of cyclic dienes,
suggesting that organozinc species XZnEt have Lewis acid
character in these reactions.
In addition to ZnEt
to give exclusively 3c in 74% yield when CF
reacted with 1c in CH Cl at 0 °C for 5 h. However,
cyclopentadiene and 1,3-cyclohexadiene monoepoxides gave
both 1,2- and 1,4-regioisomers when reacting with CF CO
ZnPh (Table 2). The 1,4-regioisomer was assigned from the
2
, ZnPh
2
underwent the same reaction
3
CO ZnPh
2
2
2
3
2
-
entry
epoxide
solvent
acid (HX)
yielda (%)
Table 2. Addition of ZnPh
2
to Epoxides in the Presence of
1
2
3
4
5
6
7
8
1c
1c
1c
1c
1c
1c
1a
1b
CH2Cl2
toluene
n-hexane
Et2O
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CF3CO2H
CF3CO2H
CF3CO2H
CF3CO2H
CCl3CO2H
66
52
7
0
20
0
3
2
CF CO H
CF3CO2H
CF3CO2H
58
63
a
Isolated yields.
group and the ethyl group was assigned on the basis of the
proton NMR spectrum.12 The relative configuration was
further confirmed as cis by X-ray analysis of the crystal
structure (Figure 1).13 The trans isomer of the 1,2-addition
3/4a
yield b (%)
entry
epoxide
1
2
3
1a
1b
1c
39/61
25/75
100
81
79
74
a
Determined by GC-MS analysis. b Isolated yields.
chemical shift of the carbinol proton owing to its allylic
character. On the other hand, the cis stereochemistry of 4a,
for example, is supported by the relative value of the
chemical shifts of H
between H and H
the product is cis-1,4-disubstituted cyclopentene.
c
(δ 2.87) and H
is larger than 1 ppm, demonstrating that
d
(δ 1.58). The difference
c
d
15
Encouraged by this initial result, the reaction was inves-
tigated using Lewis acids in place of acid HX, since
organozinc species XZnEt could be formed by the reaction
Figure 1. Crystal structure of cis-2c.
of ZnEt
could be obtained when ZnEt
which is formed in situ by the reaction of ZnEt
COOH. Analysis of the crude reaction mixture using GC-
MS shows that a small amount of 1,4-addition product is
always obtained under the reaction conditions used. It is
worth noting that ZnCl was found to be reactive under these
2
reaction conditions, affording good yield (78%) of 2c but
with a mixture of stereoisomer. The same reaction carried
out with ZnBr gave the homoallylic alcohol 2c in a low
2
2
with ZnX
2
. As shown in Table 3, 60% yield of 2c
reacts with (CF CO Zn,
with CF
2
3
2 2
)
2
3
-
1
product was not observed by H NMR. The choice of the
2 2
solvent was crucial to the success of the reaction. CH Cl
and toluene were suitable solvents. The use of a more
nonpolar solvent such as hexane gave a 7% yield of cis-2c.
2
However, Et O failed to result in the reaction as a result of
coordination to Lewis acidic zinc species thereby attenuating
its reactivity. The reactivity of the organozinc species XZnEt
was highly dependent on the X group. The species CCl
CO ZnEt, in place of CF CO ZnEt, only afforded a 20%
yield using similar reaction conditions. In addition, when
3
-
yield (39%) with a decrease in both stereoselectivity and
regioselectivity.
2
3
2
3
acid HX was anhydrous TsOH or CH COOH, no reaction
occurred after stirring for 2 h at 0 °C.
(
14) Shi reported that CF3CO2H accelerated the cyclopropanation of
olefins. Yang, Z. Q.; Lorenz, J. C.; Shi, Y. Tetrahedron Lett. 1998, 39,
621.
15) Marino, J. P.; de la Pradilla, R. F.; Laborde, E. J. Org. Chem. 1987,
54, 4898.
8
3 2
Similarly, the reaction of CF CO ZnEt with cyclopenta-
(
diene and 1,3-cyclohexadiene monoepoxides gave the same
906
Org. Lett., Vol. 4, No. 6, 2002

Table 3. Addition of ZnEt
2
to 1c Mediated by Lewis Acids
Scheme 1
ZnEt2
Lewis acid
(equiv)
yield 2ca
(cis/trans)b
entry
(equiv)
2c/5cc
1
2
3
4
5
6
7
8
0.6
0.6
1.2
1.2
0.6
1.2
1.2
1.2
(CF3CO2)2Zn (0.6)
(CF3CO2)2Zn (1.0)
(CF3CO2)2Zn (0.6)
(CF3CO2)2Zn (1.0)
ZnCl2 (0.6)
ZnCl2 (0.6)
ZnCl2 (1.0)
ZnBr2 (1.0)
60 (100)
53 (100)
36 (100)
52 (100)
26 (91/9)
52 (88/12)
78 (94/6)
39 (80/20)
99/1
98/2
98/2
98/2
97/3
94/6
94/6
89/11
a
b
1
Isolated yields. Determined by H NMR [cis (δ 3.81), trans (δ 3.52),
c
CH-OH]. Determined by GC-MS analysis.
organozinc species. The cis-addition products were obtained
when reacting with CF
of ZnEt with CF CO
of the scope are in progress.
3
CO
H or (CF
2
ZnEt, which is formed by mixture
2
3
2
3
CO Zn. Additional studies
2 2
)
The syn addition appears to be occurring via the coordina-
tion of zinc to oxygen of the epoxide and intramolecular
transfer of R group. The mechanism is closely related to that
Acknowledgment. We thank University of Science and
Technology of China for financial support and the Natural
Science Foundation of Anhui province.
9
proposed by Rainier and Cox in their work and outlined in
Scheme 1. We considered the transfer of R group from XZnR
occurred from the same face as the oxygen of epoxide and
resulted in a syn addition, since organozinc reagents XZnR
could act as a Lewis acid system as well as being nucleo-
philic in character.
Supporting Information Available: Spectroscopic data
for all new products. This material is available free of charge
via the Internet at http://pubs.acs.org.
In conclusion, we have demonstrated a new nucleophilic
ring-opening reaction of cyclo-1,3-diene monoepoxide using
OL017279O
Org. Lett., Vol. 4, No. 6, 2002
907