Stereospecific syntheses of chiral epoxides bearing 1,4-diyne or 1,4-enyne unit via alkylative epoxide rearrangement

Article abstract of DOI:10.1081/SCC-200043198

Stereospecific syntheses of a series of chiral epoxides bearing the 1,4-diyne or 1,4-enyne unit were achieved through alkylative epoxide rearrangement, which proceeded in two steps: 1) coupling of epoxy tosylate with alkynyltrifluoroborate; and 2) ring-cl

Full text of DOI:10.1081/SCC-200043198

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Stereospecific Syntheses
of Chiral Epoxides Bearing
1,4‐Diyne or 1,4‐Enyne
Unit Via Alkylative Epoxide
Rearrangement
Chao Che a b & Zhongning Zhang a b
a State Key Laboratory of Integrated Management
of Insects and Rodents , Institute of Zoology,
Chinese Academy of Sciences , No. 19,
Zhongguancun Road, Beijing, 100080, P. R. China
b Graduate School of the Chinese Academy of
Sciences , Beijing, P. R. China
Published online: 10 Jan 2011.
To cite this article: Chao Che & Zhongning Zhang (2004) Stereospecific Syntheses
of Chiral Epoxides Bearing 1,4‐Diyne or 1,4‐Enyne Unit Via Alkylative Epoxide
Rearrangement, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:24, 4499-4505, DOI: 10.1081/
SCC-200043198
To link to this article: http://dx.doi.org/10.1081/SCC-200043198
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 24, pp. 4499–4505, 2004
Stereospecific Syntheses of Chiral Epoxides
Bearing 1,4-Diyne or 1,4-Enyne Unit Via
Alkylative Epoxide Rearrangement
Chao Che1,2 and Zhongning Zhang1,2,
*
1State Key Laboratory of Integrated Management of Insects and Rodents,
Institute of Zoology, Chinese Academy of Sciences, Beijing, P. R. China
2Graduate School of the Chinese Academy of Sciences,
Beijing, P. R. China
ABSTRACT
Stereospecific syntheses of a series of chiral epoxides bearing the 1,4-
diyne or 1,4-enyne unit were achieved through alkylative epoxide
rearrangement, which proceeded in two steps: 1) coupling of epoxy tosy-
late with alkynyltrifluoroborate; and 2) ring-closure of the resulting
intermediate.
Key Words: Alkylative epoxide rearrangement; 1,4-Diyne; 1,4-Enyne;
Chiral epoxides; Stereospecific synthesis.
*
Correspondence: Zhongning Zhang, State Key Laboratory of Integrated Management
of Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, No. 19,
Zhongguancun Road, Beijing 100080, P. R. China; Fax: 86-10-62565689; E-mail:
zhangzn@panda.ioz.ac.cn.
4499
DOI: 10.1081/SCC-200043198
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

4500
Che and Zhang
Optically active epoxides are an important class of natural products
encountered as sex pheromones of Lepidopteran pests[1] and self-defensive
substances against rice blast disease.[2] Most reported syntheses of chiral
epoxides involved Sharpless asymmetric epoxidation[3] or Payne rearrange-
ment.[4] In pioneering studies,[5] Bell and Ciaccio have demonstrated that
alkylative epoxide rearrangement is a remarkably efficient method for the syn-
thesis of internal epoxides. Noteworthy, the method has a strategic synthetic
advantage over Payne rearrangement and complements Sharpless asymmetric
epoxidation.[5b] To our knowledge, however, alkylative epoxide rearrange-
ment performed on 1,4-diyne or 1,4-enyne has not been defined with the
exception of 1,4-heptdiyne due to their susceptibility to the basic conditions.
As part of our current research program was directed toward the total synthesis
of sex pheromonal components of Hyphantria cunea (Drug),[6] we sought to
explore a method for the synthesis of chiral epoxides bearing 1,4-diyne or
1,4-enyne unit. In the end, we attempted to extend the scope of an alkylative
epoxide rearrangement process to a range of 1,4-diynes and 1,4-enynes.
Herein, we present the results and the synthesis of chiral epoxides bearing
the 1,4-diyne or 1,4-enyne unit.
As shown in Sch. 1, the alkylative epoxide rearrangement process pro-
ceeded in two steps. Alkynyltrifluoroborate salt, readily generated in situ by
.
the addition of BF3 OEt2 to alkynyllithium of 1, mediated the regioselective
C-O ring cleavage of epoxy tosylate (2S,3S)-2 to afford the ring-opening inter-
mediate, and this intermediate could be used directly in the next ring-closure
reaction under the basic conditions to furnish 3.
Our initial experiments in alkylative epoxide rearrangement involved the
use of 1,4-heptdiyne 1a, with which the coupling of (2S,3S)-2a proceeded
Scheme 1. Coupling of various 1,4-diyne and 1,4-enyne with (2S,3S)-2 via alkylative
.
epoxide rearrangement. Reagents and conditions: a) n-BuLi, BF3 Et2O, 2788C,
30 min; b) 2, THF, 2788C, 3 h; c) K2CO3, CH3OH, rt., 30 min.

Stereospecific Syntheses of Chiral Epoxides
4501
smoothly and afforded the desired chiral epoxide product 3a (Fig. 1) in 69%
yield. In sharp contrast, the coupling of (2S,3S)-2a with 1b under the similar
conditions had proven abortive. Repeated attempts to modify the procedure
by numerous experimental variations in base, reaction solvent, and tempera-
ture failed to furnish the product. Analysis showed that introduction of an
electron-withdrawing vinyl group lead to isomerization of molecules,
mainly due to deprotonation of a methylene between two triple bonds. To
probe the effects of structural variations of 1,4-diyne on the course of
coupling, we synthesized five additional 1,4-diynes (1c, 1d, 1e, 1f, 1g)
and utilized them in alkylative epoxide rearrangement. As a result, 1e, 1f,
and 1g were coupled with (2S,3S)-2a to afford the desired products 3e,
3f, and 3g, respectively. The TMS-protected 1,4-pentdiyne 1c failed, and
1,4-pentdiyne 1d bearing two terminal triple bonds afforded the mixture of
two isomerizing products (3d1, 3d2), which demonstrated their susceptibility
to the basic conditions. In addition, 1,4-enyne 1h was synthesized and
employed in the alkylative epoxide rearrangement process. To our delight,
1h was stable enough to endure the basic conditions and coupled with 2b
to furnish 3h in 67% yield.
In summary, we have examined the scope of alkylative epoxide
rearrangement utilizing 1,4-diynes or 1,4-enynes in the reaction, through
which a series of chiral epoxides bearing 1,4-diyne or 1,4-enyne unit were
successfully synthesized.
Figure 1. Results for the synthesis of chiral epoxides via alkylative epoxide
rearrangement.

4502
Che and Zhang
EXPERIMENTAL
General Methods
1H NMR spectra were recorded on a Bruker AMX-400 spectrometer
using TMS as internal standard. All the coupling constants are reported in
Hz. 13C NMR spectra were recorded on the same instrument, and chemical
shifts were measured relative to residual solvent resonances [d
(CDCl3) ¼ 77.0]. The IR spectra were determined by Bruker Tensor 27 spec-
trometer. Mass spectra were recorded with Agilent-5973N instrument. High-
resolution mass spectra were obtained on a Micromass UK GCT-MS instru-
ment with EI ionization methods. The optical rotations were determined for
solutions in CHCl3 at 258C by using a Perkin-Elmer Model 241-Mc automatic
polarimeter. Melting points were determined on a Yanagimoto apparatus and
were uncorrected. Compounds (2S,3S)-2a and (2S,3S)-2b were prepared
according to the reported methods.[7] 1,4-Diyne and 1,4-enyne 1a–1h were
synthesized based on the general procedures described in the literature.[8]
Anhydrous THFs were freshly distilled under N2 from Na/benzophenone.
Purification of products was performed by flash column chromatography on
silica gel (200–300 mesh).
Typical Procedure for the Preparation of Chiral Epoxides
Bearing 1,4-Diyne or 1,4-Enyne Unit Via Alkylative Epoxide
Rearrangement
(Z,9S,10R)-9,10-Epoxyicosa-1,3-dien-6-yne (3h). To a solution of 1h
(276 mg, 3 mmol) in 15 mL of anhydrous THF was added dropwise at
2788C a solution of 2.5 M n-BuLi in hexane (1 mL, 2.5 mmol) by syringe.
The resulting dark green solution was stirred for 15 min, and then
.
BF3 Et2O (0.31 mL, 2.5 mmol) was added via syringe. After another
15 min, a solution of 2b (368 mg, 1 mmol) in 4 mL of THF was added also
by syringe, and the reaction mixture was stirred for 3 h at 2788C. After
addition of 10 mL of saturated aqueous NH4Cl, the aqueous layer was
extracted with ether (10 mL ꢀ 2). The combined organic layer was dried
over anhydrous Na2SO4, and the concentration afforded a brown residue.
This crude sample was redissolved in anhydrous methanol (10 mL), and
400 mg anhydrous K2CO3 was added with vigorous stirring at room tempera-
ture. After 30 min, reaction mixture was filtered. Concentration of the filtrate
and purification by flash chromatography (Hexane : ether, 10 : 1) afforded the
product 3h (200 mg, 67% in two steps) as a colorless oil, which solidified at
room temperature. [a]2D5 ¼ 20.5 (C ¼ 1, CHCl3); IR (neat) n 3086, 3030,

Stereospecific Syntheses of Chiral Epoxides
4503
2925, 2285 (weak), 1645, 1595 cm21
;
1H NMR (CDCl3) d 6.63 (ddd,
3
3Jtrans ¼ 16.8, Jcis ¼ 10.2, 3J ¼ 10.7, 1H, CH¼CHCH¼CH2), 6.04 (t,
3J ¼ 3Jcis ¼ 10.7, 1H, CH¼CHCH¼CH2), 5.44 (dt, Jcis ¼ 10.7, J ¼ 7.2,
3
3
3
1H, CH¼CHCH¼CH2), 5.24 (d, Jtrans ¼ 16.8, 1H, CH¼CHCH¼CHH),
3
5.16 (d, Jcis ¼ 10.2, 1H, CH¼CHCH¼CHH), 3.06 ꢀ 3.12 (m, 3H, HC;
CCH2C¼CH, oxirane CH), 2.95 (dt, J ¼ 4.2, 5.5, 1H, oxirane CH),
2.52 ꢀ 2.58 (ddt, 2J ¼ 17, 3J ¼ 5.5, 5J ¼ 2.7, 1H, C;CCHHCH(O)CH),
2.22 ꢀ 2.28 (ddt, 2J ¼ 17, 3J ¼ 7.2, 5J ¼ 2.5, 1H, C;CCHHCH(O)CH),
1.56 (br, m, 2H, CH(O)CHCH2), 1.26 (br, s, 16H, (CH2)8), 0.88 (t, J ¼ 6.6,
3H, CH3); 13C NMR (CDCl3) d131.3, 130.2, 126.5, 118.5, 79.8, 75.4, 57.1,
55.2, 31.9, 29.7, 29.6, 29.5, 29.3, 27.5, 26.5, 22.7, 18.8, 17.6, 14.1; MS
(m/z) 288 (Mþ, 1), 273 (2), 259 (2), 161 (11), 147 (31), 133 (37), 107 (87),
91 (100), 79 (65), 67(44); HRMS (m/z) calc. for C20H32O 288.2453, found
288.2450.
Compounds 3a, 3e, 3f, and 3g were prepared in the same manner to that
described above.
(9S,10R)-9,10-Epoxyhenicos-3,6-diyne (3a). A colorless oil that solidi-
fied at room temperature (208 mg, 69%), [a]2D5 ¼ 22.5 (C ¼ 1, CHCl3), lit.
1
[a]2D3 ¼ 52.2 (C ¼ 3.6, CCl4)5b; IR (neat) n 2920, 2210 (weak) cm21; H
NMR (CDCl3) d 3.09 ꢀ 3.14 (m, 3H, C;CCH2C;C, oxirane CH), 2.95
(dt, J ¼ 4.5, 5.5, 1H, oxirane CH), 2.25 and 2.56 (2m, 2H, C;CCH2-
3
5
CH(O)CH), 2.18 (qt, J ¼ 7.5, J ¼ 2.3, 2H, C;CCH2CH3), 1.51 (br, m,
2H, CH(O)CHCH2), 1.26 (br, s, 18H, (CH2)9), 1.12 (t, J ¼ 7.5, 3H,
CH3CH2C;C), 0.88 (t, J ¼ 6.9, 3H, CH3); 13C NMR (CDCl3) d 81.9, 76.6,
75.2, 73.2, 60.0, 54.9, 31.8, 29.6, 29.5, 29.3, 27.5, 26.4, 22.6, 19.5, 18.7,
14.0, 13.8, 12.3, 9.6; MS (m/z) 302 (Mþ, 0.8), 301 (2), 287 (4), 273 (9),
147 (86), 133 (100), 119 (60), 105 (80), 91 (94), 67 (72); HRMS (m/z)
calc. for C21H34O 302.2601, found 302.2608.
(11S,12R)-11,12-Epoxytricos-5,8-diyne (3e). A colorless oil that solidi-
fied below room temperature (214 mg, 65%), [a]2D5 ¼ 23.3 (C ¼ 1, CHCl3); IR
1
(neat) n 2930, 2213 (weak) cm21; H NMR (CDCl3) d 3.09 ꢀ 3.13 (m, 3H,
C;CCH2C;C, oxirane CH), 2.94 (dt, J ¼ 4.6, 5.4, 1H, oxirane CH), 2.25
3
5
and 2.55 (2m, 2H, C;CCH2CH(O)CH), 2.15 (tt, J ¼ 7.0, J ¼ 2.4, 2H,
C;CCH2CH2), 1.51 (br, m, 2H, CH(O)CHCH2), 1.26 (br, s, 22H, (CH2)11),
0.89 (m, 6H, (CH3)2); 13C NMR (CDCl3) d 80.7, 76.8, 75.3, 73.8, 57.1,
55.1, 31.9, 30.8, 29.6, 29.5, 29.4, 29.3, 27.5, 26.5, 22.7, 21.9, 18.7, 18.4,
14.1, 13.6, 9.7; HRMS (m/z) calc. for C23H38O 330.2923, found 330.2922.
2-((9S,10R)-9,10-Epoxyhenicos-3,6-diynyloxy)-tetrahydro-2H-pyran
(3f). A colorless oil (225 mg, 56%), [a]2D5 ¼ 14.2 (C ¼ 1, CHCl3); IR (neat) n
1
2930, 2220 (weak), 1120, 1030 cm21; H NMR (CDCl3) d 4.64 (t, J ¼ 2.8,
1H, OCHO), 3.53 and 3.85 (2m, 4H, (OCH2)2), 3.09 ꢀ 3.14 (m, 3H,
C;CCH2C;C, oxirane CH), 2.95 (dt, J ¼ 4.5, 5.5, 1H, oxirane CH), 2.25

4504
Che and Zhang
and 2.55 (2m, 2H, C;CCH2CH(O)CH), 2.45 (m, 2H, C;CCH2CH2OTHP),
1.5 ꢀ 1.8 (m, 8H, CH(O)CHCH2, (CH2)3), 1.26 (br, s, 18H, (CH2)9), 0.88
(t, J ¼ 6.4, 3H, CH3); 13C NMR (CDCl3) d 98.7, 75.4, 75.1, 71.8, 68.5,
65.7, 62.2, 57.1, 55.0, 31.9, 30.5, 29.7, 29.6, 29.5, 29.4, 29.3, 27.5, 26.4,
25.4, 22.6, 20.1, 19.4, 18.7, 14.1, 9.7; HRMS (m/z) calc. for C26H42O3
402.3134, found 402.3136.
(9S,10R)-9,10-Epoxyhenicos-3,6-diyn-1-ol (3g). A white solid (165 mg,
52%), mp 48 ꢀ 508C; [a]2D5 ¼ 23.5 (C ¼ 1, CHCl3); IR (KBr) n 3393, 2930,
1
2280 (weak) cm21; H NMR (CDCl3) d 3.71 (t, J ¼ 6.2, 2H, CH2OH), 3.15
(m, 2H, C;CCH2C;C), 3.11 (dt, J ¼ 5.5, 1.6, 1H, oxirane CH), 2.95 (dt,
J ¼ 4.5, 5.5, 1H, oxirane CH), 2.29 and 2.52 (2m, 2H, C;CCH2CH(O)CH),
2.45 (tt, 3J ¼ 6.2, 5J ¼ 2.3, 2H, C;CCH2CH2OH), 1.51 (m, 2H,
CH(O)CHCH2CH2), 1.26 (br, s, 18H, (CH2)9), 0.88 (t, J ¼ 6.6, 3H, CH3);
13C NMR (CDCl3) d 77.1, 76.3, 76.2, 75.7, 61.1, 57.1, 55.0, 31.9, 29.6,
29.5, 29.4, 29.3, 27.5, 26.4, 23.1, 22.7, 18.7, 14.1, 9.8; HRMS (m/z) calc.
for C21H34O2 318.2559, found 318.2553.
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Received in Japan June 16, 2004