Planar chiral dialkoxysilane: Introduction of inherent chirality and high reactivity in conventional achiral alkene

Article abstract of DOI:10.1002/chem.201402434

A simple eight-membered dialkoxysilane (E)-1 prepared from 2-pentene-1,5-diol, showed remarkably stable planar chirality along with high reactivity toward epoxidation, Diels-Alder reaction, and cycloaddition reaction with azide. Enriching alkenes: A simple eight-membered dialkoxysilane, prepared from 2-pentene-1,5-diol, shows remarkably stable planar chirality along with quite a high reactivity in epoxidation reactions, Diels-Alder reactions, and in cycloaddition reactions with azide (see scheme).

Full text of DOI:10.1002/chem.201402434

DOI: 10.1002/chem.201402434
Communication
&
Chiral Alkenes
Planar Chiral Dialkoxysilane: Introduction of Inherent Chirality
and High Reactivity in Conventional Achiral Alkene
Katsuhiko Tomooka,*[a] Shouji Miyasaka,[b] Shougo Motomura,[c] and Kazunobu Igawa[a]
To realize this concept, we designed new eight-membered
Abstract:
A
simple eight-membered dialkoxysilane
olefinic dialkoxysilanes (E)-1 (ꢀii, m and n=1, Y=O, Z=SiR2),
in which silicon acts as the buckle to connect both side of
1,5-diol.[4] Conformational analysis by DFT (density functional
theory) calculation suggests that the alkene moiety of
(E)-1 forms stereogenic planes in the most stable conforma-
tion, as shown in Figure 2.[5] Furthermore, estimated barrier to
racemization is high enough to isolate an enantiomer (see
below). Herein, we describe the detailed synthesis, stereo-
chemical behavior, and reaction of dialkoxysilanes (E)-1.[6,7]
(E)-1 prepared from 2-pentene-1,5-diol, showed remark-
ably stable planar chirality along with high reactivity
toward epoxidation, Diels–Alder reaction, and cycloaddi-
tion reaction with azide.
Functionalization of alkenes with discrimination of the stereo-
topic faces is one of the most fundamental and efficient ap-
proaches in asymmetric synthesis, and hence, numerous dia-
stereoselective and enantioselective methods have been devel-
oped so far.[1] Basically, an alkene has no chiral element; there-
fore, introduction of an external chiral element such as an sp3
carbon chirality into the adjacent position of the alkene or into
the reagent is necessary to discriminate between the stereo-
topic faces of the alkene. In contrast, if an alkene having inher-
ent chirality is available, unique and efficient asymmetric syn-
thesis can be performed without the aid of external chiral ele-
ment.[2,3]
To create an “inherent chiral alkene,” we envisioned the
Figure 2. Most stable conformers of (E)-1.
transformation of
a conventional achiral alkene i into
a medium-sized cyclic molecule ii via ring formation with a de-
tachable “buckle Z” (Figure 1). The resulting ii should have
planar chirality because of its conformational constraint.
An ideal approach to (E)-1 is assembling achiral diol (E)-2-
pentene-1,5-diol [(E)-2] and dichlorosilane, however, the en-
tropically unfavorable cyclization of (E)-2 might be difficult.
Therefore, we carried out a detour-route synthesis involving
the photochemical isomerization of (Z)-1, as illustrated in
Scheme 1. At the outset, we prepared (Z)-1a (R=Ph) and
(Z)-1b (R=tBu) from (Z)-2 and commercially available dichloro-
silanes. The reaction of (Z)-2 and R2SiCl2 (R=Ph or tBu) in the
Figure 1. Introduction of chirality and high reactivity in achiral alkene i.
[a] Prof. Dr. K. Tomooka, Dr. K. Igawa
Institute for Materials Chemistry and Engineering
Kyushu University
Kasuga, Fukuoka 816-8580 (Japan)
Fax: (+81)92-583-7810
E-mail: ktomooka@cm.kyushu-u.ac.jp
[b] S. Miyasaka
Department of Applied Chemistry
Tokyo Institute of Technology
Meguro-ku, Tokyo 152-8552 (Japan)
[c] S. Motomura
Department of Molecular and Material Sciences
Kyushu University
Kasuga, Fukuoka 816-8580 (Japan)
Scheme 1. Synthesis of (E)-1a,b. Reagents and conditions: a) R2SiCl2, AgNO3,
N,N-dimethylformamide, 08C, (Z)-1a: 71%, (Z)-1b: 77%. b) Grubbs’ 1st gen-
eration catalyst (5 mol%), CH2Cl2, RT, (Z)-1a: 87%, (Z)-1b: 72%. c) dimethyl
isophthalate (20 mol%), hn: 280 nm, CH3CN, RT, (E)-1a: 25%, (E)-1b: 31%.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402434.
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presence of AgNO3 under high-dilution conditions afforded
(Z)-1a and (Z)-1b in 71% and 77% yields, respectively.[8]
An alternative approach, the RCM (ring-closing olefin meta-
thesis) of 3a and 3b, was also efficient, and (Z)-1a and (Z)-1b
were obtained in 87% and 72% yields, respectively.[9,10] Photo-
chemical isomerization of (Z)-1a,b was performed by irradia-
tion with 280 nm UV light in the presence of dimethyl iso-
phthalate (sensitizer) in acetonitrile, and 1a and 1b were ob-
tained as 25:75 and 33:67 E/Z mixtures, respectively.[11] Pure
(E)-1a,b were successfully isolated by AgNO3-impregnated
silica gel chromatography.[12,13] The existence of isolable enan-
tiomers of (E)-1a was revealed by HPLC analysis using a chiral
stationary column equipped with a CD (circular dichroism) de-
tector. As shown in Scheme 2, both enantiomers of (E)-1a
Scheme 3. Synthesis and X-ray analysis of (E)-5a and ORTEP drawing of
(S)-5a (50% probability ellipsoids).
Scheme 2. Stereochemical behavior of (E)-1a. [a] CHIRALCEL OJ-H
(4.6ꢁ250 mm), hexane/iPrOH=90:10, flow rate: 0.5 mLminꢁ1, CD 254 nm,
UV: 254 nm.
20
were separated: the first eluate was the (ꢁ)-isomer (½aꢂD
=
ꢁ65.4, c 1.66, CHCl3) and the second eluate was the (+)-isomer
(½aꢂ2D1 = +63.6, c 1.61, CHCl3).[14] Further, the remarkable stereo-
chemical stability of (E)-1a was revealed. Namely, the enantio-
purity of the isolated enantiomer of (E)-1a was almost un-
changed in toluene solution at ambient temperature for two
months or at 808C for at least two weeks.
Scheme 4. Transformation of (E)-1b into 5b and separation of the enantio-
mers. [a] CHIRALPAK AD-H (4.6ꢁ250 mm), hexane/iPrOH=95:5, flow rate:
0.5 mLminꢁ1, CD: 254 nm, UV: 300 nm. Reagents and conditions: a) semi-
preparative HPLC: CHIRALPAK AD-H (25ꢁ250 mm), hexane/iPrOH=95:5,
flow rate: 4.0 mLminꢁ1, UV: 300 nm, b) PPh3, CH2Cl2, 08C, (ꢁ)-(E)-1b: 57%,
(+)-(E)-1b: 90%.
Because straightforward determination of the absolute con-
figuration of non-crystalline (E)-1a was difficult, we decided to
prepare Pt-complexes of the enantiomers by our previously de-
veloped method.[15] Reaction of (ꢁ)-(E)-1a with PtCl2(2,4,6-
trimethylpyridine)(CH2=CH2) (4) in CH2Cl2 at RT afforded the de-
sired 5a in 95% yield, as crystals suitable for X-ray analysis.
The analysis results showed that the absolute configuration of
(ꢁ)-(E)-1a is (S) (Scheme 3).[16]
tiomers of 5b were successfully separated by HPLC using
a chiral stationary column. Removal of the Pt moiety from
(+)-and (ꢁ)-5b using PPh3 afforded (ꢁ)-(E)- and (+)-(E)-1b, re-
spectively.[17] The enantiopurity of the isolated enantiomers of
1b was almost unchanged in toluene at 808C for two weeks.
Elucidation of the detailed stereochemical stability of (E)-1a
and (E)-1b by measuring the change in the optical purity is dif-
ficult owing to their remarkable reactivity of the E-alkene
moiety.[18] Therefore, we estimated the racemization energy by
In contrast to the case of (E)-1a, direct separation of the
enantiomers of (E)-1b using a chiral stationary column was un-
successful. Hence, we examined for the Pt-complex derivatiza-
tion method. As shown in Scheme 4, Pt-complex 5b was pre-
pared in racemic form from rac-(E)-1b and 4, and both enan-
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DFT calculations: (E)-1a is much more stable than (E)-1b
[DE° K) =32.6 and 28.7 kcalmolꢁ1 for (E)-1a and (E)-1b, re-
(298
spectively].[5] From these data, the half-lives of the optical ac-
tivity (t1/2) of (E)-1a and (E)-1b at 258C were calculated as
1,375 years and 1.9 years, respectively. These results mean that
the synthesis of remarkably stable planar chiral alkene was re-
alized by the simple transformation of acyclic olefinic diol into
cyclic dialkoxysilane and that the stereochemical stability of
the resulting (E)-1 can be adjusted by appropriate choice of
the substituent R on the silylbuckle Z.
The obtained (E)-1 is unique in that it is a highly reactive
chiral alkene. As shown in Scheme 5, the reaction of (S)-(E)-1a
with mCPBA (1.2 equiv) in CH2Cl2 at 08C proceeded to comple-
tion within 1 h to afford epoxide (R,R)-6 quantitatively in a ste-
reospecific manner (>98% d.r., >98% ee).[19] In general, a con-
Scheme 6. Diels–Alder reaction of (E)-1a and 1,3-diphenyl isobenzofuran. Re-
agents and conditions: a) 1,3-diphenylisobenzofuran (1.5 equiv), toluene, RT,
2.5 h, 90%; b) TBAF, THF, 08C, 75%.
Scheme 5. Epoxidation of enantioenriched (E)-1a. Reagents and conditions:
a) mCPBA (1.2 equiv), CH2Cl2, 08C, 1 h, quant.; b) TBAF, THF, RT, quant.;
c) pBrC6H4COCl, Et3N, N,N-dimethyl-4-dimethylaminopyridine (cat.), CH2Cl2,
08C, 97%. mCPBA=meta-chloroperbenzoic acid, TBAF=tetrabutylammoni-
um fluoride.
ventional (Z)-alkene is more reactive toward epoxidation than
is an (E)-alkene.[20] However, a similar epoxidation reaction of
(Z)-1 was rather slow, taking approximately 24 h for comple-
tion. The observed significantly high reactivity of (E)-1 would
be attributable to the distorted structure of the olefinic bond.
The silyl buckle moiety could be removed from 6 by treatment
with TBAF to quantitatively afford epoxide 7 having an acyclic
skeleton. The stereochemical purity of 7 (>98% d.r.,>98% ee)
was reconfirmed by HPLC analysis of bromobenzoate deriva-
tive 8 using a chiral stationary column.
(E)-1a showed very high reactivity for Diels–Alder reactions
as well. The reaction of (R)-(E)-1a with 1,3-diphenyl isobenzo-
furan proceeded to completion within 2.5 h even at RT to
afford the cycloaddition product 9 in 90% yield as a diastereo-
meric mixture (d.r.=69:31), as shown in Scheme 6.[21] The ste-
reochemistry of the diastereomers of 9 was unambiguously de-
termined as (1R,8S,9S,10R) and (1S,8R,9S,10R) by X-ray analy-
sis.[16] Optically pure diols (1R,8S,9S,10R)-10 and (1S,8R,9S,10R)-
10 were afforded from 9 by removal of the silyl buckle moiety.
In sharp contrast, a similar reaction of (Z)-1a did not proceed
under the similar conditions:[22] the reaction of an equimolar
mixture of (E)-1a, (Z)-1a, and excess 1,3-diphenyl isobenzofur-
an at RT for 4 h gave only 9 (quant.), and (Z)-1a was recovered
almost intact (94%).
Scheme 7. Competitive reactions of (E)-1a and trans-cyclooctene (11).
isobenzofuran at RT for 20 h provided 9 (d.r.=61:39) and 12 in
79% and 19% yields, respectively; this result meant that (E)-1a
has 4.2 times greater reactivity than does 11.[24] Furthermore,
(E)-1a showed greater reactivity than did 11 for the [3+2] cy-
cloaddition reaction [Scheme 7-(2)].[25] Namely, a similar com-
petitive reaction of (E)-1a and 11 with benzyl azide at RT for
48 h afforded 13 (13a/13b=52:48) and 14 in 67% and 31%
yields, respectively.[26–29]
In conclusion, we have developed a simple and efficient ap-
proach to introduce chirality and enhance reactivity to conven-
tional achiral alkenes. The resulting novel alkene shows re-
markably stable chirality as well as high reactivity toward epox-
idation, Diels–Alder reaction, and cycloaddition reaction with
azides. Further studies to extend the concept of introducing
The Diels–Alder reactivity of (E)-1a was higher than that of
trans-cyclooctene (11), which is the well-known highly strained
and reactive alkene.[23] As shown in Scheme 7-(1), the reaction
of an equimolar mixture of rac-(E)-1a, rac-11, and 1,3-diphenyl
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[10] Recently, Kobayashi and colleagues reported an E-selective silicon-teth-
ered RCM reaction that afforded eight-membered dialkoxysilanes in
a limited number of cases, in which the conformation of substrates are
highly and properly restricted by the substituents, see: R. Matsui, K.
Seto, K. Fujita, T. Suzuki, A. Nakazaki, S. Kobayashi, Angew. Chem. 2010,
122, 10266–10271; Angew. Chem. Int. Ed. 2010, 49, 10068–10073.
[11] Photochemical isomerization was performed according to Inoue’s pro-
cedure for Z to E isomerization of a medium-sized cyclic alkene, see:
a) Y. Inoue, S. Takamuku, Y. Kunitomi, H. Sakurai, J. Chem. Soc. Perkin
Trans. 2 1980, 1672–1677; b) N. Yamasaki, Y. Inoue, T. Yokoyama, A. Tai,
J. Photochemistry and Photobiology, A: Chem. 1989, 48, 465–467.
[12] Review for AgNO3-impregnated silica gel chromatography.C. M. Wil-
liams, L. N. Mander, Tetrahedron 2001, 57, 425–447.
chirality and reactivity in alkenes, along with investigations of
the synthetic applications of the inherent chiral alkene, are in
progress.
Acknowledgements
This research was supported by the JSPS KAKENHI, Grant
Number Nos. 22350019, 24106734, and 24350048; the Global
COE Program (Kyushu Univ.), the MEXT Project of Integrated
Research on Chemical Synthesis, and the Nagase Science and
Technology Foundation. We thank Y. Tokito and K. Ideta
(Kyushu Univ.) for assistance in the HRMS measurements and
NMR analysis, respectively.
[13] Reasonable amounts of (E)-1a,b were obtained by repeated photoiso-
merization of the recovered (Z)-1a,b.
[14] The specific rotation value of the enantiopure (ꢁ)-isomer was estimated
from the value of the (ꢁ)-isomer with 94% ee (½aꢂ2D0 =ꢁ61.5, c 1.66,
CHCl3).
[15] K. Tomooka, M. Shimada, K. Uehara, M. Ito, Organometallics 2010, 29,
6632–6635. Pioneering work on Pt-complex preparation from strained
cyclic alkene, see: A. C. Cope, C. R. Ganellin, H. W. Johnson, J. Am. Chem.
Soc. 1962, 84, 3191–3192.
[16] Selected crystallographic data are provided in Supporting Information
along with the CCDC numbers.
Keywords: alkenes
dialkoxysilanes · stereoselective transformations
·
chirality
·
cyclic molecules
·
[1] For general reviews on the stereoselective transformation of alkenes,
see: a) Comprehensive Organic Synthesis Vol. 4 (Ed.: B. M. Trost), Perga-
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[2] Planar chiral carbocycles are well known to be inherent chiral alkenes.
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[5] All DFT calculations were performed using the Gaussian 03 program at
the B3LYP/6–311G(d,p) level of theory. See the Supporting Information
for details.
[6] A related eight-membered olefinic dialkoxysilane with a methyl sub-
stituent at the allylic position has been synthesized by Kuwajima,
Tanion, and colleagues, see: K. Tanino, N. Yoshitani, F. Moriyama, I. Ku-
wajima, J. Org. Chem. 1997, 62, 4206–4207. However, there is no men-
tion of the stereochemical behavior of this compound.
[7] Recently, Woerpel and colleagues reported the elegant synthesis of an
eight-membered olefinic dialkoxysilane having chiral carbons by their
originally developed silaoxetane reaction. They also reported the diaste-
reomeric property of this alkene caused by the presence of central chir-
ality and planar chirality, along with the high reactivity, see: M. Prꢂvost,
K. A. Woerpel, J. Am. Chem. Soc. 2009, 131, 14182–14183.
[17] The absolute stereochemistry of (E)-1b was not determined, yet.
[18] An attempt to perform kinetic studies of racemization at high tempera-
ture failed because of the concomitant E-Z isomerization. Detailed
study on the observed unusual thermal isomerization of alkene is now
underway.
[19] Woerpel and colleagues reported the highly diastereoselective epoxida-
tion of eight-membered olefinic dialkoxysilane having a chiral carbon
by use of mCPBA. See the ref. [7].
[20] General trend in the reactivity of (E)- and (Z)-alkenes, see: T. A. van Beek,
D. Subrtova, Phytochem. Anal. 1995, 6, 1–19.
[21] The high reactivity of strained (E)-alkenes with 1,3-diphenyl isobenzo-
furan has been reported, see: a) G. Wittig, R. Polster, Liebigs Ann. Chem.
1958, 612, 102–108; b) E. J. Corey, F. A. Carey, R. A. E. Winter, J. Am.
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Soc. 1999, 121, 10702–10710.
[22] The reaction of (Z)-1a and 1,3-diphenyl isobenzofuran at 808C for 75 h
gave another diastereomer of 9 (>95% d.r.) in only 29% yield, along
with a significant amount of a recovered (Z)-1a (71%).
[23] The high reactivity of (E)-cyclooctene in the Diels–Alder reaction has
been reported. See the references [21a], [21b].
[24] To clarify the correlation between the structure and reactivity of al-
kenes, we compared the structures of the alkene moieties of (E)-1a and
11. Because straightforward comparison of the structures of non-crys-
talline (E)-1a and 11 was difficult, we compared the X-ray structures of
the corresponding Pt-complexes 5a and iii. However, the no significant
trend was observed: as shown in below, 5a and iii show approximately
the same length of the olefinic double bond Cb=Cc [5a: 1.387(8) ꢃ, iii:
1.380(6) ꢃ] and torsional angle of the alkene plane ffCaCbCcCd [5a:
130.5(6)8, iii: 130.2(5)8].
[8] Silver-salt-promoted silyl etherification, see: K. Furusawa, K. Ueno, T.
Katsura, Chem. Lett. 1990, 97–100.
[9] Silicon-tethered RCM reactions to form medium-sized rings have been
reported, see: a) G. C. Fu, R. H. Grubbs, J. Am. Chem. Soc. 1992, 114,
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[25] The [3+2] cycloaddition reaction of (E)-cyclooctene and azide has been
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b) K. R. Henery-Logan, R. A. Clark, Tetrahedron Lett. 1968, 9, 801–806;
c) T. Aratani, Y. Nakanisi, H. Nozaki, Tetrahedron 1970, 26, 4339–4346;
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1
[26] The yields of triazolines 13 and 14 were determined by H NMR analysis
using bromoform as an internal standard.
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[27] Triazolines 13 and 14 were air sensitive, and hence, the structural analy-
ses of these compounds were performed using crude products or par-
tially purified products to avoid the decompositions during workup op-
erations and purification processes.
[28] Recently, highly reactive trans-cyclooctene derivatives have been re-
ported. For (E)-bicyclo[6.1.0]non-4-ene, see: a) M. T. Taylor, M. L. Black-
man, O. Dmitrenko, J. M. Fox, J. Am. Chem. Soc. 2011, 133, 9646–9649;
for (E,E)-1,5-cyclooctadiene, see: b) H. Stçckmann, A. A. Neves, H. A. Day,
S. Stairs, K. M. Brindle, F. J. Leeper, Chem. Commun. 2011, 47, 7203–
7205.
[29] As the one of the most reactive olefin, trans-cycloheptene has been re-
ported. However, it is quite unstable (t1/2 =9.7 min at 18C in MeOH),
and hence, its isolation and standard handling are difficult, see: Y.
Inoue, T. Ueoka, T. Kuroda, T. Hakushi, J. Chem. Soc. Perkin Trans. 2 1983,
983–988.
Received: March 1, 2014
Published online on May 6, 2014
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