Asymmetric carboselenenylation reaction of alkenes with aromatic compounds

Article abstract of DOI:10.1002/anie.200500573

(Chemical Equation Presented) High diastereoselectivity is attained in the carboselenenylation reaction of simple alkenes with aromatic compounds by using a C₂-symmetric areneselenenyl triflate (see scheme). This asymmetric Friedel-Crafts-type

Full text of DOI:10.1002/anie.200500573

Communications
Selenenylation
of simple alkenes with carbon-centered nucleophiles. We
describe herein the first example of the asymmetric carbose-
lenenylation reaction of simple alkenes with aromatic com-
pounds by using an optically active electrophilic selenium
reagent.[14]
Asymmetric Carboselenenylation Reaction of
Alkenes with Aromatic Compounds**
Treatment of an optically active areneselenenyl trifluoro-
methanesulfonate (triflate) 1a (which is generated in situ
from the reaction of a diaryl diselenide 2a with bromine and
silver triflate) with excess (E)-b-methylstyrene (3a) at À788C
for 10 min in dichloromethane in the presence of molecular
sieves (4ꢀ) and then with 2-methylfuran (4a) at À788C for
2 h gave 2-(1-phenyl-2-arylselenopropyl)-5-methylfuran (5a)
in 73% yield with 91:9 d.r. (Scheme 1). Typical results are
Kazuki Okamoto, Yoshiaki Nishibayashi,*
Sakae Uemura, and Akio Toshimitsu*
Asymmetric functionalization of simple alkenes is one of the
most attractive subjects in organic synthesis. A variety of
asymmetric reactions such as epoxidation,[1] dihydroxyla-
tion,[2] aminohydroxylation,[3] hydroboration,[4] hydrosilyla-
tion,[5] cyclopropanation,[6] and carbonylation[7] have
been reported for the introduction of new functional
groups into alkene substrates to produce optically
active compounds. The stereoselective addition of
electrophilic reagents to simple alkenes is another
versatile approach to provide synthetically useful
compounds that bear various functionalized
groups.[8,9] Recently, electrophilic selenium reagents
with optically active moieties have been successfully
employed in a number of stereoselective additions to
simple alkenes.[10] Typically, the stereoselective sele-
Scheme 1. Asymmetric carboselenenylation reaction of (E)-b-methylstyrene (3a)
with 2-methylfuran (4a) by using an optically active electrophilic selenium
reagent (1a). Tf=trifluoromethanesulfonyl.
nenylation of simple alkenes with heteroatom-cen-
tered nucleophiles such as alcohols, nitriles, oximes,
and azides gave the corresponding functionalized
organoselenium compounds with high diastereose-
lectivity.[11,12] In all cases, the selenenylation proceeds via
chiral episelenonium ions as key intermediates, which then
undergo a ring-opening reaction by nucleophilic attack.
We recently reported the stereospecific reactions of chiral
episelenonium ions generated from optically active (b-
arylseleno)ethyl alcohols with carbon-centered nucleophiles
such as alkenyl silyl ethers, trimethylsilyl cyanide, allyltrime-
thylsilane, and aromatic compounds.[13] This result prompted
us to investigate the asymmetric carboselenenylation reaction
shown in Table 1. The presence of the 4-ꢀ molecular sieves is
essential to obtain 5a in high yields (Table 1, entries 1–3). In
fact, in the absence of the 4-ꢀ molecular sieves, the yield of 5a
Table 1: Asymmetric carboselenenylation reaction of (E)-b-methylstyrene
(3a) with 2-methylfuran (4a) by using an optically active electrophilic
selenium reagent (1a).[a]
[*] K. Okamoto, Dr. Y. Nishibayashi,+ Prof. Emeritus Dr. S. Uemura
Department of Energy and Hydrocarbon Chemistry
Graduate School of Engineering
Entry
3a [equiv]
Additive
Yield [%][b]
d.r.[c]
Kyoto University
Katsura, Nishikyo-ku, Kyoto, 615-8510 (Japan)
Fax: (+81)75-383-2517
E-mail: ynishiba@scl.kyoto-u.ac.jp
1
2
3
4
5
10
10
10
10
2
M.S. (4ꢀ) (300 mg)
M.S. (4ꢀ) (100 mg)
M.S. (3ꢀ) (100 mg)
–
–
73
57
91:9
91:9
91:9
91:9
91:9
50
41[d]
25[e]
Prof. Dr. A. Toshimitsu
International Innovation Center
Kyoto University
Sakyo-ku, Kyoto, 606-8501 (Japan)
Fax: (+81)75-753-9174
E-mail: akiot@iic.kyoto-u.ac.jp
[a] All the reactions of 3a (2.00 mmol) with 4a (1.00 mmol) by using 1a
(0.20 mmol) were carried out at À788C for 2 h. [b] Yield of isolated
product. [c] Determined by 1H NMR. M.S.=molecular sieves. [d] 1-
Phenyl-2-areneselenopropanol (6) was formed in 25% yield. [e] 1-Phenyl-
2-areneselenopropanol (6) was formed in 35% yield.
[+] Current address:
Institute of Engineering Innovation
School of Engineering, The University of Tokyo
Yayoi, Bunkyo-ku, Tokyo, 113-8656 (Japan)
Fax: (+81)35-841-1175
decreased, with an increase in the amount of 1-phenyl-2-
aryleselenopropanol (6) (Table 1, entry 4). The
compound 6 is considered to be formed by
nucleophilic attack of adventitious water at the
episelenonium ion intermediate. The use of a
smaller amount of 3a decreased the yield of 5a
[**] This work was supported by a Grant-in-Aid for Scientific Research
for Young Scientists (A) (No. 15685006) to Y.N. from the Ministry
of Education, Culture, Sports, Science, and Technology, Japan.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
3588
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/anie.200500573
Angew. Chem. Int. Ed. 2005, 44, 3588 –3591

Angewandte
Chemie
Table 2: Asymmetric carboselenenylation reaction of (E)-b-methylstyrene (3a) with aromatic compound
(4) by using 1a.[a]
(Table 1, entry 5). A high diastereoselectiv-
ity was only attained by the use of 1a. When
other C2-symmetric areneselenenyl triflates
bearing two ethoxy groups (1b)[15] and two
benzyloxy groups (1c) were used instead of
1a, a lower diastereoselectivity of the prod-
uct and no formation of the product were
observed, respectively. Although extremely
high diastereoselectivities were reported in
the selenenylation of 3a with heteroatom-
centered nucleophiles such as alcohols by
using a variety of active areneselenenyl
triflates (Scheme 2, 1d–1 f),[11,12h] these are-
neselenenyl triflates did not work effec-
tively in this carboselenenylation reaction.
Detailed results are given in the Supporting
Information.
The asymmetric carboselenenylation
reactions of 3a with other furans 4b–4d by
using 1a as an optically active electrophilic
selenium reagent under similar reaction
conditions gave the corresponding alkylated
furans 5b–5d in good yields with high
diastereoselectivity (Table 2). In the reac-
tion with furan (4b), the product 5b was
obtained in slightly lower yield (Table 2,
entry 1). Other heterocyclic aromatic com-
pounds such as 2-methylthiophene (4e) and
N-methylpyrrole (4 f) can be alkylated at
the a position of the heterocyclic rings. In
both cases, high diastereoselectivities (91:9
and 89:11 d.r., respectively) were attained
(Table 2, entries 4 and 5). Unfortunately, no
reaction occurred when N-methylindole
was used as a heterocyclic aromatic com-
pound. Not only heterocyclic aromatic com-
pounds but also electron-rich benzene
derivatives can be used in this asymmetric
carboselenenylation reaction. The best dia-
stereoselectivity was found in the reaction
of 3a with 1,3,5-trimethoxybenzene (4i),
and the corresponding alkyl substituted
Entry
1
ArH (4)
Product (5)
Yield[%][b]
36
d.r.[c]
91:9
4b
5b
X=O; R1 =H; R2 =H
X=O; R1 =Et; R2 =H
2
3
4
5
4c
4d
4e
4 f
5c
5d
5e
5 f
67
63
52
48
91:9
92:8
91:9
89:11
X=O; R1 =Me; R2 =Me
X=S; R1 =Me; R2 =H
X=NMe; R1 =H; R2 =H
6
7
4g
4h
0
0
–
–
8
4i
5i
77
95:5
9
4j
5j
51
34
90:10
91:9
10
4k
5k
[a] All the reactions of 3a (2.00 mmol) with 4 (1.00 mmol) in the presence of 1a (0.20 mmol) were
1
carried out at À788C for 2 h. [b] Yield of isolated product. [c] Determined by H NMR.
derivative was formed with 95:5 d.r. (Table 2, entry 8).
Recrystallization of the mixture from methanol gave only
the major diastereoisomer in pure form. The molecular
structure of the major diastereoisomer of 5i was unambigu-
ously determined by X-ray crystallographic analysis (see
Supporting Information).[16] In contrast to the good reactivity
of N,N-dimethylaniline (4j) and azulene (4k) (Table 2,
entries 9 and 10), no reaction proceeded when anisole (4g)
and 1,4-dimethoxybenzene (4h) were used as benzene
derivatives (Table 2, entries 6 and 7).
The asymmetric carboselenenylation reaction of other
alkenes (3) was investigated next (Table 3). The introduction
of a p-fluoro or p-phenyl substituent in the aromatic ring of b-
methylstyrene slightly increased the diastereoselectivity
(Table 3, entries 1 and 2). On the other hand, a slightly
lower diastereoselectivity was attained in the reaction of p-
methyl-(E)-b-methylstyrene (3d) (Table 3, entry 3). The
introduction of a chloro substituent in the aromatic ring
decreased the reactivity (Table 3, entries 4 and 5). Further-
more, the reaction of 2-((E)-1-propenyl)naphthalene (3g)
proceeded smoothly to give the corresponding alkylated
furan (5q) in good yield with 87:13 d.r. (Table 3, entry 6).
Although the reason is not known, the presence of 4-ꢀ
molecular sieves decreased both the reactivity and the
Scheme 2. Optically active electrophilic selenium reagents.
Angew. Chem. Int. Ed. 2005, 44, 3588 –3591
www.angewandte.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3589

Communications
Table 3: Asymmetric carboselenenylation reaction of alkenes (3) with with 2-methylfuran (4a) by using
1a.[a]
similar trend of lower diastereoselectivity in
the cases of 3h and 3i has been observed in
the asymmetric oxyselenenylation with
methanol by using 1b.[15] Unfortunately, no
reaction occurred in the reactions of ali-
phatic alkenes such as 1-octene (3j) and 3,3-
dimethylbutene (3k).
Entry
Alkene (3)
Product (5)
Yield[b]
d.r.[c]
The stereochemistry of the major dia-
stereoisomer of 5i (R configuration at the
benzylic position) indicates that 3a under-
goes Si-face attack by the chiral arenesele-
nium moiety (Figure 1). This stereoselective
approach is supported by previous theoret-
ical studies with density-functional calcula-
tions on the transition states by using 1a.[17]
Separately, we confirmed that the reductive
cleavage of a chiral arylselenium moiety of
5j (90:10 d.r.) with Bu3SnH in the presence
of a catalytic amount of AIBN in toluene at
reflux for 6 h afforded optically active 1-
(N,N-dimethylaminophenyl)-1-phenylpro-
pane (7) in quantitative yield with 90:10 d.r.
(HPLC) (Scheme 3). This result indicates
that the removal of the arylselenium moiety
in 5 proceeded without loss of optical purity
at the benzylic position.
In summary, we have developed an
asymmetric carboselenenylation reaction
of simple alkenes with aromatic compounds
by using a C2-symmetric areneselenenyl
triflate. The carbon–carbon bond-forming
reaction proceeds with high diastereoselec-
tivity. This reaction is a convenient proce-
dure for the preparation of chiral hydro-
carbons that bear an aryl moiety at the
stereogenic carbon atom and can be con-
1
2
3
4
5
R=p-F
R=p-Ph
R=p-Me
R=p-Cl
R=m-Cl
3b
3c
3d
3e
3 f
5l
55
55
67
39
39
93:7
94:6
89:11
90:10
94:6
5m
5n
5o
5p
6
3g
3h
3i
5q
5r
70
40
45
87:13
90:10
78:22
7[d]
8
5s
9
3j
5t
0
0
–
–
10
3k
5u
[a] All the reactions of 3 (2.00 mmol) with 4a (1.00 mmol) in the presence of 1a (0.20 mmol) were
carried out at À788C for 2 h. [b] Yield of isolated product. [c] Determined by 1H NMR. [d] In the absence
of 4-ꢀ molecular sieves.
diastereoselectivity of the reaction of a-methylstyrene (3h)
(Table 3, entry 7). A lower diastereoselectivity was observed
when styrene (3i) was used as an alkene (Table 3, entry 8). A
sidered as a new type of asymmetric Friedel–Crafts alkylation
reaction of aromatic compounds with alkenes. Further work is
aimed at the elucidation of the reaction mechanism in detail
and broadening the scope of the asymmetric reaction.
Experimental Section
5a: Molecular sieves (4ꢀ) (300 mg) and a solution of bromine
(0.12 mmol) in CCl4 (0.12 mL) were added to a solution of diselenide
2a (54.4 mg, 0.10 mmol, > 99% ee) in CH2Cl2 (4.0 mL) at À788C.
After 30 min, silver triflate (61.7 mg, 0.24 mmol) was added. The
resulting heterogeneous mixture was stirred at À788C for 30 min. (E)-
b-Methylstyrene (3a) (236.4 mg, 2.00 mmol) was then added to the
mixture at À788C followed by 2-methylfuran (4a) (81.2 mg,
1.00 mmol). The mixture was stirred for 2 h, quenched with saturated
aqueous NaHCO3 at À788C, and extracted with CH2Cl2. The
combined organic layers were dried over MgSO4 and concentrated.
The residue was purified by silica-gel chromatography to give 5a as a
colorless oil (68.4 mg, 0.145 mmol, 73% yield, 91:9 d.r.). The
diastereoisomers could not be separated by flash chromatography.
The diastereoselectivity does not change during the purification. The
ratio of two diastereoisomers was determined by 1H NMR and
77Se NMR; 1H NMR (CDCl3, 400 MHz): major diastereoisomer: d =
1.24 (d, J = 6.8 Hz, 3H), 1.39 (d, J = 6.4 Hz, 6H), 2.26 (s, 3H), 3.12 (s,
6H), 3.74 (dq, J = 10 and 6.8 Hz, 1H), 4.06 (d, J = 10 Hz, 1H), 5.13 (q,
Figure 1. Stereochemistry of the major diastereoisomer of 5i.
Scheme 3. Reductive cleavage of a chiral arylselenium moiety of 5j.
AIBN=azobisisobutyronitrile.
3590
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2005, 44, 3588 –3591

Angewandte
Chemie
J = 6.4 Hz, 2H), 5.86 (d, J = 3.2 Hz, 1H), 6.03 (d, J = 3.2 Hz, 1H),
7.27–7.46 ppm (m, 8H); minor diastereoisomer: d = 3.83 (dq, J = 8.8
and 6.4 Hz, 1H), 4.11 ppm (d, J = 8.8 Hz, 1H); 13C{1H} NMR (CDCl3,
100 MHz): major diastereoisomer: d = 13.7, 20.6, 24.2, 44.3, 52.4, 56.3,
78.4, 105.9, 107.5, 125.2, 127.2, 128.1, 128.3, 128.5, 129.7, 140.6, 148.3,
151.2, 153.0 ppm; 77Se{1H} NMR (CDCl3, 76 MHz): major diaster-
eoisomer: d = 236.9 ppm (s); minor diastereoisomer: d = 236.3 ppm
(s). Elemental analysis: calcd for C26H32O3Se: C 66.23, H 6.84; found:
C 66.31, H 6.92.
G. Fragale, T. Wirth, Chem. Eur. J. 2002, 8, 1125; j) M. Tiecco, L.
Testaferri, C. Santi, C. Tomassini, F. Marini, L. Bagnoli, A.
Temperini, Angew. Chem. 2003, 115, 3239; Angew. Chem. Int.
Ed. 2003, 42, 3131.
[13] a) A. Toshimitsu, K. Nakano, T. Mukai, K. Tamao, J. Am. Chem.
Soc. 1996, 118, 2756; b) K. Okamoto, Y. Nishibayashi, S.
Uemura, A. Toshimitsu, Tetrahedron Lett. 2004, 45, 6137.
[14] An asymmetric intramolecular cyclization of alkenes with
aromatic compounds by using an optically active electrophilic
selenium reagent was reported, but the reaction is not a direct
carboselenenylation; the stepwise reaction first involves an
oxyselenenylation and then a stereoselective intramolecular
cyclization of an episelenonium ion with benzene derivatives to
give the corresponding cyclic products with high diastereoselec-
tivity: R. Dꢁziel, E. Malenfant, C. Thibault, Tetrahedron Lett.
1998, 39, 5493.
Received: February 16, 2005
Published online: May 4, 2005
Please note: Minor changes have been made to this manuscript
since its publication in Angewandte Chemie Early View. The Editor.
[15] R. Dꢁziel, S. Goulet, L. Grenier, J. Bordeleau, J. Bernier, J. Org.
Chem. 1993, 58, 3619.
Keywords: alkenes · asymmetric synthesis · diastereoselectivity ·
selenium · synthetic methods
.
[16] The molecular structure of a major diastereoisomer of 5i was
unambiguously clarified by X-ray crystallographic analysis.
CCDC-261554 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[17] a) T. Wirth, G. Fragale, M. Spichty, J. Am. Chem. Soc. 1998, 120,
3376; b) X. Wang, K. N. Houk, M. Spichty, T. Wirth, J. Am.
Chem. Soc. 1999, 121, 8567; c) M. Spichty, G. Fragale, T. Wirth, J.
Am. Chem. Soc. 2000, 122, 10914.
[1] For a review, see: T. Katsuki, Coord. Chem. Rev. 1995, 140, 189,
and references therein.
[2] For a review, see: H. C. Kolb, M. S. Van Nieuwenhze, K. B.
Sharpless, Chem. Rev. 1994, 94, 2483, and references therein.
[3] a) G. Li, H.-T. Chang, K. B. Sharpless, Angew. Chem. 1996, 108,
449; Angew. Chem. Int. Ed. Engl. 1996, 35, 451; b) G. Li, H. H.
Angert, K. B. Sharpless, Angew. Chem. 1996, 108, 2995; Angew.
Chem. Int. Ed. Engl. 1996, 35, 2813.
[4] a) T. Hayashi, Y. Matsumoto, Y. Ito, J. Am. Chem. Soc. 1989, 111,
3426; b) K. Burgess, M. J. Ohlmeyer, Chem. Rev. 1991, 91, 1179,
and references therein.
[5] a) Y. Uozumi, T. Hayashi, J. Am. Chem. Soc. 1991, 113, 9887;
b) T. Hayashi, Acc. Chem. Res. 2000, 33, 354, and references
therein.
[6] For a recent review, see: H. Lebel, J.-F. Marcoux, C. Molinaro,
A. B. Charette, Chem. Rev. 2003, 103, 977, and references
therein.
[7] For a review, see: F. Agbossou, J.-F. Carpentier, A. Mortreux,
Chem. Rev. 1995, 95, 2485, and references therein.
[8] a) O. Kitagawa, T. Hanano, K. Tanabe, M. Shiro, T. Taguchi, J.
Chem. Soc. Chem. Commun. 1992, 1005; b) S. H. Kang, S. B.
Lee, C. M. Park, J. Am. Chem. Soc. 2003, 125, 15748.
[9] a) S. H. Kang, M. Kim, J. Am. Chem. Soc. 2003, 125, 4684;
b) S. H. Kang, M. Kim, S. Y. Kang, Angew. Chem. 2004, 116,
6303; Angew. Chem. Int. Ed. 2004, 43, 6177.
[10] For recent reviews, see: a) Organoselenium Chemistry (Ed.:
T. G. Back), Oxford University Press, Oxford, 1999; b) T. Wirth
(Ed.), Top. Curr. Chem. 2000, 208; c) T. Wirth, Angew. Chem.
2000, 112, 3890; Angew. Chem. Int. Ed. 2000, 39, 3741.
[11] a) S. Fukuzawa, Y. Kasugahara, S. Uemura, Tetrahedron Lett.
1994, 35, 9403; b) Y. Nishibayashi, S. K. Srivastava, H. Takada, S.
Fukuzawa, S. Uemura, J. Chem. Soc. Chem. Commun. 1995,
2321; c) H. Takada, Y. Nishibayashi, S. Uemura, J. Chem. Soc.
Perkin Trans. 1 1999, 1511.
[12] a) S. Tomoda, M. Iwaoka, Chem. Lett. 1988, 1895; b) T. Wirth,
Angew. Chem. 1995, 107, 1872; Angew. Chem. Int. Ed. Engl.
1995, 34, 1726; c) S. Fukuzawa, K. Takahashi, H. Kato, H.
Yamazaki, J. Org. Chem. 1997, 62, 7711; d) M. Tiecco, L.
Testaferri, C. Santi, C. Tomassini, F. Marini, L. Bagnoli, A.
Temperini, Eur. J. Org. Chem. 2000, 3451; e) M. Tiecco, L.
Testaferri, F. Marini, S. Sternativo, C. Santi, L. Bagnoli, A.
Temperini, Tetrahedron: Asymmetry 2001, 12, 3053; f) M.
Tiecco, L. Testaferri, L. Bagnoli, V. Purgatorio, A. Temperini,
F. Marini, C. Santi, Tetrahedron: Asymmetry 2001, 12, 3297;
g) T. G. Back, Z. Moussa, M. Parvez, J. Org. Chem. 2002, 67, 499;
h) M. Tiecco, L. Testaferri, C. Santi, C. Tomassini, F. Marini, L.
Bagnoli, A. Temperini, Chem. Eur. J. 2002, 8, 1118; i) L. Uehlin,
Angew. Chem. Int. Ed. 2005, 44, 3588 –3591
www.angewandte.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3591