Catalytic Selenium-Promoted Intermolecular Friedel-Crafts Alkylation with Simple Alkenes

Article abstract of DOI:10.1021/acs.orglett.5b03579

A method for conducting selenium-promoted intermolecular Friedel-Crafts (F-C) alkylation reactions has been developed with simple alkenes using trimethylsilyl trifluoromethanesulfonate as a catalyst and N-phenylselenophthalimide as an efficient selenium s

Full text of DOI:10.1021/acs.orglett.5b03579

Letter
pubs.acs.org/OrgLett
Catalytic Selenium-Promoted Intermolecular Friedel−Crafts
Alkylation with Simple Alkenes
,†,‡
‡,§
‡,§
‡
‡
‡
E Tang,* Yinjiao Zhao, Wen Li, Weilin Wang, Meng Zhang, and Xin Dai
†
‡
Key Laboratory of Medicinal Chemistry for Natural Resources (Yunnan University) Ministry of Education and School of Chemical
Science and Technology, Yunnan University, 2 Green Lake North Road, Kunming 650091, China
*
S Supporting Information
ABSTRACT: A method for conducting selenium-promoted inter-
molecular Friedel−Crafts (F−C) alkylation reactions has been
developed with simple alkenes using trimethylsilyl trifluoromethane-
sulfonate as a catalyst and N-phenylselenophthalimide as an efficient
selenium source. Electron-rich arenes smoothly underwent F−C
alkylation with a variety of alkenes to afford alkylated products in good
yield and with high regioselectivity and diastereoselectivity. The regioselectivity and stereoselectivity of arenes and alkenes as well
as a preliminary mechanism of the F−C alkylation reaction are discussed.
s an important cornerstone of chemistry, Friedel−Crafts
(F−C) alkylation provides a powerful method for forming
alkylation is uneconomical because they use large quantities
(specifically 5−10 times the quantity of selenides) of alkenes,
aromatic compounds, and Lewis acids. Yoshida treated alkenes
with benzenenselenenyl arenesulfonate and anisole in acetoni-
trile or nitromethane to give anisylselenenylated compounds in
low to high yields. However, 46 equiv of anisole was used in the
A
new carbon−carbon bonds and has been widely utilized in
contexts ranging from academic experiments to industrial
1
processes. The stereoselective version of this reaction with
alkenes has attracted considerable interest and has been
2
10e
enhanced by significant recent progress. Despite considerable
anisylselenenylation reaction. Here, we report an economical,
effort, most successful examples of these processes have focused
efficient, trimethylsilyl trifluoromethanesulfonate (TMSOTf)
catalyzed and weak electrophilic selenium-promoted intermo-
lecular F−C alkylation with alkenes that could provide an
alternative method for synthesizing 1,1-diaryl-2-phenylselenoal-
kanes in good yields and with high regioselectivity and
stereoselectivity. Moreover, the resulting alkylated arenes
containing α-seleno functionality could provide a further avenue
for structural elaboration.
on relatively reactive aromatic compounds such as furans,
3
pyrroles, and indoles with activated alkenes via 1,4-conjugate
4
addition or with intermediate compounds derived from alkenes,
5
such as epoxides, and three-membered ring halonium ions
6
generated by a ring-opening reaction. Therefore, there is an
urgent requirement to develop novel stereoselective F−C
reactions, particularly for undeveloped arenes such as benzene
derivatives with simple alkenes.
A current interest in our laboratory is the Lewis acid catalyzed
Organoselenium compounds are potentially bioactive and can
13
selenofunctionalization of olefins. Inspired by the Brønsted
7
,8
be used as valuable synthetic intermediates. Similarly to
12
acid catalyzed carboselenenylation of styrenes with indole and
9
halonium ions, a three-membered ring seleniranium ion is
14
Lewis acid mediated carboannulation, we found that Lewis
attacked by external carbon-centered nucleophiles such as
alkenyl silyl ethers, trimethylsilyl cyanide, allyltrimethylsilane,
and aromatic compounds to afford different carboselenenylation
acids and Brønsted acids could activate weak electrophilic
organoselenides, such as N-phenylselenosuccinimide (NPSS)
and N-phenylselenophthalimide (NPSP), and facilitate the
formation of episelenonium ions from olefins. Recently, we
have described TMSOTf-catalyzed and polymer-supported
NPSS-promoted intramolecular F−C alkylation with tethered
10
products of alkenes with good trans stereospecificity. Although
the utility of electrophilic selenium reagents for carbon−
heteroatom bond-formation reactions has been well docu-
mented, the potency of electrophilic organoselenium reagents
for carbon−carbon bond-formation reactions has been examined
15
alkenes for the synthesis of annulated aromatic heterocycles.
1
1
12
Fortunately, only 0.10 equiv of TMSOTf was used in our
relatively infrequently. With the exception of indoles,
16
intramolecular F−C alkylation reactions (Scheme 1), whereas
aromatic compounds such as furan, thiophene, N-methylpyrrole,
azulene, and a few electron-rich benzene derivatives have been
used to afford the products of selenium-promoted intermolecular
F−C alkylation of alkenes in low yields. Furthermore, the key
three-membered cyclic episelenonium ion intermediate was
derived from the strongly electrophilic areneselenenyl trifluor-
omethanesulfonate via addition to olefins or from an alcohol
bearing a phenylseleno group on the adjacent carbon atom via an
2
.10 equiv of TMSOTf was used in the reported carboannula-
14
tion. Accordingly, we anticipated that a suitable Lewis acid
might catalyze the selenium-promoted intermolecular F−C
alkylation of arenes with alkenes. To achieve this objective, we
screened different Lewis acids as catalysts for the selenium-
Received: December 16, 2015
10
acid-induced reaction. However, the aforementioned F−C
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b03579
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Letter
Scheme 1. Selenium-Promoted Intramolecular F−C
Alkylation with Tethered Alkenes
Scheme 2. Scope of Intermolecular Selenium-Promoted F−C
−
a c
Alkylation with Alkenes
promoted F−C alkylation of 1,3,5-trimethoxy benzene (1a) with
styrene (2a), using NPSP as the selenium source, and optimized
the reaction conditions. In the absence of a Lewis acid catalyst,
the reaction afforded no F−C-alkylated product. In addition,
TiCl , AlCl , FeCl , ZnCl , SnCl , BF ·Et O, AgOTf, and
4
3
3
2
4
3
2
Sm(OTf) did not exhibit catalytic activity. TMSOTf was
3
found to be the best catalyst, resulting in an isolated yield of
product 3aa of up to 97%. The optimized F−C alkylation
reaction conditions are 0.10 equiv of TMSOTf, 1.0 equiv of
alkenes, 1.0 equiv of arenes, and 1.1 equiv of NPSP in CH Cl at
2
2
−
78 °C for 2 h and then at −20 °C for 7 h.
With the optimized conditions established, we then expanded
the substrate scope; the results are indicated in Scheme 2. In
general, the tested reactions all proceeded smoothly to afford
products in moderate to good yields and with high
regioselectivity. In particular, good yields and 99% regioselectiv-
ity were achieved with styrene and styrene bearing electron-
withdrawing nitro, chloro, fluoro, and bromo substituents and
electron-donating methyl and methoxy substituents (Scheme 2,
3
aa−f,ba−f,ca−e,da−f,ea−f,fa,gc). In contrast, the F−C
alkylation reaction was rather sluggish when electron-deficient
olefins such as α,β-unsaturated carbonyl compounds were used
as the substrate (Scheme 2, 3ka,la). Moreover, simple cyclic
alkenes such as cyclohexene reacted smoothly to generate
products with high diastereoselectivity (Scheme 2 and Figure 1,
3
ja). (Z)- and (E)-β-methylstyrenes afforded products in good
yields and with 99% regioselectivity and diastereoselectivity
Scheme 2, 3h−ia). In addition, benzene bearing more than two
(
electron-donating substituents and m-dialkoxybenzenes pro-
duced good results (Scheme 2, 3aa−g,ba−f,ca−e,da−f,ea−
f,fa,gc,h−ja), whereas ortho- and para-disubstituted benzenes,
monosubstituted benzenes, and benzenes bearing electron-
withdrawing substituents such as formyl afforded yields of less
than 5% (Scheme 2, 3ah−k) and instead generated hydrox-
yselenenylation products and small quantities of amidoseleneny-
lated products and diaryl selenides because the F−C alkylation
reactions were quenched with a saturated aqueous solution of
NaHCO and phthalimide counteranion has poor nucleophil-
3
a
icity; these results indicate that the F−C alkylation reaction
occurred more readily if more electron-donating substituents
were present in the benzene ring. For unsymmetrical substituted
benzenes, the combined effects of the carbon nucleophile and
steric hindrance in the benzene ring governed the regioselectivity
of the substituted benzenes in the F−C alkylation reaction;
trisubstituted benzenes, tetrasubstituted benzenes, and sym-
metrical meta-disubstituted benzenes afforded the products with
high regioselectivity (Scheme 2, 3ab−f,bb,3be−f,cb−e,db−
f,eb−f,gc,kb−c), whereas unsymmetrical meta-disubstituted
benzenes, such as 1-ethoxy-2-methoxybenzene, afforded prod-
ucts with low regioselectivity (Scheme 2, 3ag). In addition,
Markovnikov-type adducts with good yields derived from the
highly regioselective carboselenenylation of styrenes and trans-
The general reaction was performed on a 0.5 mmol scale in 5 mL of
CH Cl with a 1/2 molar ratio of 1/1; products from 3aa to 3gc were
produced from styrene (2a) and substituted styrene (2b−g); products
3
2
2
h−ja were produced, respectively, from (E)-β-methylstyrene (2h),
b
c
(
Z)-β-methylstyrene (2i), and cyclohexene (2j). Isolated yield. The
1
d
value of dr was determined by H NMR. Combined yield of 4-
ethoxy-2-methoxy-1-[1-phenyl-2-(phenylseleno)ethyl]benzene (3ag)
and 2-ethoxy-4-methoxy-1-[1-phenyl-2-(phenylseleno)ethyl]benzene
e
(3ag′). The reaction generated hydroxyselenenylation products and
a small quantity of diaryl selenides.
type adducts were obtained regioselectively and diastereoselec-
tively via the carboselenenylation of β-methylstyrenes and cyclic
alkenes. According to the ROESY spectrum of 5ha and the
B
DOI: 10.1021/acs.orglett.5b03579
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Letter
reduction and deselenenylation with NaBH in the presence of
4
NiCl ·6H O (Scheme 4).
2
2
Scheme 4. Synthesis of (E)-α-(4-Alkoxy-2,3,6-
trimethylphenyl)-β-(phenylseleno)styrene (7) from
,
a b
Phenylacetylene and the Hydride Reduction and
,
b c
Deselenenylation Reaction of Compound 7
Figure 1. ORTEP structures of compounds 3ja and 5ab.
1
a
correlation of δ (7.24) and δ (6.34), together with the H
The general reaction was performed on a 0.5 mmol scale in 5 mL of
b c
H
H
NMR and 13C NMR spectra, the following structure of
compound 5ha can be deduced as (Z)-1-(1-phenyl-1-propen-
yl)-2,4,6-trimethoxybenzene. Therefore, the alkene 5ha was
synthesized from (E)-β-methylstyphene (2h) via anti-addition
with NPSP and syn-elimination of selenoxide (Scheme 3),
CH
Cl for 9 h. Isolated yield. The general reaction was performed
2
2
on a 0.2 mmol scale in 2 mL of CH Cl and 2 mL of THF at 0 °C,
with a 7/NaBH /NiCl ·6H O molar ratio of 1/6.8/2.3.
2
2
4
2
2
In addition, chiral NPSP 10, which was synthesized in situ
16
from chiral diaryl diselenide 9, was used in the F−C alkylation
reaction of styrene and 1,3,5-trimethoxybenzene (1a) and 1-
ethoxy-2,3,5-trimethylbenzene (1c) to afford the corresponding
carboselenenylation products in good yields and with moderate
diastereoselectivity (Scheme 5).
Scheme 3. Selenoxide Syn Elimination of Compound 3ab −
a c
Scheme 5. Synthesis of Chiral NPSP 10 and Intermolecular
−
a d
Chiral Selenium-Promoted F−C Alkylation with Alkenes
a
The general reaction was performed on a 0.2 mmol scale in 8 mL of
b
c
THF and 0.5 mL of H O aqueous solution. Isolated yield. ORTEP
of the molecular structure of compound 5ab. The correlation of δH
2
2
d
3
a
2
The reaction was performed on a 0.55 mmol scale in 5 mL of CH Cl
2
(7.24) and δH (6.34) in the ROESY spectrum of 5ha.
2
b
and with a 9/Br molar ratio of 11/12. The reaction was performed
2
on a 1.1 mmol scale in 5 mL of hexane and with a selenium bromide/
c
phthalimide potassium molar ratio of 1/1. The reaction was
d
whereas the alkene 5ia was obtained from (Z)-β-methylstyphene
2i) via anti-addition with NPSP and syn-elimination of
selenoxide because of no correlation of δH (7.25) and δH
performed on a 1.0 mmol scale in 10 mL of CH Cl . Isolated yield.
2
2
(
(
5.69) in the ROESY spectrum of 5ia (Scheme 3).
Therefore, the F−C alkylation reaction of (E)-β-methylsty-
Mechanistically, it appears that TMSOTf activates NPSP by
chelating to the amide carbonyl group to facilitate the formation
of the episelenonium ion intermediate 12 from alkenes; the
subsequent reaction with arenes led to the formation of F−C-
alkylated products 3 and the regeneration of the TMSOTf
catalyst. Thus, a plausible mechanism has been proposed for the
F−C alkylation reaction (Scheme 6). In this scenario, the
byproduct phthalimide 15 was found and the silyl enol ether
intermediate 13 was verified by ReactIR spectra revealing the
phene (2h) produces (1S,2S) and (1R,2R) adducts (± )-3ha, and
the reaction of (Z)-β-methylstyphene (2i) produces (1S,2R) and
(
1R,2S) adducts (± )-3ia. The regioselectivity of the products of
the carboselenenylation of alkenes was verified by treating
compounds 3ab with 30% H O aqueous solution in THF at 0
2
2
°
C for 1.5 h and then at room temperature for 30 min to afford
ab in 91% yield via a selenoxide syn-elimination reaction, and
the regioselectivity of the F−C alkylation reaction of 1-methoxy-
,3,5-trimethylbenzene (1b) with styrene was established by X-
5
−1
stretching vibrational absorption of the O−Si bond at 1033 cm
(Figure 2).
2
ray analysis of 5ab (Figure 1). Subsequently, the reaction was
investigated using phenylacetylene 6 as a substrate, which
afforded β-(phenylseleno)styrene 7 in moderate yields and with
high regioselectivity. This product was verified via hydride
In conclusion, we have developed a catalytic, efficient,
intermolecular F−C alkylation reaction with simple alkenes
and arenes that uses NPSP as a selenium source. The
intermolecular carbon−carbon bond-forming reaction proceeds
C
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Letter
Scheme 6. Mechanistic Hypothesis for the Intermolecular
NPSP-Promoted F−C Alkylation Reaction with Alkenes
ACKNOWLEDGMENTS
■
The project was supported by the Ministry of Education of the
People’s Republic of China (Program for Changjiang Scholars
and Innovative Research Team in University, IRT13095) and the
Natural Science Foundation of China (NSFC 21162032).
REFERENCES
■
(
1) (a) Olah, G. A.; Krishnamurti, R.; Prakash, G. K. S. Friedel−Crafts
Alkylation. In Comprehensive Organic Synthesis; Trost, B. M., Fleing, I.,
Eds.; Pergamon: Oxford, 1991; Vol. 3, pp 293−339. (b) Roberts, R. M.;
Khalaf, A. A. Friedel−Crafts Alkylation Chemistry: A Century of Discovery;
Dekker: New York, 1984. (c) Bandini, M.; Melloni, A.; Umani-Ronchi,
A. Angew. Chem., Int. Ed. 2004, 43, 550.
(
2) For selected reviews on F−C alkylation, see: (a) Poulsen, T. B.;
Jørgensen, K. A. Chem. Rev. 2008, 108, 2903. (b) Bandini, M.; Melloni,
A.; Umani-Ronchi, A. Angew. Chem., Int. Ed. 2004, 43, 550.
(
3) For examples, see: (a) Palomo, C.; Oiarbide, M.; Kardak, B. G.;
Garcιa, J. M.; Linden, A. J. Am. Chem. Soc. 2005, 127, 4154. (b) Evans, D.
A.; Fandrick, K. R.; Song, H. J. J. Am. Chem. Soc. 2005, 127, 8942.
́
(c) Terada, M.; Sorimachi, K. J. Am. Chem. Soc. 2007, 129, 292.
(d) Kang, Q.; Zhao, Z. A.; You, S. L. J. Am. Chem. Soc. 2007, 129, 1484.
(4) For examples, see: (a) Manabe, K.; Aoyama, N.; Kobayashi, S. Adv.
Synth. Catal. 2001, 343, 174. (b) Bandani, M.; Cozzi, P. G.; Giacomini,
M.; Melchiorre, P.; Selva, S.; Umani-Ronchi, A. J. Org. Chem. 2002, 67,
3
700. (c) Srivastava, N.; Banik, B. K. J. Org. Chem. 2003, 68, 2109.
(5) For examples, see: (a) Taylor, S. K.; May, S. A.; Stansby, E. S. J. Org.
Chem. 1996, 61, 2075. (b) Reddy, R.; Jaquith, J. B.; Neelagiri, V. R.;
Saleh-Hanna, S.; Durst, T. Org. Lett. 2002, 4, 695.
(
(
6) Hajra, S.; Maji, B.; Bar, S. Org. Lett. 2007, 9, 2783.
7) For examples, see: (a) Nogueira, C. W.; Zeni, G.; Rocha, J. B. T.
Chem. Rev. 2004, 104, 6255. (b) Tojino, M.; Otsuka, N.; Fukuyama, T.;
Matsubara, H.; Ryu, I. J. Am. Chem. Soc. 2006, 128, 7712. (c) Clive, D. L.
J.; Pham, M. P.; Subedi, R. J. Am. Chem. Soc. 2007, 129, 2713.
Figure 2. ReactIR spectrum of the F−C alkylation reaction of
compound 1b with styrene and NPSP: 1-methoxy-2,3,5-trimethylben-
−1
−1
zene (1b), (υC−O−C) 1116 cm ; 15, 1067 cm ; 3ab, (υC−O−C)
(
8) Wirth, T. Organoselenium Chemistry: Synthesis and Reactions;
Wiley−VCH: Weinheim, 2012.
9) For examples, see: (a) Liotta, D. Organoselenium Chemistry; John
−1
−1
−1
1
119 cm ; NPSP, 1045 cm ; 13, (υSi−O) 1033 cm .
(
Wiley and Sons: New York, 1987. (b) Paulmei, C. Selenium Reagents and
Intermediates in Organic Synthesis; Pergamon Press: Oxford, 1986.
with high regioselectivity and diastereoselectivity. This reaction
is a convenient procedure for the preparation of 1,1-diaryl-
substituted alkenes via selenoxide syn elimination and chiral
hydrocarbons that bear an aryl moiety at the stereogenic carbon
atom if a chiral selenium reagent is used. Efforts to study the
asymmetric F−C alkylation reaction using chiral selenium
reagents are currently underway.
(10) (a) Toshimitsu, A.; Nakano, K.; Mukai, T.; Tamao, K. J. Am.
Chem. Soc. 1996, 118, 2756. (b) Okamoto, K.; Nishibayashi, Y.; Uemura,
S.; Toshimitsu, A. Tetrahedron Lett. 2004, 45, 6137. (c) Okamoto, K.;
Nishibayashi, Y.; Uemura, S.; Toshimitsu, A. Angew. Chem., Int. Ed.
2005, 44, 3588. (d) Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.;
Marini, F.; Bagnoli, L.; Temperini, A. Angew. Chem., Int. Ed. 2003, 42,
3
131. (e) Yoshida, M.; Satoh, N.; Kamigata, N. Chem. Lett. 1989, 1433.
(11) (a) Mukherjee, A. J.; Zade, S. S.; Singh, H. B. Chem. Rev. 2010,
10, 4357. (b) Organoselenium Chemistry; Liotta, D., Ed.; Wiley: New
ASSOCIATED CONTENT
Supporting Information
■
1
*
S
York, 1987. (c) Krief, A.; Hevesi, L. Organoselenium Chemistry; Springer:
Berlin, 1998. (d) Organoselenium Chemistry-Modern Development in
Organic Synthesis. In Topics in Current Chemistry; Wirth, T., Ed.;
Springer-Verlag: Berlin, 2000; Vol. 208.
(12) Zhao, X. D.; Yu, Z. K.; Xu, T. Y. Org. Lett. 2007, 9, 5263.
(13) (a) Tang, E.; Cheng, B. Z. Synlett 2011, 2011, 707. (b) Huang, X.;
Tang, E.; Xu, W. M.; Cao, J. J. Comb. Chem. 2005, 7, 802. (c) Xu, W. M.;
Huang, X.; Tang, E. J. Comb. Chem. 2005, 7, 726. (d) Tang, E.; Huang,
X.; Xu, W. M. Tetrahedron 2004, 60, 9963. (e) Tang, E.; Wang, W. L.;
Zhao, Y. J.; Zhang, M.; Dai, X. Org. Lett. 2016, 18, 176.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.5b03579.
Table presenting the optimization of selenium-promoted
1
F−C alkylation with styrene, experimental procedures, H
1
3
NMR and C NMR spectral data for compounds 3, 5, 7,
8
5
, and 18, and 2D NMR spectral data for compounds 3ae,
ha, and 5ia (PDF)
X-ray data for compound 3ja (CIF)
X-ray data for compound 5ab (CIF)
(14) Edstrom, E. D.; Livinghouse, T. Tetrahedron Lett. 1986, 27, 3483.
(15) (a) Tang, E.; Li, W. Synlett 2012, 23, 907. (b) Tang, E.; Mao, D. S.;
Li, W.; Gao, Z. Y.; Yao, P. F. Heterocycles 2012, 85, 667. (c) Tang, E.; Li,
W.; Gao, Z. Y.; Gu, X. Chin. Chem. Lett. 2012, 23, 631.
AUTHOR INFORMATION
Corresponding Author
■
(16) Zhao, L. W.; Li, Z.; Wirth, T. Eur. J. Org. Chem. 2011, 2011, 7080.
*E-mail: tange@ynu.edu.cn.
Author Contributions
§
Y.Z. and W.L. contributed equally to this work.
Notes
The authors declare no competing financial interest.
D
DOI: 10.1021/acs.orglett.5b03579
Org. Lett. XXXX, XXX, XXX−XXX