ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
NBS-Initiated Electrophilic
Phenoxyetherification of Olefins
Zhihai Ke and Ying-Yeung Yeung*
3 Science Drive 3, Department of Chemistry, National University of Singapore,
Singapore 117543
Received February 28, 2013
ABSTRACT
A one-pot electrophilic phenoxyetherification using an olefin, a cyclic ether, a phenol, and N-bromosuccinimide has been developed. This type of
multicomponent reaction (MCR) is useful in the synthesis of building blocks that are potentially applicable to self-assembly complex construction.
To synthesize target compounds with great efficiency
and atom economy, many highly effective and powerful
synthetic tools have been developed in modern green
chemistry.1 Among these, multicomponent reactions
(MCRs) have been considered as the “cream of the crop”,
by generating structural complexity in a single step from
three or more reactants generally and reliably.2 Although
successes had been reported on MCRs, developing new
reactions is still of significant importance.3 Partly due to
the common incompatibility of electrophiles with the other
components, electrophilic MCRs have been relatively less
reported.4
In the course of our endeavor to develop electrophilic
MCR utilizing N-bromosuccinimide (NBS) as the bromi-
nating initiator, we have disclosed a number of electro-
philic cascades using various nucleophilic partners.5 In
these studies, it was found that a nucleophile that contains
an acidic proton is necessary to achieve high reaction yield.
The acidic proton may be used to activate the halogen
source NBS. Herein, we report the use of electron-deficient
phenol as the nucleophilic partner in this type of MCR.
The resulting products B, which contain a ether linkage
and a functionalized phenoxy unit, can be further manipu-
lated to give building blocks (e.g., C) that are potentially
useful for self-assembly complex construction (vida infra)
(Scheme 1).
(1) (a) Constable, D. J. C.; Dunn, P. J.; Hayler, J. D.; Humphrey,
G. R.; Leazer, J. L.; Linderman, R. J., Jr.; Lorenz, K.; Manley, J.;
Pearlman, B. A.; Wells, A.; Zaks, A.; Zhang, T. Y. Green Chem. 2007, 9,
411. (b) Rosamilia, A. E.; Scott, J. L.; Strauss, C. R. Org. Lett. 2005, 7,
1525. (c) Rosamilia, A. E.; Strauss, C. R.; Scott, J. L. Pure Appl. Chem.
2007, 79, 1869. (d) Shi, D. Q.; Ni, S. N.; Yang, F.; Ji, S. J. J. Heterocycl.
Chem. 2008, 45, 1275. (e) Andriushchenko, A. Y.; Desenko, S. M.;
Chernenko, V. N.; Chebanov, V. A. J. Heterocycl. Chem. 2011, 48, 365.
€
(2) For selected reviews on MCRs, see: (a) Ugi, I.; Domling, A.; Horl,
€
W. Endeavour 1994, 18, 115. (b) Domling, A.; Ugi, I. Angew. Chem., Int.
ꢀ
Ed. 2000, 39, 3168. (c) Multicomponent Reactions; Zhu, J., Bienayme,
€
H., Eds.; Wiley-VCH: Weinheim, 2005. (d) Domling, A. Chem. Rev. 2005,
ꢀ
106, 17. (e) Ganem, B. Acc. Chem. Res. 2009, 42, 463. (f) Toure, B. B.;
Hall, D. G. Chem. Rev. 2009, 109, 4439. (g) Sunderhaus, J. D.; Martin,
S. F. Chem.;Eur. J. 2009, 15, 1300.
ꢀ
(3) Ramon, D. J.; Yus, M. Angew. Chem., Int. Ed. 2005, 44, 1602.
(4) For selected electrophilic MCRs, see: (a) Serguchev, Y. A.;
Ponomarenko, M. V.; Lourie, L. F.; Chernega, A. N. J. Fluorine Chem.
2003, 123, 207. (b) Nair, V.; Menon, R. S.; Beneesh, P. B.; Sreekumar, V.;
Bindu, S. Org. Lett. 2004, 6, 767. (c) Nair, V.; Beneesh, P. B.; Sreekumar,
V.; Bindu, S.; Menon, R. S.; Deepthi, A. Tetrahedron Lett. 2005, 46, 201.
(d) Yeung, Y. Y.; Gao, X. R.; Corey, E. J. J. Am. Chem. Soc. 2006, 128,
9644. (e) Church, T. L.; Byrne, C. M.; Lobkovsky, E. B.; Coates, G. W.
J. Am. Chem. Soc. 2007, 129, 8156. (f) Hajra, S.; Bar, S.; Sinha, D.; Maji,
B. J. Org. Chem. 2008, 73, 4320. (g) Abe, T.; Takeda, H.; Miwa, Y.;
Yamada, K.; Yanada, R.; Ishikura, M. Helv. Chim. Acta 2010, 93, 233.
(h) Braddock, D. C.; Millan, D. S.; Perez-Fuertes, Y.; Pouwer, R. H.;
Sheppard, R. N.; Solanki, S.; White, A. J. P. J. Org. Chem. 2009, 74,
1835. (i) Bonney, K. J.; Braddock, D. C.; White, A. J. P.; Yaqoob, M.
J. Org. Chem. 2011, 76, 97. (j) Snyder, S. A.; Treitler, D. S.; Bruchks,
A. P.; Sattler, W. J. Am. Chem. Soc. 2011, 133, 15898.
(5) (a) Zhou, L.; Tan, C. K.; Zhou, J.; Yeung, Y.-Y. J. Am. Chem.
Soc. 2010, 132, 10245. For other examples of electrophilic Br initiated
cascades, see: (b) Zhou, L.; Zhou, J.; Tan, C. K.; Chen, J.; Yeung, Y.-Y.
Org. Lett. 2011, 13, 2448. (c) Zhou, L.; Chen, J.; Zhou, J.; Yeung, Y.-Y.
Org. Lett. 2011, 13, 5804. (d) Chen, J.; Chng, S.; Zhou, L.; Yeung, Y.-Y.
Org. Lett. 2011, 13, 6456. (e) Zhou, J.; Zhou, L.; Yeung, Y.-Y. Org. Lett.
2012, 14, 5250. For some selected recent examples of cohalogenation
reactions, see: (f) Cai, Y.; Liu, X.; Hui, Y.; Jiang, J.; Wang, W.; Chen,
W.; Lin, L.; Feng, X. Angew. Chem., Int. Ed. 2010, 49, 6160. (g) Cai, Y.;
Liu, X.; Jiang, J.; Chen, W.; Lin, L.; Feng, X. J. Am. Chem. Soc. 2011,
133, 5636. (h) Cai, Y.; Liu, X.; Jiang, J.; Li, J.; Chen, W.; Wang, W.; Lin,
L.; Feng, X. Chem.;Eur. J. 2011, 17, 14916.
r
10.1021/ol4005646
XXXX American Chemical Society