E
T. R. Ramadhar et al.
Letter
Synlett
References and Notes
Br
Br
1) Boc2O (3.5 equiv)
OH
Ot-Bu
Sc(OTf)3 (5 mol%)
CH2Cl2, rt, 24 h
(1) Koh, M. J.; Nguyen, T. T.; Zhang, H.; Schrock, R. R.; Hoveyda, A. H.
Nature (London, U.K.) 2016, 531, 459; and references cited
therein.
(2) Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.;
Snieckus, V. Angew. Chem. Int. Ed. 2012, 51, 5062.
11
80%
8b
2) resubject to
reaction conditions
OMe
OMe
Suzuki–Miyaura
(3) (a) Tucker, C. E.; Majid, T. N.; Knochel, P. J. Am. Chem. Soc. 1992,
114, 3983. (b) Klatt, T.; Markiewicz, J. T.; Sämann, C.; Knochel, P.
J. Org. Chem. 2014, 79, 4253. (c) Yanagisawa, A. In Science of Syn-
thesis, 7: Category 1, Organometallics; Yamamoto, H., Ed.;
Thieme: Stuttgart, 2004, 527.
no isolated product
Br
Br
OMe
OH
Me2SO4 (3.6 equiv)
K2CO3 (1.5 equiv)
(4) See, for example: (a) Duspara, P. A.; Batey, R. A. Angew. Chem.
Int. Ed. 2013, 52, 10862. (b) Rosocha, G.; Batey, R. A. Tetrahedron
2013, 69, 8758. (c) Taylor, R. R. R.; Batey, R. A. J. Org. Chem. 2013,
78, 1404. (d) Ramadhar, T. R.; Batey, R. A. Comp. Theor. Chem.
2011, 976, 167. (e) Ramadhar, T. R.; Batey, R. A. Comp. Theor.
Chem. 2011, 974, 76. (f) Smith, C. D.; Gavrilyuk, J. I.; Lough, A. J.;
Batey, R. A. J. Org. Chem. 2010, 75, 702. (g) Rodrigues, A.; Lee, E.
E.; Batey, R. A. Org. Lett. 2010, 12, 260. (h) Smith, C. D.; Rosocha,
G.; Mui, L.; Batey, R. A. J. Org. Chem. 2010, 75, 4716. (i) Smith, C.
D.; Batey, R. A. Tetrahedron 2008, 64, 652. (j) Li, S.-W.; Batey, R.
A. Chem. Commun. 2007, 3759. (k) Lee, E. E.; Batey, R. A. J. Am
Chem. Soc. 2005, 127, 14887. (l) Miller, C. A.; Batey, R. A. Org.
Lett. 2004, 6, 699.
(5) (a) Castro, A. M. M. Chem. Rev. 2004, 104, 2939. (b) Ichikawa, H.;
Maruoka, K. In The Claisen Rearrangement: Methods and Appli-
cations; Hiersemann, M.; Nubbemeyer, U., Eds.; Wiley-VCH:
Weinheim, 2007, Chap. 3.1, 45-8.
(6) For a review on the utility of dibromocyclopropane ring-
opening reactions, see: Halton, B.; Harvey, J. Synlett 2006, 1975.
(7) Gowrisankar, S.; Sergeev, A. G.; Anbarasan, P.; Spannenberg, A.;
Neumann, H.; Beller, M. J. Am. Chem. Soc. 2010, 132, 11592; and
references cited therein.
12
90%
8a
acetone, reflux, 12 h
PhB(OH)2 (1.1 equiv)
Pd(OAc)2 (6 mol%)
DavePhos (15 mol%)
Cs2CO3 (3 equiv)
THF:H2O (10:1), 70 °C, 24 h
Ph
OMe
13
80%
Scheme 5 O-Alkylation of 8b and 8a to ethers 11 and 12 and the sub-
sequent Suzuki–Miyaura cross-coupling reaction of 12
functionality is compatible with several O-arylation pro-
cesses (via Cu(II)-catalysis, Mitsunobu, and SNAr) and
Eu(III)-catalyzed aryl-Claisen [3,3]-sigmatropic rearrange-
ments. The alkenylbromide functionality can be further
elaborated through Suzuki–Miyaura cross-coupling reac-
tions. Overall, this two-step, sequential strategy readily
provides access to densely-functionalized polycyclic scaf-
folds. Further studies involving applications towards total
synthesis and for the construction of polycyclic systems
bearing axial chirality can be envisaged.
(8) (a) Chan, D. M. T.; Monaco, K. L.; Wang, R. P.; Winters, M. P. Tet-
rahedron Lett. 1998, 39, 2933. (b) Evans, D. A.; Katz, J. L.; West, T.
R. Tetrahedron Lett. 1998, 39, 2937. (c) Lam, P. Y. S.; Clark, C. G.;
Saubern, S.; Adams, J.; Winters, M. P.; Chan, D. M. T.; Combs, A.
Tetrahedron Lett. 1998, 39, 2941. (d) Evano, G.; Blanchard, N.;
Toumi, M. Chem. Rev. 2008, 108, 3054.
(9) Quach, T. D.; Batey, R. A. Org. Lett. 2003, 5, 1381.
(10) (a) Fletcher, S. Org. Chem. Front. 2015, 2, 739. (b) Swamy, K. C.
K.; Kumar, N. N. B.; Balaraman, E.; Kumar, K. V. P. P. Chem. Rev.
2009, 109, 2551. (c) Hughes, D. L. Org. Prep. Proced. Int. 1996, 28,
127.
Funding Information
We are grateful for financial support by Takeda Pharmaceutical Com-
pany (TPC) Ltd. and by the Natural Sciences and Engineering Research
Council (NSERC) of Canada for a Discovery Grant to R.A.B and Alexan-
(11) Terrier, F. Modern Nucleophilic Aromatic Substitution; Wiley-
VCH: Weinheim, 2013.
der Graham Bell Canada Graduate Scholarships M and D3 to T.R.R.
)(
(12) Reaction of phenols with allylic mesylates has also been used,
see: Yagoubi, M.; Cruz, A. C. F.; Nichols, P. L.; Elliott, R. L.; Willis,
M. C. Angew. Chem. Int. Ed. 2010, 49, 7958.
Acknowledgment
(13) Ramadhar, T. R.; Kawakami, J.; Lough, A. J.; Batey, R. A. Org. Lett.
2010, 12, 4446.
(14) For a review of catalysis of the Claisen rearrangement, see:
Majumdar, K. C.; Alam, S.; Chattopadhyay, B. Tetrahedron 2008,
64, 597.
(15) Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 1998, 120, 815.
(16) Isolated examples of aryl-Claisen [3,3]-sigmatropic rearrange-
ment of simple acyclic 2-bromoallyl aryl ethers have been
reported, see: (a) Parker, K. A.; Casteel, D. A. J. Org. Chem. 1988,
53, 2847; PhNMe2, Δ, reflux. (b) Yoo, S.; Lee, S.-H.; Kim, S.-K.;
Lee, S.-H. Bioorg. Med. Chem. 1997, 5, 445; BCl3, -40 °C.
(c) Ndungu, J. M.; Larson, K. K.; Sarpong, R. Org. Lett. 2005, 7,
5845; Et2AlCl, rt. (d) Goundry, W. R. F.; Lee, V.; Baldwin, J. E.
We thank Dr. Matthew Forbes and Dr. Alex B. Young for MS analysis,
and Dr. Alan J. Lough for X-ray structure determination of 8b.
Supporting Information
Supporting information for this article is available online at
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–F