Journal of the American Chemical Society
each closes, competitively, with the same energetics to produce the
same 2:1 ratio of benzynes.
Page 4 of 5
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Y.; Wang, K.; Lee, N.; Mamidipalli, P.; Lee D. J. Am. Chem. Soc. 2013, 135,
2
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3 Reviews: (a) Holden, C.; Greaney, M. F. Angew. Chem Int. Ed. 2014,
53, 5746–5749. (b) Li, W.; Zhou, L.; Zhang, J. Chem. Eur. J. 2016, 22,
OMe CO2Me
Ar1
Ar2
Ar2/
Ar1
c-C8H16
+
Ar2
Ar2 Ar1
1558–1571. (c) For the most recent review, which contains
a
Ar1
H
Ar1/
Ar2
comprehensive compilation of citations to HDDA-related studies, see:
90 °C
14 h
M
M
Diamond, O. J.; Marder, T. B. Org. Chem. Front. 2017, 4, 891–910.
M
H
4
or
Niu, D.; Willoughby, P. H.; Baire, B.; Woods, B. P.; Hoye, T. R.
H
H
300 nm
Nature 2013, 501, 531–534.
36
51%, Δ
36'
24%, Δ
2:1
5
rt
35/35'
(a) Niu, D.; Hoye, T. R. Nature Chem. 2014, 6, 34–40. (b) Woods, B.
M
P.; Baire, B.; Hoye, T. R. Org. Lett. 2014, 16, 4578–4581. (c) Woods, B. P.;
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M = C(CO2Me)2 = dimethyl malonyl 55%, hv
27%, hv
7c
FIGURE 5. Competitive formation of the two isomeric benzynes 35
and 35’ as revealed by the ratio of products 36:36’. They are produced
in the same ratio under both thermal and photochemical initiation.
6
(a) Kitamura, T. Aust. J. Chem. 2010, 63, 987–1001. (b) Most often,
We have described here the first examples of photo-initiated
cycloisomerizations of multi-yne substrates to form benzynes—the
photochemical-HDDA (hv-HDDA) reaction. This class of reaction
was shown to be effective for a number of different tetrayne
substrates that vary both in the nature of the aryl substituents on
the terminus of each conjugated butadiyne subunit as well as in the
type of atoms that compose the linkage between the two diynes.
Each of the hv-HDDA reactions described here was also performed
thermally; in most cases, very little variation in isolated yields was
observed (see Supporting Information for details). The behavior of
the benzyne intermediates generated either photochemically or
thermally was shown to give indistinguishable outcomes by several
additional criteria, suggesting that the benzyne from each mode of
activation was in identical rather than different electronic states.
We speculate that this hν-HDDA reaction could prove
advantageous in activating benzyne chemistry in, for example, light-
addressable settings or biological media.
by the method of: Himeshima, Y., Sonoda, T. & Kobayashi, H. Chem. Lett.
1983, 12, 1211–1214.
7 (a) Ajaz, A.; Bradley, A. Z.; Burrell, R. C.; Li, W. H. H.; Daoust, K. J.;
Bovee, L. B.; DiRico, K. J.; Johnson, R. P. J. Org. Chem. 2011, 76, 9320-
9328. (b) Skraba-Joiner, S. L.; Johnson, R. P.; Agarwal, J. J. Org. Chem.
2015, 80, 11779−11787.
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Jiao, H.; Schleyer, P. V. R.; Beno, B. R.; Houk, K. N.; Warmuth, R.
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4581. (b) Karmakar, R.; Lee, D. Org. Lett. 2016, 18, 6105–6107.
10
Photochemical tetradehydro-Diels-Alder reactions, in which an
alkyne engages four contiguous atoms of conjugated arylalkynes to produce
naphthalene-like derivatives, are known: (a) Wessig, P.; Mìller, G.; Kìhn,
A.; Herre, R.; Blumenthal, H.; Troelenberg, S. Synthesis 2005, 1445–1454.
(b) Wessig, P.; Matthes, A. J. Am. Chem. Soc. 2011, 133, 2642–2650. (c)
Wessig, P.; Matthes, A. Molecules 2013, 18, 1314–1324 and references
therein.
11 (a)Liang, Y.; Hong, X.; Yu, P.; Houk, K. N. Org. Lett., 2014, 16,
5702–5705. (b) Marell, D. J.; Furan, L. R.; Woods, B. P.; Lei, X.;
Bendelsmith, A. J.; Cramer, C. J.; Hoye, T. R.; Kuwata, K. T. J. Org.
Chem., 2015, 80, 11744–11754. (c) Wang, T.; Niu, D.; Hoye, T. R. J. Am.
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ASSOCIATED CONTENT
Supporting Information
12 Xu, F.; Hershey, K. W.; Holmes, R. J.; Hoye, T. R. J. Am. Chem. Soc.
2016, 138, 12739–12742.
The Supporting Information is available free of charge on the ACS
Publications website at DOI: ----------
13
Xu, F.; Xiao, X.; Hoye, T. R. Org. Lett. 2016, 18, 5636–5639.
(a) Hamura, T.; Ibusuki, Y.; Sato, K.; Matsumoto, T.; Osamura, Y.;
14
Experimental details for the preparation of all new compounds, as
1
well as their spectral characterization data and copies of H, 13C,
Suzuki, K. Org. Lett. 2003, 5, 3551−3554. (b) Cheong, P. H. Y.; Paton, R.
S.; Bronner, S. M.; Im, G.-Y. J.; Garg, N. K.; Houk, K. N. J. Am. Chem. Soc.
2010, 132, 1267−1269. (c) Garr, A. N.; Luo, D.; Brown, N.; Cramer, C. J.;
Buszek, K. R.; VanderVelde, D. Org. Lett. 2010, 12, 96−99.
and 19F NMR spectra (PDF).
AUTHOR INFORMATION
15
Chen, J.; Palani, V.; Hoye, T. R. J. Am. Chem. Soc. 2016 , 138 , 4318–
Corresponding Author
* hoye@umn.edu
4321.
16
(a) o-benzyne + disulfide: Nakayama, J.; Tajiri, T.; Hoshino, M. Bull.
Chem. Soc. Jpn. 1986, 59 2907–2908. (b) HDDA-benzyne + diselenide:
Hu, Y.; Ma, J.; Li, L.; Hu, Q.; Lv, S.; Liu, B.; Wang, S. Chem. Commun.
2017, 53, 1542–1545.
Notes
The authors declare no competing financial interest.
17
For an example of a 1,3-dipolar cycloaddition reaction of benzyne
ACKNOWLEDGMENTS
derivative in which a steric bias overrode the distortion-imposed electronic
bias, see: Bronner, S. M.; Mackey, J. L.; Houk, K. N.; Garg N. K. J. Am.
Chem. Soc. 2012, 134, 13966−13969.
Essential and much appreciated financial support for this research was
provided by the National Institute of General Medical Sciences of the
NIH (R01 GM108762). Some of the NMR data were recorded on an
instrument purchased with support of the NIH Shared
Instrumentation Grant program (S10OD011952).
18
Zhang, M.-X.; Shan, W.; Chen, Z.; Yin, J.; Yu, G.-A.; Liu, S. H.
Tetrahedron Lett. 2015, 56, 6833–6838.
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