Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
a Reactions conducted on 0.25 mmol scale. Isolated yield after purification by column
chromatography.
Mukherjee, Y. Tan, Z. C. Litman and J. F. Hartwig, J. Am.
DOI: 10.1039/C6OB00073H
Chem. Soc., 2013, 135, 8480; (d) J. P. Wolfe, S. Wagaw,
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For select examples, see: (a) G. Evano, N. Blanchard and
M. Toumi, Chem. Rev., 2008, 108, 3054; (b) S. V. Ley
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DeVasher, in Organic Reactions, John Wiley & Sons,
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For select examples, see: (a) N. A. Romero, K. A.
Margrey, N. E. Tay and D. A. Nicewicz, Science, 2015,
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Am. Chem. Soc., 2014, 136, 3354; (d) B. J. Stokes and T.
G. Driver, Eur. J. Org. Chem., 2011, 4071.
Encouraged by the direct conversion of phenols into
anilines and based on our interest in nitroso chemistry,10a, 10b, 10d
we sought to extend our methodology to a one pot synthesis of
nitrosobenzene derivatives using hydroxylamine (Table 3).
Treatment of the substituted quinone adducts generated in situ
with hydroxylamine sulphate and pyridine (2 equiv) resulted in
moderate to good yields of the desired nitroso compounds (32,
34–38). The reaction works well for the conversion of 4-
methoxyphenol into 4-methoxynitrosobenzene (32), however
this methodology does not tolerate ortho substitution (33). The
reaction works well for meta-substituted derivatives such as
dimethyl, methyl, chloro, and bromo 4-methoxyphenols (34–
37). As with the aniline derivatives, the reaction of
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W. Vermerris and R. Nicholson, Phenolic Compound
Biochemistry, Springer Netherlands, 2008.
M. Weber and M. Weber, in Phenolic Resins: A Century
of Progress, ed. L. Pilato, Springer Berlin Heidelberg,
2010, ch. 2, pp. 9.
4-isopropoxyphenol in methanol gives
a distribution of
products (5:1, 38:32), where the major product corresponds to
retention of the more electron rich alkoxide group. This one
step protocol provides a direct approach to access electron rich
nitroso derivatives from readily available phenols.
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Z. Chen, H. Zeng, S. A. Girard, F. Wang, N. Chen and C.-
J. Li, Angew. Chem. Int. Ed., 2015, 54, 14487.
For select examples, see: (a) T. Mesganaw, A. L.
Silberstein, S. D. Ramgren, N. F. F. Nathel, X. Hong, P.
Liu and N. K. Garg, Chem. Sci., 2011, 2, 1766; (b) A.
Muci and S. Buchwald, in Cross-Coupling Reactions, ed.
N. Miyaura, Springer Berlin Heidelberg, 2002, vol. 219,
ch. 5, pp. 131; (c) S. D. Ramgren, A. L. Silberstein, Y.
Yang and N. K. Garg, Angew. Chem. Int. Ed., 2011, 50,
2171; (d) Y. Zhang, G. Lavigne and V. César, J. Org.
Chem., 2015, 80, 7666.
For select examples, see: (a) I. G. C. Coutts and M. R.
Southcott, J. Chem. Soc., Perkin Trans. 1, 1990, 767; (b)
M. Mizuno and M. Yamano, Org. Lett., 2005, 7, 3629;
(c) Y.-S. Xie, B. V. D. Vijaykumar, K. Jang, H.-H. Shin, H.
Zuo and D.-S. Shin, Tetrahedron Lett., 2013, 54, 5151.
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Velasco and J. Read de Alaniz, J. Am. Chem. Soc., 2015,
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de Alaniz, J. Am. Chem. Soc., 2011, 133, 10430; (c) L. I.
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Amant, J. E. Hein and J. Read de Alaniz, Org. Biomol.
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E. C. Taylor, G. E. Jagdmann and A. McKillop, J. Org.
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Conclusions
We have described a one-pot, metal-free synthesis of
nitrogen-containing aryl compounds using the underdeveloped
iSOAr reaction. The mild access to a variety of electron-rich
anilines complements the existing methods from electron-poor
phenols. The scope of nitrosobenzenes was explored, providing
access to these useful intermediates directly from phenols. Our
analysis of leaving groups in mixed quinone monoketals allows
the prediction of products and has applications beyond the
chemistry described herein. The exploration of the scope,
limitations, and mixed quinone monoketals lays the foundation
for a powerful method to form aryl-nitrogen bonds from
phenols.
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Acknowledgements
This work was supported by UCSB. A. H. St. Amant thanks the
National Science and Engineering Research Council of Canada
(NSERC) for financial support. We also thank Professor. R.
Daniel Little (UCSB) for helpful discussions.
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