Journal of the American Chemical Society
COMMUNICATION
’ AUTHOR INFORMATION
Corresponding Author
’ ACKNOWLEDGMENT
T.H.L. is grateful for an Alfred P. Sloan Research Fellowship
and Young Investigator Awards from Abbott and Amgen. J.M.A.
is an NSF Graduate STEM Fellow.
Figure 4. Mechanistic alternatives for tropylium ion mediated amine
oxidation.
’ REFERENCES
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Germany, 2004; Vol. 2, p 497. (c) Murahashi, S.-I.; Komiya, N. In
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(2) For selected recent examples, see: (a) Condie, A. G.; Gonzꢀalez-
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the homoallylic amine substrate 24 via allylation of N-cyclohexyl-
methyl benzophenone imine. In the presence of 1.5 equiv of
tropylium BF4- at 120 °C in acetonitrile (sealed vial), 24 under-
went facile oxidation/aza-Cope rearrangement to provide imine
25 in 73% yield. It is notable that this oxidative procedure was
successful even in the presence of a secondary amine. We presume
N-alkylation by tropylium ion was suppressed due to significant
steric encumbrance by the gem-diphenyl group.
Chem. Eur. J. 2005, 11, 2327. (d) DeBoef, B.; Pastine, S. J.; Sames, D.
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Finally, in regard to the mechanism of tropylium-mediated
amine oxidation, we recognize two likely possibilities, the first
being direct hydride abstraction from amine 26 and the second
involving initial electron transfer to produce an amine radical
cation intermediate 28 and tropyl radical (Figure 4).14 Although
at present we cannot say which of these two possibilities might be
operative, we reemphasize that oxidation of substrate leading to
product 10 (Table 1) with DDQ, typically a single electron
oxidant,3 resulted in a significantly different ratio of regioisomers
for benzylic versus aliphatic oxidation.
(6) For a review of other organic amine oxidants, see: Kaitmazova,
G. S.; Gambaryan, N. P.; Rokhlin, E. M. Russ. Chem. Rev. 1989, 58, 1145.
(7) For the oxidation with trityl ion, see: Damico, R.; Broaddus,
C. D. J. Org. Chem. 1966, 31, 1607. As an issue of practicality, we note
that, in contrast to tropylium ion, the byproduct of hydride abstraction
by trityl ion is triphenylmethane, which is a nonvolatile, non water-
soluble compound.
(8) (a) Doering, W. v. E.; Knox, L. H. J. Am. Chem. Soc. 1957, 79, 352.
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D. J. Top. Nonbenzenoid Aromat. Chem. 1973, 1, 29.
Another important consideration is the possibility of electron
donor-acceptor (EDA) complexes (cf. 29) with substrates posses-
sing aryl rings. Such EDA complexes with tropylium ion are known15
and their formation might be expected to drastically alter the
reactivity and selectivity of aromatic substrates. Positing intermedi-
ates of the type 29 would also help explain the relatively poor
efficiency of the benzylic oxidations in Table 1 relative to the purely
aliphatic substrates. In this regard, it is noteworthy that the efficiency
of formation of the p-methoxybenzyl product 12 (Table 1) was
especially poor, since a more stable EDA complex would be expected
to form in this case. Further experiments to determine the presence
and potential impact of these putative structures are underway.
As demonstrated here, aromatic cations such as tropylium ion have
the capacity to serve as useful reagents for amine oxidation. The broad
structural and electronic tunability of these reagents should offer
unique opportunities for reaction design and the pursuit of novel
selectivities. Mechanistic investigations and further development of
aromatic cation oxidations will be the focus of our future efforts.
(10) Doering, W. v. E.; Knox, L. H. J. Am. Chem. Soc. 1954, 76, 3203.
(11) McGeachin, S. G. Can. J. Chem. 1969, 47, 151.
(12) Doering, W. v. E.; Knox, L. H. J. Am. Chem. Soc. 1957, 79, 352.
(13) McGeachin reported the quaternary ammonium salt resulting
from addition of trimethylamine to tropylium ion. See ref 11.
(14) Single electron reduction of tropylium ion is more difficult than
trityl cation by about 440 mV. Wasielewski, M. R.; Breslow, R. J. Am.
Chem. Soc. 1976, 98, 4222.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures and
b
(15) Takahashi, Y.; Sankararaman, S.; Kochi, J. K. J. Am. Chem. Soc.
1989, 111, 2954.
product characterization data. This material is available free of
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dx.doi.org/10.1021/ja109617y |J. Am. Chem. Soc. 2011, 133, 1260–1262