ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Palladium-Catalyzed Aerobic
Dehydrogenative Aromatization of
Cyclohexanone Imines to Arylamines
Alakananda Hajra, Ye Wei, and Naohiko Yoshikai*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical
Sciences, Nanyang Technological University, Singapore 637371, Singapore
Received September 18, 2012
ABSTRACT
Dehydrogenative aromatization of cyclohexanone imines to arylamines has been achieved using a palladium catalyst under aerobic conditions.
The reaction is applicable to a variety of imines that are either preformed or generated in situ from cyclohexanone derivatives and aryl or
alkylamines.
Arylamines are common core structures of a wide variety
of functional molecules with biological activities and opto-
electronic properties relevant to pharmaceuticals and materi-
als science, respectively. Consequently, efficient and selective
preparation of arylamines has received considerable atten-
tion. The most powerful and versatile contemporary syn-
thetic method for arylamines is undoubtedly the transition-
metal-catalyzed CꢀN cross-coupling between aryl halides
and amines, as represented by the palladium-catalyzed
BuchwaldꢀHartwig coupling and the copper-catalyzed
Ullmann-type coupling reactions.1ꢀ3 Nevertheless, the
development of conceptually different and complementary
synthetic methods, those not employing halogenated starting
materials and basic reaction conditions in particular, remains
an important subject.4
Recently, we developed a palladium-catalyzed aerobic
oxidative cyclization reaction of N-aryl imines to indoles.5
During this study, we noted that an imine derived from
R-tetralone and p-anisidine underwent dehydrogenation
rather than oxidative cyclization to afford an amino-
naphthalene derivative (Scheme 1a). This finding, together
with the recent development of aerobic palladium catalysis6
for dehydrogenation of cyclohexanones to phenols7 and
R,β-dehydrogenation of alkyl ketones and aldehydes,8ꢀ10
prompted us to explore the feasibility of the aerobic dehy-
drogenative approach for the synthesis of arylamines. Here,
we report that a variety of cyclohexanone imines, either
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10.1021/ol302568b
XXXX American Chemical Society