ORGANIC
LETTERS
2
013
Vol. 15, No. 18
872–4875
Copper-Catalyzed Electrophilic Amination
of Organolithiums Mediated by
Recoverable Siloxane Transfer Agents
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Minh H. Nguyen and Amos B. Smith, III*
Department of Chemistry, University of Pennsylvania, Philadelphia,
Pennsylvania 19104, United States
Received August 13, 2013
ABSTRACT
The development and validation of copper-catalyzed, electrophilic amination of aryl and heteroaryl organolithiums with N,N-dialkyl-O-
benzoylhydroxylamines have been achieved exploiting recoverable siloxane transfer agents. Given the ready availability of organolithium com-
pounds, the mild reaction conditions, the ease of product purification, and the ready recovery of the siloxane transfer agents, this transformation
comprises a useful tactic to access diverse aryl and heteroaryl amines.
Transition-metal-mediated CÀN bond construction is
one of the most important transformations in organic
synthesis for the elaboration of diverse aryl and heteroaryl
amines, given the prevalence of this structural motif in
natural products, pharmaceutical agents, and functional
Indeed, various organometallic reagents are known to under-
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go electrophilic amination, including organomagnesiums,
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6
6,7
8
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-zincs, -tins, -borons, -silicons, and -titaniums. These
reagents however are frequently prepared from the cor-
responding organolithium reagents. The direct use of
organolithiums would eliminate the need for additional
synthetic manipulations and/or the isolation of suitable
nucleophilic partners. Although organolithium reagents
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materials. Among them, the BuchwaldÀHartwig palla-
dium-catalyzed cross-coupling of aryl halides with amines,
the Ullmann-type copper-catalyzed cross-coupling of aryl
halides with amines, and the ChanÀLam copper-mediated
oxidative coupling of aryl metals with amines have proven
(
4) (a) Tsutsui, H.; Hayashi, Y.; Narasaka, K. Chem. Lett. 1997, 26,
2
to be powerful methods for CÀN bond formation. An
317. (b) Campbell, M. J.; Johnson, J. S. Org. Lett. 2007, 9, 1521. (c)
Hatakeyama, T.; Yoshimoto, Y.; Ghorai, S. K.; Nakamura, M. Org.
Lett. 2010, 12, 1516.
umpolung tactic, involving transition-metal-catalyzed
amination of organometallic reagents with electrophilic
aminating reagents (e.g., chloroamines and hydroxyl-
(
5) (a) Berman, A. M.; Johnson, J. S. J. Am. Chem. Soc. 2004, 126,
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E. R. J. Am. Chem. Soc. 2009, 131, 15598.
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amines), provides a valuable complementary approach.
(
6) (a) Liu, S.; Yu, Y.; Liebeskind, L. S. Org. Lett. 2007, 9, 1947. (b)
(
1) (a) Hili, R.; Yudin, A. K. Nat. Chem. Biol. 2006, 2, 284. (b) Amino
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ARKIVOC 2011, 230.
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0.1021/ol4023084 r 2013 American Chemical Society
Published on Web 09/03/2013