C O M M U N I C A T I O N S
Table 2. Scope of the Copper-Catalyzed Amination of
equiv of (2-MePh)2Zn (eq 6) instead of the standard 1.1 equivalents
(Table 2, entry 7).
Diorganozinc Reagentsa
From a preparative standpoint, this amination protocol has several
attractive features. The reaction proceeds at ambient temperature
in less than 1 h for all substrates tested. Isolation of analytically
pure product via a simple acid/base extractive workup is suitable
in most instances. The successful use of diorganozinc reagents
generated in situ from the corresponding Grignard or organolithium
obviates the need for isolation and distillation of R2Zn nucleophiles.
The starting N,N-dialkyl O-acyl hydroxylamine electrophiles are
easily prepared in one step by Ganem’s method.18 These materials
are crystalline solids that show good stability: they can be purified
via column chromatography and stored for months in a freezer with
no evidence of decomposition or loss of reactivity.
The copper-catalyzed electrophilic amination of diorganozincs
offers a general, convenient, and high-yielding means of preparing
tertiary amines under mild conditions. Catalytic delivery of R2N-
(+) synthons is a topic of continuing interest in our laboratory,
and findings from this research will be the subject of future
publications.
Acknowledgment. Funding for this work was provided by
Research Corporation and a UNC Junior Faculty Development
award.
Supporting Information Available: Experimental procedures for
electrophilic amination reactions and spectral data for new compounds.
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
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a 1.1 equiv of diorganozinc were employed. R2Zn reagents were prepared
via transmetalation of the corresponding RLi or RMgX reagent with 0.5
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1H NMR spectroscopy and GLC analysis (average of at least two
experiments). Yield is based on the starting R2N-OBz.
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(14) For a tabular summary of conditions that were evaluated, see the
Supporting Information.
The use of other copper salts is also feasible. Identical results
are obtained when CuCl2 is substituted for CuOTf under the
standard reaction conditions (eqs 4 and 5; cf. Table 2, entries 1
and 13, respectively).
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Guijarro, A.; Rieke, R. D. Tetrahedron Lett. 1998, 39, 9157-9160.
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(17) An analogous reaction of PhMgBr and O-benzoyl-N-hydroxypiperidine
gives N-phenylpiperidine in 4% isolated yield in the absence of CuOTf
and 13% yield with 2.5 mol % CuOTf.
(18) Biloski, A. J.; Ganem, B. Synthesis 1983, 537-538.
Preliminary results also indicate the feasibility of transferring
both aryl groups of the diorganozinc reagent. N-(o-Tolyl)piperidine
is obtained in 86% yield when Cu(II)-catalyzed arylation of
O-benzoyl-N-hydroxypiperidine (1.0 equiv) is conducted with 0.6
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