COMMUNICATIONS
generate the imine intermediate 5,[6,9,10] but only after
the copper salt has coordinated with 5 to form the ac-
tivated copper complex A.[5c,10] Consequently, the
morpholine 2a undergoes nucleophilic attack to A to
produce product 3aa.[6,10] Product 3aa is hydrolyzed by
H2O to produce 4aa with the aid of Cu(OAc)2, BPO,
and O2.[6]
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In summary, we have presented a general and effi-
À
cient method for C N oxidative cross-coupling
3
À
through direct C(sp ) H bond functionalization of a-
aminocarbonyl compounds with amines using inex-
pensive copper salts as catalysis. This transformation
could selectively furnish 2-amino-2-iminocarbonyl and
2-amino-2-oxocarbonyl compounds by slightly modi-
fying the reaction conditions. A variety of substituted
a-aminocarbonyl compounds could be tolerated by
this procedure which proceeds smoothly in moderate
to good yields. Thus, it represents a facile pathway for
the functionalization of a-amino ketones.
Experimental Section
Typical Experimental Procedure for the Cu-Catalyzed
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Synthesis of 2-Amino-2-iminocarbonyl Compounds
(3)
An oven-dried tube with a magnetic stir bar was charged
with the a-aminocarbonyl compound 1 (0.2 mmol), amine 2
(0.6 mmol), Cu(OAc)2 (0.5 equiv.), Et3N (1.5 equiv.) and
CH2Cl2 (2 mL). Then the reaction mixture was stirred at
room temperature under air for the indicated time (Table 2)
until complete consumption of the starting material as moni-
tored by TLC. After the reaction was finished, the mixture
was concentrated in vacuum, and the residues were purified
by silica gel column chromatography (hexane/ethyl ace-
tate=5:1) to afford the desired product 3.
Typical Experimental Procedure for the Cu-Catalyzed
Synthesis of 2-Amino-2-oxocarbonyl Compounds (4)
0.2 mmol of a-aminocarbonyl compound 1, 0.6 mmol of
amine 2, 10 mol% of Cu(OAc)2, 1.5 equiv. of BPO and 2 mL
of DMSO were added to a test tube equipped with a mag-
netic stir bar. The reaction tube was evacuated and back-
filled with O2 (3 times, balloon). Then the reaction mixture
was stirred at 1108C under O2 balloon for the indicated time
(Table 3) until complete consumption of the starting materi-
al as monitored by TLC. After the reaction was finished, the
reaction mixture was washed with brine. The organic ex-
tracts were dried over Na2SO4, concentrated in vacuum, and
the resulting residue was purified by silica gel column chro-
matography (hexane/ethyl acetate=4:1) to afford the de-
sired product 4.
References
[1] a) S. Hunt, Chemistry and Biochemistry of the Amino
Acids, (Ed.: G. C. Barrett), Chapman and Hall,
Adv. Synth. Catal. 0000, 000, 0 – 0
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ÞÞ
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