Copper-mediated electrophilic imination of alkenylzirconocenes with O-benzoyl ketoximes and aldoximes

Article abstract of DOI:10.1039/c3cc41574k

Copper-mediated electrophilic imination of alkenylzirconocenes generated in situ from alkynes and zirconocenes is accomplished under mild reaction conditions. The reaction can be used to prepare various 2-azadienes.

Full text of DOI:10.1039/c3cc41574k

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Copper-mediated electrophilic imination of
alkenylzirconocenes with O-benzoyl ketoximes
and aldoximes†
Hailan Liu,ab Xiaoyu Yan,b Chao Chen,b Qingbin Liu*a and Chanjuan Xi*b
Cite this: Chem. Commun., 2013,
49, 5513
Received 1st March 2013,
Accepted 25th April 2013
DOI: 10.1039/c3cc41574k
www.rsc.org/chemcomm
Copper-mediated electrophilic imination of alkenylzirconocenes
generated in situ from alkynes and zirconocenes is accomplished
under mild reaction conditions. The reaction can be used to pre-
pare various 2-azadienes.
Scheme 1 Cu-mediated imination of alkenylzirconocenes with O-benzoyl oximes.
Nitrogen-substituted alkenes probably represent the most versa-
tile class of olefinic compounds. The electron-donating ability of
nitrogen strongly polarizes the double bond, which allows for an
exceptionally high level of reactivity together with a strong
differentiation of the two sp2 carbon atoms.1–3 Consequently, a
number of reactions have been developed for the synthesis of
N-substituted alkenes, for example, condensation of a secondary
amine with a carbonyl compound4 or hydroaminations of alkynes
afforded enamines.5 Although significant contributions have
been made, these methods still remain rather limited, which is most
certainly due to their harsh reaction conditions, low functional group
tolerance, and low selectivity. On the other hand, in recent years,
metal-promoted olefinic C–N cross-coupling reactions provided
a powerful and convenient approach to the abovementioned
N-substituted alkenes. Among them, Pd- or Cu-catalyzed cross-
coupling reaction of electrophilic alkenyl halides with nucleophilic
amides provided a straightforward method for the formation of
N-substituted alkenes.6–8 Meanwhile, an umpolung,9 electrophilic
amination of organometals using a reagent of type R2N+ such as
chloro- and hydroxylamines has also provided a significant
complement to the formation of C–N bonds.10 Our group also
focused on this type of transformation and succeeded in the
copper-catalyzed electrophilic aminations of alkenylzirconocenes
to obtain a wide range of enamines.11 In the course of this study,
we envisioned that the umpolung strategy using oxime esters
as the electrophilic nitrogen reagents could be applied to the
imination of alkenylzirconocenes, which would provide a use-
ful method for the synthesis of 2-azadienes that are often used
for the synthesis of various heterocycles3 and are generally
prepared by aza-Wittig reaction or enolization of N-acyl imines.12
A
few related cross-coupling reactions were studied by Narasaka13 and
Liebeskind14 and their co-workers using oxime reagents and alkenyl
Grignard reagents or alkenylboronic acids or alkenylstannanes.
Herein, we describe a copper-mediated electrophilic imination
of alkenylzirconocenes with O-benzoyl oximes (Scheme 1). This
reaction affords a convenient method for the synthesis of
2-azadienes in one-pot from alkynes.
Alkenylzirconocenes are useful intermediates in a number of
organic syntheses,15 since they are easily prepared from available
alkynes or alkenyl halides with zirconocene species.16,17 As part of our
ongoing project on alkenylzirconocene chemistry, our initial investi-
gation explored the cross-coupling of alkenylzirconocene derivatives
with benzophenone O-benzoyloxime 2a. A typical procedure is as
follows. To a solution of alkenylzirconocene 1a,18 which was pro-
duced by alcoholysis of the corresponding zirconacyclopentene pre-
pared from diphenylacetylene and Cp2ZrEt2,16d CuCl (1 equiv.) and
O-benzoyloxime 2a (1.5 equiv.) were added. 2-Azadiene 3aa was
formed at 50 1C for 12 h (Scheme 2). After workup, 2-azadiene
3aa was isolated in 76% yield. In this case, benzophenone and
diphenylmethanimine were also detected as by-products using
GC-MS, and benzophenone was isolated in 11% yield, which is readily
separated with the desired product using flash chromatography.
a Institute of Chemistry and Chemical Engineering, Hebei Normal University,
Shijiazhuang 050091, China
b Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology
(Ministry of Education), Department of Chemistry, Tsinghua University,
Beijing 100084, China. E-mail: cjxi@tsinghua.edu.cn
† Electronic supplementary information (ESI) available: Experimental proce-
dures, full characterization including 1H NMR and 13C NMR data for all new
compounds and NOESY of compound 3hc. See DOI: 10.1039/c3cc41574k
Scheme 2 Imination of 1a with 2a.
c
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In the absence of CuCl, the 2-azadiene 3aa was only detected
in a trace amount using GC-MS. Use of a catalytic amount of
CuCl (10%) afforded the product 3aa in 8% yield. Replacement
of THF with toluene or dichloromethane after formation of
alkenylzirconocenes from alkynes and zirconocenes did not
allow this reaction to proceed either and the starting materials
remained. Other cuprous salts such as CuBr, CuI, and CuOAc
afforded the product 3aa in 47%, 28%, and 35% yields, respec-
tively. Transitioning from O-benzoyl to O-pentafluorobenzoyl (used
by Narasaka13 and Liebeskind14 in their studies) did not improve
the yield of product 3aa. Thus, we use the O-benzoyloximes as
electrophilic nitrogen reagents.
Fig. 1 Range of O-benzoyloxime substrates.
The imination with 2a was performed with a number of
alkenylzirconocene species, including alkyl, aryl, allyl, and
alkynyl substituents. The representative results are summarized
in Table 1. Alkenylzirconocenes 1a–1f (generated in situ by
carbozirconation of alkynes)11,16d were treated with O-benzoyl-
oxime 2a under the optimized conditions and the corre-
sponding 2-azadienes 3aa–3fa were formed in 48% to 76%
isolated yields (entries 1–6). Alkenylzirconocenes 1g and 1h,
which were prepared by reaction of zirconacyclopentenes with
Table 1 Electrophilic imination of various alkenylzirconocenesa
Scheme 3 The scope of electrophilic imination.
Entry
Alkenylzirconocene
2-Azadiene
Yieldb (%)
76 (63)c
diallyl ethers,16g were employed, skipped dienimines 3ga and 3ha
were formed in 55% and 85% yield, respectively (entries 7 and 8).
To establish the full scope of the imination reaction, we
further explored a range of O-benzoyloximes (Fig. 1) with
alkenylzirconocenes 1. O-Benzoyloxime 2b derived from bis-
(4-chloropehnyl)methanone14 was used in the reaction to afford
the corresponding 2-azadiene 3cb in 48% isolated yield
(Scheme 3). (E)-1-Phenyl-ethanone O-benzoyloxime 2c derived
from acetophenone19 was used in the reaction to give the
corresponding 2-azadienes 3ac, 3cc, 3gc, and 3hc in good
yields. The stereochemistry of 3hc was determined using 2-D
NMR. The NOESY spectra (see ESI†) revealed that the methyl
group and the vinyl group were in a cis-fashion, which is
consistent with 2c. When O-benzoyloximes 2d–2f derived from
alkyl–alkyl ketones such as cyclohexanone, pentan-3-one,
or acetone19 were employed in the reaction, the expected
2-azadienes were detected using GC-MS in a trace amount
and the starting materials remained. O-Benzoylaldoximes
2g–2i derived from aldehydes such as benzaldehyde, p-tolu-
aldehyde, and p-chlorobenzaldehyde19 were used, the corre-
sponding products 3cg, 3ah–3hh, and 3ai–3hi were obtained in
moderate to good yields. In Liebeskind’s work, utilization of
aldoxime O-carboxylates did not give the desired aldimines,
rather they underwent b-elimination to give the corresponding
nitrile products under their reaction conditions.14 It is worth
mentioning that abovementioned products are stable and
could be purified using flash chromatography on alumina
(for details of purification, see ESI†).
1
2
3
54 (45)c
48 (38)c
4
69
5
6
51
62
7
55
85
8
a
Reaction conditions: alkenylzirconocene 1 prepared in situ from alkynes
(0.5 mmol) with zirconocenes in 3 mL of THF solution, O-benzoyloxime 2a
b
Transmetalation of the C–Zr bond to the C–Cu bond has
been extensively observed.20 Oxidative additions to N–O bonded
(0.75 mmol), CuCl (0.5 mmol), N2, 50 1C, 12 h. Isolated yield based on
alkynes. Reaction was run on a 10 mmol scale.
c
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Scheme 4 Possible reaction pathway.
species are precedented.14,21 In combination with known facts,
a plausible mechanism is shown in Scheme 4. In the first step,
alkenylzirconocene 1 is transmetalated with CuCl to give inter-
mediate 4. Then oxidative addition of O-benzoyloximes to N–O
bonds forms the intermediate 5. Finally, subsequent reductive
elimination affords 2-azadiene 3.
In summary, a general copper-mediated electrophilic imina-
tion of alkenylzirconocene reagents with O-benzoyl ketoximes
and aldoximes has been developed. This reaction represents an
interesting entry to the synthesis of 2-azadienes within one-pot
reaction from alkynes. Further studies on the use of 2-azadienes
will be reported in due course.
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This work was supported by the National Key Basic Research
Program of China (973 program) (2012CB933402) and National
Natural Science Foundation of China (21032004 and 21272132).
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Chem. Commun., 2013, 49, 5513--5515 5515