Three-component [2+2+2] cycloaddition of carboryne, unactivated alkene, and alkyne via zirconacyclopentane mediated by nickel: One-pot synthesis of dihydrobenzocarboranes

Article abstract of DOI:10.1002/anie.201106212

Mix threea get one: The complexation of a transition-metal center to an olefin or alkyne can significantly modify its reactivity, which makes the selective coupling of different alkenes or alkynes to carboryne possible. An example of a three-component [2+2+2] cycloaddition reaction of carboryne with unactivated alkene (see scheme, blue) and alkyne (red) mediated by zirconium and nickel complexes is described. Copyright

Full text of DOI:10.1002/anie.201106212

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DOI: 10.1002/anie.201106212
Selective Cycloaddition
Three-Component [2+2+2] Cycloaddition of Carboryne, Unactivated
Alkene, and Alkyne via Zirconacyclopentane Mediated by Nickel:
One-Pot Synthesis of Dihydrobenzocarboranes**
Shikuo Ren, Zaozao Qiu, and Zuowei Xie*
Transition-metal-mediated cycloaddition of alkynes and/or
alkenes serves as a powerful strategy to construct a wide
range of compounds, since complexation of the metal center
to an olefin or alkyne significantly modifies the reactivity of
this moiety.[1] A variety of transition-metal complexes can
catalyze this type of reactions.[2] This catalysis is an attractive
approach, but it remains a major challenge to achieve
selectivity among different alkenes or alkynes. Therefore,
the development of new systems that display both high
reactivity and predictable selectivity is essential to increase
the efficiency with which complex molecular architectures
can be assembled. Carboryne (1,2-dehydro-o-carborane) can
be viewed as a three-dimensional relative of benzyne.[3] In the
presence of a nickel complex, carboryne can undergo, in a
controlled manner, coupling reaction with alkenes to gener-
ate alkenyl carboranes,[4] two-component [2+2+2] cycloaddi-
tion with two equivalents of alkynes to afford benzocarbo-
ranes,[5] and three-component [2+2+2] cyclotrimerization
with activated alkene and alkyne to give dihydrobenzocarbo-
ranes.[6] In the latter case, activated alkenes such as methyl
acrylate and 2-vinylpyridine must be employed, because they
are more reactive than alkynes in the system and the donor
atom of the olefin can stabilize the intermediate by intra-
molecular coordination, thereby preventing the b-H elimi-
nation and making the subsequent alkyne insertion possible
to realize the three-component cycloaddition. However,
attempts to achieve nickel-mediated selective cycloaddition
of carboryne with unactivated alkene and alkyne have not
been successful to date but gave a mixture of alkenyl
carboranes and benzocarboranes.
incorporating a carboranyl unit is also very thermally stable
and inert toward alkenes and alkynes, which is significantly
different from those zirconacyclopentanes without carboranyl
groups.[10] In view of literature work on transmetalation from
zirconacycles to nickel,[11] we wondered whether the resultant
nickelacyclopentane generated through transmetalation from
the corresponding zirconacyclopentane would be active
toward alkyne insertion. Such an approach may lead to one-
pot synthesis of dihydrobenzocarboranes through an equiv-
alent of a three-component [2+2+2] cycloaddition of carbo-
ryne, unactivated alkene, and alkyne. The results are reported
herein.
Zirconacyclopentanes
[1,2-{Cp2ZrCH2CH(nBu)}-1,2-
C2B10H10] (1a; Cp = C5H5) and [1,2-{Cp2ZrCH(Ph)CH2}-1,2-
C2B10H10] (1b) were prepared by treatment of [Cp2Zr(m-
Cl)(m-C2B10H10)Li(OEt2)2][12] with one equivalent of 1-hexene
or styrene in toluene heated to reflux and isolated in more
than 87% yield (Scheme 1). The reversed insertion regiose-
lectivity can be rationalized by electronic effects of the
substituents on the alkenes.[13] They are very thermally stable
Scheme 1. Preparation of zirconacyclopentanes (left). Crystal structures
of 1a and 1b (right).
Our previous work shows that the nature of transition
metals dominates the reactivity pattern of the corresponding
metallacycles.[7] For example, nickelacyclopentene incorpo-
rating a carboranyl moiety is a reactive intermediate toward
alkynes,[5,8] whereas the zirconacyclopentene analogue is
inert.[9] We have recently found that the zirconacyclopentane
and inert toward alkynes even at reflux in toluene for several
days, whereas the corresponding nickelacyclopentanes are
thermally unstable, leading to the formation of alkenyl
carboranes through b-H elimination upon heating in the
absence of other substrates.[4] Addition of nickel(II) to the
zirconacyclopentanes 1 can effectively promote the further
insertion of alkynes to form dihydrobenzocarboranes. Only
trace amount of b-H elimination product was observed in the
reaction of 1a. The optimization of reaction conditions for the
[*] Dr. S. Ren, Dr. Z. Qiu, Prof. Dr. Z. Xie
Department of Chemistry and State Key Laboratory on Synthetic
Chemistry
The Chinese University of Hong Kong
Shatin, N.T., Hong Kong (China)
E-mail: zxie@cuhk.edu.hk
ꢀ
reaction of 1a with PhC CnBu (2g) is summarized in Table 1.
[**] The work described in this paper was supported by grants from the
Research Grants Council of the Hong Kong Special Administration
Region (Project No. 404011) and The Chinese University of Hong
Kong.
A variety of NiII species were examined for this reaction. No
detectable product was observed in the presence of one
equivalent NiCl2 at 908C in toluene owing to the poor
solubility of NiCl2 (Table 1, entry 1). An increase of the
reaction temperature to 1108C resulted in a low yield of
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201106212.
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Table 1: Optimization of reaction conditions.[a]
Table 2: Preparation of dihydrobenzocarboranes.[a]
2, R3/R4
Product
3/3’
3:3’ [b] Yield of
Entry
[Ni][b]
T [8C]
Solvent
3g:3g’
Yield
[%][c]
Entry
1
3:3’ [%][g]
1
2
3
4
5
6
7
8
NiCl2
NiCl2
NiCl2
NiCl2
90
110
90
110
90
110
110
110
110
110
110
toluene
toluene
THF
THF
DME
toluene
THF
DME
toluene
toluene
toluene
–
0
22
95
95
90
91
93
93
96
94
91
1
2
3
4
5
6
7
8
1a 2a, Et/Et
3a
3b
3c
3d
3e/3e’
3 f/3 f’
3g/3g’
3h
–
–
–
–
83
85
86
88
71:8
71:9
72:7
81
78:22
90:10
90:10
84:16
64:34
60:40
62:38
39:61
51:49
60:40
1a 2b, nPr/nPr
1a 2c, nBu/nBu
1a 2d, Ph/Ph
1a 2e, Me/Ph
1a 2 f, Et/Ph
1a 2g, nBu/Ph
1a 2h, Ph/TMS
1a 2i, nBu/TMS
1a 2j, nBu/tBu
1a 2k, Me/tBu
1a 2l, Me/iPr
1a 2m, Me/Et
NiCl2
90:10
89:11
85:15
–
[NiCl2(PMe3)2]
[NiCl2(PMe3)2]
[NiCl2(PMe3)2]
[NiCl2(PPh3)2]
[NiCl2(dppe)]
[NiCl2(dppp)]
9
10
11
9
3i
–
86
10
11[c]
12
13
14
15
16
17[e]
18
19
20[f]
21[f]
22[f]
23[f]
24[f]
3j/3j’
3k/3k’
3l/3l’
3m/3m’ 53:47
3n
3o
3p/3p’
3q/3q’
70:30
73:27
70:30
51:–
45:–
79[d]
79[d]
37
[a] Conditions: 1a (0.02 mmol), 2g (0.07 mmol), and [Ni] (0.02 mmol) in
the solvent (0.6 mL). [b] dppe=1,2-bis(diphenylphosphino)ethane;
dppp=1,3-bis(diphenylphosphino)propane. [c] Yields determined by
GC–MS. DME=1,2-dimethoxyethane.
ꢀ
1a 2n, Ph/C CPh
–
–
=
1a 2o, CH2CH CH2/Ph
23
1a 2p, (CH2)3Cl/Ph
1a 2q, CH2OMe/Ph
1a 2r, (CH2)3O(C5H9O)/Ph 3r
1a 2s, CH2NMe2/Ph
1b 2a, Et/Et
1b 2c, nBu/nBu
1b 2e, Me/Ph
1b 2 f, Et/Ph
86:14
71:29
–
42:6
33:13
21
23:6
39
41
27
30
32
3s/3s’
3t
3u
3v
3w
3x
81:19
dihydrobenzocarboranes 3g/3g’ with poor selectivity
(Table 1, entry 2). However, the reaction in THF afforded
3g/3g’ in excellent yield with very good selectivity even at
908C (Table 1, entries 3 and 4). In DME, both selectivity and
yield decreased a little (Table 1, entry 5). Phosphine-coordi-
nated nickel complexes all gave the product in yields higher
than 91% but with poor selectivity (Table 1, entries 6–11).
Under the optimal reaction conditions (Table 1, entry 4),
a variety of alkynes was examined (Table 2). Symmetrical
alkynes gave the single products 3a–d, which could be
isolated in very good yields (Table 2, entries 1–4). For unsym-
metrical alkynes, the regioselectivity was dependent on both
the polarity of alkynes and relative bulkiness of two
substituents. Phenyl- and trimethylsilyl-substituted alkynes
2e–i afforded very good regioselectivity owing to electronic
effects (Table 2, entries 5–9),[13,14] but substituted alkyl
alkynes 2j,k gave 3j,k as the major regioisomers because of
steric effects (Table 2, entries 10 and 11). For alkynes bearing
functional groups 2n–s, the cycloaddition products were
formed in low yields, which might be ascribed to the
–
–
–
–
–
1b 2g, nBu/Ph
[a] Conditions: 1 (0.2 mmol), 2 (0.6 mmol), and [Ni] (0.2 mmol) in THF
(6 mL). [b] The molar ratio of 3/3’ was determined by GC–MS.
[c] [NiCl2(PMe3)2] was used. [d] Yield for inseparable mixture of 3/3’.
[e] [NiCl2(PPh3)2] was used. [f] For all reactions with 1b, [1-(PhCH CH)-
1,2-C2B10H11] was isolated in about 30% yield in addition to 3. [g] Yield of
=
isolated product.
[2+2+2] cycloaddition of carboryne with one alkene and
one alkyne.
Compounds 3 were fully characterized by H, 13C, and
1
11B NMR spectroscopy as well as high-resolution mass
spectrometry.[15] The molecular structures of 3h, 3n, 3o, and
3w were further confirmed by single-crystal X-ray analyses.[16]
We attempted to isolate the nickelacycle to understand
the reaction mechanism. Reaction of 1a with NiCl2 in the
absence of alkynes resulted in a complicated mixture
containing alkenyl carboranes as b-H elimination products.
After many attempts, the transmetalation intermediate,
ꢀ
functional group competing with the C C unit for the
vacant site at nickel (Table 2, entries 14–19). For zirconacy-
clopentane 1b, the alkyne annulation products 3t–x were
obtained in low yields together with the isolation of alkenyl
=
carborane [1-(PhCH CH)-1,2-C2B10H11] in about 30% yield.
The latter resulted from b-H elimination of the nickelacycle
intermediate, in which the phenyl group may facilitate such an
elimination process.[4]
It was noted that these dihydrobenzocarboranes were also
prepared in similar yields from the one-pot reaction of
[Cp2Zr(m-Cl)(m-C2B10H10)Li(OEt2)2] with alkene and subse-
quent treatment with alkyne in the presence of NiCl2. This
reaction represents an equivalent of a three-component
nickelacyclopentane
[1,2-[Ni(dppe)CH2CH(nBu)]-1,2-
C2B10H10] (4) was isolated in 48% yield after the reaction of
1a with [NiCl2(dppe)] in refluxing toluene (Scheme 2).
Complex 4 was fully characterized by various NMR spectro-
scopic techniques and elemental analyses. A single-crystal X-
ray diffraction study revealed that the nickel atom in 4 adopts
a square-planar geometry (Figure 1).[17] It is obvious that the
coordination of the dppe ligand to the nickel atom can
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carboryne, unactivated alkene, and alkyne for the preparation
of dihydrobenzocarboranes. This offers an example of how to
control the selectivity among different alkenes and alkynes to
assemble complex molecular architectures.
Experimental Section
Scheme 2. Synthesis of intermediate 4 and its reaction with alkyne 2c.
1: 1-Hexene (168 mg, 2.0 mmol) was added to [Cp2Zr(m-Cl)(m-
C2B10H10)Li(OEt2)2] (554 mg, 1.0 mmol) in toluene (20 mL), and the
reaction mixture was heated to reflux for 48 h. After removal of the
precipitate (LiCl) by filtration, the clear solution was concentrated to
about 5 mL, from which 1a was isolated as light-yellow crystals after
this solution stood at room temperature overnight (394 mg, 88%).
Complex 1b was prepared in the same manner as red crystals in 87%
yield.
4: A suspension of 1a (90 mg, 0.2 mmol) and [NiCl2(dppe)]
(110 mg, 0.2 mmol) in toluene (10 mL) was heated to reflux for two
hours and stirred. The mixture was filtrated to give a brown solution,
from which complex 4 was isolated as light-brown crystals after this
solution stood for two days at room temperature (66 mg, 48%).
Received: September 2, 2011
Revised: October 4, 2011
Published online: December 8, 2011
Keywords: carboranes · carborynes · cycloaddition ·
.
synthetic methods · transition metals
Figure 1. X-ray crystal structure of [1,2-{(dppe)NiCH2CH(nBu)}-1,2-
C2B10H10] (4). Thermal ellipsoids are set at the 35% probability level.
Selected bond lengths [ꢀ] and angles [8]: Ni1–C2 1.935(3), Ni1–C16
1.953(2), Ni1–P1 2.154(1), Ni1–P2 2.214(1), C1–C2 1.708(4), C1–C11
1.527(5), C11–C16 1.501(5); C2-Ni1-C16 86.5(1), C16-Ni1-P1 86.5(1),
P1-Ni1-P2 86.7(1), P2-Ni1-C2 101.3(1).
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nickelacyclopentane. Further reaction of 4 with alkyne 2c in
THF at 1108C gave 3c in greater than 90% yield as
determined by GC (Scheme 2). Accordingly, the formation
of products 3 can be rationalized by the steps of trans-
À
metalation of Zr to Ni, insertion of alkyne into the Ni
C(alkyl) bond and reductive elimination reaction (Scheme 3).
In summary, we have developed an efficient transition-
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Scheme 3. Proposed reaction mechanism.
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[15] Experimental details and complete characterization data are
provided in the Supporting Information.
[16] CCDC 840641 (1a), 840642 (1b), 840643 (4), 840644 (3h),
840645 (3n), 840646 (3o), and 840647 (3w) contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[17] Crystal data for 4: C34H46B10NiP2, Mr= 683.5, triclinic, space
ꢀ
group P1, a = 11.100(1), b = 11.619(1), c = 15.742(1) ꢁ, a =
74.34(1)8, b = 73.30(1)8, g = 89.08(1)8, V= 1868.3(2) ꢁ3, T=
296 K, Z = 2, 1calcd = 1.215 gcmÀ3
, 2qmax = 50.58, m(MoKa) =
0.71073 ꢁ. A total of 6543 reflections were collected and led to
5441 unique reflections, 5441 of which with I > 2s(I) were
considered as observed, R1 = 0.040, wR2(F2) = 0.106. This struc-
ture was solved by direct methods and refined by full-matrix
least-squares on F2 by using the SHELXTL/PC package of
crystallographic software.[18] All non-hydrogen atoms were
refined anisotropically and all hydrogen atoms were geometri-
cally fixed using the riding model.
[18] G. M. Sheldrick, SHELXTL 5.10 for Windows NT: Structure
Determination Software Programs. Bruker Analytical X-ray
Systems, Inc., Madison, Wisconsin, USA, 1997.
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