Spiro-fused six-membered N-heterocyclic carbene: A new scaffold toward unique properties and activities

Article abstract of DOI:10.1039/c4cc01627k

A six-membered N-heterocyclic carbene fused with a spiro-scaffold is designed. The new NHC shows stronger σ-donation ability than typical 5-membered NHCs. This property leads to interesting reactivities of this spiro-fused six-membered NHC. For example, the NHC-BF₃ Lewis pair complex can be readily prepared by using LiBF₄ as the BF₃ source, or through a direct bond-reconstruction of the tetrafluoroborate salt NHC·HBF₄.

Full text of DOI:10.1039/c4cc01627k

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Spiro-fused six-membered N-heterocyclic
carbene: a new scaffold toward unique properties
and activities†
Cite this: Chem. Commun., 2014,
50, 7163
Received 4th March 2014,
Accepted 7th May 2014
Bin-Miao Yang, Kai Xiang, Yong-Qiang Tu,* Shi-Heng Zhang, Deng-Tao Yang,
Shao-Hua Wang and Fu-Ming Zhang
DOI: 10.1039/c4cc01627k
www.rsc.org/chemcomm
A six-membered N-heterocyclic carbene fused with a spiro-scaffold is
designed. The new NHC shows stronger r-donation ability than typical
5-membered NHCs. This property leads to interesting reactivities of this
spiro-fused six-membered NHC. For example, the NHC–BF3 Lewis pair
complex can be readily prepared by using LiBF4 as the BF3 source, or
through a direct bond-reconstruction of the tetrafluoroborate salt
NHCꢀHBF4.
Fig. 1 Design of spiro-fused 6-membered NHC 1.
auxiliaries or ligands, due to their rigid structural characteristics,
have proved to show excellent stereochemical control in a lot of
asymmetric reactions.7 In connection with our long-term interest
in these spirocyclic units,8 we decided to employ spiro-cyclic
scaffolds to control the structural rigidity of 6-membered NHCs
with the aim of developing a class of catalysts and ligands with
new activities (Fig. 1). Here we present our preliminary results
under this topic concerning the synthesis of the first 6-membered
NHC (1) fused with a spirocyclic frame and the evaluation of its
interesting properties and reactivities.
Our synthesis started with the spiro[4,4]nonane-1,6-dione 2
(Scheme 1), which was readily prepared from ethyl 2-oxocyclo-
pentanecarboxylate according to literature procedures.9 Thus 2
was subjected to condensation with aniline, followed by reduction
of the formed imine with NaBH4 to give the major cis,cis-diamine 3.
Cyclization of 3 with HC(OEt)3/NH4BF4 in acidic medium at reflux
furnished the tetrafluoroborate salt 1ꢀHBF4. Treatment of the salt
1ꢀHBF4 with LiHMDS (lithium hexamethyldisilazide) at room tem-
perature afforded the desired NHC 1, which could be purified
through re-crystallization from petroleum ether/toluene in a glove
N-heterocyclic carbenes (NHCs)1 are important molecules. They
are widely explored as reaction reagents,2 ligands for metals,3 and
small molecule organocatalysts.4 Over the past two decades,
several types of NHCs, which vary in the sizes of cyclic frameworks
(from 4 to 8 members) and/or hetero-atom species (N, O, S, and P),
have been explored and examined. Among the NHCs reported,
5-membered NHCs derived from imidazolylidenes, imidazolidinyl-
idenes, triazolylidenes, and thiazolylidenes have been extensively
studied. In contrast, the related expanded 6-membered NHCs
received impressive yet still much less attention.5 Both synthesis
and application of these 6-membered NHCs are much less devel-
oped. The relatively scarce studies on 6-membered NHCs are in
part caused by the challenges associated with the less rigid
6-membered rings, in comparison with their 5-membered analo-
gues. On the other hand, the strong s-donating property6 of
6-membered NHCs makes them attractive catalyst/ligand candi-
dates especially for the discovery of new catalytic modes and
reactions. In addition, the enormous practices in using NHCs as
either ligands or organocatalysts have clearly shown that the
catalytic activation modes, reaction efficiencies and selectivities
are all heavily controlled by the structure of the NHCs. Therefore, it
is undoubtedly that some of the future breakthroughs in reaction
development should come from the employment of NHCs with
unique scaffolds. Additionally, the spirocyclo[4,4]nonane-derived
State Key Laboratory of Applied Organic Chemistry & College of Chemistry and
Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. China.
E-mail: tuyq@lzu.edu.cn
† Electronic supplementary information (ESI) available. CCDC 973596–973602.
For ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/c4cc01627k
Scheme 1 Synthesis of NHC 1.
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Fig. 2 X-ray structures of 1ꢀHBF4 and NHC 1.
box at ꢁ40 1C. Its structure was determined by NMR and X-ray
1
diffraction. The H and 13C NMR signals of NHC 1 indicated that
the two phenyl groups and two fused methynes have respectively the
same chemical environment. The single-crystal X-ray diffraction
analysis of the 6-membered ring structure showed that the five
atoms (N1, C1, N2, C2, and C4) were almost in one plane, and the
middle C3 was out of the plane (Fig. 2).10 Comparing the X-ray
diffraction data (see ESI†) of 1 with those of the corresponding
Scheme 3 Direct reaction of the tetrafluroborate salt or NHC with LiBF4
for convenient preparation of the NHC–BF3 complex.15
solvent and base was critical. When PhH/THF (20/1) was used,
reaction of 1ꢀHBF4 with LiHMDS could be readily completed
within 13 hours at ambient temperature to give complex 6 in
95% yield. If PhH was used as the solvent, a much longer reaction
time (over seven days) and lower yield (58%) were observed. No
desired product 6 could be obtained in the presence of bases such
as NaHMDS, KHMDS or KOtBu. Encouraged by this interesting
observation, we applied our method to a known non-fused
9
spirocyclodiol 20 and the non-fused NHC 6-Mes5h revealed an
obvious difference in bond lengths (the largest D = 0.060 Å) and
angles (the largest D = 6.9001) around the fused C2–C4. Details of
this comparison are included in the ESI.† Furthermore, as we
expected, NHC 1 was quite stable at room temperature for at least
two months either in solution or in the solid state in a glove box.
Next, the reactivities and properties of the new NHC 1 were
investigated. Firstly, its nucleophilic coordination with transition
metal species (Scheme 2) was tested. Reaction of 1ꢀHBF4 with
[Rh(COD)Cl]2 and then with CO under basic conditions afforded
the corresponding Rh–NHC complex 4 and 5 in 74% and 95%
yields, respectively. The IR spectrum of 5 showed the CO stretching
6-membered NHC 7 that has a TEP (2042.6 cm )
ꢁ1 14 value similar
to that of NHC 1. To our delight, the tetrafluoroborate salt 7ꢀHBF4
could react readily with LiHMDS in PhH/THF (20/1) at ambient
temperature to produce the corresponding NHC–BF3 complex 8 in
99% yield. In contrast, the typical 5-membered NHC 9 has a higher
TEP value (2051.5 cmꢁ1 11d
than that of NHC 1. The tetrafluoro-
)
borate salt 9ꢀHBF4 could not be converted to the corresponding
complex 10 under otherwise identical conditions. To the best
of our knowledge, our result is the first observation that the
6-membered NHC displays a stronger nucleophilic reactivity than
its 5-membered analog toward trifluoroboranation.
vibrations of similar intensity at 1990.6 cmꢁ1 and 2070.8 cmꢁ1
.
From these values, we inferred a Tolman electronic parameter
(TEP)6a,11 value of 2043.9 cmꢁ1. This value indicated that 1 would
have a stronger s-donation nature than most of the normal
5-membered NHCs,6 which thus prompted us to further evaluate
its possible unusual nucleophilic properties.
We also examined the reactivities of NHC 1 with other non-metal
and metal species. As shown in Scheme 4, NHC 1 generated in situ
from 1ꢀHBF4 with LiHMDS could be trapped with S8 at room
temperature affording thiourea 11 as a light yellow solid in an
excellent yield of 96%. When carbon disulfide was added to the
reaction system at ambient temperature of 1ꢀHBF4 and LiHMDS,
the dipolar cross-coupling product 12 was formed smoothly as
a deep red solid in 88% yield. NHC 1 could also react with
3,4-dimethoxycyclobut-3-ene-1,2-dione to afford the carbon-inserted
product 13 in 58% yield. Our NHC also behaves as an excellent
ligand for transition metals. For example, 1 could react easily with
Au(Me2S)Cl in a glove box at ambient temperature, and a coordinate
14 was obtained in nearly quantitative yield as a white stable solid.
Interestingly, a cationic Cu(I) bis-(NHC) compound 15 could also be
obtained in 71% yield from the reaction between 1 and CuCl. The
crystal structures of 11, 14, and 15 have been determined (see ESI†).
In summary, we have designed, synthesized, and characterized a
new spirocarbocyclo-fused N-heterocyclic carbene 1, which has C2
symmetry axis. For the first time, we observed stronger nucleophilic
properties of 6-membered NHC (e.g., 1) than typical 5-membered
NHC (e.g. 9) toward the trifluoroboranation. This carbene trifluoro-
boranation reaction might be used as a general method to estimate
Following the above deduction, we tested the trifluoroborana-
tion of NHC 1 toward preparation of the Lewis pair NHC–BF3 6,
because this kind of complex recently proved to possess some
promising reactivity as non-metal catalysts, reactants, and
reagents.12 As reported, the previous preparation of NHC–BF3
normally required the use of active reagents such as THFꢀBF3 or
Et2OꢀBF3.13 With careful studies (Scheme 3), we found that a
simple and normally inactive reagent, LiBF4, could be used to
react with NHC 1 in a mixture of PhH/THF (20/1) as the solvent at
room temperature. The reaction smoothly afforded complex 6 in
73% yield. Our further studies showed that tetrafluoroborate salt
1ꢀHBF4 could directly undergo effective transformation to give
complex 6. In the case of using 1ꢀHBF4 directly, the choice of
Scheme 2 Synthesis of RhCl(COD)(NHC) 4 and RhCl(CO)2(NHC) 5.
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‘‘973’’ Program of MOST (2010CB833203), the ‘‘111’’ Program of
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