Aluminepin: Aluminum analogues of borepin and gallepin

Article abstract of DOI:10.1021/jo201992q

We report synthesis of dibenzoaluminepin as the first aluminepin, an aluminum analogue of borepin and gallepin. This compound contains one molecule of ethereal solvent on the Al atom, which adopts a tetrahedral geometry. The central 7-membered aluminepin

Full text of DOI:10.1021/jo201992q

Note
pubs.acs.org/joc
Aluminepin: Aluminum Analogues of Borepin and Gallepin
Kengo Yoshida,*,†,‡ Taniyuki Furuyama,‡ Chao Wang,†,‡ Atsuya Muranaka,‡ Daisuke Hashizume,‡
Shuji Yasuike,‡ and Masanobu Uchiyama*,†,‡
†Graduate School of Pharmaceutical Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
‡RIKEN-ASI, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan
S
* Supporting Information
ABSTRACT: We report synthesis of dibenzoaluminepin as the
first aluminepin, an aluminum analogue of borepin and gallepin.
This compound contains one molecule of ethereal solvent on the
Al atom, which adopts a tetrahedral geometry. The central 7-
membered aluminepin ring has a boatlike conformation and was
characterized by single-crystal X-ray diffraction, 1H/13C NMR, and
DFT studies. In addition, NICS, NBO, and theoretical calculations
provide insight into the nature of the bonding and aromaticity of
aluminepins.
ropylium cation (1) is a well-known nonbenzenoid
T
aromatic compound (Chart 1).1 Since Vol’pin first
Chart 1
proposed borepin (2a, M = B), which is isoelectronic with 1,
as a neutral and Huckel 6π-aromatic tropylium analogue,2 the
̈
aromatic character of borepins has been extensively inves-
tigated.3 With regard to other heteropins incorporating group
13 metals, there is only one recent report on dibenzo[b,f]-
gallepin (3c, M = Ga),4 which was isolated as a nonplanar 7-
membered ring with a molecule of TMEDA coordinated to the
Ga atom, while the corresponding aluminum-containing
heteropin (aluminepin) has not been reported to date. Thus,
it is of interest to investigate the generality and aromatic
properties of heteropins incorporating group 13 metals. Here,
we report the synthesis and spectroscopic/computational
characterization of aluminepins.
Figure 1. Energy levels of three Kohn−Sham orbitals and the contour
plots for phenanthrene and group 13 dibenzoheteropins (B3LYP/6-
311+G*).
metal atom without any energy barrier to form the planar
structure. The LUMO+1 orbital of 4 is energetically stabilized
by a group 13 metal in proportion to its electronegativity (B:
2.04, Al: 1.61, Ga: 1.81).
DFT calculations5 indicated that group 13 dibenzoheteropins
(3a-, b-, and -c-H, M = B, Al, and Ga) meet the requirements
of aromaticity (Figure 1); i.e., they have planar structures and
the computed frontier π-orbitals at the B3LYP/6-311+G*
level6 show very similar features to those of phenanthrene (4).
Incidentally, they have rather lower HOMO−LUMO energy
gaps than that of the relevant aromatic hydrocarbon 4. We
confirmed that the planar geometry is the local minimum by
starting with an artificial nonplanar geometry of 3. Geometry
optimization then resulted in smooth migration of the group 13
In order to get the first aluminepin in hand and to investigate
its chemical properties, we planned to synthesize dibenzo[b,f ]-
aluminepin. An aluminum-containing 5-membered heterocycle
(aluminole) has been reported,7 but an attempt to generate a 7-
membered heterocycle (aluminepin) by ring expansion of
benzoaluminole was unsuccessful.8 To develop a synthetic
route to dibenzoaluminepin (3-R, M = Al), we therefore started
Received: October 11, 2011
Published: November 22, 2011
© 2011 American Chemical Society
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Scheme 1. (a) Synthesis of 2,2′-Dibromo-Z-stilbene. (b) Synthesis of Dibenzo[b,f]aluminepin
our investigation from two directions, via tin−aluminum and
lithium−aluminum exchange reactions. 2,2′-Dibromo-Z-stil-
bene (9) was synthesized from 2-bromoiodobenzene in four
steps by means of two Sonogashira coupling reactions and
DIBAL-mediated partial cis reduction of the acetylene moiety as
described by a member of our group9 (Scheme 1). Most
borepins have been synthesized by tin−boron exchange
reaction of the appropriate stannepin with boron halides.
Although tin−aluminum exchange reactions of 11 using various
kinds of aluminum reagents were investigated, all attempts were
unsuccessful and the reaction mixtures showed only complex
NMR spectra. Next, we focused on direct alumination of 9 via a
dilithio intermediate, as used to synthesize gallepin4 and 5-,10
6-,11 and 7-membered9 heterocycles.
After extensive experimentation using 9, we found that
ethylaluminum dichloride reacted smoothly with the dilithio
intermediate (10) at −78 °C to give an aluminepin. After the
reaction, the solvents were removed under reduced pressure.
The residue was extracted with pentane, and cooling in a
freezer for 3 days afforded colorless crystals containing a
molecule of diethyl ether as a ligand (Figure 2).12 As judged
Al(1)−C(14) (109.89°), C(1)−Al(1)−C(15) (114.20°), and
C(14)−Al(1)−C(15) (116.68°)), the Al atom adopts a
tetrahedral geometry and the central 7-membered aluminepin
ring has a boatlike conformation. All attempts to remove the
diethyl ether coordinated to the aluminum atom failed. NMR
experiments in solution also supported the presence of one
molecule of diethyl ether per dibenzoaluminepin. The
coordination of diethyl ether to dibenzoaluminepin could also
1
be detected in H and 13C NMR spectra, since the signals of
diethyl ether were clearly shifted. These observations are similar
to those in the case of dibenzogallepin 3c4 but very different
from those for borepins.
To address the aromaticity and coordination properties of
group 13 heteropins, we performed theoretical/computational
studies of 2a−c as model heteropins. Nucleus-independent
chemical shifts (NICS)13 for 2a−c were first computed at the
B3LYP/6-311+G* level to assess the aromatic character. The
NICS(0) and NICS(1) values of 2a (−3.55 and −6.88), 2b
(−0.80 and −3.08), and 2c (−1.16 and −3.56) suggest that all
group 13 heteropins show aromatic nature, i.e., aromatic 6π-
electron structures (although their NICS values are small)
(Figure 3). The aromatic character becomes weaker in the
order of 2a, 2c, and 2b.14 Solvation reactions of the heteropins
with a molecule of dimethyl ether were then examined. DFT
calculations indicated that aluminepin 2b and gallepin 2c
coordinate with Me2O to form a solvation complex 12b and
12c with large exothermicity (−12.9 and −5.9 kcal/mol,
respectively), whereas there is no stabilization energy gain in
the case of borepin 2a. Indeed, the planar structure of 2a and its
NICS values showed little change in the absence/presence of
Me2O. On the other hand, solvation of the group 13 atom of 2b
or 2c with a Me2O molecule resulted in a marked change of the
geometry of the heteropin ring to generate a boatlike structure,
decreasing the aromatic character. The origin of the
coordinating effect was investigated by NBO analysis.15
Second-order perturbation analysis of the aluminepin complex
with Me2O indicated a large stabilization energy (59.8 kcal/
mol) between the lone pair of the O atom (donor NBO) and
the vacant p* orbital of the Al atom (acceptor NBO). In the
case of gallepin, the stabilization energy between O and Ga
atoms is 40.8 kcal/mol, while the stabilization energy between
2a and Me2O is below the 0.5 kcal/mol default NBO threshold.
Figure 2. Molecular structure of dibanzoaluminepin (3b-Et) (thermal
ellipsoids are shown at 50% probability levels).
from the bond length of Al(1)−O(1) (1.905 Å), as well as the
sum of the bond angles around the Al atom (340.77°: C(1)−
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extracted with ethyl acetate, and the combined organic layer was
washed with sodium bicarbonate and brine, dried over magnesium
sulfate, filtered, and concentrated under reduced pressure. The residue
was treated with a short silica gel column with hexane as an eluent to
give 6 as pale brown liquid, which was directly used for next reaction.
2-Ethynylbromobenzene (7).17 In an ice bath, the above
obtained 6 (12.6 g, 50 mmol) was mixed with a solution of potassium
hydroxide (13 g, 0.2 mol) in methanol (100 mL) and then stirred for
18 h at room temperature before being quenched with 2 N
hydrochloric acid. The aqueous phase was extracted with hexane,
and the combined organic layer was washed with brine, dried over
magnesium sulfate, filtered, and concentrated under reduced pressure.
The residue was purified by column chromatography (silica gel,
1
hexane) to give 7 as a pale yellow oil (9.0 g, yield: 100% from 5). H
NMR (300 MHz, 25 °C, CDCl3, SiMe4), δ (ppm): 7.61−7.52 (2H),
7.30−7.18 (2H), 3.78 (1H).
2,2′-Dibromodiphenylacetylene (8).17 To a suspension of
bis(triphenylphosphine)palladium dichloride (0.55 g, 0.78 mmol)
and copper(I) iodide (61 mg, 0.32 mmol) in diethylamine (45 mL) in
an ice bath were added dropwise 2-bromoiodobenzene (9.4 mL, 73
mmol) and 7 (13.2 g, 73 mmol) successively. The mixture was stirred
for 18 h at room temperature before being quenched with 2 N
hydrochloric acid. The aqueous phase was extracted with ethyl acetate,
and the combined organic layer was washed with sodium bicarbonate
and brine, dried over magnesium sulfate, filtered, and concentrated
under reduced pressure. The residue was purified by column
chromatography (silica gel, hexane) to give 8 as a brown powder.
Figure 3. Optimized bond length (Å) and angles (deg) for group 13
heteropins with and without dimethyl ether. Relative energies ΔE are
given in kcal/mol.
1
(12.7 g, yield: 52%). H NMR (400 MHz, 25 °C, CDCl3, SiMe4), δ
(ppm): 7.63−7.60 (2H), 7.33−7.18 (6H).
2,2′-Dibromo-Z-stilbene (9).18 A solution of DIBAL-H in
hexane (1.03 M, 86.7 mL) was added dropwise to a suspension of 8
(12.7 g, 38 mmol) in hexane (30 mL) in ice bath. After that, the
mixture was refluxed with stirring for 18 h and then quenched with
water. The aqueous phase was extracted with ethyl acetate, and the
combined organic layer was washed with brine, dried over magnesium
sulfate, filtered, and concentrated under reduced pressure. The residue
was purified by column chromatography (silica gel, hexane) to give 9
NBO analysis revealed that donation from the π-bond of the
triene moiety of 2a or 2b to the vacant p* orbital of the group
13 atom, i.e., an indicator of aromatic interaction, corresponds
to 23.8 or 8.7 kcal/mol, respectively (Supporting Information).
In summary, we have prepared the first isoelectronic
aluminum analogue of the iconic tropylium cation and
characterized it by means of X-ray, NMR, and theoretical
studies. DFT calculations indicate that group 13 heteropins (M
= B, Al, and Ga) all meet the requirements of aromaticity, but
the electronic structures and physical properties of aluminepin
synthesized here (also the gallepin synthesized by Robinson et
al.)4 are quite different from those of the well-known borepins.
The present work underlines that the aromatic characters of
group 13 heteropins are deeply related to electronegativity,
Lewis acidity, and the nature of the vacant orbital of the central
metal. Efforts to extend heteropin chemistry in order to
develop new functional materials and to elucidate the physical
properties of these compounds (including indinepins and
solvent-free aluminepins/gallepins) by means of synthetic,
theoretical, and spectroscopic studies are in progress.
1
as a white powder. (11.5 g, yield: 90%). H NMR (400 MHz, 25 °C,
CDCl3, SiMe4), δ (ppm): 7.56 (2H), 7.05−6.98 (6H), 6.78 (1H)
Dibenzostannepin (11). To a solution of 9 (1.69 g, 5 mmol) in
diethyl ether (20 mL) was added t-BuLi (1.51 M in pentane, 6.6 mL,
10 mmol) at −78 °C. The mixture was stirred for an additional 2 h
before a solution of dimethyltin dichloride (1.36 g, 6.0 mol) in diethyl
ether (5 mL) was added dropwise at the same temperature. This
mixture was stirred for for 18 h at room temperature and then
quenched with water. The aqueous phase was extracted with diethyl
ether and the combined organic layer was washed with brine, dried
over magnesium sulfate, filtered and concentrated under reduced
pressure. The residue was purified by column chromatography (silica
1
gel, hexane) to give 11 as pale yellow oil. (920 mg, 56%). H NMR
(400 MHz, 25 °C, CDCl3, SiMe4), δ (ppm): 7.47 (2H), 7.41−7.22
(6H), 6.90 (1H), 0.50 (6H). 13C NMR (100 MHz, 25 °C, CDCl3,
SiMe4), δ (ppm): 143.4, 141.7, 134.7, 134.2, 129.0, 128.3, 127.0,
−11.7.
EXPERIMENTAL SECTION
General Methods. Unless otherwise noted, all experiments were
■
t
carried out under Ar atmosphere with anhydrous solvent. BuLi was
Dibenzoaluminepin (3b-Et). To a solution of 9 (676 mg, 2
mmol) in diethyl ether (5 mL) was added t-BuLi (1.49 M in pentane,
2.7 mL, 4 mmol) at −78 °C. The mixture was stirred for an additional
2 h before a solution of ethylaluminum dichloride (1.0 M in pentane, 2
mL, 2 mmol) was added dropwise at the same temperature. This
mixture was stirred for 18 h at room temperature before solvent was
removed under reduced pressure. The residue was extracted with
pentane, and the extracts was allowed to cool in a freezer for 3 days to
afford 3b-Et−diethyl ether complex as colorless crystals (250 mg,
titrated prior to use.16 NMR data were collected at room temperature.
For 3b-Et, the sample was run in a CH2Cl2 solution. 1H NMR spectra
were referenced to a solvent (CH2Cl2) signal (5.24 ppm). The
capillary tube contained THF-d8 used as the 13C chemical shift
reference and lock solvent. All spectra were recorded in CDCl3 with
tetramethylsilane as an internal standard.
2-(Trimethylsilylethynyl)bromobenzene (6).17 To a suspen-
sion of bis(triphenylphosphine)palladium dichloride (1.4 g, 2 mmol)
and copper(I) iodide (156 mg, 0.8 mmol) in diethylamine (45 mL) in
an ice bath were added dropwise 2-bromoiodobenzene (5) (6.4 mL,
50 mmol) and trimethylsilylacetylene (8.5 mL, 60 mmol) successively.
The mixture was then stirred for 18 h at room temperature before
being quenched with 2 N hydrochloric acid. The aqueous phase was
1
yield: 53%). H NMR (400 MHz, 25 °C, CH2Cl2), δ (ppm): 7.69
(2H), 7.22−7.11 (6H), 6.68 (2H), 3.76 (4H), 1.23 (3H), 0.98 (6H),
0.40 (2H). 13C NMR (100 MHz, 25 °C, CH2Cl2/THF-d8), δ (ppm):
150.5, 145.7, 137.6, 134.4, 130.5, 128.1, 126.4, 68.1, 13.8, 10.1, −1.9.
731
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Note
ASSOCIATED CONTENT
* Supporting Information
■
S
NMR spectra of 11 and 3b-Et, computational details, and X-ray
crystallographic file (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Fax: (+81)48-467-2879. Email: kengoyoshida@riken.jp
(K.Y.); uchi_yama@riken.jp (M.U.).
■
ACKNOWLEDGMENTS
DFT calculations were performed using the RIKEN Integrated
Cluster of Clusters (RICC).
■
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