Ortho-magnesiation of boron-substituted benzenes by using (TMP) 2Mg

Article abstract of DOI:10.1002/chem.201101022

Magnesiation ortho to boron: Borylbenzenes with an N-methyl-1,3- ethylenediamino group on the boron atom undergo ortho-magnesiation upon exposure to 2,2,6,6-tetramethylpiperidide (TMP)₂Mg, and the resulting ortho-magnesiated borylbenzenes can be trapped with electrophiles (see scheme).

Full text of DOI:10.1002/chem.201101022

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DOI: 10.1002/chem.201101022
ortho-Magnesiation of Boron-Substituted Benzenes by Using (TMP)2Mg**
Atsushi Kawachi,* Saori Nagae, Yasuhiro Onoue, Osamu Harada, and
Yohsuke Yamamoto[a]
The ortho-metalation (hydrogen–metal exchange) of aro-
matic compounds assisted by heteroatom-containing func-
tional groups is one of the most efficient methods for the
transformation of aromatic compounds.[1] Among a variety
of ortho-directing groups developed so far, good ortho-di-
recting groups have two essential features. The first is the
coordinating ability to the metal through the lone pair elec-
trons on the heteroatom, which facilitates the approach of
the metal base to the deprotonation site (in other words, the
complex-induced proximity effect)[1c] and contributes to the
stabilization of the ortho-metalated species through intramo-
lecular coordination. The second is an electron-withdrawing
inductive effect on the aromatic ring, which increases the
acidity of the aromatic protons and stabilizes the resulting
carbanion. Therefore, the metalation ortho to electropositive
elements is considered inefficient and has received little at-
tention.[2] To our knowledge, there is no example of the
ortho-metalation of boron-substituted arenes.
basicity, high steric bulkiness, and low nucleophilicity) could
compensate for the disadvantages of the electropositive ele-
ments.
We report here the first example of the direct ortho-met-
alation of borylbenzenes by using (TMP)2Mg.[8b] Borylben-
zenes with an N-methyl-1,3-ethylenediamino group on the
boron atom undergo ortho-magnesiation upon exposure to
(TMP)2Mg, and the resulting ortho-magnesiated borylben-
zenes can be trapped with electrophiles. The molecular
structure of the magnesiated compound is revealed by X-ray
crystallographic analysis.
(Diaminoboryl)benzenes 1 were prepared in moderate
yields by the condensation of the corresponding phenylbor-
onic acids with N-methyl-1,3-diaminopropane, followed by
azeotropic distillation.[9] The reaction of (diaminoboryl)ben-
zene 1a with (TMP)2Mg (2.5 molequiv) in refluxing THF
and the subsequent treatment with Me2SO4, which is a pow-
erful electrophile, at room temperature afforded ortho-me-
thylated borylbenzene 2a together with the ortho-protonat-
ed product 3a, as shown in Scheme 1. Since the diaminobor-
yl moiety is moisture sensitive, compounds 2a and 3a were
converted into pinacolate derivatives 4a (20% yield) and 5a
(48% yield), respectively, by treatment of the reaction mix-
ture with MeOH in the presence of NH4Cl and then with pi-
nacol in THF.
ortho-Metalated borylbenzenes, however, have potential
utility for the functionalization of benzenes and recent re-
ports have illustrated alternative pathways to them, such as
1) the iodine–magnesium exchange reaction of o-(iodo)bor-
ylbenzenes,[3] 2) the insertion of a transition metal into a
carbon–halogen bond of o-(halo)borylbenzenes,[4] 3) the re-
action of a metal–benzyne complex with a boron reagent,[5]
À
and 4) the transition-metal-catalyzed ortho C H activation
Although the mechanistic details remain unclear, we
postulated a two-step mechanism for the ortho-magnesiation
(Scheme 1). In the initial step, (TMP)2Mg abstracts the
amino proton in 1a, resulting in the formation of intermedi-
ary {borylamide}-Mg-TMP complex 6a. In the second step,
the TMP-Mg moiety in 6a intramolecularly abstracts an
ortho-proton on the benzene to form ortho-magnesiated
borylbenzene 7a. The magnesium in 7a is chelated with the
nitrogen and the ortho-carbon atom. The intramolecular re-
action mode[1c] in the second step may be one of the key fac-
tors to promote unfavorable metalation ortho to the electro-
positive atom. When initial intermediate 6a fails to undergo
deprotonation, ortho-protonated product 5a is formed.
The reaction between 1a and (TMP)2Mg (1:2.5) was
monitored by 13C NMR spectroscopy, as shown in Figure 1.
After 0.5 h at room temperature, compound 1a (Figure 1a)
was completely consumed and the signals of 6a and 8a ap-
peared (Figure 1b): the latter may be formed by the reaction
of 1a with (TMP)2Mg in the ratio of 2:1. The signals were
characterized by comparison with those of authentic samples
prepared independently (see the Supporting Information).
of borylbenzenes.[6] However, crystal-structure determina-
tion was accomplished only for transition-metal (Ti, Zr, Ni,
and Pd) derivatives.[4,5]
Recently, TMP-based metallic reagents (TMP=2,2,6,6-
tetramethylpiperidide) have successfully achieved the direct
ortho-metalation of functionalized aromatic compounds
with excellent regioselectivity and high functional group tol-
erance.[7,8] Thus, we anticipated that TMP-based metallic re-
agents could promote the ortho-metalation of borylbenzenes
because the advantages of the TMP-based reagents (high
[a] Prof. Dr. A. Kawachi, S. Nagae, Y. Onoue, O. Harada,
Prof. Dr. Y. Yamamoto
Department of Chemistry, Graduate School of Science
Hiroshima University, Kagamiyama 1-3-1
Higashi-Hiroshima 739-8526 (Japan)
Fax : (+81)82-4240723
E-mail: kawachi@sci.hiroshima-u.ac.jp
[**] TMP=2,2,6,6-tetramethylpiperidide.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101022.
Chem. Eur. J. 2011, 17, 8005 – 8008
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
8005

Scheme 1. ortho-Magnesiation of 1a and trapping with Me2SO4 and its plausible mechanism. THF solvation to the magnesium may be involved through-
out the process from 1a to 2a. a) (TMP)2Mg (ꢂ2.5)/THF/RT, 0.5 h; reflux, 2 h; b) Me2SO4 (ꢂ3)/08C–RT, 12 h; c) MeOH/NH4Cl/RT, overnight; d) pi-
nacol/hexane/RT, overnight.
Scheme 2. ortho-Magnesiation of 1 and trapping with I2. a) (TMP)2Mg (ꢂ
2.5)/THP/RT, 0.5 h; reflux, 2 h; b) I2/RT, overnight; c) MeOH/NH4Cl/RT,
overnight; d) pinacol/hexane/RT, overnight.
Figure 1. The aromatic regions of the 13C NMR spectra of a) 1a and
b) the reaction mixture prepared by the reaction of 1a with (TMP)2Mg
yield of 9d was increased to 38% by reducing the amount
&
*
(1:2.5) in THF at room temperature for 0.5 h; represents 6a and rep-
of I2 (3 molequiv). It is also notable that the product expect-
ed from the magnesiation ortho to the methoxy group was
not detected.[8f] A sequence of the present transformations
illustrates a new pathway to multifunctionalized arenes.
The ortho-magnesiated borylbenzene prepared by the re-
action of 1a with (TMP)2Mg (1.7 molequiv) crystallized
from THP–hexane as a centrosymmetric dimer coordinated
with two molecules of (TMP)2Mg, which is considered as a
co-complex between 7a and (TMP)2Mg and designated as
resents 8a.
After being refluxed for 2 h, the reaction mixture exhibited
several new signals that may be attributed to 7a, in addition
to those of remaining 6a and 8a. Precise characterization of
the signals attributed to 7a, however, was difficult due to
the complexity of the spectra.
The yield of 4a was improved to 34% when tetrahydro-
pyran (THP) was used as the solvent. It is plausible that the
ortho-magnesiated compound is so basic that it gradually ab-
stracts the a-proton of THF under the refluxing condition to
form 3a. The a-proton of THP is less acidic than that of
THF and thus less prone to abstraction.[10]
o-(Iodo)borylbenzene 9a was obtained in 54% yield by
using I2 (6 molequiv) as the trapping agent for 7a, as shown
in Scheme 2. Whereas p-fluoro 1b produced 9b in only 9%
yield under the same reaction conditions, p-chloro 1c afford-
ed 9c in 41% yield. p-Methoxy 1d provided 9d in 29%
yield together with 3,4-diiodoanisole (15%) and 4-iodoani-
sole (6%). These two byproducts may arise from the boron–
iodine exchange reaction[11] with the remaining I2 because
an electron-donating methoxy group can promote the elec-
trophilic substitution reaction on the benzene. Hence, the
[7a·Mg
tures of [7a·Mg
standpoint of not only an ortho-magnesiated benzene, but
also complexed model for crystal structure of
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
a
a
(TMP)2Mg, which itself is still unknown. First, the ortho
magnesiation led to the formation of the distorted five-
membered MgNBC2 ring. The magnesium (Mg1) is chelated
by the anionic ortho-carbon (C2) and the amide nitrogen
(N1) with an acute bite angle (C2-Mg1-N1=90.50(13)8).
À
The amide–magnesium bond length (N1 Mg1=2.098(3) ꢁ)
À
and the aryl–magnesium bond length (C2 Mg1=
2.261(4) ꢁ) fall in the ranges observed for magnesium
amides (1.90–2.44 ꢁ based on the Cambridge structural da-
tabase (CSD)) and arylmagnesium compounds (2.09–2.34 ꢁ
based on the CSD), respectively.[13] The N1 B1 bond
À
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ortho-Magnesiation of Boron-Substituted Benzenes
COMMUNICATION
were hardly soluble in common organic solvents. This result
may suggest that coordination of the (TMP)2Mg molecules
to 7a may occur during the crystallization process.
In conclusion, the ortho-magnesiation of (diaminoboryl)-
benzenes 1 with (TMP)2Mg was achieved for the first time.
The ortho-magnesiated borylbenzenes were trapped with
Me2SO4 and I2, the latter of which led to the formation of
multifunctionalized arenes. X-ray crystallographic analysis
revealed that the magnesium cation was chelated by the
ortho-carbon of the benzene and one of the nitrogen atoms
of the 1,3-diaminopropane moiety. Although the yields of 9
are low to moderate, this is the important step toward a
better system for the ortho-metalation of boron–aryl species.
Further studies of the structure of 7a in solution and the
mechanistic details of the ortho-magnesiation are currently
under investigation in our laboratory.
Figure 2. Molecular structure of [7a·Mg
ellipsoids. The hydrogen atoms are omitted for clarity.
ACHTUGNRTEN(NUGN TMP)2]2 with 30% probability
À
(1.436(5) ꢁ) is slightly longer than the N2 B1 bond
(1.419(5) ꢁ). Therefore, the lone pair of electrons on N1 is
shared with Mg2, which is mentioned later, whereas that on
N2 participates in the p bonding with B1. The geometry
around B1 is trigonal planar (the sum of the bond angles=
359.88). The plane defined by N1, N2, and B1 is rotated out
of the phenyl ring by about 508 (N1-B1-C1-C2=47.6(5)8).
Second, the dimerization formed the centrosymmetric four-
membered Mg2C2 ring. Each of the two phenyl groups acts
as a bridge between the two magnesium atoms (Mg1 and
Mg1*) and rotated out of the Mg2C2 ring by about 508. The
Mg1···Mg1* atomic distance (2.808(2) ꢁ) is similar to that
observed for the Mg2C2 rings in arylmagnesium compounds
(2.79–2.85 ꢁ),[14] and there is no bonding interaction be-
tween them. Each of the amide ligands is coordinated to
Mg1 and Mg1* from above and below the Mg2C2 plane, re-
spectively. Third, the two molecules of (TMP)2Mg are coor-
Acknowledgements
This work was supported by Grants-in-Aid for Scientific Research from
the Ministry of Education, Culture, Sports, Science and Technology,
Japan.
Keywords: amides · boron · magnesium · metalation ·
synthetic methods
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À
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À
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À
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N(À) groups in [7a·Mg
(TMP)2]2.
G
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Chem. Eur. J. 2011, 17, 8005 – 8008
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Gçttingen, Germany). R1 (I>2s(I))=0.0897, wR2 (all data)=
0.2551, S=1.107 for 346 parameters and 6637 unique reflections.
Maximum and minimum electron density 0.419/À0.292 eꢁÀ3
.
CCDC-816159 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
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0.40ꢂ0.40ꢂ0.20 mm3; monoclinic; P21/c; a=10.5756(5), b=
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Received: April 4, 2011
Published online: June 1, 2011
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Chem. Eur. J. 2011, 17, 8005 – 8008