Substituent effects in NHC-boranes: Reactivity switch in the nucleophilic fluorination of NHC-boranes

Article abstract of DOI:10.1055/s-0033-1338847

Substituents on the boron atom of NHC-boranes direct the reactivity of the ligated boreniums obtained through hydride abstraction. Depending on the electronics of the substituent, the reaction is selectively steered toward either B-substitution or Lewis b

Full text of DOI:10.1055/s-0033-1338847

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cluster
Substituent Effects in NHC–Boranes: Reactivity Switch in the Nucleophilic
Fluorination of NHC–Boranes
NHC–Borane Fluorination
Malika Makhlouf Brahmi,a Max Malacria,a Dennis P. Curran,b Louis Fensterbank,a Emmanuel Lacôte*a,c
a
UPMC Université Paris 06, IPCM (UMR 7201), 4 Pl. Jussieu, C. 229, 75005 Paris, France
b
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
c
Université de Lyon, Institut de chimie de Lyon, UMR 5265 CNRS-Université Lyon I-ESCPE Lyon, 43 Bd du 11 novembre 1918, 69616
Villeurbanne, France
Fax +33(4)72431795; E-mail: emmanuel.lacote@univ-lyon1.fr
Received: 23.04.2013; Accepted after revision: 03.05.2013
We hypothesized that boreniums would abstract a fluoride
Abstract: Substituents on the boron atom of NHC–boranes direct
the reactivity of the ligated boreniums obtained through hydride ab-
straction. Depending on the electronics of the substituent, the reac-
tion is selectively steered toward either B-substitution or Lewis base
exchange.
–
from the tetrafluoroborate ion (BF4 ). In turn, we selected
–
Ph3C+·BF4 as reagent envisioning that the tritylium cat-
ion would serve for borenium generation (Scheme 1, b).7
–
Fluoride transfer from BF4 would generate the neutral
and highly Lewis acidic BF3. To side-step the possible bo-
ron exchange at the NHC, we added phenol to trap the BF3
generated.
Key words: boron, carbene complexes, fluorine, cations, Lewis
acids
Boreniums [LBR2]+ are tricoordinate boron cations for-
mally obtained from complexation of the highly unstable
borinium cations [BR2]+ and Lewis bases L. They are
gaining increased attention because of their original struc-
tures and reactivities.1
(a) known fluorination of dipp-Imd-BH3
dipp
N
F–
HX
NHC BH2X
NHC BH2F
BH3
or I2
N
dipp
dipp = 2,6-i-Pr-C6H3
N-Heterocyclic carbenes (NHC) have proved especially
good at stabilizing the [BR2]+ moiety, including rarely ob-
served structures, such as the dihydroxyborenium.2 NHC–
borenium cations have also been used to functionalize
NHC–boranes with different nucleophiles,3 and most re-
cently they have been introduced as catalysts for main-
group catalytic hydrogenation.4
(b) this work (postulated)
Ph3C+
–
BF4
+
"
"
NHC BHAr
NHC BH2Ar
NHC BHFAr
handle for tuning reactivity?
Scheme 1 General scheme for NHC–borane fluorinations
Because of their promise, the elucidation of the factors
governing how substituents at boron influence the ligated
boreniums and/or electrophilic NHC–boranes is an im-
portant task. In the present paper we examine how aryl
substituents in NHC–monofluoroboranes can selectively
direct reactivity either toward bis-B-fluorination or to-
ward Lewis base exchange.
In
a
typical
experiment,8
triphenylcarbenium
tetrafluoroborate7a (1 equiv) was added to NHC–borane
1a in dichloromethane at room temperature, then phenol
(1 equiv) was immediately added. After five minutes at
room temperature, the solvent was evaporated in vacuo
and the product was purified by flash chromatography.
NHC–difluoroborane 2a was isolated in 68% yield as the
sole NHC-containing product of the reaction (Scheme 2
and Table 1, entry 1). Interestingly, the reaction did not
stop after the first fluorination. A second fluorine was in-
troduced on the boron, as shown by 19F (δ = –153.2 ppm),
11B NMR analysis (broad singlet at δ = 4.8 ppm), and
mass spectrometry.
We recently showed that B-aryl-substituted NHC–boryl
radicals are delocalized.5 If this were the case for NHC–
boreniums as well, then this feature could be used to influ-
ence the reactivity at boron toward new boreniums or
electrophilic NHC–boranes usable for hydrogenations.6
We decided to probe this issue by studying a new method
to make NHC–fluoroboranes from NHC–hydridoboranes.
The current process is two steps (introduction of a leaving
group and displacement) and is limited in scope (Scheme
1, a).3
The difluorination was also observed with B-aryl IPr–bo-
ranes bearing electron-withdrawing groups on the aryl
ring (Table 1, entries 2–4, IPr = 2,6-diisopropylphenyl
imidazolydinene). On the contrary, aryl rings with elec-
tron-rich substituents or the electron-rich heteroaryl thio-
SYNLETT 2013, 24, 1260–1262
Advanced online publication: 28.05.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1338847; Art ID: ST-2013-R0379-C
© Georg Thieme Verlag Stuttgart · New York

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NHC–Borane Fluorination
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phene led to IPr–BF3 3 as the only product of the reaction electrophilic deboration of the B-aryl group followed by
(entries 5 and 6).
perfluorination. In the cases where the NHC–BF3 com-
plexes 3 and 4 were isolated, we observed the formation
of the boronic acids derived from the arylboranes (large
singlets around δ = 30 ppm in 11B NMR). This tends to fa-
vor the first hypothesis (boron exchange, see Scheme 4,
b).
Difluorination was again observed with the less sterically
demanding IMe–BH2Ph (1g, IMe = 2,6-dimethyl imidaz-
olydinene) as well as with the corresponding B-EWG-
substituted aryl borane 1h (Ar = p-trifluoromethylphenyl,
Table 1, entry 8). Conversely, the BF3 adduct 4 was iso-
lated from the p-methoxy derivative 1i (Table 1, entry 9). The unsubstituted IPr–BH3 (5) cannot undergo deboration
because it does not have an aryl group (Scheme 3). This
delivered an approximately 1:2 mixture of IPr–BF3 (4)
and difluoroborane adduct 6 (78% overall yield), in which
one molecule of phenol has been incorporated in the final
complex (Scheme 2, a). Alternatively, with triphenylcar-
beniums with counterions that do not release fluorine (Cl–,
TfO–), monosubstituted chloro (7a, 57%), or trifluoro-
methanesulfonyl (7b) adducts were observed (Scheme 3,
b). Compound 7a was isolated, but not 7b which is not
stable to column chromatography.2d,3
Ph3C+, BF4
–
PhOH
NHC BF2Ar
NHC BF3
or
NHC BH2Ar
CH2Cl2, r.t.
1a–j
2a–d,g,h,j
3, 4
Scheme 2 Fluorination of B-aryl NHC–boranes
Table 1 Fluorination of B-Aryl NHC–Boranes
Entry
Starting
material
NHC
Ar
Product,
yield (%)
–
Ph3C+, BF4
PhOH
(a)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
IPr
Ph
2a 68
2b 100
2c 83
2d 86
3 80
F2
B
+
IPr BH3
IPr BF3
IPr
4-MeO2CC6H4
4-F3CC6H4
3-BrC6H4
4-MeOC6H4
2-thiophenyl
Ph
IPr
OPh
CH2Cl2, r.t.
5
6 50%
4 28%
IPr
IPr
Ph3C+, X–
PhOH
(b)
IPr
H2
B
IPr BH3
IPr
3 59
IPr
X
CH2Cl2, r.t.
5
7a-b
1g
1h
1i
IMe
IMe
IMe
2g 51
2h 81
4 80
7a X = Cl 57%
7b X = OTf only product
4-F3CC6H4
4-MeOC6H4
Scheme 3 Reaction of the unsubstituted NHC–borane 5
With these data, we propose the following mechanistic
hypothesis to explain the reactivity pattern exhibited by
the NHC–boranes in the borenium-mediated fluorination
(Scheme 4).
A crystal of suitable for X-ray diffraction was obtained
upon slow evaporation of a hexane solution of difluoro-
borane 2g, and its structure was solved (Figure 1). The
crystal structure confirmed the bisfluorination, as well as
the presence of a tetrahedral boron atom.
Initial hydride abstraction from 1 or 5 by the triphenylcar-
benium ion delivers boreniums such as A, which captures
a fluoride to deliver NHC–monofluoroboranes like 8 and
BF3.
When the carbenium counterion is Cl– or TfO–, there is no
byproduct of the nucleophilic addition to the borenium
and the reaction delivers the corresponding NHC–BH2–
Nu derivatives (Scheme 3, b).
With the tetrafluoroborate salt, the reaction continues be-
cause of the BF3 generated after the nucleophilic addition
to the boreniums, and the products depend on the aryl
group. When the aromatic group is electron-deficient, BF3
is trapped by phenol quickly. However, this generates one
equivalent of HF, which is the source of the second fluo-
rination, through an acid–base reaction.3 The yields in
difluorinated compounds are generally high.
Figure 1 X-ray structure of compound 2g
The results show that the reaction outcome is influenced
by the nature of the substituent on the aryl group at boron,
giving either NHC–BF2Ar 2 or NHC–BF3 3 and 4 prod-
ucts exclusively.
When the aryl is electron-rich, however, the Lewis basic
carbene liberates BArHF and complexes the more Lewis
The BF3 adducts 3 and 4 could derive from NHC migra-
tion to the BF3 formed during fluoride abstraction or from
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1260–1262

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M. M. Brahmi et al.
CLUSTER
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N
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BF4
H
A
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Ar
Ar
N
N
N
B
B
H
F
N
H
H
8
1
+
BF3
(a) Ar is electron-rich: ligand exchange
Ar
N
F
Ar
B
N
N
BF3
+
+
B
B
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F
F
F
H
N
F
H
8
3, 4
(b) Ar is electron-deficient: protonation
Ar
BF3
N
N
8
PhOH
+O
BF3
B
F
– H2
– PhO BF2
Ph
H
F
2
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Scheme 4 Proposed mechanism
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acidic BF3. This certainly also reduces the steric strain in
the case of the more sterically demanding IPr carbene.
When there is no substituent, as is the case with 5 (Scheme
3, a), the reaction paths compete as we isolated com-
pounds from NHC exchange with both BF3 and PhO–BF2.
To conclude, we have expanded the understanding of
NHC–borane and electronic borenium chemistries. The
subtituents at boron provide a handle to steer the reactivity
through electronic effects beside steric effects. This latter
possibility has been demonstrated for fluorine introduc-
tion, but it also opens perspectives for controlling other
borenium-based reactions, such hydroborations, electro-
philic borylations, as well as catalytic hydrogenations.
(8) General Procedure
To a solution of NHC–borane complex (1 equiv) in CH2Cl2
(0.07 M) was added the triphenylcarbenium derivative
(1 equiv), then phenol (1 equiv). The reaction mixture was
stirred at r.t. for 5 min. The solvent was then evaporated in
vacuo, and the residue was purified by flash chromatography.
Typical Characterization Data for Compound 2a
Mp 222–227 °C. IR (diamond): ν = 2960, 2930, 2870, 2360
(B–F), 1460, 1260, 1060, 1015, 930, 800, 760, 735 cm–1. 1H
NMR (400 MHz, CDCl3): δ = 7.50 (t, J = 7.8 Hz, 2 H, p-H
of IPr), 7.28 (d, J = 7.8 Hz, 4 H, m-H of IPr), 7.04 (s, 2 H,
NCH), 6.94 (t, J = 6.9 Hz, 1 H, p-H of Ph), 6.88 (t, J = 6.8
Hz, 2 H, m-H of Ph), 6.77 (d, J = 6.6 Hz, 2 H, o-H of Ph),
2.61–2.55 [m, 4 H, CH(CH3)2], 1.20 [d, J = 6.8 Hz, 12 H,
CH(CH3)2], 1.13 [d, J = 6.8 Hz, 12 H, CH(CH3)2]. 13C NMR
(100 MHz, CDCl3): δ = 145.5 (C arom.), 134.2 (C arom.),
131.7 (CH arom.), 130.4 (CH arom.), 126.6 (CH arom.),
125.9 (CH arom.), 123.8 (NCH), 123.8 (CH arom.), 29.0
Acknowledgment
This work was supported by grants from ANR (BLAN0309 Radi-
caux Verts and 08-CEXC-011-01, Borane), CNRS, UPMC, and
IUF (L. F., M. M.). Technical assistance (MS, elemental analyses)
was generously offered by FR 2769. We thank Ms. Hélène Rousse-
lière and Dr. Lise-Marie Chamoreau (UPMC) for the X-ray diffrac-
tion analysis.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
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References and Notes
[CH(CH3)2], 25.9 (CHCH3CH3), 22.3 (CHCH3CH3). 11
B
NMR (133 MHz, BF3·OEt2): δ = 4.8 (br s). 19F NMR (376
MHz, CFCl3): δ = –153.2 (br s). HRMS: m/z calcd. for
C33H41N211BF2Na [M + Na]+: 537.3223; found: 537.3224.
(1) For reviews, see: (a) De Vries, T. S.; Prokofjevs, A.; Vedejs,
E. Chem. Rev. 2012, 112, 4642. (b) Piers, W. E.; Bourke, S.
C.; Conroy, K. D. Angew. Chem. Int. Ed. 2005, 44, 5016. For
Synlett 2013, 24, 1260–1262
© Georg Thieme Verlag Stuttgart · New York