Stability of some aryllithiums in the presence of cyano group: Synthesis of biaromatic cyanoarylboronic acids and silanes

Article abstract of DOI:10.1002/aoc.2856

Lithium diisopropylamine (LDA)-mediated deprotonation reactions of halogenated cyanobenzyloxy-benzenes and cyanobiphenyls were investigated. The resultant organolithium derivatives were converted into the corresponding arylboronic acids or silanes. It was

Full text of DOI:10.1002/aoc.2856

Full Paper
Received: 9 January 2012
Revised: 9 March 2012
Accepted: 9 March 2012
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.2856
Stability of some aryllithiums in the presence
of cyano group: synthesis of biaromatic
cyanoarylboronic acids and silanes
Krzysztof Durka,a Krzysztof Gontarczyk,a Tomasz Kliś,a*
Janusz Serwatowskia and Krzysztof Woźniakb
Lithium diisopropylamine (LDA)-mediated deprotonation reactions of halogenated cyanobenzyloxy-benzenes and cyanobi-
phenyls were investigated. The resultant organolithium derivatives were converted into the corresponding arylboronic acids
or silanes. It was found that the stability of the obtained aryllithiums towards isomerization to the respective benzyllithiums
depends strongly on the number of fluorine atoms in the phenyl ring and on the position of the cyano group. Halogenated
cyanobiaryls were selectively deprotonated in the position flanked by two halogen atoms; however, the yield depended
strongly on the reaction conditions. Addition of LDA to the cyano group was observed on the lithiation of 4-cyano-3′,5′-
dichlorobiphenyl rather than deprotonation. Copyright © 2012 John Wiley & Sons, Ltd.
Keywords: lithiation; nitriles; boronic acids; silanes
using lithium diisopropylamine (LDA) at À90ꢀC.[11] To the best of
Introduction
our knowledge, studies on lithiation of benzonitriles have only in-
Lithiation of benzene derivatives containing electrophilic nitrogen
substituents has been investigated for many years. It has been al-
ready demonstrated that some aryllithiums can be generated in
the presence of the highly reactive -NO2 group.[1,2] The first studies
concerning lithiation of benzonitriles were carried out by Gilman
and Melstrom, who obtained 4-lithiobenzonitrile with limited yield
using Br–Li interconversion between 4-bromobenzonitrile and n-
butyllithium in diethyl ether at À70ꢀC.[3] Parham and Jones gener-
ated the series of isomeric lithiobenzonitriles from the respective
bromobenzonitriles at À100ꢀC in high yield (70–82%).[4] Recent
studies have shown that lithiation of bromobenzonitriles is very
sensitive towards reaction conditions and may result in many side
reactions like addition of organolithiums to the cyano group or
subsequent deprotonation of the unreacted starting material.[5]
The addition of organolithiums and Grignard reagents to nitriles
is a common way to synthesize various carbonyl compounds.[6]
The mechanism of this reaction is well known and organolithium
compounds are generally more reactive than Grignard reagents.[7]
The successful Br–Li interconversion in nitriles can be achieved at
À70ꢀC using the reverse addition order (reaction carried out in ex-
cess of n-BuLi) in THF or THF/Et2O mixture.[8] Interestingly, the ad-
dition of n-BuLi to the cyano group was not observed under these
reaction conditions. The authors assumed that the carbanionic
character of the aromatic ring in the lithiated benzonitriles signifi-
cantly decreased the electrophilic properties of the cyano group
due to the negative charge accumulation at this group. They also
suggested that this effect can be explained by assuming polarizing
interactions.[9] Lithiation of benzonitriles can be also performed via
directed deprotonation; however, lithium amides should be used
as a base in order to prevent addition to the cyano group.[10]
Indeed, 1-cyanonaphtalene was successfully ortho-lithiated with
N-lithio 2,2,6,6-tetramethylpiperidine (LTMP) in THF at À78ꢀC and
1,3-dicyanobenzene was lithiated in high yield at the 2-position
volved systems containing lithium atom and cyano group bonded
to the same benzene ring. As a result, the cyano group in the
lithiated benzonitrile is protected from attack by the organo-
lithium reagent. We decided to check the approach towards prep-
aration of aryllithiums containing the cyano group, which is not
involved in the mesomeric stabilization of the negative charge.
We tested the reactivity of the selected cyanobenzyloxybenzenes.
As the lithiation centre and the cyano group in these compounds
are in two separate benzene rings, special care should be taken
in order to stabilize the obtained aryllithiums towards decom-
position. Our approach would allow for the synthesis of new cya-
noarylboronic acids[12] or silanes[13] in which the cyano group
and boron or silicon atom are bonded to different benzene rings.
Results and Discussion
Our initial efforts focused on lithiation of 1a (Scheme 1, entry a). It
is known that the position between fluorine and oxygen atoms
can be readily deprotonated with LDA owing to their cooperating
acidifying effect.[14,15] However, using LDA in THF at À68ꢀC in the
presence of Me3SiCl as the in situ electrophile, we obtained a mix-
ture of 1b (35%), 1c (53%), 1d (6%) and unreacted 1a (6%). Anal-
ysis revealed that the benzylic position was deprotonated rather
than that between fluorine and oxygen atoms. The reactions
occurs with formation of the intermediates 1b-Li and 1c-Li. The
formation of 1d shows that 1b-Li and 1c-Li undergo a second
*
Correspondence to: Tomasz Kliś, Faculty of Chemistry, Warsaw University of Tech-
nology, Noakowskiego 3, 00–664 Warsaw, Poland. E-mail: ktom@ch.pw.edu.pl
a Faculty of Chemistry, Warsaw University of Technology, 00-664 Warsaw, Poland
b Faculty of Chemistry, Warsaw University, 02-093 Warsaw, Poland
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.

K. Durka et al.
Scheme 1. Influence of the position of the cyano group on the selectivity of lithiation of some cyanobenzyloxy-benzenes
deprotonation to give 1d-Li2. Interestingly, the sequential lithia-
tion–silylation of 1a (1 equiv. of LDA and 1 equiv. of Me3SiCl)
afforded exclusively 1c (Scheme 1, entry b). This can be rational-
ized by assuming isomerization of the ortho-lithiated 1b-Li to
the more stable benzyllithium derivative 1c-Li. These results
showed that the cyano group increases drastically the acidic
properties of the benzylic hydrogen atom in 1a. Replacement of
the cyano group with the less electron-withdrawing bromine
atom in 2a resulted in the selective ortho-lithiation with
formation of 2b-Li which was trapped in situ using B(OiPr)3 with
formation of boronic acid 2b (Scheme 1, entry d).
selective monosilylation of 6a to give 6b (Table 1, entry 4) and
disilylation using LDA (2 equiv.) and Me3SiCl (2 equiv.) with for-
mation of 6c (Table 1, entry 5). The above results prompted us
to synthesize the respective boronic acids from 4a to 7a. Thus
4a was treated with LDA (1 equiv.) at À68ꢀC in the presence of
B(OiPr)3 (1 equiv.). However, we recovered the starting material
quantitatively. We believe that the reaction did not occur be-
cause of the sterical hindrance caused by B(OiPr)3. The quantita-
tive recovery of the starting material in this reaction, however,
was a clear sign that the ortho-lithiated 4a is stable at À68ꢀC.
Attempted sequential lithiation–boronation of 4a using LDA (1
equiv.) and B(OMe)3 at À68ꢀC resulted in selective formation of
4c (Table 1, entry 2). This procedure was next applied to synthe-
size boronic acids from 5a, 6a and 7a. Whereas boronic acids 6d
and 7b were obtained almost quantitatively (Table 1, entries 6,7),
the attempt to prepare boronic acid from 5a resulted in a mixture
which did not contain any of the desired product. Quite obvi-
ously, the ortho-lithiated 5a is not stable on a macroscopic time-
scale and reacts via benzylic deprotonation. The obtained results
suggest that the stability of the ortho-lithiated 4a–7a is the result
of the interplay between basicity of the aryllithium, which can be
tuned by varying the number and position of fluorine atoms, and
the acidity of the benzylic hydrogen, which depends on the posi-
tion of cyano group.
Crystallization of 6d from THF gave single crystals suitable for
analysis by X-ray diffraction methods. The obtained data revealed
that 6d belongs to the triclinic P-1 space group symmetry with
one molecule in the asymmetric part of the unit cell. The -B
(OH)2 group adopts syn-anti conformation as shown in Fig 1. Con-
trary to the X-ray structures of benzyloxyarylboronic acids pub-
lished by our group, the 6d molecule is essentially planar, except
for the -B(OH)2 group, which is distorted out of the plane of the
phenyl ring by 26ꢀ.[19–21] In the crystal lattice, the adjacent
molecules are linked by O-H. . .O interactions in R22(8) and R44(8)
arrangement leading to hydrogen-bonded chain formation,
which propagate along the [100] direction (Fig. 2). The geometri-
cal parameters of hydrogen bonds are given in Table 2. Besides
the strong O2-H2. . .O3 interaction, the H2 atom is also involved
in intramolecular contact with the F1 fluorine atom. This contact
can be regarded as a bifurcated hydrogen bond as the angle sum
at the H2 atom is close to 355ꢀ.
The role of the cyano group here relies not only on the acidifi-
cation of the benzylic hydrogen by means of the inductive effect,
but also on the conjugative stabilization of the formed carban-
ion.[16,17] It was demonstrated recently that N,N-diisopropylamide
group favours benzylic deprotonation over aromatic ring depro-
tonation.[18] The resulting benzylic anion is stabilized conjuga-
tively by withdrawal of electrons from the benzylic group and
the lithium atom gains some additional stabilization caused by
coordination of the oxygen atom lone pairs to the metal centre.
Although the cyano substituent is not capable of forming such
a coordinated species, we believe that its electron-withdrawing
properties combined with conjugative stabilization ability is suffi-
cient to stabilize the benzylic carbanion. We expected that the
change in position of the cyano group from ortho in 1a to meta
in 3a will result in an increase of selectivity towards deprotona-
tion in the phenyl ring. Indeed, the reaction proceeds via inter-
mediates 3b-Li, 3c-Li and 3d-Li2, which were next trapped with
electrophile to give a mixture of 3b (48%), 3c (40%), 3d (6%)
and unreacted 3a (6%) (Scheme 1, entry e). The formation of a
significant amount of 3c shows that the cyano group enhances
the acidity of the benzylic hydrogen even when placed in the
meta position. We believe that the inductive effect is responsible
for reactivity in this case. Interestingly, sequential di-silylation of
1a using LDA (2 equiv.) and Me3SiCl (2 equiv.) afforded exclu-
sively 1d containing one Me3Si- group in the benzylic position
and one between the fluorine and oxygen atoms (Scheme 1,
entry c). We believe the reaction occurs with formation of the
intermediate 1d-Li2. On the basis of the obtained results we con-
clude that lithiation of 1a occurs at the benzylic position rather
than at the phenyl ring. The inability to lithiate 1a and 3a selec-
tively in the ortho position forced us to move towards the use
of 4a because it contains a very acidic hydrogen atom flanked
by two fluorine atoms (Table 1, entry 1). We expected that two
fluorine atoms would stabilize the obtained aryllithiums and pre-
vent isomerization. The in situ lithiation–silylation of 4a using LDA
(1 equiv.) and Me3SiCl (1 equiv.) resulted in selective formation of
4b. We found that this protocol can be successfully applied for
In the continuation of our studies we tested the reactivity of 4-
cyano-3′,5′-difluorobiphenyl 8a towards deprotonation (Scheme 2).
This compound contains two benzene rings connected directly
and we wanted to check whether 8a-Li, formed after deprotona-
tion between fluorine atoms, would gain some additional stabil-
ity via polarization effect extended to both the benzene rings
and the cyano group. The cyano group in 8a-Li should be then
wileyonlinelibrary.com/journal/aoc
Copyright © 2012 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2012)

Stability of some aryllithiums in the presence of cyano group
Table 1. Preparation of functionalized cyanobenzyloxy-benzenes by deprotonation and subsequent treatment with electrophiles
Entry
1
Starting material
Conditions
Product
LDA, Me3SiCl in situ THF, <À68ꢀC
2
3
4
4a
1. LDA, THF, <À68ꢀC
2. B(OMe)3
3. HClaq
1. LDA, THF, <À68ꢀC
2. B(OMe)3
Mixture of products, no desired boronic acid
3. HClaq
1. LDA, Me3SiCl, in situ THF, <À68ꢀC
5
6
7
6a
2LDA, 2Me3SiCl, in situ THF, <À68ꢀC
6a
1. LDA, THF, <À68ꢀC
2. B(OMe)3
3. HClaq
1. LDA, THF, <À68ꢀC
2. B(OMe)3
3. HClaq
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

K. Durka et al.
two halogen atoms as well as with addition to the cyano group.
The obtained lithiated derivatives react with B(OMe)3 or Me3SiCl
to give the respective arylboronic acids or silanes.
Experimental
1H and 13C NMR spectra were recorded at room temperature on a
Bruker 400 MHz spectrometer. Chemical shifts are given in ppm
1
relative to TMS in H and 13C NMR spectra. All chemicals were
received from Aldrich. THF and Et2O were stored over sodium
prior to use. All reactions were carried out under dry argon using
standard Schlenk techniques. Melting points were determined in
Pyrex capillary tubes with MeI-Temp apparatus.
Figure 1. ORTEP drawing of 6d with displacement ellipsoids plot (50%
probability). Selected bond lengths (Å) and angles (ꢀ): B1–O3 1.353(2),
B1–C1 1.579(3), O2–B1–C1–C2 26.06(3), C4–O1–C7–C8 177.13(2), C4–
O1–C7 120.46(2). Crystallographic data for this structure have been
deposited with the Cambridge Crystallographic Data Centre as supple-
mentary publication number CCDC 833972
Typical Procedure for in situ Lithiation–Silylation
protected towards reaction with LDA. On treatment of 8a with
LDA at À68ꢀC, this compound undergoes clean ortho-lithiation
between two fluorine atoms to give the respective boronic acid
8b after boronation using B(OMe)3 as the electrophile (Scheme 2,
entry a). Unexpectedly, the similar lithiation–silylation of 4-cyano-
3′,5′-dichlorobiphenyl 9a afforded the respective silane 9c in very
low yield and 9b was isolated as the main product (Scheme 2, en-
try c). Formation of 9b resulted from nucleophilic attack of the
LDA molecule on the cyano group. Interestingly, in situ silylation
of 9a using LDA and Me3SiCl afforded exclusively 9c (Scheme 2,
entry d). A possible explanation is that the equilibrium of depro-
tonation of 9a is shifted towards LDA, which is consumed via
irreversible addition to the cyano group. Interestingly, using 2
equiv. of LDA and Me3SiCl per 1 equiv. of 8a or 9a we obtained
8c and 9d respectively (Scheme 2, entries b, e).
LDA: THF (20 ml) and diisopropylamine (1.4 ml, 10 mmol) were
added to the Schlenk flask and the obtained solution was cooled
to ~ À68ꢀC (internal temperature) using an acetone–CO2 bath.
The solution of n-BuLi 1.6 M in hexane (6.2 ml, 10 mmol) was next
added to the Schlenk flask and the obtained solution was stirred
at ~ À68ꢀC for 30 min.
THF (30 ml), 5-(3-cyanobenzyloxy)-1,3-difluorobenzene 4a (2.5
g, 10 mmol) and Me3SiCl (1.1 g, 10 mmol) were added to 100
ml three-neck reaction flask equipped with a thermometer and
magnetic stirrer. The obtained solution was cooled to ~ À68ꢀC
(internal temperature). Freshly prepared LDA (10 mmol) solution
was dropped over 10 min via cannula to the cooled solution of
reactants. The initially colourless reaction mixture became yellow
and next a brownish slurry was formed. The resultant slurry was
stirred for 1 h and then the cooling bath was removed and the
reaction mixture poured on to water (100 ml). The obtained mix-
ture was acidified with H2SO4 (1 M) to attain a slightly acidic pH.
Et2O (50 ml) was next added and the mixture was stirred for 5
min. The organic phase was separated and the aqueous phase
was extracted with Et2O (20 ml). The combined organic solutions
were next dried with anhydrous MgSO4 and evaporated to give a
solid which was washed and recrystallized from hexane (20 ml) to
give 4b as colourless crystals, m.p. 115–116ꢀC; 1H NMR (400 MHz,
Conclusion
Cyanobenzyloxy-benzenes 1a and 3a–7a undergo ortho-lithiation
using LDA; however, benzylic lithiation can compete as the cyano
group increases the acidity of the benzylic hydrogen atoms. This is
especially important for 1a and 5a as the mesomeric and induc-
tive effects caused by the cyano group accelerate deprotonation
of the benzylic position. The increase in the number of fluorine
atoms in 4a, 6a and 7a stabilizes the ortho-lithiated species, pre-
venting isomerization to the corresponding benzyllithiums. Lithia-
tion of halogenated cyanobiphenyls 8a and 9a is very sensitive to
reaction conditions and proceeds with ortho-lithiation between
acetone-d6): d 7.89 (s, Ar, H-C-C-CN, 1H), 7.82 (d, Ar, H-C-Cipso
J = 8Hz, 1H), 7.75 (d, Ar, H-C-C-CN, J = 8Hz, 1H), 7.64 (t, Ar, Cipso
C-C-H, J = 8 Hz, 1H), 6.63 (d, Ar, H-C-C-F, J = 9.6 Hz, 2H), 5.26 (s, -
CH2-, 2H), 0.32 (s, CH3, 9H); 13C{1H} NMR (100.6 MHz, CDCl3):
167.71 (d, C-F, J = 241 Hz, J = 20 Hz), 161.02 (t, C-CF J = 14 Hz),
,
-
Figure 2. One-dimensional chain arrangement of molecules in the crystal structure of 6d with intermolecular O-H. . .O and intramoecular O-H. . .
F
hydrogen bonds (red dashed lines)
wileyonlinelibrary.com/journal/aoc
Copyright © 2012 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2012)

Stability of some aryllithiums in the presence of cyano group
Table 2. Geometry of hydrogen bond interactions in the structure of
6d. (d and θ denote distance and angle, respectively)
(d, C-CF, J = 10.6 Hz), 130.45, 130.07, 128.62, 122.68, 109.00,
108.75, 108.19 (d, C-CCF, J = 3Hz), 70.44 (Cbenz). Anal. Calcd for
C13H11BBrFO3: C, 48.05, H, 3.41. Found: C, 46.91, H, 3.84.
Interaction D–H. . .
A
dD–H (Å) dH. . .A (Å) dD. . .A (Å) θ D–H. . .A (ꢀ)
O2—H2. . .O3#1
O3—H3. . .O2#2
O2—H2. . .F1a
0.84
0.84
0.84
2.07
1.92
2.31
2.731 (2)
2.750 (2)
2.823 (2)
135 (1)
169 (1)
120 (1)
Compound 4c
M.p. 162–163ꢀC; 1H NMR (400 MHz, acetone-d6): d 7.89 (s, H-C-C-
CN, Ar, 1H), 7.82 (d, Ar, H-C-Cipso, J = 8.0 Hz, 1H), 7.76 (d, Ar, H-C-C-
CN, J = 8.0 Hz, 1H), 7.64 (t, Ar, Cipso-C-C-H, J = 8.0 Hz, 1H), 6.63 (d,
Ar, H-C-C-F, J = 9.2 Hz, 2H) 5.25 (s, -CH2-, 2H); 13C{1H} NMR (100.6
MHz, acetone-d6): 167.10 (m, C-F, J = 240 Hz), 162.14 (t, C-CF,
J = 14.6 Hz), 139.25, 132.84, 132.51, 131.71, 130.57, 119.08 (CN),
113.32, 99.16 (d, C-CF, J = 32.6 Hz), 69.74 (Cbenz). Anal. Calcd for
C14H10BF2NO3: C, 58.17, H, 3.49, N, 4.85 Found: C, 58.84, H, 3.84,
N, 4.25.
aStands for intramolecular contact. Symmetry transformations:
#1
() x + 1, y, z;
#2
() À x + 2, Ày + 3, Àz.
137.60, 131.81, 131.38, 130.59, 129.50, 118.46 (CN), 112.87, 98.37
(dd, C-CF, J = 32 Hz, J = 2 Hz), 68.89 (Cbenz), 0.18 (t, 3CH3,
J = 3Hz). Anal. Calcd for C17H17F2NOSi: C, 64.33, H, 5.40, N, 4.41.
Found: C, 64.00, H, 5.55, N, 4.53.
Compound 6b
1
M.p. 41–43ꢀC; H-NMR (400 MHz, CDCl3): d 7.71 (m, Ar, 2H), 7.66
Compound 1c
M.p. 66–67ꢀC; 1H NMR (400 MHz, CDCl3): d 7.48 (m, Ar, Cipso-C-C-H,
J = 8 Hz, 1H), 7.35 (m, Ar, H-C-C-CN, J = 8.0 Hz, 1H), 7.21 (m, Ar, H-
C-Cipso, J = 8 Hz, 1H), 7.11 (m, Ar, H-C-C-CN, J = 8.0 Hz, 1H), 6.95 (m,
Ar, H-C-C-F J = 8.0 Hz, 1H), 6.44 (m, Ar, 3H), 5.21 (s, -CHbenz-, 1H),
0.19 (s, CH3, 9H); 13C{1H} NMR (100.6 MHz, CDCl3): 163.48 (d, C-F,
J = 244 Hz), 160.38 (d, C-CF, J = 11 Hz), 144.94, 132.96 (d, J = 20
Hz), 130.17 (d, J = 10 Hz), 126.54, 126.16, 117.74 (CN), 110.70 (d,
J = 2 Hz), 108.81, 107.91, 103.41, 103.16, 73.69 (Cbenz), À3.93
(3CH3). Anal. Calcd for C17H18FNOSi: C, 68.19, H, 6.06, N, 4.68
Found: C, 68.46, H, 6.43, N, 4.64.
(td, Ar, Cipso-C-C-C-H, J = 7.6 Hz, J = 1.6 Hz, 1H), 7.48 (td, Ar, Cipso
-
C-C-H, J = 7.6 Hz, J = 1.6 Hz, 1H), 5.44 (s, -CH2-, 2H), 0.38 (t, CH3,
J = 1.6 Hz, 9H); 13C{1H} NMR (100.6 MHz, CDCl3): 149.11 (m, C-F,
J = 240 Hz), 140.54 (m, C-F, J = 242 Hz), 139.20, 133.11, 132.92,
129.08, 129.02, 116.66 (CN), 111.62, 110.19 (t, C-CF, J = 22.0 Hz),
110.43 (t, J = 22.8 Hz), 73.92 (t, J = 3.8 Hz, Cbenz), À0.06 (3CH3).
Anal. Calcd for C17H15F4NOSi: C, 57.78, H, 4.28, N, 3.96 Found: C,
58.08, H, 4.94, N, 4.06.
Compound 6c
1
M.p. 70–72ꢀC; H NMR (400 MHz, CDCl3): d 7.61 (m, Ar, 3H), 7.30
Compound 1d
(m, Ar, Cipso-C-C-H, 1H), 5.69 (s, CHbenz, 1H), 0.33 (t, CH3Ar, J = 1.2
Hz, 9H), 0.18 (s, CH3, 9H). 13C{1H} NMR (100.6 MHz, CDCl3):
149.11 (m, C-F, J = 240 Hz), 143.97, 140.34 (m, C-F, J = 242 Hz),
132.80, 132.58, 126.94, 126.40, 117.43 (CN), 109.22, 80.97 (Cbenz),
À0.03 (3CH3Ar), À4.13 (3CH3). Anal. Calcd for C20H23F4NOSi2: C,
56.45, H, 5.45, N, 3.29. Found: C, 56.25, H, 5.59, N, 3.38.
M.p. 81–83ꢀC; 1H NMR (400 MHz, CDCl3): d 7.65 (dd, Ar, Cipso-C-H,
J = 8 Hz, J = 1.6 Hz, 1H), 7.50 (td, Ar, Cipso-C-C-H, J = 8.0 Hz, J = 0.8
Hz, 1H), 7.37 (dd, Ar, H-C-CN, J = 7.6 Hz, J = 0.8 Hz, 1H), 7.26 (td,
Ar, Cipso-C-C-C-H, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.10 (q, Ar, H-C-C-C-F,
J = 8.0 Hz, 1H), 6.53 (t, Ar, H-C-C-O, J = 7.6 Hz, 1H), 6.44 (d, H-C-C-
F, Ar, J = 7.6 Hz, 1H), 5.46 (s, -CHbenz-, 1H), 0.46 (d, CH3Ar, J = 2.4
Hz, 9H), 0.19 (s, CH3, 9H); 13C{1H} NMR (100.6 MHz, CDCl3):
167.65 (d, C-F, J = 241 Hz), 164.31 (d, C-CF, J = 14 Hz), 145.05,
133.21, 132.78, 131.57 (d, C-CF, J = 10.7 Hz), 126.60, 126.32,
117.81 (CN), 109.32, 108.33, 108.05, 106.95 (d, C-CCF, J = 3 Hz),
73.65 (Cbenz), 1.21 (d, J = 3.8 Hz, 3CH3Ar), À3.78 (3CH3). Anal. Calcd
for C20H26FNOSi2: C, 64.64, H, 7.05, N, 3.77 Found: C, 63.45, H, 6.63,
N, 3.67.
Compound 6d
1
M.p. 145–146ꢀC; H-NMR (400 MHz, acetone-d6): d 8.06 (s, -OH,
2H), 7.86 (d, Ar, Cipso-C-C-C-H, J = 7.6 Hz, 1H), 7.77 (d, Ar, J = 7.6
Hz, 2H), 7.63 (m, Ar, Cipso-C-C-H, 1H), 5.52 (s, -CH2- 2H); 13C{1H}
NMR (100.6 MHz, acetone-d6): 148.51 (m, C-F, J = 242 Hz), 141.61
(m, C-F, J = 249 Hz), 139.82, 134.13, 133.97, 131.01, 130.59,
117.40 (CN), 113.33, 74.66 (Cbenz). Anal. Calcd for C14H8BF4NO3:
C, 51.73, H, 2.48, N, 4.31 Found: C, 51.31, H, 2.94, N, 4.82.
Compound 2b
Compound 7b
1
M.p. 131–133ꢀC; H NMR (200 MHz, acetone-d6): d 7.67 (td, Ar,
J = 8 Hz, J = 1.2 Hz, 2H), 7.37 (m, Ar, 4H), 6.85 (d, Ar, H-C-C-C-F,
J = 8 Hz, 1H), 6.70 (td, H-C-C-O, Ar, J = 8 Hz, J = 0.4 Hz, 1H), 5.18
(s, -CH2- 2H). 13C{1H} NMR (100.6 MHz, acetone-d6): 166.46 (d, C-
F, J = 241 Hz), 163.00 (d, C-CF, J = 14 Hz), 137.00, 133.36, 132.24
M.p. 76–79ꢀC; 1H NMR (400 MHz, acetone-d6): d 7.91 (s, Ar, H-C-C-
CN, 1H), 7.85 (d, Ar, H-C-Cipso, J = 8.0 Hz, 1H), 7.79 (d, Ar, H-C-C-CN,
J = 8.0 Hz, 1H), 7.65 (t, Ar, Cipso-C-C-H, J = 8.0 Hz, 1H), 5.42 (s, -CH2- ,
2H); 13C{1H} NMR (100.6 MHz, acetone-d6): 148.57 (m, C-F, J = 246
Scheme 2. Preparation of functionalized cyanobiphenyls by deprotonation and reaction with electrophiles
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

K. Durka et al.
Hz), 141.57 (m, C-F, J = 245 Hz), 138.82, 138.24, 133.54, 133.09,
132.43, 130.64, 118.98 (CN), 113.35, 75.75 (Cbenz). Anal. Calcd for
C14H8BF4NO3: C, 51.73, H, 2.48, N, 4.31 Found: C, 51.32, H, 2.95,
N, 4.43.
corrected for Lorentz and polarization effects. The multiscan
absorption correction, scaling, and merging of reflection data
were done with SORTAV.[24] All structures were solved by direct
methods using SHELXS-97 and refined using SHELXL-97.[25] The
refinement was based on F2 for all reflections except those with
very negative F2. Weighted R factors (wR) and all goodness-of-fit
(GooF) values are based on F2. All non-hydrogen atoms were refined
anisotropically. All hydrogen atoms were placed in calculated posi-
tions with C-H distance of 0.95 Å (phenyl), 0.99 Å (methylene) and
O-H distance of 0.84 Å. They were visible in difference maps and
they were included in the refinement in riding-motion approxima-
tion with Uiso(phenyl H) = 1.2Ueq(C), Uiso(methylene H) = 1.5Ueq(C)
and Uiso(OH H) =1.5Ueq(O). The components of the anisotropic dis-
placement parameters in the direction of the bond of C9 and C14
were restrained to be equal within an effective standard deviation.
C14H8BF4NO3; MW = 325.02 a.u.; T= 100(2) K; triclinic space group
P-1; a = 4.976(1) Å, b = 5.938(1) Å, c = 21.801(1) Å, a = 95.55(1)ꢀ,
Compound 8b
M.p. 161ꢀC (dec.); 1H NMR (400 MHz, acetone-d6): d 7.90 (m, ArCN
,
J = 8.4 Hz, 4H), 7.32 (m, Ar, J = 8.8 Hz, 2H); 13C{1H} NMR (100.6
MHz, acetone-d6): 166.33 (m, C-F, J = 242 Hz), 143.55 (d, C-CF,
J = 5 Hz), 133.73, 133.65, 128.98, 128.68, 119.07 (CN), 112.83,
110.37 (m, J = 30 Hz). Anal. Calcd for C13H8BF2NO2: C, 60.28, H,
3.11, N, 5.41 Found: C, 60.51, H, 3.94, N, 5.72.
Compound 8c
M.p. 77–78ꢀC; 1H NMR (200 MHz, acetone-d6): d 7.75 (d, Ar, H-C-C-
CO, J = 8 Hz, 2H), 7.36 (d, Ar, H-C-Cipso, J = 8 Hz, 2H), 7.27 (d, Ar, H-
C-C-F, JC-F = 8 Hz, 2H), 3.62 (hp, N-C-H, J = 7 Hz, 2H), 1.34 (d, CH3iPr
J = 7 Hz, 12H), 0.39 (s, SiCH3, 9H); 13C{1H} NMR (100.6 MHz, CDCl3):
167.35 (dd, C-F, J = 243 Hz, J = 17 Hz), 166.80 (CO), 144.43 (t, Cipso
ipso, J = 11 Hz), 139.85, 138.97, 127.28, 127.07, 126.71, 109.40 (d,
,
b =92.23(1)ꢀ, g =95.31(1)ꢀ, V=637.6(1) Å3; Z=2; dcalc =1.693 g cmÀ3
;
-
m = 0.155 mmÀ1; Of 15 387 reflections collected, 4770 were unique
(Rint = 0.0325). Refinement on F2 concluded with the values
R1 = 0.0902 and wR2 = 0.1365 for 208 parameters (58 restraints)
and 3986 data with I > 2s(I).
C
J = 30 Hz), 48.79 (2CHiPr), 20.72 (4CH3iPr), 0.22 (3CH3-Si). Anal.
Calcd for C22H29Cl2NOSi: C, 67.83, H, 7.50, N, 3.60 Found: C,
67.91, H, 7.62, N, 3.62.
Compound 9b
Acknowledgements
1
M.p. 124–125ꢀC; H NMR (400 MHz, CDCl3): d 7.52 (d, Ar, H-C-C-
This work was supported by the Warsaw University of Technology.
The X-ray measurements of compound 6d were undertaken at
the Crystallographic Unit of the Physical Chemistry Laboratory,
Chemistry Department, University of Warsaw. Support from Aldrich
Chemical Company, Milwaukee, WI, USA, through the donation of
chemicals and equipment is gratefully acknowledged.
CO, J = 8 Hz, 2H), 7.45 (d, Ar, H-C-Cipso, J = 1.6 Hz, 2H), 7.34 (d, Ar,
H-C-Cipso, J = 8 Hz, 2H), 7.24 (t, Ar, H-C-C-Cl, J = 1.6 Hz, 1H), 3.63
(hp, N-C-H, J = 6.8 Hz, 2H), 1.32 (d, CH3 iPr, J = 6.8 Hz, 12H); 13C
{1H} NMR (100.6 MHz, CDCl3): 167.27 (CO), 143.37, 141.20,
138.27, 135.34, 127.39, 127.21, 126.60, 125.56, 48.41 (2CHiPr),
20.81 (4CH3iPr). Anal. Calcd for C19H21Cl2NO: C, 65.15, H, 6.04, N,
4.00 Found: C, 65.31, H, 5.94, N, 4.06.
References
Compound 9c
[1] a) G. Köbrich, P. Buck, Chem. Ber. 1970, 103, 1412; b) G. Köbrich, P.
Buck, Chem. Ber. 1970, 103, 1420.
1
M.p. 106–107ꢀC; H NMR (400 MHz, dmso-d6): d 7.92 (m, Ar, 4H),
[2] W. C. Black, B. Guay, F. Scheuermayer, J. Org. Chem. 1997, 62, 758.
[3] H. Gilman, D. S. Melstrom, J. Am. Chem. Soc. 1948, 70, 4177.
[4] W. E. Parham, L. D. Jones, J. Org. Chem. 1976, 41, 1187.
[5] K. Menzel, E. L. Fisher, L. DiMichelle, D. E. Frantz, T. D. Nelson, M. H.
Kress, J. Org. Chem. 2006, 71, 2188.
[6] a) J. Clayden, N. Greeves, S. Warren, P. Wothers, Organic Chemistry,
Oxford University Press, Oxford, 2001, p. 301; b) J. Clayden, Organo-
lithiums: Selectivity for Synthesis, Pergamon, Oxford, 2002, p. 286.
[7] C. G. Swain, J. Am. Chem. Soc. 1947, 69, 2306.
[8] S. Luliński, K. Zając, J. Org. Chem. 2008, 73, 7785.
[9] M. Schlosser, E. Castagnetti, Chem. Eur. J. 2002, 8, 799.
[10] R. R. Fraser, S. Savard, Can. J. Chem. 1986, 64, 621.
[11] T. D. Krizan, J. C. Martin, J. Org. Chem. 1982, 47, 2681.
[12] M. Lysen, P. Vedsø, M. Begtrup, J. L. Kristensen, J. Org. Chem. 2006,
71, 2518.
7.74 (s, Ar, H-C-C-Cl, 2H), 0.48 (s, CH3, 9H); 13C{1H} NMR (100.6
MHz, CDCl3): 142.44, 142.39, 141.59, 136.89, 132.78, 127.53,
127.01, 118.46 (CN), 112.14, 2.73 (3CH3). Anal. Calcd for
C16H15Cl2NSi: C, 60.00, H, 4.72, N, 4.37 Found: C, 60.31, H, 4.94,
N, 4.48.
Compound 9d
M.p. 152–153ꢀC; 1H NMR (400 MHz, acetone-d6): d 7.73 (d, Ar, H-C-
C-CO, J = 8 Hz, 2H), 7.64 (s, Ar, H-C-C-Cl, 2H), 7.35 (d, Ar, H-C-Cipso
,
J = 8 Hz, 2H), 3.60 (hp, iPr, J = 7 Hz, 2H), 1.33 (d, iPr, J = 7 Hz, 12H),
0.53 (s, CH3, 9H); 13C{1H} NMR (100.6 MHz, acetone-d6): 167.29
(CO), 144.30, 142.86, 142.82, 137.79, 135.58, 127.96, 127.69,
127.34, 48.93 (2CHiPr), 20.94 (4CH3iPr), 2.94 (3CH3-Si). Anal. Calcd
for C22H29Cl2NOSi: C, 62.55, H, 6.92, N, 3.32 Found: C, 62.71, H,
6.94, N, 3.38.
[13] V. Diemer, J. S. Garcia, F. R. Leroux, F. Colobert, J. Fluorine Chem.
2012, 134, 146.
[14] W. Bauer, P. V. R. Schleyer, J. Am. Chem. Soc. 1989, 111, 7191.
[15] A. I. Meyers, P. D. Pansegran, Tetrahedron Lett. 1983, 24, 4935.
[16] Y. Ito, K. Kobayashi, T. Saegusa, J. Am. Chem. Soc. 1977, 99, 3532.
[17] Y. Ito, K. Kobayashi, N. Seko, T. Saegusa, Bull. Chem. Soc. Jpn. 1984,
57, 73.
Crystal Data for 6d
[18] A. E. H. Wheatley, J. Clayden, I. H. Hillier, A. C. Smith, M. A. Vincent, L.
J. Taylor, J. Haywood, Beilstein J. Org. Chem. 2012, 8, 50.
[19] T. Klis, J. Serwatowski, Acta Cryst. 2009, E65, 2348.
[20] K. Kacprzak, T. Klis, J. Serwatowski, Acta Cryst. 2006, E62, 1308.
[21] K. Kacprzak, T. Klis, J. Serwatowski, Acta Cryst. 2009, E65, 2250.
[22] APEX2, 2010.3-0; Bruker AXS, Madison, WI, 2010.
[23] SAINT, 7.68A, Bruker AXS, Madison, WI, 2010.
[24] a) R. H. Blessing, J. Appl. Cryst. 1989, 22, 396;
b) R. H. Blessing, Acta Cryst. 1995, A51, 33.
[25] G. M. Sheldrick, Acta Cryst. 2008, A64, 112.
Single-crystal data were collected on a Bruker AXS Kappa APEX II
Ultra diffractometer with TXS rotating anode (Mo KR radiation,
l = 0.71073 Å) and multilayer optics and equipped with an Oxford
Cryosystems nitrogen gas flow attachment. The data collection
strategy was optimized and monitored using the appropriate
algorithms applied in the APEX2 program package.[22] Data reduc-
tion and analysis were carried out with the APEX2 suite of pro-
grams (integration was done with SAINT).[23] The data were
wileyonlinelibrary.com/journal/aoc
Copyright © 2012 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2012)