Ortho-Selective nucleophilic addition of amines to 3-borylbenzynes: Synthesis of multisubstituted anilines by the triple role of the boryl group

Article abstract of DOI:10.1039/c3ob41787e

Nucleophilic addition of amines to 3-[(dan)boryl]benzynes (dan = 1,8-diaminonaphthalene) generated by a fluoride ion proceeded with high ortho-selectivity to give 2-borylaniline derivatives, under conditions that are tolerant to various functional groups. The (dan)boryl group of the adduct was hydrolyzed into a boronic acid under acidic conditions, which could further serve for various C-C, C-O, C-N, and C-H bond-formation reactions. The overall process provides a promising entry for preparing multisubstituted aniline derivatives.

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ortho-Selective nucleophilic addition of amines to 3-borylbenzynes:
Synthesis of multisubstituted anilines by triple role of boryl group
Akira Takagi,a Takashi Ikawa,*a,b Kozumo Saito,a Shigeaki Masuda,a Toyohiro Itoa and Shuji Akai*a,b
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
Nucleophilic addition of amines to 3-[(dan)boryl]benzynes (dan = 1,8-diaminonaphthalene), generated by
a fluoride ion, proceeded with high ortho-selectivity to give 2-borylaniline derivatives, under conditions
that are tolerant to various functional groups. The (dan)boryl group of the adduct was hydrolyzed into a
boronic acid under acidic conditions, which could further serve for various C–C, C–O, C–N, and C–H
10 bond-formation reactions. The overall process provides a promising entry for preparing multisubstituted
aniline derivatives.
45 silyl group and the nucleophiles, whose regiochemistry is thought
to be caused by the electron-donating inductive effect of the silyl
substituent. We expected a similar ortho-selective nucleophilic
addition of amines to 3-borylbenzynes,14–18 which would provide
another useful method for synthesizing various functionalized 2-
50 substituted anilines19 after the well-known conversion of the
boryl group into carbon-, nitrogen-, or oxygen-substituents.20 In
this study, we validate this idea by the fluoride-mediated
Introduction
Anilines are abundant in the core structures of natural and/or
biologically active compounds,1 and synthesis of aniline moieties
15 has constantly been drawing attention during the last several
decades.2 In addition to the classical aniline syntheses, which
include electrophilic nitration of arenes followed by reduction of
the nitro groups3 and copper-mediated arylation of amines
(Ullmann condensation),4 Buchwald and Hartwig independently
20 developed a highly efficient synthesis of anilines by the
palladium-catalyzed cross-coupling reaction of aryl halides (or
pseudohalides) and amines.5 This reaction has become one of the
most useful methods for synthesizing various types of aniline
derivatives.6
generation of 3-[(dan)boryl]benzynes
diaminonaphthalene) from
1
(dan
2-[(dan)boryl]-6-
=
1,8-
55 (trimethylsilyl)phenyl triflates 2, which upon reaction with
amines provide 2-[(dan)boryl]anilines 6 in high yields and
excellent ortho-selectivities.
Results
25
On the other hand, benzynes are highly reactive intermediates,
and amines react with benzynes to produce anilines.7,8 Further,
At first, we examined the fluoride-mediated generation21 of 3-
the regiochemistry of these reactions with unsymmetrically 60 [(pin)boryl]benzyne 1A (pin = pinacol) from 2-[(pin)boryl]-6-
substituted benzynes has been a longstanding interest. It is known
that these reactions predominantly take place at the C1-position
30 of the benzynes that possess a fluorine or an oxygen substituent at
the C3-position, which is because the C1-positions of such
(trimethylsilyl)phenyl triflate 2A as a test case. In the presence of
n-butylamine 3a, the reaction of 2A and CsF proceeded in MeCN
at 60 °C to produce a mixture of aniline derivatives.22 However,
the expected borylanilines were not observed at all, and
benzynes are more electrophilic than the C2-positions due to the 65 silylanilines (ortho- and meta-5Aa) were instead obtained in 57%
distortion and polarization caused by these substituents.8c,9 The
benzynes with a sterically bulky substituent at the C3-position
35 also undergo the addition reactions at the C1-position owing to
the steric repulsion between the substituent and the incoming
amine.10
total yield (Scheme 1). Some other trials by changing solvents,
reaction temperatures, and fluoride sources did not produce any
improvement. These results indicated that the fluoride ion
exclusively attacked the boron of 2A to generate 3-silylbenzyne
70 4A, with the silyl group remaining intact.23,24 Next, we
synthesized a new benzyne precursor 2B25 with dan as the
protective group for the boronic acid26 and used it to prepare the
corresponding benzyne followed by nucleophilic amination. We
found that the borylanilines (ortho- and meta-6Ba) were obtained
In addition to rare examples of the ortho-selective nucleophilic
addition of organolithiums to 3-(oxazolin-2-yl)benzyne via the
40 coordination of lithium to oxygen,11 we recently reported another
ortho-selective nucleophilic addition of primary amines to 3-
(trialkylsilyl)benzynes.12,13 This is more unique and intriguing 75 under similar reaction conditions, albeit in low yield (26%), and
because the reactions occurred at the vicinal position of the bulky
trialkylsilyl group without any attractive interaction between the
that the silylanilines were not observed. The precursor 2C, with
N-methyliminodiacetic acid (MIDA)27 as the protective group for
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the boronic acid, was another promising candidate; however, a
moderate (ortho/meta
=
2.4–3.8:1) (entries 4–9). Very
similar reaction of 2C resulted in the formation of a complex
mixture (Scheme 1).
interestingly, HMPA dramatically improved both the yield and
30 selectivity (entry 10). After further optimization, it was concluded
that the use of CsF and 18-crown-6 (18-c-6) in a 1:1 mixture of
THF and HMPA at 0 °C was the best reaction conditions to
produce high regioselectivity (ortho/meta = 9.2:1), product yield
(99%), and reproducibility (entry 12). To our surprise, the use of
35 2,6-lutidine as a solvent reversed the selectivity of this reaction to
predominantly produce meta-6Ba (entry 13).
Under the optimized reaction conditions obtained above, the
nucleophilic addition of various amines
3
to 3-
[(dan)boryl]benzynes 1, generated from 2, were carried out to
40 provide mixtures of ortho-6 and meta-6 (Table 2). The following
observations are worth noting: (i) All the reactions preferentially
provided ortho-6, and the total yields were very high (85–99%) in
most cases. (ii) The reactions with -unbranched aliphatic
primary amines (3a, 3b, 3c, and 3f–3i) proceeded with good
45 regioselectivities (ortho/meta = 9.2–20:1) (entries 1–3, and 6–9).
(iii) Even the reactions of -branched aliphatic primary amines
such as c-hexylamine 3d and t-butylamine 3e and those of
secondary amines (3k–3m) predominantly afforded ortho-6,
5
Scheme 1 Fluoride-mediated generation of benzyne (from precursors
2A–2C) followed by nucleophilic amination.
50 Table 2 Nucleophilic addition of various amines 3 to 3-borylbenzynes 1,
generated from 2a
With the potential results of the chemoselective generation of
10 3-borylbenzyne 1B and its ortho-selective amination in hand, we
proceeded to optimize the reaction conditions by varying the
fluoride sources, solvents, and temperature (Table 1).
A
significant amount of silylaniline 5Aa was generated in less polar
solvents (entries 1 and 2). In contrast, ortho-6Ba was obtained as
15 the major product in polar solvents, such as THF, DMF, NMP,
DMPU, and DMSO, although the ortho/meta-selectivities were
6
entry R1 (2)
NR2R3
3
ortho/metab yield (%)c
Me (2B)
H (2D)
NH(n-C10H21
NH(n-Bu)
)
3b 6Bb
3a 6Da
1
2
3
4
5
6
9.2:1
14 :1
>20 :1
10 :1
2.5:1
99
99
87
99
94
97
Table 1 Optimization of reaction conditionsa
H (2D)
3c 6Dc
NH(c-Hex)
NH(t-Bu)
NHBn
H (2D)
H (2D)
H (2D)
3d 6Dd
3e 6De
3f 6Df
12 :1
85d
H (2D)
H (2D)
3g 6Dg
3h 6Dh
7
8
10 :1
15 :1
5Aa
6Ba
ortho/metab
2.0:1
93
fluoride
source
temp.
(°C)
entry
solvent
yield
(%)b
55
27
2
4
0
0
0
0
0
0
0
0
0
yield
(%)b
33
31
26
73
87
95
92
H (2D)
3i 6Di
9
13 :1
98
1
2
3
4
5
6
7
8
9
Bu4NF
Bu4NF
Bu4NF
Bu4NF
Bu4NF
toluene
CH2Cl2
MeCN
THF
DMF
DMF
rt
rt
rt
rt
rt
40
rt
rt
rt
rt
0
1
:1.4
1.4:1
2.7:1
3.8:1
2.8:1
2.4:1
2.4:1
2.4:1
10 :1
9.0:1
9.2:1
H (2D)
H (2D)
3j 6Dj
3k 6Dk
10
11
NHC6H4-(4-Me)
NEt2
2.9:1
1.6:1
86
>99
H (2D)
H (2D)
3l 6Dl
12
13
6.7:1
5.7:1
>99
99
KF/18-c-6c
KF/18-c-6c
KF/18-c-6c
KF/18-c-6c
3m 6Dm
NMP
DMPU
DMSO
HMPA
65
H (2D)
H (2D)
Br (2E)
NHNHBoc
3n 6Dn
3o 6Do
3a 6Ea
14
15
16
17e
>20 :1
>20 :1
>20 :1
81
76d
89
71
10 KF/18-c-6c
90d
96d
99d
73
NH(n-Bu)
11 KF/18-c-6c THF/HMPAe
12 CsF/18-c-6c THF/HMPAe
13 CsF/18-c-6c 2,6-lutidine
Br (2E)
3m 6Em
2.2:1
86
0
rt
1 :2.0
Br (2E)
3p 6Ep
18
8.0:1
85
a
20 Conditions: A mixture of 2B (1.0 equiv), 3a (3.0 equiv), a fluoride
source (2.0 equiv) in a solvent (0.1 M) was stirred at the given
temperature for 2 h. b Total yield of 5Aa, that of 6Ba, and the ortho/meta
a Conditions: A mixture of 2 (1.0 equiv), 3 (3.0 equiv), CsF (2.0 equiv),
and 18-c-6 (2.0 equiv) in THF/HMPA (1:1, 0.10 M) was stirred for 2 h at
55 0 °C. b Determined by 1H NMR analysis of a mixture of two regioisomers
obtained by short column chromatography on silica gel. c Total isolated
yield of ortho-6 and meta-6. d Total 1H NMR yield of ortho-6 and meta-6.
e In THF/HMPA (1:4, 0.10 M).
1
ratio of 6Ba were based on the H NMR analysis of the crude product
using 1,4-dimethoxybenzene as the internal standard. c 18-crown-6 (18-c-
25 6) (2.0 equiv) was used as an additive. d Isolated yield by chromatography
on silica gel. e A 1:1 mixture of THF/HMPA was used as the solvent.
NMP  N-methyl-2-pyrrolidinone, DMPU  N,N-dimethyl propylene urea.
2
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although with lower regioselectivities (ortho/meta = 1.6–10:1)
(entries 4, 5, and 11–13).
From the perspective of synthetic application, the following
results present some advantages of this method: (i) In the reaction
of furfurylamine 3h, only N-arylfurylamine 6Dh was obtained,
leaving the furyl moiety unreacted, which indicated that the
outstanding potential to install different aryl groups on the
50 starting benzene scaffold 2E (Scheme 2). Thus, the Suzuki–
Miyaura coupling of 6Em and 8a provided 9 (92% yield), which
was then subjected to the acidic hydrolysis of the (dan)boryl
moiety to produce 10. The second coupling reaction with 8b
under the same reaction conditions produced the 2,4-diarylaniline
5
nucleophilic addition was significantly faster than the Diels– 55 derivative 11 (44% yield over two steps) (the reaction conditions
Alder reaction17 (Table 2, entry 8). (ii) A range of functional
were not optimized).
groups such as bromo, iodo, hydroxyl, t-butoxycarbonyl, allyl,
10 furyl, and indolyl groups were perfectly tolerant under these
conditions to produce highly functionalized aniline derivatives
(6Dc, 6Dg–6Di, 6Dn, 6Ea, 6Em, and 6Ep) (entries 3, 7–9, 14,
and 16–18). In particular, the reactions of halogen-containing
substrates produced valuable aniline derivatives possessing both
15 boryl and halogen groups, which were hardly available by the
transition-metal-catalyzed coupling reaction of multihalogen-
containing substrates. (iii) The reaction of unprotected 5-
hydroxytryptamine 3i is of particular interest (entry 9) because
the complete arylation of its primary amino group was achieved
20 while two other heteroatom nucleophilic sites remained intact.
(iv) The reaction of ethylenediamine 3o with 1D showed another
important feature of this reaction, viz., the exclusive formation of
a mono N-arylation product 6Do while another reactive alkyl
amino group remained intact (entry 15). The lower isolated yield
25 was because of the high polarity of 6Do that made it difficult to
isolate.
It should also be noted that the amination reactions of 1
generally exhibited better ortho-selectivities than those of 3-
(trimethylsilyl)benzynes12 (Table 3). For example, while the
30 addition of -unbranched aliphatic primary amines to 3-
(trimethylsilyl)benzynes 4 provided mixtures of ortho- and meta-
adducts 5 in 4.1–8.5:1 ratios, similar reactions of 1 gave the
corresponding adducts 6 in 9.2–20:1 ratios. The reaction of 4 with
tert-butylamine 3e exclusively afforded meta-5e, whereas that of
35 1D with 3e preferentially produced ortho/meta-6De in a 2.5:1
ratio (Table 2, entry 5 and Table 3). The addition of the aromatic
primary amine 3j to 1D preferentially provided N,N-diarylamine
ortho-6Dj with a moderate selectivity (ortho/meta = 2.9:1) (Table
2, entry 10), whereas a similar reaction of 3j and 4 provided a
40 1:1.6 mixture of ortho- and meta-5j.
60 Scheme 2 Stepwise Suzuki–Miyaura cross coupling reactions of the
nucleophilic adduct 6Em.
The overall process in this study could be achieved for the first
time owing to a triple role of the (dan)boryl group: (i) the
65 chemoselective generation of 3-borylbenzyne, (ii) the
regiocontrol for the nucleophilic ortho-amination reaction, and
(iii) the masked boryl group that can be arbitrarily reactivated to a
boronic acid group for further coupling reactions. These results
were also attributed to the excellent stability of the (dan)boryl
70 group under various conditions, including benzyne generation,
coupling reactions, and silica gel chromatography.
Discussion
75
In this study, we have found that the solvents have significant
effects on the reactions. We think that the solvent affects two
steps of the reactions, viz., the benzyne generation and the
nucleophilic attack to benzyne, and each effect should be
separately discussed. In the first benzyne generation step, the
80 reversible coordination of polar solvents such as DMF, DMSO
and HMPA to the boron atom protects the boron against the
fluoride-ion attack and makes the fluoride hit the silicon atom
instead. On the other hand, in less polar solvents such as toluene
and CH2Cl2, the fluoride ion preferentially attacked the boron
85 atom to form significant amounts of silylbenzyne 4A (Table 1,
entries 1 and 2), which unambiguously supports the above-
mentioned explanation. In the second nucleophilic addition step,
the stronger reversible coordination of HMPA to the boron atom
makes the borylbenzynes more distorted and polarized. As a
90 result, the yield and the selectivity of these overall reactions
became much better in HMPA (Table 1, entry 10). However, we
cannot account for the reverse selectivity when using 2,6-lutidine
as a solvent.
Table
3
Selectivity comparison between borylbezynes
1
and
silylbenzynes 4a
The possibility of the fluoride ion coordination to the boron
95 atom is another very important issue, and we have concluded that
the fluoride ion hardly coordinated to the boron atom based on
the following three results: Firstly, the use of 1.5 equivalents of a
fluoride source did not change the regioselectivity, but slightly
45 aAll data were cited from Table 2 and ref 12.
As reported by Suginome et al.,26 the products (6Ea, 6Em, and
6Ep), possessing both (dan)boryl and bromo groups, have
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lowered the yield, in which a small amount of the starting 50 and to the synthesis of biologically active compounds are
material was recovered. We have found that the use of two
equivalents of the fluoride ion is necessary to obtain the addition
products 6 in high yields (almost quantitative in many cases)
(Table 2). Secondly, if the excess fluoride ion coordinated to the
boron atom of the generated benzyne to form a boron-ate
complex (that is 3-[(dan)FB]benzyne), the complex would never
get back to the (dan)B group again. The fact that we obtained
almost quantitative yields of 6 that possessed the (dan)B group
10 clearly denied the formation of the boron-ate complexes. Thirdly,
because the nitrogen generally has a strongly electron-donating
effect, the vacant p-orbital of the boron atom should be filled with
lone pair electrons of the diaminonaphthalene’s nitrogens in some
degree.28 Therefore, a fluoride ion selectively attacked the SiMe3
15 group in the presence of the B(dan) group at the first benzyne
generation step.
Next, we analyzed the origin of the ortho-selectivities of 3-
[(dan)boryl]benzynes 1 based on theoretical calculations. The
structure of 1D29 was optimized by the B3LYP/6-31G(d) level,30
20 and the internal angles at its C1 and C2 positions were analyzed
to evaluate the contribution of distortion energy.8c,9c The electron
densities of the  orbitals of benzyne located in the same plane
with the aromatic ring were also calculated by a natural bond
orbital (NBO) method30 (Figure 1). These two sets of results
25 showed that the C2 position was more electrophilic than the C1
position. Therefore, both the aryne distortion and the electrostatic
effect caused by the (dan)boryl group overcame the steric
disadvantage of the bulky boryl group, resulting in the
preferential nucleophilic attacks at the C2 position.
currently under investigation in our laboratory.
Experimental section
5
General procedure for nucleophilic addition of amines to 3-
borylbenzynes (Table 2)
55
An oven-dried round-bottomed flask was evacuated and back-
filled with argon after cooling to room temperature. The flask
was charged with a borylbenzyne precursor 2 (1.0 equiv) and 18-
crown-6 (2.0 equiv), and then capped with a rubber septum.
60 Anhydrous THF/HMPA (THF/HMPA = 1:1, 0.10 M) and amine
3 (3.0 equiv) were successively added to the flask via syringes.
After the mixture was stirred at 0 ºC for 5 min, CsF (2.0 equiv)
was added. The reaction mixture was stirred at 0 ºC for 2 h,
quenched by a saturated aqueous NH4Cl solution and extracted
65 with EtOAc. The aqueous layer was extracted twice with EtOAc.
The combined organic layers were dried over anhydrous Na2SO4
and then filtrated. The filtrate was evaporated under reduced
pressure. The resultant residue, containing a significant amount of
HMPA, was filtered through a short pad of silica gel to afford a
70 mixture of ortho-6 and meta-6, and the ratio of these two
1
regioisomers was determined by the H NMR analyses. Further
purification of the mixture by flash column chromatography on
silica gel provided pure ortho-6.
Acknowledgements
75 We thank Prof. Hiroaki Tokiwa of Rikkyo University (Japan) for
fruitful discussions on calculations using an NBO method. This
work was supported by KAKENHI from MEXT. T.I. is grateful
to the Daicel Chemical Industry Award in Synthetic Organic
Chemistry (Japan) for a financial contribution. The Japan Society
80 for the Promotion of Science is gratefully acknowledged for the
predoctoral fellowship to A.T.
30
Notes and references
a School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada,
Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan.
Fig. 1 Internal angles of 3-[(dan)boryl]benzyne 1D optimized by
B3LYP/6-31G(d) and its electron densities analyzed by an NBO
method.30
85 b Graduate School of Pharmaceutical Sciences, Osaka University, 1-6,
Yamadaoka, Suita, Osaka 565-0871, Japan. Fax/Tel: 06-6879-8212; 06-
6879-8210; E-mail: ikawa@phs.osaka-u.ac.jp, akai@phs.osaka-u.ac.jp
† Electronic Supplementary Information (ESI) available: Experimental
procedures, synthesis of precursors, and characterization of all new
90 compounds. See DOI: 10.1039/b000000x/
35
Conclusions
In conclusion, highly ortho-selective nucleophilic addition of
amines to 3-borylbenzynes 1 has been achieved for the first time
by using the (dan)boryl group as a multifunctional directing
40 group. The fluoride-mediated benzyne generation under mild
conditions enabled excellent tolerance of various reactive
functional groups such as bromo, iodo, hydroxyl, t-
butoxycarbonyl, allyl, furyl, and indolyl groups; thus, the highly
functionalized 2-borylaniline derivatives ortho-6 were produced.
45 The adducts possessing both the (dan)boryl and bromo groups
serve as useful intermediates for the consecutive Suzuki–Miyaura
cross-coupling reactions. The overall process provides a new
entry for the synthesis of the multisubstituted aniline derivatives.
Further applications of these reactions with other nucleophiles
1
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during our project on the regiocontrolled Diels–Alder reaction of 3-
borylbenzynes. See: Ref. 17a.
24 We are currently developing a new method for generating benzynes
from 2-borylphenyl triflates, which will be published soon. For a
related recent paper, see: Y. Sumida, T. Kato and T. Hosoya, Org.
Lett., 2013, 15, 2806.
8
80
10
25 2B was synthesized by the hydrolysis of 2A17 followed by the
condensation with 1,8-diaminonaphthalene (see: Supplementary
Information in detal).
15 9 For selected recent papers, see: (a) Z. Liu and R. C. Larock,
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85
26 For the use of 1,8-diaminonaphthalene (dan) as a protective group of
the boronic acids, see: (a) H. Noguchi, K. Hojo and M. Suginome, J.
Am. Chem. Soc., 2007, 129, 758. (b) H. Noguchi, T. Shioda, C.-M.
Chou and M. Suginome, Org. Lett., 2008, 10, 377.
20
2010, 132, 17933.
10 (a) P. P. Wickham, K. H. Hazen, H. Guo, G. Jones, K. H. Reuter and
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90 27 Although MIDA was reported as another useful protecting group of
boronic acids, the corresponding boronates were readily hydrolyzed
under relatively mild basic conditions, see: E. P. Gillis and M. D.
Burke, J. Am. Chem. Soc., 2007, 129, 6716.
25
12 T. Ikawa, T. Nishiyama, T. Shigeta, S. Mohri, S. Morita, S.
Takayanagi, Y. Terauchi, Y. Morikawa, A. Takagi, Y. Ishikawa, S.
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28 Jr., F. F. Caserio, J. J. Cavallo and R. I. Wagner, J. Org. Chem., 1961,
95
26 , 2157.
29 In this study, we calculated the structure of 1D without any
coordination of solvents to obtain preliminary information of its
structure and electronic nature and have found that they are sufficient
enough to roughly discuss the regioselectivity. We are now
investigating the calculation with the coordination of solvents, which
enhances the distortion and polarization of the triple bond. The
results and discussion will be published in due course.
and M. Schlosser, Eur. J. Org. Chem., 2005, 5242. (d) V. Diemer,M. 100
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Chem. Soc., 2012, 134, 13966.
35
40
45
50
55
30 For details, see the Electronic Supplementary Information.
14 We have reported highly regioselective cycloaddition reactions of 3-
silylbenzynes with substituted furans15,16 and those of 3-
borylbenzynes.16,17 For some related regioselective cycloadditions,
see also Ref. 18.
15 S. Akai, T. Ikawa, S. Takayanagi, Y. Morikawa, S. Mohri, M.
Tsubakiyama, M. Egi, Y. Wada and Y. Kita, Angew. Chem., Int. Ed.,
2008, 47, 7673.
16 T. Ikawa, H. Tokiwa and S. Akai, J. Synth. Org. Chem. Jpn., 2012,
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17 (a) T. Ikawa, A. Takagi, Y. Kurita, K. Saito, K. Azechi, M. Egi, K.
Kakiguchi, Y. Kita and S. Akai, Angew. Chem., Int. Ed., 2010, 49,
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Y. Itoh, H. Tokiwa, Y. Kita and S. Akai, Tetrahedron, 2013, 69,
4338.
18 T. Ikawa, A. Takagi, M. Goto, Y. Aoyama, Y. Ishikawa, Y. Itoh, S.
Fujii, H. Tokiwa and S. Akai, J. Org. Chem., 2013, 78, 2965.
19 For selected examples of 2-substituted anilines as a core structure of
a natural product, see: (a) T. Sasaki, K. Furihata, A. Shimazu, H. Seto,
M. Iwata, T. Watanabe and N. Otake, J. Antibiot. (Tokyo), 1986, 39,
502. As a ligand for transition-metal-catalyzed reactions, see: (b) M.
Leblanc and K. Fagnou, Org. Lett., 2005, 7, 2849. As biologically
active compounds, see: (c) S. Jin, M. Li, C. Zhu, V. Tran and B.
Wang, ChemBioChem, 2008, 9, 1431.
60 20 Typical examples for the conversion of boryl groups into hydrogen,
see: (a) H. C. Brown and G. A. Molander, J. Org. Chem., 1986, 51,
4512. Into nitrogen substituents, see: (b) C. C. Tzschucke, J. M.
Murphy and J. F. Hartwig, Org. Lett., 2007, 9, 761. Into a cyano
group, see: (c) H.-X. Dai and J.-Q. Yu, J. Am. Chem. Soc., 2012, 134,
65
134. Into oxygen substituents, see: (d) M. M. Hussain and P. J. Walsh,
Angew. Chem. Int. Ed., 2010, 49, 1834. Into aryl groups, see: (e) T. E.
Barder, S. D. Walker, J. R. Martinelli and S. L. Buchwald, J. Am.
Chem. Soc., 2005, 127, 4685.
21 For the pioneering work on the fluoride-mediated generation of
benzynes from 2-(trimethylsilyl)phenyl triflates, see: Y. Himeshima,
T. Sonoda and H. Kobayashi, Chem. Lett., 1983, 1211.
70
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