Transition-metal-free borylation of aryltriazene mediated by BF 3·OEt2

Article abstract of DOI:10.1021/ol302024m

A practical and simple method for deaminoborylation of aryltriazene with bis(pinacolato)diboron has been developed that is mediated by BF ₃·OEt₂. Various arylboronic esters are prepared in moderate to good yields with this facile transition-metal-free procedure.

Full text of DOI:10.1021/ol302024m

ORGANIC
LETTERS
2012
Vol. 14, No. 17
4560–4563
Transition-Metal-Free Borylation of
Aryltriazene Mediated by BF3 OEt2
3
Chuan Zhu and Motoki Yamane*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical
Sciences, Nanyang Technological University, Singapore 637371
yamane@ntu.edu.sg
Received July 21, 2012
ABSTRACT
A practical and simple method for deaminoborylation of aryltriazene with bis(pinacolato)diboron has been developed that is mediated by
BF3 OEt2. Various arylboronic esters are prepared in moderate to good yields with this facile transition-metal-free procedure.
3
Arylboronic acid and ester have been widely used to
create carbonÀcarbon and carbonÀheteroatom bonds in
organic synthesis over the past several decades.1 As they
are one of the most powerful synthetic tools, various
methods for the synthesis of arylboronic acid derivatives
have been developed.2 Conventional methods to prepare
these boron compounds usually involve a stoichiometric
amount of air and moisture sensitive aryl-metal reagents in
harsh reaction conditions.3 In this aspect, transition metal-
catalyzed borylation of aryl halides which possess tre-
mendous versatility and functional group compatibility is
a more reliable route.4 Remarkably, this methodology
recently expanded to include a CÀH bond activation
strategy and significant progress was achieved.5 As transi-
tion metal catalysts are expensive and sometimes cause a
problem of metal residue in the final medicinal products,
more attention has been focused on the transition-metal-
free process in organic synthesis.6 Recently, borylation of
arylamine via oxidative deamination by alkylnitrite was
reported.7 It provides a direct conversion of arylamine
to arylboronic ester under metal-free conditions which
brought an innovative development to arylboronic ester
synthesis. However, the substrate scope was still limited.
Aryltriazene could be readily prepared from corre-
sponding arylamine in high yield and easy to handle.8
Traditionally, aryltrizene is used as equiverlant of aryldia-
zonium salt in the presence of Lewis or Brønsted acid
in nucleophilic substitution reactions or Pd-catalyzed
(1) For review, see: (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95,
2457. (b) Miyaura, N. Cross-Coupling React. 2002, 219, 11.
(2) For review, see: Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.;
Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2009, 110, 890.
coupling reactions.9 In particular, BF3 OEt2 is an effi-
3
cient reagent to activate aryltriazene in Pd-catalyzed
(3) For selected examples, see: (a) Wong, K.-T.; Chien, Y.-Y.; Liao,
Y.-L.; Lin, C.-C.; Chou, M.-Y.; Leung, M.-k. J. Org. Chem. 2002, 67,
1041. (b) Browne, D. L.; Baumann, M.; Harji, B. H.; Baxendale, I. R.;
Ley, S. V. Org. Lett. 2011, 13, 3312.
(4) For selected examples, see: (a) Ishiyama, T.; Murata, M.;
Miyaura, N. J. Org. Chem. 1995, 60, 7508. (b) Willis, D. M.; Strongin,
R. M. Tetrahedron Lett. 2000, 41, 8683. (c) Zhu, W.; Ma, D. Org. Lett.
2005, 8, 261. (d) Kleeberg, C.; Dang, L.; Lin, Z.; Marder, T. B. Angew.
Chem., Int. Ed. 2009, 48, 5350. (e) Yamamoto, T.; Morita, T.; Takagi, J.;
Yamakawa, T. Org. Lett. 2011, 13, 5766. (f) Zhang, J.; Wang, X.; Yu, H.;
Ye, J. Synlett 2012, 23, 1394.
(6) For transition-metal-free arylboronic ester synthesis, see: (a) Del
Grosso, A.; Pritchard, R. G.; Muryn, C. A.; Ingleson, M. J. Organome-
tallics 2009, 29, 241. (b) Del Grosso, A.; Singleton, P. J.; Muryn, C. A.;
Ingleson, M. J. Angew. Chem., Int. Ed. 2011, 50, 2102. (c) Niu, L.; Yang,
H.; Wang, R.; Fu, H. Org. Lett. 2012, 14, 2618.
(7) Mo, F.; Jiang, Y.; Qiu, D.; Zhang, Y.; Wang, J. Angew. Chem.,
Int. Ed. 2010, 49, 1846.
(8) For review, see: Kimball, D. B.; Haley, M. M. Angew. Chem., Int.
Ed. 2002, 41, 3338.
(9) For seleceted examples, see: (a) Naus, P.; Leseticky, L.; Smrcek,
S.; Tislerova, I.; Sticha, M. Synlett 2003, 2117. (b) Saeki, T.; Matsunaga,
T.; Son, E.-C.; Tamao, K. Adv. Synth. Catal. 2004, 346, 1689. (c) Saeki,
T.; Son, E. C.; Tamao, K. Org. Lett. 2004, 6, 617. (d) Liu, C.-Y.;
Knochel, P. Org. Lett. 2005, 7, 2543. (e) Liu, C. Y.; Knochel, P. Synlett
2007, 2081. (f) Liu, C. Y.; Gavryushin, A.; Knochel, P. Chem. Asian J.
2007, 2, 1020. (g) Nan, G. M.; Ren, F.; Luo, M. M. Beilstein J. Org.
Chem. 2010, 6. (h) Nan, G. M.; Zhu, F. H.; Wei, Z. J. Chin. J. Chem.
2011, 29, 72. (i) Wang, C.; Chen, H.; Wang, Z.; Chen, J.; Huang, Y.
Angew. Chem., Int. Ed. 2012, 51, 7242.
(5) For selected examples, see: (a) Cho, J. Y.; Tse, M. K.; Holmes, D.;
Maleczka, R. E.; Smith, M. R. Science 2002, 295, 305. (b) Ishiyama, T.;
Miyaura, N. Chem. Rec. 2004, 3, 271. (c) Frey, G. D.; Rentzsch, C. F.;
€
von Preysing, D.; Scherg, T.; Muhlhofer, M.; Herdtweck, E.; Herrmann,
W. A. J. Organomet. Chem. 2006, 691, 5725. (d) Hurst, T. E.; Macklin,
T. K.; Becker, M.; Hartmann, E.; Kugel, W.; Parisienne-La Salle, J. C.;
Batsanov, A. S.; Marder, T. B.; Snieckus, V. Chem.;Eur. J. 2010, 16,
8155. (e) Kawamorita, S.; Miyazaki, T.; Ohmiya, H.; Iwai, T.; Sawa-
mura, M. J. Am. Chem. Soc. 2011, 133, 19310.
r
10.1021/ol302024m
Published on Web 08/17/2012
2012 American Chemical Society

Suzuki-Miyaura coupling reaction.9c,g,h Moreover, poly-
mer-bonded triazenes have been extensively used in solid-
supported synthesis.10 Thus this method may potentially
have wide application in combinatorial chemistry. Herein,
Table 1. Reaction of 4-Methoxyphenyltriazene with B2pin2 in
the Presence of BF3 OEt2
a
3
we report BF3 OEt2-mediated deaminoborylation of a
3
wide range of functionalized aryltriazenes.
Our initial study began with p-methoxyphenyltriazene
1a which was reacted with 1 equiv of bis(pinacolato)-
diboron (B2pin2) in the presence of 1.1 equiv of BF3 OEt2
3
in 1,2-dimethoxyethane (Table 1, entry 1). Gratifyingly,
the reaction proceeded smoothly and the desired product,
arylboronic ester 2a was isolated in 41% yield after 10 min
at room temperature. Next, the reaction solvents were
screened in the same reaction conditions (entries 1À9),
and acetonitrile gave the highest yield, 52% (entry 6). Only
trace amount of product was observed when more polar
solvents such as DMSO and DMF were used, and aryl-
triazene 1a was recovered in a significant amount (entries 3
molar Ratio (1a/B2pin2/
time temp yield
entry
BF3 OEt2)
solvent
DME
(min) (°C) (%)
3
1
1/1/1.1
1/1/1.1
1/1/1.1
1/1/1.1
1/1/1.1
1/1/1.1
1/1/1.1
1/1/1.1
1/1/1.1
1/1/1
90
5
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
0
41
2
DCM
27
3b
DMF
120
120
90
5
trace
trace
43
4b
DMSO
EtOH
5
6
MeCN
Benzene
Acetone
52
38c
7
5
and 4). When the amount of BF3 OEt2 was reduced to 1
equiv, the yield of product was not affected at all (compare
3
8
120
trace
trace
52
9
1,4-dioxane 120
entries 6 and 10). Then catalytic amount of BF3 OEt2 was
3
10
11b
12
13
14
15
16
17
18d
19d,e
20d,f
21d,g
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
5
30
5
tested but only led to trace amount of product (entry 11).
This means that BF3 OEt2 acted as a stoichiometric
1/1/0.2
1/1/1
trace
60
3
reagent rather than a catalyst. The yields obviously in-
creased when the reaction was performed at lower tem-
peratures (entries 12 and 13). The amount of B2pin2 was
optimized in entries 14À17, and 1.5 equiv showed the
highest efficiency (entry 15). The effect of the counteranion
on the Lewis acid was investigated by using BCl3 and BBr3
1/1/1.1
1/1.1/1
1/1.5/1
1/2/1
15
5
À15 62
0
0
0
0
0
0
0
0
62
73
75
28
73
30
5
5
5
1/0.5/1
1/1.5/1
1/1.5/1
1/1.5/1
1/1.5/1
30
5
5
in replacement of BF3 OEt2 (entries 19 and 20). The
5
3
desired product 2a was obtained in both cases, however
the yields dropped toa large extent. It isknown that radical
initiators such as benzoyl peroxide (BPO) enhance the
borylation of aryl amine which was proposed a radical
mechanism, however, adding BPO gave no improvement
for both yield and reaction time (entry 21).7
5
73
a Unless otherwise stated, reactions were carried out on a 0.5 mmol scale
in 5.0 mL solvent. b p-Methoxyphenyltriazene was recovered. c 1-Methoxy-4-
phenylbenzene was obtained as a side product in 6% yield. d 2.0 mL MeCN
was used. e 1.0 equiv BCl3 (1 mol/L hexane solution) was used in place of
BF3 OEt2. f 1.0 equiv BBr3 (1 mol/L dichloromethane solution) was used in
3
place of BF3 OEt2. g 2 mol % BPO in comparison with literature.
3
As shown in Table 2, a series of aryltriazene were then
subjected to the above optimized reaction conditions. The
reaction was successful for a variety of aryltriazenes and
provided moderate to high yields of the corresponding
arylboronic esters. The reactivity of substrates is relevant
to the electronic effects of the substituent on the benzene
ring. For example, 4-methoxyphenyltriazene gave rise to
73% of 2a within 5 min (entry 2) at 0 °C, however the less
electron rich 3-methoxyphenyltriazene rendered the reac-
tion more sluggish, afforded 2bin 58% yield after 30min at
room temperature (entry 2). Unsubstituted phenyltriazene
displayed inferior reactivity and led to only 36% yield
while 1-napthyltriazene furnished 2k in 65% yield. The sub-
strates bearing 4-thionyl or 4-amino group is considered to
be unstable toward an oxidant such as nitrite which was
used in the borylation of arylamines. Even with such a sub-
strate, the reaction proceeded and gave the desired boronic
ester which has a sulfur or nitrogen functionality although
the yields are modest possibly due to the stronger coordina-
tion of sulfur and nitrogen atoms to BF3 (entries 4 and 5).
The reactions of the phenyltriazene with a simple alkyl
substituent at para-, ortho-position also proceeded to
afford 2g, 2h and 2i in 75%, 83%, and 71% yield,
respectively (entries 7À9). The borylation of ortho-methyl
substituted substrate (entry 8) led to good yield in con-
trast with ortho-methoxyl substituted one which gave no
product (entry 3). The alkynyl moiety was found to be
tolerated in the reaction conditions to give alkynylphenyl-
boronic ester 2j in 53% yield. As stated above, the reaction
is suitable for rather electron rich aryltriazenes and it was
revealed that strongly electron-defficient aryltriazenes
such as acylphenyltriazene 1l gave no desired product
(entry 12). It is noteworthy that oxime derivative which
is a synthetic equivalent of ketone could be applied for this
borylation, and boronic ester 2m which has an oxime
functionality was obtained in 70% yield (entry 13). Devel-
opment of the preparation of haloarylboronic esters,
especially bromo- and iodo-substituted ones, is important
because they are difficult to synthesize by the conventional
transition metal-catalyzed borylation of arylhalides. It is
notable that a variety of haloaryltriazenes are applicable
€
(10) For reviews, see: (a) Brase, S. Acc. Chem. Res. 2004, 37, 805. (b)
€
Gil, C.; Brase, S. J. Comb. Chem. 2008, 11, 175.
Org. Lett., Vol. 14, No. 17, 2012
4561

Table 2. Substrates Scope for the Borylation of Aryltriazenea
a Unless otherwise noted, all the reactions were carried out by adding BF3 OEt2 (0.5 mmol) to a solution of 1 (0.5 mmol) and B2pin2 (0.75 mmol) in
3
2 mL MeCN under nitrogen atmosphere. b 5 mL solvent was used. c BF3 OEt2 was added at 0 °C and the reaction mixture was warm to rt gradually.
3
for this borylation (entries 14À21). Although it required
higher temperature (60 °C) and longer reaction time (1À2
h) for the consumption of the starting material, 4-fluoro-,
4-chloro-, 4-bromo-, and 4-iodophenyltriazenes were con-
verted to the corresponding boronic esters 2nÀp, 2s in
34À54% yields (entries 14À16, 19). The reactivity and
yield were improved when electron-donating substituents
were attached on the phenyl ring (entries 18, 20, 21).
A plausible mechanism for this borylation is depicted in
Scheme 1. The formation of triazene-BF3 complex A is
followed by the generation of arenediazonium salt B.9c,gÀi
This step is supported by the observed electronic effect of
the substituent on the phenyl group of aryltriazenes which
affects the reactivity of aryltriazenes. The formation of
diazoniumsalt B is also supported by a preliminary inves-
tigation of a simple Hamett plot which gave a negative
F value (À2.06).11 The fluoride anion transfers from the
trifluoroborate anion onto B2pin2 to give diboronate C.
Then, nucleophilic substitution of N2 in arenediazonium
part takes place to give the desired product, arylboronic
ester 2 together with F-Bpin. This mechanism is also
supported by the direct reaction of aryldiazonium salt
(Scheme 2). The same borylation product 2a was obtained
in 45% yield in the reaction of methoxybenzenediazonium
tetrafluoroborate with B2pin2.
(11) See Supporting Information for details.
(12) (a) Pryor, W. A.; Gu, J. T.; Church, D. F. J. Org. Chem. 1985, 50,
185. (b) Nishino, H.; Kamachi, H.; Baba, H.; Kurosawa, K. J. Org.
Chem. 1992, 57, 3551.
(13) (a) Rahm, A.; Amardeil, R.; Degueilcastaing, M. J. Organomet.
Chem. 1989, 371, C4. (b) Miura, K.; Ichinose, Y.; Nozaki, K.; Fugami,
K.; Oshima, K.; Utimoto, K. Bull. Chem. Soc. Jpn. 1989, 62, 143. (c)
Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91, 1237.
4562
Org. Lett., Vol. 14, No. 17, 2012

stage, we cannot have a conclusion on the mechanism of
the aromatic substitution step.14 It requires further study
to clarify the detailed mechanism.
Scheme 1. Plausible Mechanism of BF3 OEt2-Mediated
Borylation of Aryltriazene
3
Scheme 3. Reaction in the Presence of Hydrogen Radical
Donora
Scheme 2. Borylation of Aryldiazonium Salta
a Reactions were carried out by adding of BF3 OEt2 (0.5 mmol) to a
solution of 1a (0.5 mmol), B2pin2 (0.75 mmol) and additive (0.5 mmol) in
MeCN (2 mL).
3
In summary, we have demonstrated a novel synthesis
of arylboronic ester via direct borylation of aryltriazene.
The reaction is simply mediated by BF3 OEt2 and com-
a The reaction was performed by mixing methoxybenzenediazonium
tetrafluoroborate (0.5 mmol), B2pin2 (0.5 mmol) in 2 mL MeOH and
stirred at rt for 2 h.
3
pletes within 5À120 min at 0 to 60 °C. The absence of
metal reagents, transition metal catalyst or radical initiator
makes this approach very easy to handle. This method
is complementary to the existing arylboronic ester synthe-
sis with the advantages of high efficiency, unique selectiv-
ity, and an environmentally friendly nature. Moreover, the
reaction conditions are very mild and can tolerate many
functional groups. Further experiments to expand the
scope of this transformation are still under investigation.
To get some information on more detailed mechanism
of this last nucleophilic arene substitution, we performed
the reaction in the presence of hydrogen radical donors
(Scheme 3). Di-t-butylhydroxytoluene (BHT)12 and tribu-
tyltin hydride13 were tested as the hydrogen donor and it
was found that any of the trapping reagents did not affect
much to the reaction and the borylation product was
obtained in around 70% yield with no significant loss.
This fact indicates that the nucleophilic arene substitution
step may not involve a free phenyl radical process. At this
Acknowledgment. We thank Nanyang Technological
University for the generous financial support.
Supporting Information Available. Experimental pro-
cedures, characterization data, and 1Hand13C NMR spectra
of all newly synthesized compounds. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
(14) For the review of mechanism of nucleophilic aromatic substitu-
tion, see: (a) Zollinger, H. Diazo Chemistry I: Aromatic and Heteroaro-
matic Compounds; VCH: Weinheim, 1994. For recent examples, see: (b)
Romsted, L. S.; Zhang, J.; Zhuang, L. J. Am. Chem. Soc. 1998, 120, 10046.
(c) Wu, Z.; Glaser, R. J. Am. Chem. Soc. 2004, 126, 10632. (d) Hari,
€
D. P.; Schroll, P.; Konig, B. J. Am. Chem. Soc. 2012, 134, 2958.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 17, 2012
4563