Mild and general access to diverse 1H-benzotriazoles via diboron-mediated N-OH deoxygenation and palladium-catalyzed C-C and C -N bond formation

Article abstract of DOI:10.1002/adsc.201400889

Benzotriazoles are a highly important class of compounds with broad-ranging applications in such diverse areas as medicinal chemistry, as auxiliaries in organic synthesis, in metallurgical applications, in aircraft deicing and brake fluids, and as antifog agents in photography. Although there are numerous approaches to N-substituted benzotriazoles, the essentially one general method to N-unsubstituted benzotriazoles is via diazotization of ortho -phenylenediamines, which can be limited by the availability of suitable precursors. Other methods to N-unsubstitued benzotriazoles are quite specialized. Although reduction of 1-hydroxy-1 H-benzotriazoles is known, the reactions are not particularly convenient or broadly applicable. This presents a limitation for easy access to and availability of diverse benzotri-ACHTUNGTRENUNGazoles. Herein, we demonstrate a new, broadly applicable method to diverse 1H-benzotriazoles via a mild diboron reagent-mediated deoxygenation of 1-hydroxy-1H-benzotriazoles. We have also evaluated sequential deoxygenation and Pd-mediated C-C and C-N bond formation as a one-pot process for further diversification of the benzotriazole moiety. However, the results indicated that purification of the deoxygenation product prior to the Pd-mediated reaction is critical to the success of such reactions. The overall chemistry allows for facile access to a variety of new benzotriazoles. Along with the several examples presented, a discussion of the advantages of the approaches is described, as is also a possible mechanism for the deoxygenation process.

Full text of DOI:10.1002/adsc.201400889

FULL PAPERS
DOI: 10.1002/adsc.201400889
Mild and General Access to Diverse 1H-Benzotriazoles via
ꢀ
Diboron-Mediated N OH Deoxygenation and Palladium-
ꢀ
ꢀ
Catalyzed C C and C N Bond Formation
a
b
a
Venkateshwarlu Gurram, Hari K. Akula, Ramesh Garlapati,
a,
b,
Narender Pottabathini, * and Mahesh K. Lakshman *
Discovery Services, GVK Biosciences Pvt. Ltd., 28A, IDA Nacharam, Hyderabad 500076, Andhra Pradesh, India
E-mail: narender.pottabathini@gvkbio.com
a
b
Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY
10031, USA
E-mail: lakshman@sci.ccny.cuny.edu
Received: September 7, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400889.
Abstract: Benzotriazoles are a highly important class cable method to diverse 1H-benzotriazoles via
of compounds with broad-ranging applications in a mild diboron reagent-mediated deoxygenation of
such diverse areas as medicinal chemistry, as auxilia- 1-hydroxy-1H-benzotriazoles. We have also evaluat-
ries in organic synthesis, in metallurgical applica- ed sequential deoxygenation and Pd-mediated CꢀC
tions, in aircraft deicing and brake fluids, and as anti- and CꢀN bond formation as a one-pot process for
fog agents in photography. Although there are nu- further diversification of the benzotriazole moiety.
merous approaches to N-substituted benzotriazoles, However, the results indicated that purification of
the essentially one general method to N-unsubstitut- the deoxygenation product prior to the Pd-mediated
ed benzotriazoles is via diazotization of ortho-phe- reaction is critical to the success of such reactions.
nylenediamines, which can be limited by the availa- The overall chemistry allows for facile access to a va-
bility of suitable precursors. Other methods to N-un- riety of new benzotriazoles. Along with the several
substitued benzotriazoles are quite specialized. Al- examples presented, a discussion of the advantages
though reduction of 1-hydroxy-1H-benzotriazoles is of the approaches is described, as is also a possible
known, the reactions are not particularly convenient mechanism for the deoxygenation process.
or broadly applicable. This presents a limitation for
easy access to and availability of diverse benzotri- Keywords: benzotriazoles; deoxygenation; diboron
ACHTUNGTRENNUNGa zoles. Herein, we demonstrate a new, broadly appli- reagents; 1-hydroxy-1H-benzotriazoles; reduction
[
6]
Introduction
in metal-cutting fluids. In photographic applications
[7]
Bts are used as antifog agents.
Bts are also powerful entities in synthesis. As exam-
As a class, benzotriazoles (Bts) are highly important
in a variety of applications. As examples, benzotri- ples, Bt is a versatile synthetic auxiliary in diverse
[
8]
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
azole (Bt) and its derivatives are medicinally and transformations, aminoacyl-Bt derivatives (several
pharmacologically important, and many have signifi- now commercially available) are reagents for peptide
[
1–3]
[9]
cant antiviral activities.
Bt has been used for de- assembly and synthesis of peptide conjugates, and
cades as a corrosion inhibitor for copper and copper Bts have been used as ligands in cross-coupling reac-
[
10]
alloys such as brass and bronze. Mechanisms by which tions.
Bt inhibits corrosion of copper have been intensely By contrast to the numerous methods for synthesis
[4]
investigated. Because of its corrosion inhibiting of N-substituted Bts (see the Supporting Information
properties of non-ferrous metals, Bt as well as 4- and for a compilation of several methods), there are far
5
-methyl-Bts are components in dishwashing deter- fewer ones to N-unsubstituted Bts, i.e., 1H-benzotri-
[5]
gent. Bts are also found in formulations that contact
ACHTUNGTRENNUaGN zoles (1H-Bts). The most common approach, limited
metals, such as aircraft deicing and brake fluids, and by the availability of appropriate precursors, is via di-
azotization of ortho-phenylenediamines [Scheme 1,
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Scheme 1. Other methods for the synthesis of 1H-benzotriazoles.
[
24]
Eq. (1)]. When appropriate precursors are available, bis(pinacolato)diboron [(pinB) ] and Cs CO . These
2
2
3
this method can be used for synthesis of both 1H-Bts had led us to develop a general reduction of amine N-
[
11,12]
and N-substituted Bts
The syntheses of alizapride, oxides to amines using (pinB) and bis(catecholato)di-
2
an antiemetic used for treating postoperative nausea boron [(catB) ], and such reactions could also be con-
2
[13]
[25]
and vomiting,
and the aromatase inhibitor vora- ducted in water. Although reduction of the zwitter-
zole, exemplify this chemistry (structures shown in ionic amine N-oxides was readily accomplished, an in-
Scheme 1).
[14]
triguing question is whether charge neutral NꢀOH
Some other specialized approaches to 1H-Bts are bonds, such as those in 1-hydroxy-1H-Bts, can be re-
shown in Scheme 1. These involve diazo transfer [Eq. duced to NH groups by diboron reagents.
[
15]
(
2)], oxidation of an ortho-acetamidophenylhydra-
[
16]
zine by Cl [Eq. (3)],
high-temperature and high-
2
pressure reaction of benzimidazolones with NaNO
Results and Discussion
2
[17]
[
(
Eq. (4)],
and reaction of benzo-1,2,4-triazin-3-
[
18]
2H)-one with ethereal chloramine [Eq. (5)].
Feasibility of the NꢀOH!NH reduction was tested
A general approach to 1H-Bts would be the reduc- with commercially available HOBt and HOAt using
tion of 1-hydroxy-1H-Bts and methods for this have (pinB) , (catB) , and B (OH) . MeCN and H O were
2
2
2
4
2
been reported. Limited use of SmI and PCl has been tested as solvents, and DBU and Et N were tested as
2
3
3
reported to deoxgenate polymer-bound 1-hydroxy- bases. Results from these initial experiments are
[19]
1
H-Bt. From the amount of the resulting polymer shown in Table 1.
loading reported, significant excesses of PCl3 and From the preliminary analysis, several factors come
SmI seem to be needed for this reduction, and these to light. (i) All three diboron reagents tested are ef-
2
methods have not been assessed for general applica- fective for the reduction, both in MeCN and in water,
bility. Other reductions involving the use of Fe but reactions in water present some product isolation
[
20]
powder in dilute HCl at 868C. H /Et N/FeCl /Pt-C problems. (ii) Reactions benefit significantly by addi-
2
3
2
[
21]
at 808C and at 0.6 MPa (~6 atm), and Pb/Al/H O tion of a base, indicating that deprotonation of HOBt
with dropwise addition of HCl at 1008C have been and HOAt facilitates reaction at the boron center. In
reported in the patent literature. The conditions used MeCN/H O the pK values of HOBt and HOAt are
do not appear particularly convenient and could pose estimated at ~5.7 and ~4.0, respectively. Thus, 1-hy-
functional group incompatibilities. droxy-1H-Bts can be readily deprotonated by Et N
We have recently become interested in the scope of and DBU. (iii) B (OH) is more reactive than (pinB) ,
2
[
22]
2
a
[
26]
3
2
4
2
[
27]
reductions that can be mediated by diboron reagents. consistent with a recent observation. (iv) In the re-
Such reagents have been briefly investigated for the duction of HOAt (2) formation of a significant polar
[
23]
reduction of three amine N-oxides,
and in prior material, possibly an amine adduct, was observed.
work we had discovered an unusual deoxygenation of This diminished over an 8 h reaction time to yield
6
O -(benzotriazolyl)inosine and deoxyinosine with 1H-7-azabenzotriazole in excellent yield. In this case,
2
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Mild and General Access to Diverse 1H-Benzotriazoles
Table 1. Evaluation of conditions for the deoxygenation of HOBt (1) and HOAt (2).
[a]
[b]
Entry
Substrate
Conditions
Conversion, Yield [%]
1
2
3
4
5
6
7
8
1
1
1
2
1
1
2
1
2
1
2
1
1
2
1
2
1
(pinB) , MeCN, r.t., 12 h
~5%, NA
~50%, NA
~95%, 92
~95%, 90
100%, 96
100%, 98
100%, 94
100%, 95
95%, 75
100%, 90
100%, 88
98%, 95
100%, 95
100%, 92
98%, 92
2
(pinB) , MeCN, 508C, 24 h
2
(pinB) , MeCN, 808C, 12 h
2
(pinB) , MeCN, 808C, 12 h
2
(pinB) , DBU, MeCN, 508C, 1 h
2
(pinB) , Et N, MeCN, 508C, 0.5 h
2
3
(pinB) , Et N, MeCN, 508C, 8 h
2
3
B (OH) , H O, 85 8C, 6 h
2
4
2
[
c]
9
1
1
1
1
1
1
1
1
B (OH) , H O, 85 8C, 12 h
2 4 2
0
1
2
3
4
5
6
7
(catB) , Et N, MeCN, 508C, 0.5 h
2
3
(catB) , Et N, MeCN, 508C, 0.5 h
2
3
B (OH) , Et N, MeCN, r.t., 1.2 h
2
4
3
B (OH) , Et N, MeCN, 508C, 0.5 h
2
4
3
B (OH) , Et N, MeCN, 508C, 8 h
2
4
3
B (OH) , Cs CO , MeCN, 508C, 1 h
2
4
2
3
B (OH) , Cs CO , MeCN, 508C, 1 h
100%, 95
~10%, NA
2
4
2
3
[d]
B (OH) , K PO , H O, 85 8C, 24 h
2
4
3
4
2
[
[
[
[
a]
Reactions with performed with 1.2 equiv. of the diboron reagent and where applicable 1.2 equiv. of base.
Yields reported are of isolated and purified products.
b]
c]
Reaction required 1.7 equiv. of B (OH) .
2
4
d]
Multiple spots were observed by TLC.
use of Cs CO eliminated this problem, producing
The 1-hydroxy-1H-Bts 1–11 were subjected to reac-
2
3
a relatively fast reaction, but work-up was cumber- tion with B (OH) (1.2 equiv.) and Et N (1.2 equiv.) at
2
4
3
some due to a pasty nature of the reaction mixture. 508C in MeCN, conditions which were determined to
When 0.5 or 1 equiv. of Et N was added to a solution be optimal. Highly efficient reduction was observed
3
of HOAt in MeCN, a polar material formed in each
1
case. These adducts were isolated and H NMR spec-
tra obtained and these clearly showed resonances
from Et N (see the mechanistic discussion below and
3
the Supporting Information). The formation of an
adduct is comparable to hydrazine adducts with 1-hy-
[
28]
droxyazabenzotriazoles.
Next, several new 1-hydroxy-1H-Bts 3–7 and 1-hy-
droxy-1H-4-aza-Bt 8 were synthesized by known
[26,28,29]
[30]
methods
(Scheme 2, Caution ), essentially via
a facile reaction of ortho-chloro or ortho-fluoro nitro
aromatic compounds with hydrazine. Further, halo
nitro aromatics are exceptionally activated toward ox-
idative addition to Pd and there are substantial differ-
ences in the ease with which this occurs for various
Cꢀhalogen bonds. This can be leveraged for generat-
ing additional compound diversity with dihalo nitro
aromatic compounds. To demonstrate this, compounds
9
2
–11 were readily synthesized from 4-bromo-1-fluoro-
-nitrobenzene via reactions with phenyl-, 1-naphthyl-
,
and 3-thienylboronic acids using Pd(PPh ) followed Scheme 2. 1-Hydroxy-1H-benzotriazoles selected for the
3
4
by reaction with hydrazine.
analysis and yields of those synthesized.
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These data evidenced that Pd-catalyzed CꢀC and
CꢀN reactions can be conducted in a general manner
and that the deoxygenation by-products could inhibit
these processes. Because compounds 20, 21, and 22
have been prepared either from 4-bromo-1-fluoro-2-
nitrobenzene or from bromobenzotriazole 18, we
have compared the two approaches. Table 3 shows the
overall three-step yields from the two sequences.
Between the two approaches Method 1 appears to
be superior at least in the cases tested. There is anoth-
er advantage to Method 1. Because halonitrobenzenes
are very reactive, simple Pd(PPh ) is adequate for
3
4
CꢀC bond formation. Nevertheless, both approaches
are eminently useful depending upon specific needs.
In contrast to the possibility for CꢀC cross-coupling
prior to assembly of the benzotriazole moiety, it is
less desirable to perform CꢀN bond formation on
a dihalo nitro aromatic due to the possibility of un-
Scheme 3. Various 1H-benzotriazoles synthesized.
wanted S Ar displacement of halide. Thus, the amina-
N
tion reactions are better conducted on the assembled
benzotriazole.
in each case with isolated product yields of ꢁ90%
We have also analyzed the possible mechanism of
Scheme 3). Reactions were complete within 30 min this reaction by H and B NMR. When HOBt and
1
11
(
except for compounds 2 and 8, which required 8 h re- HOAt were independently exposed to Et N in
3
action times.
MeCN-d , significant upfield shifts of the aromatic
3
Further diversification of the benzotriazoles was resonances were observed. This would be consistent
then considered. Because boron-based by-products with the formation of an electron-rich system by de-
are generally considered benign we evaluated protonation. Because the reduction of HOAt is
a tandem deoxygenation/CꢀC cross-coupling ap- slower than that of HOBt, (pinB) was added to the
2
proach to substituted Bts as a one-pot process. For HOAt/Et N mixture in MeCN-d and stirred at 508C.
3
3
this, compound 7 was deoxygenated with B (OH) / Aliquots were taken at regular intervals and assessed
2
4
1
11
Et N in MeCN at 508C. The crude reaction mixture by H and B NMR. During the course of the reac-
was evaporated and reactions were performed with tion, the H NMR spectrum showed disappearance of
four arylboronic acids (data shown in parenthesis in the resonances of what is presumably AtO and for-
3
1
ꢀ
Table 2).
For this attempted one-pot conversion, the combi- uct. However, these new resonances were also upfield
nation of Pd(PPh ) (0.2 equiv.)/2M aqueous Na CO shifted. Addition of an aliquot of the reaction mixture
mation of a set of resonances corresponding to prod-
3
4
2
3
in 1,4-dioxane at 1008C proved to be ineffective. On to pure 1H-7-azabenzotriazole also caused an upfield
the other hand, dichloro[1,1’-bis(dicyclohexylphosphi- shift of its resonances indicating a presently unknown
nyl)ferrocene]palladium(II) [PdCl (dcpf)] (0.2 equiv.)/ interaction with the reaction components. Purification
2
K PO (2 equiv.) in 1,4-dioxane at 1008C led to prod- of the products however led to proton resonances at
3
4
uct formation in some cases but the reactions were the expected chemical shifts.
1
1
capricious. Similarly, we attempted aryl amination as
Acquisition of B NMR data of the reaction in-
a two-step, one-pot process using compound 7, but volving HOAt, Et N, and (pinB) in MeCN-d over
3
2
3
the reactions were unsuccessful with a variety of cata- a 3 h timeframe showed resonances from (pinB) (d=
2
lysts. These data showed that the deoxygenation by- 30.6 ppm) and presumably (pinB) O (d=22.4 ppm).
2
1
1
products could have a detrimental effect on the Pd- Prolonged heating resulted in other B resonances,
catalyzed reactions, contrary to expectation. However, possibly due to interactions of the nitrogenated com-
due to the relatively sparse literature on such Pd- pounds with the boron-containing materials. Although
mediated reactions of benzotriazoles in comparison to the deoxygenation of pyridine N-oxides by (pinB)
2
[
23]
other aromatic systems, we needed to ascertain was more readily discerned by NMR as compared
whether the reactions themselves were problematic or to the conversion herein, we propose the mechanism
whether such conversions could be effectively con- shown in Scheme 4, where either the N-hydroxy and/
[
31]
ducted in a more general manner. Therefore, we eval- or the N-oxide Bt tautomer can be involved.
uated reactions of purified benzotriazole 18 with aryl-
boronic acids and arylamines, the results from which
are shown in Table 2.
4
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Mild and General Access to Diverse 1H-Benzotriazoles
Table 2. Diversification of 1H-benzotriazoles via Pd-catalyzed CꢀC and CꢀN bond formation.
[
a]
Entry
1
ArB(OH) or ArNH
Product
Compound: Yield
2
2
[b]
[c,d]
20: 90%, 99.6, (60%)
[
b]
[e]
2
3
4
21: 78%, 99.8, (NR)
[
b]
[c,d]
[c,d]
22: 88%, 99.8, (42)
[
b]
23: 75%, 99.1, (45)
[
b]
5
6
7
8
9
24: 60%, 99.1
25: 80%, 99.1
26: 72%, 99.2
[
[
b]
b]
[b]
27: 70%, 99.5
28: 68%, 98.2
29: 65%, 99.7
[b]
[b]
1
0
[
[
[
[
[
a]
Yields reported are of isolated and purified products.
Purity by UPLC analysis.
Yield for the two-step, one-pot reaction.
A significant amount of compound 18 from the deoxygenation step remained.
No reaction was observed in the two-step, one-pot reaction, and only compound 18 from the deoxygenation step re-
b]
c]
d]
e]
mained.
Conclusions
other reductive conditions remain unaffected under
these conditions. This offers a synthetic advantage for
In summary, we have disclosed a previously unknown, subsequent manipulations, such as the metal-catalyzed
mild, and general approach to 1H-benzotriazoles via reactions described. In this context, we have evaluat-
a diboron reagent-mediated NꢀO deoxygenation of 1- ed a two-step, one-pot deoxygenation/Pd-catalysis
hydroxy-1H-benzotriazoles. Using differential reactiv- protocol. However, we have found that removal of
ities of Cꢀhalogen bonds towards Pd catalysts, addi- the deoxygenation by-products is essential for success-
tional compound diversity can be easily attained. ful catalysis reactions. We have demonstrated diversi-
Also, Cꢀhalogen bonds that can be reduced under fication of the benzotriazole moiety via three Pd-cata-
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Table 3. Comparison of two methods for diversification via
CꢀC bond formation.
Pd (dba) , (t-Bu) P, and all other reagents were obtained
2 3 3
from commercial suppliers and were used without further
purification. Column chromatographic purifications were
performed on 100–200 mesh silica gel. MeCN was distilled
over CaH , 1,4-dioxane was distilled over NaBH and then
[a]
Entry
Final
Overall yield via method 1
[b]
product
vs. method 2
2
4
freshly distilled over Na prior to use. EtOAc and hexanes
were distilled over CaSO , and commercial CH Cl was re-
4
2
2
1
20: 83% vs. 70%
distilled. Other commercially available compounds were
1
used without further purification. H NMR spectra were re-
corded at 400 MHz in the solvents indicated and are refer-
1
3
enced to residual protonated solvent resonances. C NMR
spectra were recorded at 100 MHz in the solvents indicated
and are referenced to the solvent resonances. Chemical
shifts (d) are reported in parts per million (ppm) and cou-
pling constants (J) are in hertz (Hz). Standard abbreviations
2
3
21: 69% vs. 61%
22: 74% vs. 69%
1
9
are used to designate resonance multiplicities. F NMR
spectra were recorded at 376 MHz in the solvents indicated.
[
a]
Method 1: CꢀC reaction of 4-bromo-1-fluoro-2-nitroben-
zene with the arylboronic acid, construction of the hy-
droxybenzotriazole, and then deoxygenation.
[
32]
Synthesis of Precursors to Compounds 9, 10 and 11
[
b]
Method 2: synthesis of compound 7, deoxygenation to
benzotriazole 18, and then CꢀC reaction with the aryl-
4
-Fluoro-3-nitrobiphenyl: In a 100-mL oven-dried, round-
bottomed flask equipped with a stirring bar were placed 5-
bromo-2-fluoronitrobenzene (2.0 g, 9.13 mmol) and phenyl-
boronic acid (1.22 g, 10.0 mmol) in 1:1 toluene/EtOH
boronic acid.
(
40 mL). Aqueous 2M Na CO (10 mL) was added, the mix-
2 3
ture was sparged with argon gas for 5 min, and Pd(PPh3)4
0.31 g, 3 mol%) was added. The reaction mixture was
(
heated at reflux for 2 h and monitored by TLC. Upon com-
pletion of the reaction the mixture was concentrated, diluted
with EtOAc, and washed with water. The aqueous layer was
extracted with EtOAc (2ꢁ). The organic layer was dried
over anhydrous Na SO and evaporated under reduced pres-
2
4
sure. Chromatography of the crude material on a silica gel
column using 5% EtOAc in hexanes gave the title com-
pound as a pale yellow solid; yield: 1.88 g (95%); R (SiO /
f
2
1
1
0% EtOAc in hexanes)=0.53. H NMR (400 MHz,
CDCl ): d=8.25 (dd, J=2.1, 7.0 Hz, Ar-H, 2H), 7.84–7.80
3
Scheme 4. A possible mechanism for the deoxygenation.
(
m, Ar-H, 1H), 7.56 (dd, J=2.0, 8.5 Hz, Ar-H, 1H), 7.49–
7
.39 (m, Ar-H, 3H), 7.37 (t, J=9.6 Hz, Ar-H, 1H);
C NMR (100 MHz, CDCl ): d=154.6 (d, J =264.1 Hz),
1
3
3
C,F
lyzed approaches, all of which appear generally appli- 138.3 (d, JC,F =3.8 Hz), 137.6, 133.8 (d, JC,F =8.4 Hz), 129.1,
cable: (i) CꢀC bond formation prior to formation of
1
28.5, 126.9, 124.2 (d, JC,F =2.2 Hz), 118.7 (d, JC,F =20.5 Hz).
1
9
F NMR (376 MHz, CDCl ): d=ꢀ120.3.
the 1-hydroxy-1H-benzotriazoles and then deoxygena-
tion, (ii) CꢀC bond formation on the deoxygenated
product, and (iii) CꢀN bond formation on the deoxy-
3
1
-(4-Fluoro-3-nitrophenyl)naphthalene: Synthesized as
described for 4-fluoro-3-nitrobiphenyl, using 5-bromo-2-flu-
oronitrobenzene (2.0 g, 9.13 mmol), naphthalen-1-ylboronic
acid, (1.72 g, 10.0 mmol), 2M aqueous Na CO (10 mL), and
Pd(PPh ) (0.31 g, 3 mol%) in 1:1 toluene/EtOH (40 mL) at
reflux for 2 h. Work-up as described above and chromatog-
genated product. This chemistry further demonstrates
an untapped potential of diboron reagents for novel
transformations such as the NꢀOH!NH reduction
2
3
3
4
shown here, and complements the reduction of amine raphy of the crude material on a silica gel column using 5%
N-oxides by diboron reagents.
EtOAc in hexanes gave the title compound as an off-white
solid; yield: 2.19 g (90%); R (SiO /10% EtOAc in hex-
f
2
1
anes)=0.53. H NMR (400 MHz, CDCl ): d=8.16 (dd, J=
3
2
7
7
.2, 7.2 Hz, Ar-H, 1H), 8.92 (dd, J=4.8, 7.6 Hz, Ar-H, 2H),
.72–7.69 (m, Ar-H, 2H), 7.53–7.44 (m, Ar-H, 3H), 7.40–
Experimental Section
1
3
.35 (m, Ar-H, 2H); C NMR (100 MHz, CDCl ): d=154.7
3
(
8
d, JC,F =264.1 Hz), 137.6 (d, JC,F =4.6 Hz), 137.2 (d, JC,F
=
General Experimental Considerations
.0 Hz), 136.9, 136.3, 133.8, 131.0, 128.9, 128.6, 127.2, 127.1,
1
9
Thin-layer chromatography was performed on 200 mm alu-
126.8, 126.2, 125.2, 124.7, 118.2 (d, JC,F =21.2 Hz); F NMR
minum-foil-backed silica gel plates. Bis(pinacolato)diboron
(376 MHz, CDCl ): d=ꢀ119.8.
3
(
pinB) , bis(catecholato)diboron (catB)2, tetrahydroxydibor-
3-(4-Fluoro-3-nitrophenyl)thiophene: Synthesized as de-
2
on B (OH) all arylboronic acids, arylamines, PdCl (dcpf),
scribed for 4-fluoro-3-nitrobiphenyl, using 5-bromo-2-fluoro-
2
4,
2
6
asc.wiley-vch.de
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

FULL PAPERS
Mild and General Access to Diverse 1H-Benzotriazoles
nitrobenzene (2.0 g, 9.13 mmol), 3-thienylboronic acid,
1.28 g, 10.0 mmol), 2M aqueous Na CO (10 mL), and
5.84 mmol) and hydrazine hydrate (0.57 m, 11.69 mmol) in
absolute EtOH (8 mL) at reflux over 24 h. After removal of
the solvent under reduced pressure, the residue was dis-
solved in 10% aqueous Na CO (20 mL). The solution was
(
2
3
Pd(PPh ) (0.31 g, 3 mol%) in 1:1 toluene/EtOH (40 mL), at
3
4
reflux for 2 h. Work-up as described above and chromatog-
raphy of the crude material on a silica gel column using 5%
EtOAc in hexanes gave the title compound as an as off-
white solid; yield: 1.87 g (92%); R (SiO /10% EtOAc in
2
3
extracted with Et O (30 mL) and then acidified with concen-
2
trated HCl. The precipitated product was filtered, washed
with water, and dried to obtain compound 5 as a white
solid; yield: 0.56 g (65%); R (SiO /10% MeOH, 1% Et N in
f
2
1
hexanes)=0.43. H NMR (400 MHz, CDCl ): d=8.24 (dd,
3
f
2
3
ꢀ
1 1
J=2.1, 7.0 Hz, Ar-H, 1H), 7.83–7.79 (m, Ar-H, 1H), 7.51 (d,
J=4.0 Hz, Ar-H, 1H), 7.45 (t, J=4.0 Hz, Ar-H, 1H), 7.36–
CH Cl )=0.34. IR (KBr): n=3431, 1388, 809 cm ; H NMR
2 2
(400 MHz, DMSO-d ): d=13.24 (br s, OH, 1H), 7.87 (d, J=
6
1
3
7
.25 (m, Ar-H, 2H); C NMR (100 MHz, CDCl ): d=154.4
8.5 Hz, Ar-H, 1H), 7.49 (s, Ar-H, 1H), 7.25 (d, J=8.5 Hz,
3
1
3
(
d, JC,F =264.1 Hz), 138.7, 137.5, 133.0 (d, JC,F =8.4 Hz),
Ar-H, 1H), 2.49 (s, CH 3H); C NMR (100 MHz, DMSO-
3,
1
2
27.4, 125.7, 123.5 (d, J =2.3 Hz), 121.9, 118.7 (d, JC,F
=
d ): d=141.6, 137.6, 128.2, 126.8, 118.6, 108.3, 21.3; HR-MS
C,F
6
19
+
1.2 Hz); F NMR (376 MHz, CDCl ): d=ꢀ120.2.
3
(ESI/TOF): m/z=150.0659, calcd. for C H N O [M+H] :
7
8
3
1
50.0662.
-(Trifluoromethyl)-1H-benzo[d][1,2,3]triazol-1-ol
5
(6):
General Procedure for the Synthesis of 1-Hydroxy-
H-benzotriazoles
Synthesized using 2-chloro-1-nitro-4-(trifluoromethyl)ben-
zene (2.0 g, 8.88 mmol) and hydrazine hydrate (0.88 g,
1
1
7.76 mmol) in absolute EtOH (13 mL) at reflux over 24 h.
A mixture of the appropriate ortho-chloronitro- or ortho-
fluoronitrobenzene and hydrazine hydrate were heated at
reflux in absolute EtOH for the period of time indicated for
each compound. After removal of the solvent under reduced
pressure, the residue was dissolved in 10% aqueous Na CO .
After removal of the solvent under reduced pressure, the
residue was dissolved in 10% aqueous Na CO (25 mL). The
solution was extracted with Et O (30 mL) and then acidified
with concentrated HCl. The precipitated product was fil-
tered, washed with water, and dried to obtain compound 6
as a white solid; yield: 1.08 g (60%); R (SiO /10% MeOH,
2
3
2
2
3
The solution was extracted with Et O to remove any starting
2
f
2
material and then acidified with concentrated HCl to precip-
itate the product, which was filtered, washed with water,
and dried to obtain the various 1-hydroxy-1H-benzotri-
1% Et N in CH Cl )=0.33. IR (KBr): n=3437, 1330,
3 2 2
ꢀ
1
1
8
09 cm ; H NMR (400 MHz, DMSO-d ): d=14.0 (br s,
6
OH, 1H), 8.51 (s, Ar-H, 1H), 7.99 (d, J=8.7 Hz, Ar-H, 1H),
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
azoles.
1
3
7
.85 (d, J=8.7 Hz, Ar-H, 1H); C NMR (100 MHz, DMSO-
5-Chloro-1H-benzo[d][1,2,3]triazol-1-ol (3): Synthesized
d6): d=141.9, 129.2, 124.7 (q, JC,F =270.9 Hz), 125.3 (q, J
=
C,F
using 2,4-dichloro-1-nitrobenzene (1.5 g, 7.85 mmol) and hy-
drazine hydrate (0.77 mL, 15.70 mmol) in absolute EtOH
1
9
3
1.8 Hz), 123.5, 117.9 (d, JC,F =4.6 Hz), 111.3; F NMR
(
376 MHz, DMSO-d ): d=ꢀ63.2 (with internal standard
6
(
10 mL) at reflux over 36 h. After removal of the solvent
TFA-d d=ꢀ78.5); HR-MS (ESI/TOF): m/z=204.0391,
under reduced pressure, the residue was dissolved in 10%
aqueous Na CO (20 mL). The solution was extracted with
+
calcd. for C H F N O [M+H] : 204.0380.
7
5
3
3
2
3
6
-Bromo-1H-benzo[d][1,2,3]triazol-1-ol (7): Synthesized
Et O (30 mL) and then acidified with concentrated HCl.
2
using 4-bromo-1-fluoro-2-nitrobenzene (3.0 g, 13.70 mmol)
and hydrazine hydrate (1.34 mL, 27.40 mmol) in absolute
EtOH (20 mL) at reflux over 24 h. After removal of the sol-
vent under reduced pressure, the residue was dissolved in
The precipitated product was filtered, washed with water,
and dried to obtain compound 3 as an off-white solid; yield:
1
.13 g (85%); R (SiO /10% MeOH, 1% Et N in CH Cl )=
f 2 3 2 2
1 1
ꢀ
0.37. IR (KBr): n=3461, 1342, 747 cm ; H NMR
1
0% aqueous Na CO (30 mL). The solution was extracted
(
400 MHz, DMSO-d ): d=13.85 (br s, OH, 1H), 8.14 (s, Ar-
2 3
6
with Et O (30 mL) and then acidified with concentrated
HCl. The precipitated product was filtered, washed with
water, and dried to obtain compound 7 as an off-white
solid; yield: 2.48 g (85%); R (SiO /10% MeOH, 1% Et N in
H, 1H), 7.80 (d, J=8.7 Hz, Ar-H, 1H), 7.58 (d, J=8.7 Hz,
2
13
Ar-H, 1H); C NMR (100 MHz, DMSO-d ): d=143.3,
6
1
1
29.1, 127.9, 126.6, 118.4, 111.2; HR-MS (ESI/TOF): m/z=
+
70.0126, calcd. for C H ClN O [M+H] : 170.0116.
f
2
3
6
5
3
ꢀ
1 1
CH Cl )=0.38. IR (KBr): n=3436, 1206, 803 cm ; H NMR
4,5-Dichloro-1H-benzo[d][1,2,3]triazol-1-ol (4): Synthe-
2
2
(
400 MHz, DMSO-d ): d=13.45 (br s, OH, 1H), 7.96 (m,
6
13
sized using 1,2,3-trichloro-4-nitrobenzene (1.5 g, 6.66 mmol)
and hydrazine hydrate (0.65 mL, 13.33 mmol) in absolute
EtOH (10 mL) at reflux over 36 h. After removal of the sol-
vent under reduced pressure, the residue was dissolved in
Ar-H, 2H), 7.52 (d, J=8.5 Hz, Ar-H, 1H); C NMR
100 MHz, DMSO-d ): d=141.7, 128.7, 127.6, 120.9, 120.2,
(
6
1
12.2. HR-MS (ESI/TOF): m/z=213.9614, calcd. for
+
1
0% aqueous Na CO (20 mL). The solution was extracted
C
H
6
BrN
5
O [M+H] : 213.9611.
3
2
3
[26]
with Et O (30 mL) and then acidified with concentrated
1H-[1,2,3]triazolo[4,5-b]pyridin-1-ol (8):
Synthesized
2
HCl. The precipitated product was filtered, washed with
water, and dried to obtain compound 4 as a white solid;
yield: 1.04 g (77%); Rf (SiO /10% MeOH, 1% Et N in
using 2-chloro-3-nitropyridine (1.0 g, 6.32 mmol) and hydra-
zine hydrate (0.62 mL, 12.64 mmol) in absolute EtOH
(10 mL) at reflux over 24 h. After removal of the solvent
under reduced pressure, the residue was dissolved in 10%
2
3
ꢀ
1 1
CH Cl )=0.40. IR (KBr): n=3494, 1385, 796 cm ; H NMR
2
2
(
7
400 MHz, DMSO-d ): d=7.59 (d, 1H, Ar-H, J=8.8 Hz),
.55 (d, 1H, Ar-H, J=8.8 Hz); C NMR (100 MHz, DMSO-
aqueous Na
2 3
CO (20 mL). The solution was extracted with
6
1
3
Et O (20 mL) to remove the starting material and aqueous
2
d ): d=140.8, 127.7, 127.5, 126.7, 120.9, 110.2; HR-MS (ESI/
layer was acidified with concentrated HCl. The product that
precipitated slowly over 12 h was filtered, washed with
water, and dried to obtain compound 8 was obtained as an
off-white solid; yield: 0.68 g (80%); R (SiO /10% MeOH,
6
+
TOF): m/z=203.9724, calcd. for C H Cl N O [M+H] :
6
4
2
3
2
03.9726.
-Methyl-1H-benzo[d][1,2,3]triazol-1-ol (5):
sized using 1-chloro-4-methyl-2-nitrobenzene
[33]
6
Synthe-
(1.0 g,
f
2
1% Et N in CH Cl )=0.21. IR (KBr): n=3457, 1396,
3
2
2
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
7
ÞÞ
These are not the final page numbers!

Venkateshwarlu Gurram et al.
FULL PAPERS
ꢀ
1
1
7
1
(
1
77 cm ; H NMR (400 MHz, DMSO-d ): d=8.36 (dd, J= General Procedure for the Synthesis of
6
.5, 4.1 Hz, Ar-H, 1H), 7.91–7.89 (m, Ar-H, 1H), 7.03–7.00
m, Ar-H, 1H); C NMR (100 MHz, DMSO-d ): d=153.8,
46.5, 120.8, 118.9, 116.3; HR-MS (ESI/TOF): m/z=
37.0475, calcd. for C H N O [M+H] : 137.0458.
Benzotriazoles
13
6
In a clean, dry 8-mL vial equipped with a stirring bar, the 1-
hydroxy-1H-benzotriazole was dissolved in MeCN. Et N
+
1
3
5
5
4
(
1.2 equiv.) was added and the reaction mixture was stirred
6
-Phenyl-1H-benzo[d][1,2,3]triazol-1-ol (9): Synthesized
at room temperature for 30 min. Then B (OH) (1.2 equiv.)
using 4-fluoro-3-nitrobiphenyl (1.0 g, 4.67 mmol) and hydra-
zine hydrate (0.45 mL, 9.34 mL) in absolute EtOH (8 mL)
at reflux over 24 h. After removal of the solvent under re-
duced pressure, the residue was dissolved in 10% aqueous
Na CO3 (20 mL). The solution was extracted with Et O
2
4
was added and the resulting reaction mixture was stirred for
0 min (8 h for substrates 2 and 8) at 508C. After comple-
3
tion of the reaction, the mixture was concentrated and
crude material was purified by chromatography on a silica
gel column by elution with 10–50% EtOAc in hexanes and
2
2
(
20 mL) and then acidified with concentrated HCl. The pre-
cipitated product was filtered, washed with water, and dried
to obtain compound 9 as a white solid; yield: 0.89 g (92%);
R (SiO /10% MeOH, 1% Et N in CH Cl )=0.42. IR (KBr):
in the case of compound 13 with 0–5% MeOH in CH
1H-Benzo[d][1,2,3]triazole (12): Synthesized using 1H-
benzo[d][1,2,3]triazol-1-ol (200 mg, 1.48 mmol), Et
(0.24 mL, 1.77 mmol), and B (OH) (159 mg, 1.77 mmol) in
Cl .
2 2
N
3
f
2
3
2
2
ꢀ
1
1
n=3565, 1088, 695 cm ; H NMR (400 MHz, DMSO-d ):
2
4
6
d=7.77 (d, J=8.5 Hz, Ar-H, 1H), 7.62 (d, J=7.4, Hz, Ar-H
MeCN (2 mL) over 30 min at 508C. Evaporation of the vol-
atiles and chromatography of the crude material on a silica
gel column by gradient elution with EtOAc in hexanes gave
compound 12 as a white solid; yield: 168 mg (95%); Rf
2
7
H), 7.55 (s, Ar-H, 1H), 7.47 (t, J=8.11 Hz, Ar-H, 3H),
.37 (t, J=7.2 Hz, Ar-H, 1H); C NMR (100 MHz, DMSO-
13
d6): d=142.9, 140.7, 136.3, 129.3, 128.5, 127.6, 127.4, 123.1,
19.1, 108.6; HR-MS (ESI/TOF): m/z=212.0823, calcd. for
1
(SiO /50% EtOAc in hexanes)=0.46. IR (KBr): n=3468,
2
+
ꢀ1
1
C H N O [M+H] : 212.0819.
1207, 740 cm ; H NMR (400 MHz, DMSO-d +1 drop of
12
10
3
6
6
-(Naphthalen-1-yl)-1H-benzo[d][1,2,3]triazol-1-ol (10):
Synthesized using 1-(4-fluoro-3-nitrophenyl) naphthalene
1.0 g, 3.74 mmol) and hydrazine hydrate (0.36 mL,
.48 mmol) in absolute EtOH (8 mL) at reflux over 24 h.
TFA-d): d=7.95 (dd, J=3.1, 6.3 Hz, Ar-H, 2H), 7.47 (dd,
1
3
J=3.1, 6.3 Hz, Ar-H, 2H); C NMR (100 MHz, DMSO-d +
6
(
7
1 drop of TFA-d): d=138.7, 125.4, 114.9; HR-MS (ESI/
+
TOF): m/z=120.0562, calcd. for C H N [M+H] : 120.0557.
6
6
3
After removal of the solvent under reduced pressure, the
residue was dissolved in 10% aqueous Na CO (20 mL). The
3H-[1,2,3]Triazolo[4,5-b]pyridine (13): Synthesized using
3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (200 mg, 1.47 mmol),
2
3
solution was extracted with Et O (30 mL) and then acidified
2
Et N (0.24 mL, 1.76 mmol), and B (OH)
1
(158 mg,
.76 mmol) in MeCN (2 mL) over 8 h at 508C. Evaporation
3
2
4
with concentrated HCl. The precipitated product was fil-
tered, washed with water, and dried to obtain compound 10
of the volatiles and chromatography of the crude material
on a silica gel column by gradient elution with MeOH in
CH Cl gave compound 13 as a white solid; yield: 166 mg
as a white solid; yield: 0.80 g (82%); R (SiO /10% MeOH,
f
2
1
7
% Et N in CH Cl )=0.41. IR (KBr): n=3448, 1300,
3 2 2
1 1
2
2
ꢀ
54 cm ; H NMR (400 MHz, DMSO-d ): d=13.98 (br s,
6
(95%); R (SiO /10% MeOH in CH Cl )=0.10. IR (KBr):
f 2 2 2
OH, 1H), 8.11 (d, J=8.5 Hz, Ar-H, 1H), 8.05 (t, J=8.5 Hz,
Ar-H, 2H), 7.80 (d, J=8.3 Hz, Ar-H, 1H), 7.74 (s, Ar-H,
ꢀ1
1
n=3436, 1399, 783 cm ; H NMR (400 MHz, DMSO-d +
6
1
8
drop of TFA-d): d=8.75 (dd, J=1.2, 4.1 Hz, Ar-H, 1H),
1
3
1
H), 7.64–7.48 (m, Ar-H, 5H);
C NMR (100 MHz,
.47 (dd, J=1.0, 8.3 Hz, Ar-H, 1H), 7.54 (dd, J=4.4, 8.3 Hz,
DMSO-d ): d=142.2, 139.0, 138.5, 133.3, 130.8, 128.3, 128.2,
13
6
Ar-H, 1H); C NMR (100 MHz, DMSO-d +1 drop of
6
128.1, 127.3, 126.9, 126.5, 126.0, 125.5, 125.0, 118.9, 110.2;
TFA-d): d=151.2, 149.3, 130.9, 124.9, 120.9; HR-MS (ESI/
HR-MS (ESI/TOF): m/z=262.0977, calcd. for C H N O
+
16
12
3
TOF): m/z=121.0513, calcd. for C H N [M+H] :121.0509.
5
5
4
+
[
M+H] : 262.0975.
-(Thien-3-yl)-1H-benzo[d][1,2,3]triazol-1-ol (11): Synthe-
sized using 3-(4-fluoro-3-nitrophenyl)thiophene (1.0 g,
.47 mmol) and hydrazine hydrate (0.44 mL, 8.95 mmol) in
[22]
5
-Chloro-1H-benzo[d][1,2,3]triazole (14):
Synthesized
(200 mg,
6
using
5-chloro-1H-benzo[d][1,2,3]triazol-1-ol
1
.17 mmol), Et N (0.19 mL, 1.41 mmol), and B (OH)4
3
2
4
(
5
142 mg, 1.41 mmol) in MeCN (1.6 mL) over 30 min at
08C. Evaporation of the volatiles and chromatography of
absolute EtOH (10 mL) at reflux over 24 h. After removal
of the solvent under reduced pressure, the residue was dis-
solved in 10% aqueous Na CO (20 mL). The solution was
the crude material on a silica gel column by gradient elution
with EtOAc in hexanes gave compound 14 as a white solid;
yield: 166 mg (92%); R (SiO /50% EtOAc in hexanes)=
2
3
extracted with Et O (20 mL) and then acidified with concen-
2
f
2
trated HCl. The precipitated product was filtered, washed
with water, and dried to obtain compound 11 as a white
solid; yield: 0.87 g (90%); R (SiO /10% MeOH, 1% Et N in
ꢀ1
1
0
.44. IR (KBr): n=3454, 1392, 800 cm ; H NMR
(
400 MHz, DMSO-d ): d=15.86 (br s, 1H, NH), 8.01 (s, 1H,
6
f
2
3
Ar-H), 7.95 (d, 1H, Ar-H, J=8.7 Hz), 7.44 (d, 1H, Ar-H,
ꢀ
1 1
CH Cl )=0.33. IR (KBr): n=3408, 1370, 773 cm ; H NMR
2
2
13
J=8.7 Hz); C NMR (100 MHz, DMSO-d +1 drop of
6
(
400 MHz, DMSO-d ): d=7.87 (s, Ar-H, 1H), 7.81 (d, J=
6
TFA-d): d=139.4, 138.2, 130.6, 126.2, 117.0, 114.5; HR-MS
8
2
.7 Hz, Ar-H, 1H), 7.68 (s, Ar-H, 1H), 7.64–7.60 (m, Ar-H,
13
+
(ESI/TOF): m/z=154.0164, calcd. for C
54.0167.
,5-Dichloro-1H-benzo[d][1,2,3]triazole (15): Synthesized
using 4,5-dichloro-1H-benzo[d][1,2,3]triazol-1-ol (200 mg,
.98 mmol), Et N (0.16 mL, 1.18 mmol), and B (OH)4
H ClN
5
[M+H] :
6
3
H), 7.54 (d, J=4.8 Hz, Ar-H, 1H); C NMR (100 MHz,
1
DMSO-d ): d=142.2, 141.1, 132.2, 128.2, 127.1, 126.4, 122.8,
6
4
1
21.4, 118.9, 106.6; HR-MS (ESI/TOF): m/z=218.0382,
+
calcd. for C H N SO [M+H] : 218.0383.
10
8
3
0
3
2
(
5
106 mg, 1.18 mmol) in MeCN (1.3 mL) over 30 min at
08C. Evaporation of the volatiles and chromatography of
the crude material on a silica gel column by gradient elution
with EtOAc in hexanes gave compound 15 as a white solid;
8
asc.wiley-vch.de
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

FULL PAPERS
Mild and General Access to Diverse 1H-Benzotriazoles
ꢀ
1
1
yield: 171 mg (93%)(; R (SiO /50% EtOAc in hexanes)=
0.33. IR (KBr): n=3433, 1400, 785 cm ; H NMR
f
2
ꢀ
1
1
0.40. IR (KBr): n=3458, 1439, 809 cm ; H NMR
(400 MHz, DMSO-d +1 drop TFA-d): d=15.90 (br s, NH,
6
(
8
400 MHz, DMSO-d +1 drop of TFA-d): d=7.93 (d, J=
.8 Hz, Ar-H, 1H), 7.66 (d, J=8.8 Hz, Ar-H, 1H); C NMR
1H), 8.75 (dd, J=1.2, 4.3 Hz, Ar-H, 1H), 8.47 (dd, J=1.0,
8.0 Hz, Ar-H, 1H), 7.54 (dd, J=4.4, 8.2 Hz, Ar-H, 1H);
6
1
3
1
3
(
100 MHz, DMSO-d +1 drop of TFA-d): d=139.6, 137.6,
C NMR (100 MHz, DMSO-d
6
+1 drop of TFA-d): d=
6
1
1
28.2, 127.9, 118.7, 114.5; HR-MS+ (ESI/TOF): m/z=
151.4, 149.4, 131.2, 125.2, 121.1; HR-MS (ESI/TOF): m/z=
+
87.9789, calcd. for C H Cl N [M+H] : 187.9777.
121.0524, calcd. for C
6-Phenyl-1H-benzo[d][1,2,3]triazole (20): Synthesized
using 6-phenyl-1H-benzo[d][1,2,3]triazol-1-ol (200 mg,
0.94 mmol), Et (0.15 mL, 1.13 mmol), and (OH)
5
H N [M+H] : 121.0509.
5 4
6
4
2
3
[22]
6
-Methyl-1H-benzo[d][1,2,3]triazole (16):
Synthesized
(200 mg,
using 6-methyl-1H-benzo[d][1,2,3]triazol-1-ol
1
.34 mmol), Et N (0.22 mL, 1.61 mmol), and B (OH)
N
3
B
2
4
3
2
4
(
5
144 mg, 1.61 mmol) in MeCN (1.81 mL) over 30 min at
08C. Evaporation of the volatiles and chromatography of
(102 mg, 1.13 mmol) in MeCN (1.3 mL) over 30 min at
508C. Evaporation of the volatiles and chromatography of
the crude material on a silica gel column by gradient elution
with EtOAc in hexanes gave compound 20 as a white solid;
the crude material on a silica gel column by gradient elution
with EtOAc in hexanes gave compound 16 as a white solid;
yield: 160 mg (90%); R (SiO /50% EtOAc in hexanes)=
yield: 175 mg (95%); R SiO /50% EtOAc in hexanes)=
f
2
f
2
ꢀ
1
1
ꢀ
1
1
0
.43. IR (KBr): n=3435, 1209, 609 cm ; H NMR
0
.40. IR (KBr): n=3456, 1440, 795 cm ; H NMR
(
400 MHz, DMSO-d ): d=15.78 (br s, NH, 1H), 8.14 (s, Ar-
(400 MHz, DMSO-d , 1008C): d=15.21 (brs, 1H, NH), 7.79
6
6
H, 1H), 8.02 (d, J=8.0 Hz, Ar-H, 1H), 7.78 (t, J=7.5 Hz,
Ar-H, 3H), 7.53 (t, J=8.0 Hz, Ar-H, 2H), 7.43 (t, J=7.3 Hz,
(
d, 1H, Ar-H, J=4.8 Hz), 7.62 (s, 1H, Ar-H), 7.26 (d, 1H,
1
3
Ar-H, J=8.0 Hz), 2.47 (s, 3H, CH ); C NMR (100 MHz,
DMSO-d +1 drop of TFA-d): d=138.8, 138.1, 135.9, 127.3,
1
3
1
3
Ar-H, 1H); C NMR (100 MHz, DMSO-d +1 drop TFA-
6
6
d): d=140.5, 139.6, 138.9, 138.6, 129.3, 127.9, 127.7, 125.5,
15.4, 113.0 21.2; HR-MS (ESI/TOF): m/z=134.0707, calcd.
+
115.8, 112.5; HR-MS (ESI/TOF): m/z=196.0872, calcd. for
for C H N [M+H] : 134.0713.
7
8
3
+
C H N [M+H] : 196.0870.
5
-(Trifluoromethyl)-1H-benzo[d][1,2,3]triazole (17): Syn-
thesized using 5-(trifluoromethyl)-1H-benzo[d][1,2,3]triazol-
-ol (200 mg, 0.98 mmol), Et N (0.16 mL, 1.18 mmol), and
12 10
3
6
-(Naphthalen-1-yl)-1H-benzo[d][1,2,3]triazole (21): Syn-
thesized using 6-(naphthalen-1-yl)-1H-benzo[d][1,2,3]triazol-
-ol (200 mg, 0.76 mmol), Et N (0.12 mL, 0.91 mmol), and
1
3
1
B (OH)4 (105 mg, 1.18 mmol) in MeCN (1.3 mL) over
3
raphy of the crude material on a silica gel column by gradi-
ent elution with EtOAc in hexanes gave compound 17 as
a white solid; yield: 169 mg (92%); R (SiO /50% EtOAc in
3
2
B (OH) (82.4 mg, 0.91 mmol) in MeCN (1 mL) over 30 min
0 min at 508C. Evaporation of the volatiles and chromatog-
2
4
at 508C. Evaporation of the volatiles and chromatography
of the crude material on a silica gel column by gradient elu-
tion with EtOAc in hexanes gave compound 21 as a white
solid; yield: 176 mg (94%); R (SiO /50% EtOAc in hex-
f
2
ꢀ
1
f
2
hexanes)=0.43; IR (KBr): n=3467, 1326, 824 cm ;
ꢀ
1
1
1
anes)=0.50. IR (KBr): n=3467, 1203, 774 cm . H NMR
400 MHz, DMSO-d ): d=15.83 (br s, NH, 1H), 8.07–7.97
H NMR (400 MHz, DMSO-d +1 drop TAF-d): d=16.04
6
(
6
(
br s, NH, 1H), 8.42 (s, Ar-H, 1H), 8.13 (d, J=8.8 Hz, Ar-
1
3
(m, Ar-H, 4H), 7.80 (d, J=8.4 Hz, Ar-H, 1H), 7.63–7.47 (m,
H, 1H), 7.77 (d, J=8.8 Hz, Ar-H, 1H); C NMR (100 MHz,
DMSO-d +1 drop TFA-d): d=140.0, 138.7, 124.6 (q, J
2
13
Ar-H, 5H); C NMR (100 MHz, DMSO-d ): d=138.9,
6
=
C,F
6
1
33.3, 130.9, 128.3, 127.8, 127.3, 126.4, 125.9, 125.5, 125.1;
HR-MS (ESI/TOF): m/z=246.1030, calcd. for C16H N
12 3
70.2 Hz), 126.1 (q, JC,F =31.9 Hz), 122.4 (d, J =3.0 Hz),
C,F
1
9
1
15.5, 114.9 (d, JC,F =3.8 Hz); F NMR (376 MHz, DMSO-
+
[
M+H] : 246.1026.
6-(Thien-3-yl)-1H-benzo[d][1,2,3]triazole (22): Synthe-
sized using 6-(thien-3-yl)-1H-benzo[d][1,2,3]triazol-1-ol
200 mg, 0.92 mmol), Et N (0.15 mL, 1.10 mmol), and
d ): d=ꢀ59.7; HR-MS (ESI/TOF): m/z=188.0439, calcd.
6
+
for C H F N [M+H] : 188.0436.
7
5
3
3
6
-Bromo-1H-benzo[d][1,2,3]triazole (18): Synthesized
using 6-bromo-1H-benzo[d][1,2,3]triazol-1-ol (200 mg,
.93 mmol), Et N (0.15 mL, 1.12 mmol), and B (OH)
(
3
B (OH) (99.1 mg, 1.10 mmol) in MeCN (1.2 mL) over
2
4
0
(
5
3
2
4
3
0 min at 508C. Evaporation of the volatiles and chromatog-
101 mg, 1.12 mmol) in CH CN (1.3 mL) over 30 min at
3
raphy of the crude material on a silica gel column by gradi-
ent elution with EtOAc in hexanes gave compound 22 as
a white solid; yield: 166 mg (90%); R (SiO /50% EtOAc in
08C. Evaporation of the volatiles and chromatography of
the crude material on a silica gel column by gradient elution
with EtOAc in hexanes gave compound 18 as a white solid;
yield: 170 mg (92%); R (SiO /50% EtOAc in hexanes)=
f
2
ꢀ
1
hexanes)=0.41. IR (KBr): n=3485, 1203, 780 cm ;
H NMR (400 MHz, DMSO-d +1 drop of TFA-d): d=8.20
f
2
1
ꢀ
1
1
6
0
.50. IR (KBr): n=3436, 1206, 803 cm ; H NMR
(
s, Ar-H, 1H), 8.00 (s, Ar-H, 1H), 7.96 (d, J=8.5 Hz, Ar-H,
(400 MHz, DMSO-d ): d=15.89 (br s, NH, 1H), 8.20 (s, Ar-
6
1
H), 7.85 (d, J=8.8 Hz, Ar-H, 1H), 7.70–7.68 (m, Ar-H,
H, 1H), 7.92 (d, J=8.0 Hz, Ar-H, 1H), 7.58 (t, J=4.5 Hz,
Ar-H, 1H); C NMR (100 MHz, DMSO-d +1 drop of
TFA-d): d=139.8, 137.9, 128.5, 118.3, 117.5, 116.9; HR-MS
(
13
2
1
1
H); C NMR (100 MHz, DMSO-d +1 drop TFA-d): d=
13
6
6
41.5, 139.3, 138.9, 133.4, 127.4, 126.8, 125.0, 121.9, 115.9,
11.4; HR-MS (ESI/TOF): m/z=202.0443, calcd. for
+
ESI/TOF): m/z=197.9651, calcd. for C H BrN [M+H] :
+
6
5
3
C H N S [M+H] : 202.0434.
1
0
8
3
1
97.9662.
H-[1,2,3]Triazolo[4,5-b]pyridine (19 same as compound
3): Synthesized using 1H-[1,2,3]triazolo[4,5-b]pyridine
1
1
(
General Procedure for CꢀC Cross-Coupling
Reactions of 6-Bromo-1H-benzo[d][1,2,3]triazole
with Arylboronic Acids
200 mg, 1.47 mmol), Et N (0.40 mL, 2.94 mmol), and
3
B (OH) (263.5 mg, 2.94 mmol) in MeCN (2 mL) over 8 h at
5
2
4
08C. Evaporation of the volatiles and chromatography of
the crude material on a silica gel column by gradient elution
In a clean, dry 8-mL vial equipped with a stirring bar, 6-
with MeOH in CH Cl gave compound 19 as a white solid;
bromo-1H-benzo[d][1,2,3]triazole was dissolved in anhy-
2
2
yield: 158 mg (90%); R (SiO /70% EtOAc in hexanes)=
drous 1,4-dioxane. The arylboronic acid and K PO4 were
f
2
3
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
9
ÞÞ
These are not the final page numbers!

Venkateshwarlu Gurram et al.
FULL PAPERS
added, the mixture was sparged with argon gas, and then
8.3 Hz, Ar-H, 1H), 7.93 (s, Ar-H, 1H), 7.46 (d, J=8.0 Hz,
13
PdCl (dcpf) was added. The vial was capped and the mix-
Ar-H, 1H), 2.45 (s, CH3, 3H), 2.27 (s, CH3, 3H); C NMR
2
ture was stirred for 16 h at 1008C. Upon completion of the
reaction, the mixture was concentrated under reduced pres-
sure, and the crude material was purified by chromatogra-
phy on a silica gel column by gradient elution with 10–50%
EtOAc in hexanes and in the case of compound 24 with 0–
(100 MHz, DMSO-d +1 drop of TFA-d): d=165.5, 139.3,
6
138.1, 127.4, 126.9, 116.0, 115.4, 115.2, 11.3, 10.4; HR-MS
+
(ESI/TOF): m/z=215.0939, calcd. for C11
H
11
N
O [M+H] :
4
215.0928.
3
% MeOH in CH Cl .
2 2
General Procedure for CꢀN Bond-Forming
6-Phenyl-1H-benzo[d][1,2,3]triazole (20): Synthesized
using
6-bromo-1H-benzo[d][1,2,3]triazole
(200 mg, Reactions of 6-Bromo-1H-benzo[d][1,2,3]triazole
1
.01 mmol), phenylboronic acid (246 mg, 2.02 mmol), K PO
with Arylamines
3
4
(
428 mg,
12.32 mmol),
and
PdCl (dcpf)
(152 mg,
2
In a clean and dry 8-mL vial equipped with a stirring bar, 6-
bromo-1H-benzo[d][1,2,3]triazole was dissolved in anhy-
drous 1,4-dioxane. The arylamine was added, the mixture
was sparged with argon gas, and then t-BuONa, Pd (dba) ,
0
.202 mmol) in 1,4-dioxane (1.3 mL) over 16 h at 1008C.
Chromatography of the crude material on a silica gel
column by gradient elution with EtOAc in hexanes gave
compound 20 as a pale brown solid; yield: 179 mg (90%).
2
3
and (t-Bu) P were added. The vial was capped and the mix-
3
6-(Naphthalen-1-yl)-1H-benzo[d][1,2,3]triazole (21): Syn-
ture was stirred for 6 h at 1008C. Upon completion of the
thesized using 6-bromo-1H-benzo[d][1,2,3]triazole (200 mg,
1
2
reaction, the mixture was diluted with CH Cl , filtered
2
2
.01 mmol),
naphthalen-1-ylboronic
acid
(347 mg,
through Celite, and concentrated under reduced pressure.
The crude material was purified by chromatography on
a silica gel column by gradient elution with 10–50% EtOAc
in hexanes and in the case of compound 29 with 0–5%
MeOH in CH Cl .
.02 mmol), K PO (428 mg, 12.32 mmol), and PdCl (dcpf)
3
4
2
(
152 mg, 0.202 mmol) in anhydrous 1,4-dioxane (1.3 mL)
over 16 h at 1008C. Chromatography of the crude material
on a silica gel column by gradient elution with EtOAc in
hexanes gave compound 21 as a pale brown solid; yield:
2
2
N-(4-Methylphenyl)-1H-benzo[d][1,2,3]triazol-6-amine
25): Synthesized using 6-bromo-1H-benzo[d][1,2,3]triazole
150 mg, 0.76 mmol), para-toluidine (243 mg, 2.28 mmol), t-
1
95 mg (78%).
-(Thien-3-yl)-1H-benzo[d][1,2,3]triazole (22): Synthe-
sized using 6-bromo-1H-benzo[d][1,2,3]triazole (200 mg,
.01 mmol), 3-thienylboronic acid (258 mg, 2.02 mmol),
K PO4 (428 mg, 12.32 mmol), and PdCl (dcpf) (152 mg,
(
(
6
BuONa
(73 mg,
1.52 mmol),
Pd (dba)
(69.5 mg,
2
3
1
0
.076 mmol), and (t-Bu) P (23.0 mg, 0.114 mmol) in anhy-
3
3
2
drous 1,4-dioxane (0.9 mL) over 6 h at 1008C. Work-up of
the reaction mixture and chromatography of the crude ma-
terial on a silica gel column by gradient elution with EtOAc
in hexanes gave compound 25 as a pale brown solid; yield:
0
1
.202 mmol) in anhydrous 1,4-dioxane (1.3 mL) over 16 h at
008C. Chromatography of the crude material on a silica gel
column by gradient elution with of EtOAc in hexanes gave
compound 21 was obtained as a pale brown solid; yield:
1
35 mg (80%); R (SiO /50% EtOAc in hexanes)=0.40. IR
f 2
1
180 mg (88%).
ꢀ1
(
KBr): n=3483, 3391, 1515, 808 cm ; H NMR (400 MHz,
6-(4-Methoxyphenyl)-1H-benzo[d][1,2,3]triazole
(23):
DMSO-d ): d=15.05 (br s, NH, 1H), 7.81 (d, J=8.9 Hz, Ar-
6
Synthesized
using
6-bromo-1H-benzo[d][1,2,3]triazole
H, 1H), 7.20 (d, J=1.5 Hz, Ar-H, 1H), 7.14–7.09 (m, Ar-H,
(
(
200 mg, 1.01 mmol), para-methoxyphenylboronic acid
311 mg, 2.02 mmol), K PO (428 mg, 12.32 mmol), and
13
5
H), 2.24 (s, CH3, 3H); C NMR (100 MHz, DMSO-d +
6
3
4
1 drop TFA-d): d=143.8, 140.0, 129.9, 129.6, 118.7, 116.8,
91.4, 20.3; HR-MS (ESI/TOF): m/z=225.1142, calcd. for
PdCl (dcpf) (152 mg, 0.202 mmol) in anhydrous 1,4-dioxane
2
(
1.3 mL) over 16 h at 1008C. Chromatography of the crude
+
C H N [M+H] ; 225.1135.
1
3
13
4
material on a silica gel column by gradient elution with
EtOAc in hexanes gave compound 23 as a pale brown solid;
yield: 172 mg (75%); R (SiO /50% EtOAc in hexanes)=
N-(Naphthalen-1-yl)-1H-benzo[d][1,2,3]triazol-6-amine
26): Synthesized using 6-bromo-1H-benzo[d][1,2,3]triazole
(
f
2
(200 mg,
1.01 mmol),
naphthalen-1-amine
(433 mg,
ꢀ
1
1
0.41. IR (KBr): n=3391, 1604, 808 cm ; H NMR
3
.03 mmol), t-BuONa (193 mg, 2.02 mmol), Pd (dba)3
2
(400 MHz, DMSO-d +1 drop of TFA-d): d=8.06 (s, Ar-H,
6
(94.2 mg, 0.101 mmol), and (t-Bu) P (30.6 mg, 0.151 mmol)
3
1
H), 7.98 (d, J=8.5 Hz, Ar-H, 1H), 7.72 (d, J=8.8 Hz, Ar-
in 1,4-dioxane (1.0 mL) over 6 h at 1008C. Work-up of the
reaction mixture and chromatography of the crude material
on a silica gel column by gradient elution with EtOAc in
hexanes gave compound 26 as a pale brown solid; yield:
191 mg (72%); R (SiO /50% EtOAc in hexanes)=0.42. IR
H, 3H), 7.08 (d, J=8.5 Hz Ar-H, 2H), 3.85 (s, CH 3H);
3
,
13
C NMR (100 MHz, DMSO-d +1 drop of TFA-d): d=
6
1
5
39.1, 138.7, 138.1, 132.5, 128.6, 125.5, 115.7, 114.6, 111.3,
5.2; HR-MS (ESI/TOF): m/z=226.0981, calcd. for
f
2
+
ꢀ1
1
C H N O [M+H] : 226.0975.
(KBr): n=3478, 3390, 1521, and 791 cm ; H NMR
13
12
3
4-(1H-Benzo[d][1,2,3]triazol-6-yl)-3,5-dimethylisoxazole
(400 MHz, DMSO-d +1 drop of TFA-d): d=8.17 (d, J=
6
(
(
(
24): Synthesized from 6-bromo-1H-benzo[d][1,2,3]triazole
200 mg, 1.01 mmol), 3,5-dimethylisoxazol-4-ylboronic acid
283 mg, 2.02 mmol), K PO (428 mg, 12.32 mmol), and
7.6 Hz, Ar-H, 1H), 7.95 (d, J=8.3 Hz, Ar-H, 1H), 7.86 (d,
J=8.9 Hz, Ar-H, 1H), 7.64 (d, J=7.6 Hz, Ar-H, 1H), 7.56–
7.44 (m, Ar-H, 4H), 7.27 (d, J=8.9 Hz, Ar-H, 1H), 7.00 (d,
3
4
1
3
PdCl (dcpf) (152 mg, 0.202 mmol) in anhydrous 1,4-dioxane
J=1.3 Hz, Ar-H, 1H); C NMR (100 MHz, DMSO-d +
2
6
(
1.3 mL) over 16 h at 1008C. Chromatography of the crude
1 drop of TFA-d): d=145.2, 138.7, 137.6, 136.3, 134.6, 128.3,
127.8, 126.2, 125.5, 123.0, 117.9, 1177.8, 116.8, 116.7, 94.1;
HR-MS (ESI/TOF): m/z=261.1148, calcd. for C H N
4
[M+H] : 261.1135.
N-(4-Methoxyphenyl)-1H-benzo[d][1,2,3]triazol-6-amine
(27): Synthesized using 6-bromo-1H-benzo[d][1,2,3]triazole
material on a silica gel column using gradient elution with
MeOH in CH Cl gave compound 24 as a pale brown solid;
yield: 131 mg (60%); R (SiO /10% MeOH in CH Cl )=
0
2
2
16 13
+
f
2
2
2
ꢀ
1
1
.41. IR (KBr): n=3468, 1634, 1195, 798 cm ; H NMR
(400 MHz, DMSO-d +1 drop of TFA-d): d=8.02 (d, J=
6
10
asc.wiley-vch.de
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

FULL PAPERS
Mild and General Access to Diverse 1H-Benzotriazoles
(
150 mg, 0.76 mmol), para-anisidine (280 mg, 2.28 mmol), t-
BuONa (73 mg, 1.52 mmol), Pd (dba) (69.5 mg,
.076 mmol), and (t-Bu) P (23.0 mg, 0.114 mmol) in 1,4-diox-
of Health Grant G12MD007603 from the National Institute
on Minority Health and Health Disparities.
2
3
0
3
ane (0.85 mL) over 6 h at 1008C. Work-up of the reaction
mixture and chromatography of the crude material on
a silica gel column by gradient elution with EtOAc in hex-
anes gave compound 27 as a pale brown solid; yield: 127 mg
References
(
70%); R (SiO /50% EtOAc in hexanes)=0.31. IR (KBr):
f 2
1 1
ꢀ
[1] a) X.-M. Peng, G.-X. Cai, C.-H. Zhou, Curr. Top. Med.
Chem. 2013, 13, 1963–2010; b) B. V. Suma, N. N.
Natesh, V. Madhavan, J. Chem. Pharm. Res. 2011, 3,
375–381.
n=3467, 3391, 1510, 804 cm ; H NMR (400 MHz, DMSO-
d6): d=14.92 (br s, NH, 1H), 8.18 (s, NH, 1H), 7.79 (s, Ar-
H, 1H), 7.14–6.94 (m, Ar-H, 6H), 3.74 (s, CH 3H);
3
,
13
C NMR (100 MHz, DMSO-d ): d=154.5, 145.3, 138.9,
6
˙
[
2] a) K. Kopa n´ ska, A. Najda, J. Zebrowska, L. Chomicz,
1
35.3, 134.5, 121.8, 119.1, 116.0, 114.6, 89.5, 55.2; HR-MS
+
J. Piekarczyk, P. Myjak, M. Bretner, Bioorg. Med.
Chem. 2004, 12, 2617–2624; b) G. Caliendo, G. Greco,
P. Grieco, E. Novellino, E. Perissutti, V. Santagada, D.
Barbarulo, E. Esposito, A. De Blasi, Eur. J. Med.
Chem. 1996, 31, 207–213; c) G. Caliendo, R. Di Carlo,
G. Greco, R. Meli, E. Novellino, E. Perissutti, V. Santa-
gada, Eur. J. Med. Chem. 1995, 30, 77–84.
(
ESI/TOF): m/z=241.1086, calcd, for C H N O [M+H] :
1
3
13
4
2
41.1084.
N-(1H-Benzo[d][1,2,3]triazol-6-yl)isoquinolin-5-amine
28): Synthesized using 6-bromo-1H-benzo[d][1,2,3]triazole
200 mg, 1.01 mmol), isoquinolin-5-amine (436 mg,
.03 mmol), t-BuONa (193 mg, 2.02 mmol), Pd (dba)
(
(
3
2
3
(
92.4 mg, 0.101 mmol), and (t-Bu) P (30 mg, 0.151 mmol) in
3
[
3] a) K. H. G. Verschueren, K. Pumpor, S. Anemꢂller, S.
anhydrous 1,4-dioxane (1 mL) over 6 h at 1008C. Work-up
of the reaction mixture and chromatography of the crude
material on a silica gel column by gradient elution with
EtOAc in hexanes gave compound 28 as a brown solid;
yield: 178 mg (68%); R (SiO /10% MeOH in CH Cl )=
Chen, J. R. Mesters, R. Hilgenfeld, Chem. Biol. 2008,
1
5, 597–606; b) C.-Y. Wu, K.-Y. King, C.-J. Kuo, J.-M.
Fang, Y.-T. Wu, M.-Y. Ho, C.-L. Liao, J.-J. Shie, P.-H.
Liang, C.-H. Wong, Chem. Biol. 2006, 13, 261–268;
c) M. Bretner, A. Baier, K. Kopa n´ ska, A. Najda, A.
Schoof, M. Reinholz, A. Lipniacki, A. Piasek, T. Kuli-
kowski, P. Borowski, Antiviral Chem. Chemother. 2005,
f
2
2
2
ꢀ
1
0
.54. IR (KBr): n=3437, 3272, 1518, 1387, 824 cm ;
1
H NMR (400 MHz, DMSO-d +1drop TFA-d): d=9.91 (s,
6
Ar-H, 1H), 8.73 (s, Ar-H, 2H), 8.12 (d, J=7.8 Hz, Ar-H,
1
6, 315–326; d) K.-L. Yu, Y. Zhang, R. L. Civiello, K. F.
1
H), 7.97–7.89 (m, Ar-H, 3H), 7.45 (s, Ar-H, 1H), 7.37 (d,
13
Kadow, C. Cianci, M. Krystal, N. A. Meanwell, Bioorg.
Med. Chem. Lett. 2003, 13, 2141–2144; e) P. Borowski,
J. Deinert, S. Schalinski, M. Bretner, K. Ginalski, T.
Kulikowski, D. Shugar, Eur. J. Biochem. 2003, 270,
1645–1653.
J=8.8 Hz, Ar-H, 1H); C NMR (100 MHz, DMSO-d +
6
1
1
drop TFA-d): d=147.5, 141.6, 140.3, 138.0, 137.3, 131.6,
31.1, 130.7, 128.6, 122.6, 121.2, 120.7, 119.5, 117.8, 99.7;
HR-MS (ESI/TOF): m/z=262.1099, calcd. for C H N
1
5
12
5
+
[
M+H] : 262.1087.
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Acknowledgements
Support of this work by NSF Grant CHE-1265687 (MKL)
and GVKBIO (NP) is gratefully acknowledged. Infrastruc-
tural support at CCNY was provided by National Institutes
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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FULL PAPERS
Mild and General Access to Diverse 1H-Benzotriazoles via
Diboron-Mediated NꢀOH Deoxygenation and Palladium-
Catalyzed CꢀC and CꢀN Bond Formation
13
Adv. Synth. Catal. 2014, 356, 1 – 13
Venkateshwarlu Gurram, Hari K. Akula, Ramesh Garlapati,
Narender Pottabathini,* Mahesh K. Lakshman*
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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ÞÞ
These are not the final page numbers!