NaIO4-NaN3-mediated diazidation of styrenes, alkenes, benzylic alcohols, and aryl ketones

Article abstract of DOI:10.1016/j.tetlet.2012.05.140

Sodium periodate and sodium azide combination has been found to be an excellent reagent system suitable for the direct diazidation of styrenes, alkenes, benzylic alcohols, and aryl ketones to produce the corresponding vicinal and geminal diazides respecti

Full text of DOI:10.1016/j.tetlet.2012.05.140

Tetrahedron Letters 53 (2012) 4195–4198
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
NaIO4–NaN3-mediated diazidation of styrenes, alkenes, benzylic alcohols,
and aryl ketones
⇑
Dayanand A. Kamble, Pratibha U. Karabal, Pandurang V. Chouthaiwale, Arumugam Sudalai
Chemical Engineering & Process Development Division, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, Maharashtra, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Sodium periodate and sodium azide combination has been found to be an excellent reagent system suit-
able for the direct diazidation of styrenes, alkenes, benzylic alcohols, and aryl ketones to produce the cor-
responding vicinal and geminal diazides respectively in high yields under mild reaction conditions.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 18 April 2012
Revised 28 May 2012
Accepted 30 May 2012
Available online 7 June 2012
Keywords:
Alkenes
Aryl ketones
Sodium periodate
Vicinal diazides
Geminal diazides
Vicinal diazides are important precursors to 1,2-diamines,1
which are useful functional groups present in a variety of natural
products, pharmaceutical substances (e.g.,
phenylethane (2a) was isolated in 35% yield. However, this yield
was increased to 85% when the stoichiometry of NaN3 was in-
creased to 3 equiv (Scheme 1). After several experimentation with
alkenes, the best yields of diazides could be obtained with the opti-
mum combination of NaN3 (3 equiv) and NaIO4 (1 equiv). This
prompted us to further examine the effectiveness of the NaIO4–
NaN3 in DMSO–AcOH system in the 1,2-diazidation of several al-
kenes. This new diazidation procedure was indeed found to be
quite general for a variety of alkenes and the results of the study
are presented in Table 1.
Several styrenic substrates as well as aliphatic olefins including
linear and cyclic alkenes gave good yields of the corresponding vic-
inal 1,2-diazides (entries a–o). In the case of internal olefins, the
diazides were also obtained in high yields with dr = 1:1 as deter-
mined from their 1H NMR spectra. However, no reaction took place
D
-(+)-biotin),2 etc. In
addition, 1,2-diamines find increasing utilization in organic syn-
thesis either as chiral auxiliaries or as metallic ligands especially
in the field of catalytic asymmetric synthesis.3 Quite recently, a
few useful methods of introducing vicinal diazide functionality
onto alkenes have been reported.4 These include combinations like
Mn3+–NaN3 (large excess)-AcOH5 or TFA,6 Fe2+–H2O2–NaN3,7
PhIO–NaN3–AcOH,8 and SN2 displacements involving multi-step
reactions.9 However, some of them suffer from drawbacks like
use of expensive metal salts and oxidants, low yields, and multi-
step reaction sequences. In this Letter, we wish to report a new
NaIO4-mediated procedure for the direct diazidation of alkenes
and aryl ketones with NaN3 that affords vicinal and geminal diaz-
ides (2 and 4) respectively in excellent yields (Tables 1 and 2).
In continuation of our studies on NaIO4-mediated oxidative
functionalization of organic compounds (e.g., halogenation of aro-
matics,10a halohydroxylation of alkenes,10b C–H activation of
hydrocarbons,10c and quite recently, azidoiodination of alkenes10d),
we reasoned that, in the absence of KI, sodium periodate/sodium
azide/DMSO–AcOH combination can be an effective and simple re-
agent system for the 1,2-diazidation of alkenes. Accordingly, when
styrene (1a) was heated initially with NaIO4 and NaN3 (1 equiv
each) in DMSO–AcOH at 75 °C, the corresponding 1,2-diazido-1-
in the case of
esters and (R)-(À)-carvone) as well as sterically hindered alkenes
(e.g., -pinene), which may be a limitation of this method.
a,b-unsaturated carbonyl compounds (e.g., cinnamic
a
We further extended the scope of this reagent system to several
aryl ketones 3 and some of the corresponding benzylic alcohols for
the direct azidation. As can be seen from Table 2, linear and cyclic
aryl ketones with
selective oxidative diazidation with NaIO4 (1 equiv) and NaN3
(3 equiv) in AcOH–DMSO (1:4) as solvent at 75 °C, to give -diaz-
ido aryl ketones (4a–f) in 91–96% yields (Table 2). Isobutyrophe-
none (entry f) produced the corresponding -monoazido ketone
a-methylene group (–CO–CH2–) underwent
a,a
a
4f in 35% yield. At low temperatures, no reaction took place and
only starting material was recovered. However, at higher temper-
atures the formation of monoazidoketone was not detected (as
⇑
Corresponding author. Tel.: +91 20 25902174; fax: +91 20 25902676.
E-mail address: a.sudalai@ncl.res.in (A. Sudalai).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.05.140

4196
D. A. Kamble et al. / Tetrahedron Letters 53 (2012) 4195–4198
Table 1
a
NaIO4-mediated 1,2-diazidation of styrenes and alkenes with NaN3
NaIO4 (1 equiv),
NaN3 (3 equiv),
N3
R1
R1
R = alkyl, aryl
R1= H, alkyl
R
R
DMSO:AcOH (4:1)
75 C, 2h
°
N3
1 a-o
2 a-o
Entry
Olefins (1a–o)
Vicinal diazides (2a–o)
Yieldb (%)
a
b
c
d
e
f
g
h
i
Styrene
1,2-Diazido-1-phenylethane
1,2-Diazido-1-(3-methoxyphenyl)ethane
1,2-Diazido-1-(4-methylphenyl)ethane
5-(1,2-Diazidoethyl)benzo[1,3]dioxole16
1,2-Diazido-1-(2-chlorophenyl)ethane
1,2-Diazido-1-(4-bromophenyl)ethane
1,2-Diazido-1-(4-fluorophenyl)ethane17
1,2-Diazido-1-cyclohexylethane
1,2-Diazidohexane
85
90
87
90
85
90
89
80
3-Methoxystyrene
4-Methylstyrene
3,4-Methylenedioxy-styrene
2-Chlorostyrene
4-Bromostyrene
4-Fluorostyrene
1-Cyclohexylethylene
Hex-1-ene
70
j
Hept-1-ene
1,2-Diazidoheptane
68
k
l
m
n
o
Dec-1-ene
1-Indene
trans-Cinnamyl alcohol
Cyclohexene
Cyclooctene
1,2-Diazidodecane
1,2-Diazidoindane
2,3-Diazido-3-phenylpropan-1-ol
1,2-Diazidocyclohexane
1,2-Diazidocyclooctane
63
75c
78c
49c,d
60c
Reaction conditions:
a
alkene (5 mmol), NaIO4 (5 mmol), NaN3 (15 mmol), 20 ml of DMSO–AcOH (4:1), 75 °C, 2 h.
Yield refers to isolated yield after column chromatography.
Refers to 1:1 ratio of syn:anti isomers of 1,2-diazide.
b
c
d
Excess of cyclohexene was used.
Table 2
NaIO4-mediated
a
a
,
a-diazidation of aryl ketones with NaN3
Entry
a
Aryl ketones (3a–f)
Geminal diazides (4a–f)
Yieldb (%)
O
CH3
Propiophenone
96 (75)c
N3
N3
N3
N3
O
b
c
1,3-Diphenylpropan-1-one
94
N3
O
3-(4-Methoxyphenyl)-1-phenylpropan-1-one
95
N3
OMe
O
d
e
1-indanone
1-Tetralone
N3
N3
95
O
O
N3
N3
93 (70)c (28)d
CH3
CH3
f
2-Methyl-1-phenylpropan-1-one
35
N3
Reaction conditions:
a
Aryl ketone (5 mmol), NaIO4 (5 mmol), NaN3 (15 mmol), 20 ml of DMSO–AcOH (4:1), 75 °C, 2 h.
Yield refers to isolated yield after column chromatographic purification.
Yield corresponds to 1-phenyl-1-propanol and 1-tetralol as starting materials.
Yield obtained using NaIO4 (5 mmol) and NaN3 (5 mmol).
b
c
d
monitored by GC) even after carrying out the reaction for longer
probably occurred via the initial oxidation of benzylic alcohols
duration. The only product obtained in this case was 2,2-
diazidoketone.
(5a & 5e) to form the corresponding aryl ketones, which then sub-
sequently underwent diazidation at the
a-position (Scheme 2).
Benzylic alcohols, when treated under
tions (entries a & e), gave the corresponding
tones (4a18
4e) in good yields. This diazidation reaction
a
,
a
a
-diazidation condi-
The structures of 1,2-diazides 2a–o and a,a
4a–f were ascertained on the basis of spectroscopic data. The
methine and methylene protons attached to azido groups in all
-diazido arylketones
,a-diazido arylke-
&

D. A. Kamble et al. / Tetrahedron Letters 53 (2012) 4195–4198
4197
N3
OH
.
O
OH
O
NaIO4 (1 equiv)
NaN3 (3 equiv),
H+
N3
R
NaIO4
o
.
R
Ar
R
Ar
75 o
C
Ar
N3
N3
DMSO: AcOH (4: 1),
75 °C, 2 h
3 a-f
A
1a
2a, yield: 85%
OH
+
O
Scheme 1. NaIO4-mediated 1,2-diazidation of styrene with NaN3.
R
fast
R
R
Ar
Ar
Ar
H
N3 N3
4 a-f
N3
N3
B
NaIO4 (1 equiv)
NaN3 (3 equiv),
O
OH
Scheme 4. Proposed mechanism for the a,a-diazidation of aryl ketones.
R
R
Ar
Ar
DMSO: AcOH (4: 1),
75 °C, 2 h
N3
N3
and NaN3, 2 equiv), the only product obtained was 2,2-diazido-1-
phenylpropan-1-one (20 min; 92% yield). This observation
suggests that the rate of diazidation of monoazidoketone is much
faster as compared to the diazidation of the parent aryl ketone.
In conclusion, we have developed a simple procedure15 with
NaIO4–NaN3 as a new combination for the 1,2-diazidation of al-
5
4a
, Ar = phenyl; R = CH3; 75%
, Ar = tetralol; R = H; 70%
4e
Scheme 2. NaIO4-mediated a,a-diazidation of benzylic alcohols with NaN3.
kenes and
a,a-diazidation of aryl ketones, that provides direct
and efficient entry to vicinal 1,2-diazidoalkanes and geminal 1,1-
diazidoarylketones respectively in high yields. The transformation
the 1,2-diazido compounds exhibited a typical signal in the range d
2.36–4.02 in their 1H NMR spectra whereas the carbons attached to
azido groups have shown signal in the range d 52.91–67.64 in their
of aryl ketones and benzylic alcohols to the corresponding
a,a-
13C NMR spectra. In the case of
a,a-diazido ketones (4a–f) quater-
diazides is unprecedented and being reported for the first time.
The geminal diazides (4a–e) are potential candidates to be used
as future generation high energy materials for defense
applications.14
nary carbon attached to diazido groups show d values ranging from
80.1 to 85.7 in the 13C NMR spectra. A strong characteristic IR
absorption in the range 2076–2108 cmÀ1 for all the diazides con-
firms the presence of azide functionality. The formation of
a,a-
Acknowledgments
diazido aryl ketones 4a was further confirmed by its conversion
to an interesting di-triazole 6 using click chemistry reaction condi-
tions11 (Scheme 3).
D.A.K., P.U.K. and P.V.C. thank CSIR and DST New Delhi (Sanc-
tion No. SR/S1/OC-67/2010) for financial support. The authors are
also thankful to Dr. V. V. Ranade, Chair, Chemical Engineering
and Process Development Division for his encouragement and
support.
Mechanistically, the reaction is believed to follow a radical
pathway10d for both alkenes and aryl ketones. When the diazida-
tion of styrene was carried out in the presence of catalytic amount
of TEMPO, a dramatic decrease in the yield of diazido product 2a
(10%) was obtained, probably due to the radical quenching effect.
It has been established that azide anion can be oxidized to the cor-
responding azide radical by Fe2+–H2O2,7 simple metal salts (Pb4+ or
Supplementary data
Mn3+ 12,5b or electrochemically,12,13 and can readily add to C@C to
)
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.
05.140.
give vicinal diazido derivatives. In a similar manner, NaIO4 oxidizes
NaN3 to generate an azide radical which then adds to alkenes to
produce a more stable alkyl radical followed by its trapping with
another azide radical resulting in the formation of 1,2-diazides
2a–o. In the case of aryl ketones 3a–f, the enol form of ketone re-
acts with azide radical to form a more stable benzylic radical spe-
cies A which probably undergoes one electron oxidation with
NaIO4 to form a cationic species B. Expulsion of proton from B gen-
erates monoazidoketone which then subsequently undergoes sec-
References and notes
1. (a) Kemp, J. E. G. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Eds.; Pergamon: Oxford, 1991; Vol. 7, p 469; (b) De Figueiredo, R. M. Angew.
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1486.
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3. Mortensen, M. S.; O’Doherty, G. A. Chemtracts: Org. Chem. 2005, 18, 555.
4. Saibabu Kotti, S. R. S.; Timmons, C.; Li, G. Chem. Biol. Drug Des. 2006, 67, 101.
5. (a) Suzuki, T.; Shibata, A.; Morohashi, N.; Ohba, Y. Chem Lett. 2005, 34, 1476; (b)
Fristad, W. E.; Brandvold, T. A.; Peterson, J. R.; Thompson, S. R. J. Org. Chem.
1985, 50, 3647.
ond azidation at the
a-CH position in a similar fashion to afford
1,1-diazides 4a–f. In order to confirm the formation of monoazi-
doketone intermediate (Scheme 4), we carried out the diazidation
of tetralone with 1 equiv each of NaN3 and NaIO4. However, the
only product obtained was
a
,
a
-diazidoketone 4e in 28% yield. Fur-
6. Lin, H.; Snider, B. B. Synth. Commun. 1913, 1998, 28.
7. Minisci, F.; Galli R., F. R. Patent 1, 350, 360 (A) 1964.
8. Moriarty, R. M.; Khosrowshahi, J. S. Tetrahedron Lett. 1986, 27, 2809.
9. (a) Skarzewski, J.; Gupta, A. Tetrahedron Asymmetry 1861, 1997, 8; (b) Swift, G.;
Swern, D. J. Org. Chem. 1967, 32, 511.
thermore, when 2-azido-1-phenylpropan-1-one, was prepared
separately from the corresponding 2-bromo-1-phenylpropan-1-
one, and was subjected to diazidation conditions (NaIO4, 1 equiv
N
O
O
N
N
Ph
CH3
N3
CuSO4.5H2O, (2 mol%)
+
Ph
2
N
N3
4 a
sodium ascorbate (5 mol%)
Ph
yield: 50%; mp 195-200 o
Scheme 3. Synthesis of ditriazole derivative 6.
N
t-BuOH:H2O (1:1), 25 oC, 8 h.
N
6
C

4198
D. A. Kamble et al. / Tetrahedron Letters 53 (2012) 4195–4198
10. (a) Shaikh, T. M.; Sudalai, A. Tetrahedron Lett. 2005, 46, 5587; (b) Dewkar, G. K.;
Narina, S. V.; Sudalai, A. Org. Lett. 2003, 5, 4501; (c) Chouthaiwale, P. V.;
Suryavanshi, G.; Sudalai, A. Tetrahedron Lett. 2008, 49, 6401; (d) Chouthaiwale,
P. V.; Karabal, P. U.; Suryavanshi, G.; Sudalai, A. Synthesis 2010, 22, 3879.
11. Singh, B. K.; Yadav, A. K.; Kumar, B.; Gaikwad, A.; Sinha, S. K.; Chaturvedi, V.;
Tripathi, R. M. Carbohydr. Res. 2008, 343, 1153.
12. Hugl, H.; Zbiral, E. Tetrahedron 1973, 29, 759.
13. (a) Schafer, H. Angew. Chem., Int. Ed. 1970, 9, 158; (b) Kosten, K.;
Riemenschneider, P.; Wendt, H. Isr. J. Chem. 1979, 18, 141.
behind a safety shield. However, we have not experienced any hazardous
problem associated with NaN3–NaIO4 mixtures. Yet, care must be taken when
dealing with mixture containing azides and oxidizing agents.
16. 5-(1,2-Diazidoethyl)benzo[1,3]dioxole (2d)
Yield: 90%; pale yellow liquid; IR (neat, cmÀ1): 730, 933, 1102, 1247, 1444,
1504, 2100, 2902; 1H NMR (200 MHz, CDCl3): d 3.31–350 (m, 2H), 4.53–4.60
(dd, J = 5.39, 7.79 Hz, 1H), 6.00 (s, 2H), 6.75–6.84 (m, 3H); 13C NMR (50 MHz,
CDCl3): d 55.9, 65.3, 101.4, 107, 108.5, 120.8, 130.1, 148.3; GC–MS: m/z (% rel.
intensity) 232 (M+, 1) and 148 (100); Anal. Calcd for C9H8N6O2: C, 46.55; H,
3.47; N, 36.19; Found: C, 46.53; H, 3.47; N, 36.20.
14. Kopach, M. E.; Murray, M. M.; Braden, T. M.; Kobierski, M. E.; Williams, O. L.
Org. Process Res. Dev. 2009, 13, 152.
17. 1,2-Diazido-1-(4-fluorophenyl)ethane (2g)
15. General experimental procedure for 1,2-diazidation of alkenes and
a
,
a
-diazidation
Yield: 89%; pale yellow liquid; IR (neat, cmÀ1): 835, 1229, 1333, 1511, 1604,
2102; 1H NMR (200 MHz, CDCl3): d 3.35–3.54 (m, 2H), 4.62–4.68 (dd, J = 5.6,
7.7 Hz, 1H), 7.06–7.16 (m, 2H), 7.27–7.37 (m, 2H); 13C NMR (50 MHz, CDCl3): d
55.9, 64.8, 115.9, 116.3, 128.7, 128.8, 132.2, 132.3, 160.4, 165.4; GC–MS: m/z (%
rel. intensity) 206 (M+, 4) and 95 (100); Anal. Calcd for C8H7FN6: C, 46.60; H,
3.42; N, 40.70; Found: C, 46.58; H, 3.37; N, 40.76.
of arylketones: To a suspension of NaN3 (15 mmol) and NaIO4 (5 mmol) in
20 ml of DMSO–glacial AcOH (4:1) was added alkenes (5 mmol) or arylketone
(5 mmol), as the case may be, and the reaction mixture was stirred at 75 °C for
2 h. It was monitored by TLC and then poured into water (100 ml) and
extracted with EtOAc (3 Â 50 ml). The combined organic layers were washed
with saturated solution of aqueous NaHCO3 (50 ml) followed by aqueous
Na2S2O3 (5%, 50 ml), dried over anhyd Na2SO4. Concentration of the organic
layer gave crude diazides, which were purified by silica gel-packed column
chromatography using hexane/ethyl acetate (19:1) as eluent to obtain pure
18. 2,2-Diazido-1-phenyl-propan-1-one (4a)
Yield: 96%; pale yellow liquid; IR (neat, cmÀ1): 739, 1230, 1456, 1602, 1690,
2104, 2937; 1H NMR (200 MHz, CDCl3): d 1.86 (s, 3H), 7.44–7.53 (m, 2H), 7.57–
7.66 (m, 1H), 8.11 (t, J = 1.5 Hz, 1H), 8.14 (t, J = 1.3 Hz, 1H); 13C NMR (50 MHz,
CDCl3): d 20.0, 83.1, 128.3, 130.1, 132.5, 133.6, 191.7; Anal. Calcd for C9H8N6O:
C, 50.00; H, 3.73; N, 38.87; Found: C, 50.10; H, 3.68; N, 38.79.
1,2-diazides 2a–o or
a,a-diazidoketones 4a–e, respectively.
Caution: All reactions employing NaN3 and NaIO4 were conducted in a hood