Selective reductions. Part 60: Chemoselective reduction of organyl azides with dichloroborane-dimethyl sulfide

Article abstract of DOI:10.1016/S0040-4020(02)01322-4

The rate and stoichiometry of the reduction of an organyl azide with BH₃·THF was examined under standardized conditions at room temperature. Borane derivatives, such as dialkyl-, alkoxy-, and haloboranes were also examined for the reduction of azides. This study revealed BHCl₂·SMe₂ to be the most suitable reagent for the reduction of azides. The chemoselectivity of this reagent was also studied by reducing n-hexyl azide in the presence of representative series of functional groups, including esters, halides, nitriles, and nitro groups. BHCl₂·SMe₂ reduces azides in the presence of all of the above functional groups as well as olefins. Taking advantage of the differences in reactivity of BHCl₂·SMe₂ and BH₃·THF or BH₃·SMe₂, it is now possible to reduce selectively an azide in the presence of olefins or to hydroborate an olefin in the presence of azides by a judicious choice of the reagent.

Full text of DOI:10.1016/S0040-4020(02)01322-4

Tetrahedron 58 (2002) 10059–10064
Selective reductions. Part 60: Chemoselective reduction of organyl
azides with dichloroborane–dimethyl sulfide
†
Ashok M. Salunkhe, P. Veeraraghavan Ramachandran and Herbert C. Brown
*
*
Department of Chemistry, Herbert C. Brown Center for Borane Research, Purdue University, West Lafayette, IN 47907-2038, USA
Received 3 July 2002; revised 8 October 2002; accepted 9 October 2002
Abstract—The rate and stoichiometry of the reduction of an organyl azide with BH3·THF was examined under standardized conditions at
room temperature. Borane derivatives, such as dialkyl-, alkoxy-, and haloboranes were also examined for the reduction of azides. This study
revealed BHCl2·SMe2 to be the most suitable reagent for the reduction of azides. The chemoselectivity of this reagent was also studied by
reducing n-hexyl azide in the presence of representative series of functional groups, including esters, halides, nitriles, and nitro groups.
BHCl2·SMe2 reduces azides in the presence of all of the above functional groups as well as olefins. Taking advantage of the differences in
reactivity of BHCl2·SMe2 and BH3·THF or BH3·SMe2, it is now possible to reduce selectively an azide in the presence of olefins or to
hydroborate an olefin in the presence of azides by a judicious choice of the reagent. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
halo boranes have not been examined. Consequently, a
systematic study of the rate and stoichiometry as well as the
chemoselectivity was undertaken of different classes of
boranes for the reduction of azides. The results are
summarized herein.
Nitrogen-containing molecules are extremely important in
organic and bio-chemistry.1 A large majority of pharma-
ceutical compounds are nitrogen containing molecules. Of
the several methods to prepare amines, reduction of azides
occupies a prime position.2 Since numerous methods are
available for the preparation of azides with excellent regio-,
enantio-, and stereocontrol,3 the reduction of azides permits
a controlled introduction of an amine functionality. A large
number of reagents have been reported in the literature for
the reduction of azides.4 However, these reagents suffer
from limitations with regard to general applicability,
selectivity, operational convenience, and toxicity. For
example, the most commonly employed reagent for the
reduction of azides, LiAlH4, is used in large excess to
achieve the reduction and does not tolerate many function-
alities, such as esters, nitro, etc.5 Catalytic hydrogenation
has limitations when applied to molecules with unsatura-
tion, such as olefins or alkynes.6 Borohydrides and modified
borohydride reagents are generally milder reagents, but also
face certain disadvantages with regard to the rate and
selectivity.7 Although boranes are highly selective reagents
for the reduction of many reducible functional groups,8 a
literature survey reveals that very little attention has been
focused on the reduction of azides until our initial report.9
Although reduction of azide using BH3·THF is known,10
several other important borane derivatives, such as
2. Results and discussion
The reduction of azides with BH3–THF has been known for
over three decades.10 However, the rates and stoichiometry
of this reaction have not been studied thus far. Such an
investigation was undertaken with n-hexyl azide as a
representative azide.
In order to ascertain whether azides complex with boranes,
BH3·THF, BH3·SMe2, BF3·OEt2, and BHCl2·SMe2 were
treated with 1 equiv. of n-hexyl azide at 0.5 M concentration
at 0 8C and examined using 11B NMR spectroscopy. There
was no change in their chemical shifts suggesting that there
is no coordination of the azides with boron.
2.1. Procedure for rate and stoichiometry studies
n-Hexyl azide was subjected to the reaction with BH3·THF
at room temperature (RT) in different ratios and concen-
trations with respect to borane and azide. The reactions were
followed by (1) 11B NMR spectroscopy, (2) gasimetric
analysis of residual hydride,11 (3) gas chromoatographic
(GC) analysis of residual azide with dodecane as an internal
standard, and (4) by measuring nitrogen evolution. Both the
rate and the stoichiometry (the number of hydrides utilized
per mole of the azide) were thus established.
Keywords: azides; reduction; amines; borane; chloroborane.
*
Corresponding authors. Tel.: þ1-765-494-5316; fax: þ1-765-494-6027;
e-mail: hcbrown@purdue.edu
Present address: Pierce Chemical Co., 3747 N. Meridian Rd., P.O. Box
117, Rockford, IL 61105, USA.
†
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01322-4

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A. M. Salunkhe et al. / Tetrahedron 58 (2002) 10059–10064
Table 1. Reduction of n-hexyl azide with BH3·THF (1:1.3) at RT
Table 3. Reduction of n-hexyl azide with BH3·THF (1:1) at RT at higher
concentration
Time (h)
Hydride useda
Azide usedb
% Reactionc
Time (h) Hydride useda Azide usedb Nitrogen evolvedc % Reaction
1.0
2.0
4.0
8.0
12
0.176
0.39
0.55
0.70
0.80
0.96
0.96
0.174
0.42
0.55
0.68
0.78
0.94
0.95
17
42
55
68
78
94
95
0.5
1.0
2.0
4.0
6.0
17
0.64
0.74
0.756
0.86
0.91
0.64
0.73
0.76
0.88
0.91
0.94
0.95
0.65
0.76
0.80
0.87
0.92
0.94
0.95
65
75
80
87
92
94
95
24
32
0.935
0.958
32
12.5 Mmol of azide was added to 16.6 mmol of BH3·THF.
a
Mmol of hydride/Mmol of azide.
Determined by GC analysis.
Based on azide consumed during reduction.
17.12 Mmol of azide was added to 17.12 mmol of BH3·THF.
a
b
Mmol of hydride/Mmol of azide.
Determined by GC analysis.
c
b
c
Based on azide consumed during reduction and mmols of nitrogen
evolved during reduction.
2.2. Reaction of n-hexyl azide with BH3·THF
maintained at RT and the reaction was monitored as
described above. As can be seen from Table 2, the rate
increased with concentration: 83% reaction complete in 6 h
and 95% in 17 h.
Initially, the reaction was studied using excess borane. The
procedure adopted was to add 12.5 mmol of n-hexyl azide to
16.6 mmol of BH3·THF in sufficient THF to make a 50 mL
solution. This makes the reaction mixture 0.25 M in the
azide and 0.33 M in borane (i.e. 1.00 M in hydride). The
reaction was slow at 08C; hence the solution was maintained
at RT and the reaction was monitored as described above. It
was observed that the reduction of the azide is very slow and
requires 24 h for ,95% completion. During this time, 94%
of the azide had reacted as shown by GC analysis. This
experiment clearly proved that only one hydride is used per
mole of the azide (Table 1).
To facilitate the reaction, the concentration was increased
further. 17.12 Mmol of n-hexyl azide was added to
17.12 mmol of BH3·THF (2.14 M) in sufficient THF to
make 11 mL of solution (1.56 M in borane as well as in
azide). The solution was maintained at RT and the reaction
was monitored as described above. The rate of the reduction
increased significantly; 91% in 6 h as indicated by nitrogen
evolution, consumed hydride and remaining azide (Table 3).
In order to determine the optimal concentration for the
reduction of azide with BH3·THF, the following experi-
ments were carried out.
The above study established that only one hydride is used
per mole of the azide reduced and the rate of the reduction
accelerates as the concentration of the reaction mixture
increases. The reaction pathway is shown in Eq. (1).12
The reaction was conducted with a 1:1 molar ratio of the
azide and hydride with a concentration of 0.33 M in
the reactants. n-Hexyl azide (12.5 mmol) was added to
12.5 mmol of BH3·THF in sufficient THF to make 37.5 mL
of solution. The reaction mixture was thus 1.00 M in
hydride (three hydrides per BH3) and 0.33 M in the azide.
The solution was maintained at RT and the reaction was
monitored as described above. In this case also the rate of
the reduction is slow and is only 84% complete in 24 h as
was indicated by the consumption of the azide and hydride.
ð1Þ
Table 4. Reduction of n-hexyl azide with boranes
Entry
Reagent
BH3·THFc
BH3·SMe2
1,4-Oxathiane·borane
Catecholboraned
9-BBN
BHCl2·THF/THPe
BHCl2·THF/THP
BHCl2·OEt2
Solvent
Time (h)a
% Reactionb
The reaction was repeated with 1 M concentration of the
reactants. 25 Mmol of n-hexyl azide was added to 25 mmol
of BH3·THF in sufficient THF to make 25 mL of solution
(1.00 M in borane as well as in azide). The solution was
1
2
3
4
5
6
7
8
THF
Et2O
Et2O
THF
Et2O
THF
CH2CI2
Et2O
Et2O
6.0
21
24
22
24
24
24
2–3
24
2–3
2–3
91
5
76
40
–
49
70
82
86
100
100
Table 2. Reduction of n-hexyl azide with BH3·THF (1:1) at RT
Time (h)
Hydride useda
Azide usedb
% Reactionc
9
10
11
BHCl2·SMe2
BHCl2·SMe2
BHBr2·SMe2
e
CH2Cl2
CH2Cl2
e
1.0
2.0
4.0
6.0
17
0.4799
0.6695
0.7722
0.8275
0.938
0.48
48.0
68.8
78.8
84.0
94.8
0.688
0.788
0.84
All reactions were carried out at 1.0 M concentration unless otherwise
mentioned.
a
Time after which nitrogen evolution ceased.
% of the reaction based on nitrogen evolution.
Reaction concentration was 1.56 M in boranes and azide.
Reaction concentration is 0.9 M.
1.5 equiv. of reagent was used and reaction mixture refluxed for 1 h at the
end.
0.948
b
c
25 Mmol of azide was added to 25 mmol of BH3·THF.
a
d
Mmol of hydride/Mmol of azide.
Determined by GC analysis.
Based on azide consumed during reduction.
b
e
c

A. M. Salunkhe et al. / Tetrahedron 58 (2002) 10059–10064
10061
2.3. Examination of boranes for reduction of azides
Table 5. Reduction of representative azides with BHCl2·SMe2 in
dichloromethane
Having established the rate and stoichiometry of the
reaction of n-hexyl azide with BH3·THF, our attention
was turned to testing different Lewis base complexes of
borane and borane derivatives to determine the most
efficient reagent for the reduction of organyl azides.
BH3·SMe2, 1,4-oxathiane·borane,13 9-BBN, catechol-
borane, and haloboranes, such as BHCl2·THP/THF14
Entry
Azide
Amine
Yield (%)
1
2
3
4
5
6
7
8
1-Azidohexane
Hexylamine
95a
78b
85b
93a
80b
94a
82b
75b
1-Azidododecane
2-Azidoundecane
Azidocyclohexane
Azidocycloheptane
Phenyl azide
Dodecylamine
2-Undecylamine
Cyclohexylamine
Cycloheptylamine
Aniline
BHCl2·OEt2,15 BHCl2·SMe2 and BHBr2·SMe2 were
examined.
16
17
Benzyl azide
1-Azidoadamantane
Benzylamine
Adamantanamine
All reactions were carried out using 1.5 equiv. of BHCl2·SMe2 in
dichloromethane at 1.0 M concentration with respect to BHCl2·SMe2.
The reaction of boranes with azide was followed by
measuring the rate of nitrogen evolution after the addition
of n-hexyl azide to the particular borane at RT. The results
are summarized in Table 4. This study revealed that
BH3·SMe2 is extremely slow in reducing azides, whereas
1,4-oxathiane–borane reduces azides at a faster rate. This
may be due to weaker Lewis base complexation with
borane. Among the borane complexes tested for the
reduction of azide, BH3·THF gave the best results (Table 4).
a
Yield determined by 1H NMR by adding internal standard.
Yield of the isolated product.
b
(75% reduction in 1 h), but requires a longer time for
complete reduction to occur. However, the reduction was
essentially quantitative when carried out in dichloro-
methane. Thus, among all of the haloboranes tested,
BHCl2·SMe2 in dichloromethane gave the best results.9
Similar results were obtained with BHBr2·SMe2 also (Table
4). For procedural convenience and simplicity, BHCl2·SMe2
in dichloromethane was utilized for further study. In order to
achieve complete reduction within a short period, 1.5 equiv.
of the reagent was used and the reaction mixture was
refluxed for 1 h (Eqs. (3) and (4)).
Surprisingly, 9-BBN, an excellent reducing reagent for
many functional groups,18 did not reduce n-hexyl azide in
ethyl ether (Et2O) at RT. We observed the evolution of
1 equiv. of nitrogen in 24 h. However, the product obtained
after alkaline peroxide oxidation was an amino alcohol. The
formation of the amino alcohol is illustrated in Eq. (2).
Indeed, similar reactions of B-alkyl-9-BBN for the prepa-
ration of 28-amines are known.19
ð3Þ
1: H3Oþ
RNHBCl2
!
RNH2 þ 2KCl þ KBðOHÞ4
ð4Þ
ð2Þ
2: KOH
Having established the most suitable reagent and the
optimum reaction conditions for the reduction of n-hexyl
azide, our attention was directed in testing the efficacy of
this reagent for the reduction of a series of organic azides of
varying structural requirements, such as primary, secondary,
and tertiary alkyl, cyclic, aromatic, and benzylic azides.
As shown in Table 5, BHCl2·SMe2 in dichloromethane
reduces all classes of organyl azides in excellent yields in a
relatively short period of time. The reagent is efficient even
for the reduction of tertiary alkyl azides (Table 5).
The reduction of n-hexyl azide with haloboranes was then
investigated. BHCl2·THP/THF and BHCl2·OEt2 needed for
study were prepared according to literature procedures.14,15
These haloboranes were treated with n-hexyl azide at RT
and the rate of the reduction was followed by measuring the
nitrogen evolved. The reduction of n-hexyl azide with
BHCl2·THP in THF was very slow; only 49% reaction was
observed in 24 h as indicated by nitrogen evolution. This
may be due to strong complexation of BHCl2 with THF, the
reaction medium. Presumably free BHCl2 is essential for
the reduction to occur. Carrying out the reaction in a non-
coordinating solvent, such as dichloromethane supports this
hypothesis. The rate of the reduction increased to 70% in
24 h as was shown by nitrogen evolution. Since BHCl2·
THP/THF did not give the anticipated rate of reduction,
attention was turned to other complexes of BHCl2.
BHCl2·OEt2 reduces azide at a faster rate and 80% reduction
was achieved in 2–3 h as determined by evolution of
nitrogen. BHCl2·SMe2 and BHBr2·SMe2 were then exam-
ined. BHCl2·SMe2 in Et2O reduces azide in 86% yield
within 24 h. Initially the rate of reduction was very fast
2.4. Chemoselectivity of BHCl2·SMe2
A search of the current literature reveals several procedures
for the reduction of azides.3 However, chemoselectivity has
been a concern for several of these reagents. It has been
shown that dichloroborane in THF can be utilized for the
selective deoxygenation of sulfoxides in the presence of
ketones, esters, nitriles, or a nitro group.20 This study
suggested the possibility of achieving a highly selective
reduction of azides with dichloroborane–dimethyl sulfide
even in the presence of other readily reducible functional
groups. In order to elucidate the selectivity of this reagent,
n-hexyl azide was reduced in the presence of an equivalent
amount of nitropropane, nitrobenzene, ethyl benzoate,
bromohexane, and benzonitrile. In all of the cases, the

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A. M. Salunkhe et al. / Tetrahedron 58 (2002) 10059–10064
Table 6. Chemoselective reduction of n-hexyl azide with BHCl2·SMe2 at RT
Entry
Reducible compounda
% Amineb
Recovered reducible compound (%)c
1
2
3
4
5
1-Bromohexane
1-Nitropropane
Nitrobenzene
Benzonitrile
74
75
76
72
75
94
100
100
93
Ethyl benzoate
97
All reactions were carried out at RT in dichloromethane at 1.0 M concentration with respect to reducible compound and 1-hexyl azide.
a
Ratio of reducible compound/azide/BHCl2·SMe2 is 1:1:1.
Amine (%) by nitrogen evolution in 1.0–1.5 h.
b
c
Recovery of reducible compounds determined by 1H NMR by adding suitable internal standard.
progress of the reduction was monitored by the nitrogen
evolution for 1–1.5 h and the reaction mixture was
hydrolyzed with water. A suitable internal standard was
added to the mixture and GC analysis revealed the
percentage of reducible compound remaining in the reaction
mixture. In all cases, 72–75% reduction of the azide was
observed on the basis of the nitrogen evolution whereas the
added reducible compound was recovered almost quanti-
tatively (Table 6). It is evident from the table that the
reagent is highly selective and many functional groups
survive during the reduction of azide with dichloroborane–
methyl sulfide.
progress of the hydroboration was followed by 11B NMR
spectroscopy. In all cases, the olefins were hydroborated
cleanly as indicated by the formation of di- or trialkyl-
boranes and essentially quantitative recovery of the azide
(Table 8).
Thus, it is possible to hydroborate an olefin in the presence
of an azide or reduce an azide in the presence of an olefin by
a judicious choice of the reagent (Eq. (5)).
Previous studies with dichloroborane have shown it to be a
poor hydroborating reagent as a complex with a Lewis base
(Me2S or Et2O) and olefins are readily hydroborated by free
dichloroborane after removing the base with boron
trichloride.15 It was envisaged that even a double bond
may survive during the reduction of azide. Accordingly, the
reduction of n-hexyl azide was carried out in the presence
of olefins (Table 7). It was found that this reagent
preferentially reduces azides with little effect on the olefin,
with ,90% of the olefin was recovered along with 4–7% of
the corresponding alkyldichloroboranes.
ð5Þ
3. Conclusions
The rate and stoichiometry of the reduction of azides with
boranes has been established. Of the several borane
derivatives examined, dichloro- and dibromoborane–
methyl sulfide in dichloromethane reduces azides to the
corresponding amines in high yields within a short time. We
have also established that dichloroborane–methyl sulfide is
a chemoselective reducing agent for azides in the presence
of several other reducible compounds. It is now possible to
2.5. Chemoselectivity of BH3·THF or BH3·SMe2
As mentioned earlier, the reduction of azide with BH3·THF
at 08C is slow. This suggested that it should be possible to
hydroborate olefins in the presence of azides. Accordingly,
we selected a representative series of terminal, di- and
trisubstituted, and cyclic olefins and examined their
hydroboration in the presence of n-hexyl azide. The
Table 8. Hydroboration of olefins with BH3·THF or BH3·SMe2 in the
presence of n-hexyl azide
Entry
Olefina
Reagent Time (h)b Recovered azide (%)c
Table 7. Reduction of n-hexyl azide in the presence of olefins by
BHCl2·SMe2 in CH2Cl2 at RT
1
2
3
4
5
6
7
5
1-Hexene
2-Methyl-1-butene BH3·THF 3.0
2-Methyl-2-butene BH3·THF 4.0
Cyclopentene
Norbornylene
1-Hexene
2-Methyl-2-butene BH3·SMe2 1.5
Norbornylene BH3·SMe2 4.0
BH3·THF 0.5
100
100
95
95
96
95
98
95
Entry
Olefina
RBCl2
(%)b
% of
aminec
Recovered
olefind
BH3·THF 1.5
BH3·THF 2.0
BH3·SMe2 2.0
1
2
3
4
1-Decene
4
5
6
7
71
72
73
72
90
90
89
88
2-Methyl-1-butene
Cyclopentene
Norbornylene
All reactions were carried out at 0.5 M concentration with respect to
BH3·THF and 1.0 M concentration with respect to BH3·SMe2 unless
otherwise mentioned.
All reactions were carried out at 1.0 M concentration with respect to
BHCl2·SMe2.
a
In all cases, 3 equiv. of olefin was used except in case of 2-methyl-2-
butene where only 2 equiv. of olefin was used.
a
Ratio of olefin/azide/BHCl2·SMe2 is 1:1:1.
Determined by 11B NMR.
% of amine based on nitrogen evolution.
Recovery of the olefin was calculated by 1H NMR by adding biphenyl as
an internal standard.
b
b
Time after which all borane was consumed and dialkyl- or trialkylborane
was formed. Reactions were followed by 11B NMR.
c
d
c
Recovery of the azide was calculated by 1H NMR by adding biphenyl as
an internal standard.

A. M. Salunkhe et al. / Tetrahedron 58 (2002) 10059–10064
10063
reduce an azide in the presence of an olefin or vice versa by
a judicious choice of the reagent.
extracted with ethyl ether (3£5 mL). The combined ether
extracts were washed with water, brine, and dried over
anhydrous magnesium sulfate. Removal of the solvent
provided an 85% yield of essentially pure 2-undecylamine.
The spectroscopic data was in agreement with authentic
samples. A similar procedure was adopted for the reduction
of all other azides.
4. Experimental
4.1. General methods
4.5. General procedure for chemoselectivity study with
BHCl2·SMe2 in dichloromethane at RT
All operations were carried out under an inert atmosphere.
Techniques for handling air- and moisture-sensitive
materials have been previously described.11
The reduction of n-hexyl azide with BHCl2·SMe2 in
dichloromethane in the presence of nitrobenzene is
representative. To a 25 mL R. B. flask equipped with rubber
septum and magnetic stir bar was charged with n-hexyl
azide (0.381 g, 3 mmol) and nitrobenzene (0.34 mL,
3 mmol) in 2.2 mL of anhydrous dichloromethane. The
reaction flask was then attached to a hydride estimation
apparatus to measure the evolved gas. BHCl2·SMe2 in
dichloromethane (0.3 mL, 3 mmol) was added slowly with
stirring and the evolved nitrogen was measured. In 1.5–
2.0 h, 76% nitrogen was evolved. The reaction mixture was
then hydrolyzed with water and ethyl benzoate was added as
internal standard to determine the recovered nitrobenzene.
The reaction mixture was extracted with ethyl ether
(3£15 mL), washed with water and dried over anhydrous
magnesium sulfate. The solvent was removed and the
4.2. Materials
All of the azides used in this study were prepared according
to the literature procedure.21 BHCl2·OEt2 and BHCl2·THP
were prepared as reported.14,15
4.3. General procedure for the determination of rate and
stoichiometry of the reduction of azides with BH3·THF
at RT
The following procedure for the reduction of n-hexyl azide
with BH3·THF in 1:1 molar ratio and at 1.56 M concen-
tration both in azide and borane is representative. A dry
50-mL flask equipped with a magnetic stir bar, septum inlet
and reflux condenser was charged with BH3·THF (2.14 M,
17.12 mmol, 8 mL) and dodecane (2.72 mmol, 0.463 g,
0.6 mL) as an internal standard. The reaction flask was
connected to a gas buret through a dry ice–acetone trap to
measure the evolved nitrogen. To this, n-hexyl azide
(17.12 mmol, 2.17 g, 2.46 mL) was added slowly at RT
and the reaction was monitored by the nitrogen evolved
during the reduction. At different intervals, 1 mL aliquots of
the mixture were withdrawn, quenched with conc. HCl and
the hydrogen evolved was measured volumetrically to
determine the consumed hydride. After the reaction was
complete, the mixture was treated with conc. HCl, made
strongly alkaline, extracted with ether, dried over anhydrous
magnesium sulfate and concentrated to provide the product
amine which was identified by 1H NMR. All other
experiments using different molar ratios and different
concentration were carried out as described above.
1
unreacted nitrobenzene was determined by H NMR and
found to be almost quantitative. A similar procedure was
used for the reduction of n-hexyl azide with BHCl2·SMe2 in
the presence of other reducible compounds.
4.6. General procedure for the reduction of n-hexyl azide
in the presence of olefins by BHCl2·SMe2 in
dichloromethane at RT
The reduction of n-hexyl azide in the presence of 1-decene
by BHCl2·SMe2 in dichloromethane is representative.
n-Hexyl azide (0.381 g, 3 mmol) and 1-decene (0.421 g,
3 mmol) in 2 mL of anhydrous dichloromethane was added
to a 25 mL R. B. flask equipped with rubber septum and
magnetic stirring bar and attached to a gasimeter to measure
the evolved gas. BHCl2·SMe2 (0.34 mL, 3 mmol) was added
to the flask, slowly, with stirring and evolved nitrogen was
measured. In 1.5 h, 71% nitrogen was liberated. At this
stage, the reaction mixture was hydrolyzed with water and
biphenyl was added as an internal standard to quantify the
recovered olefin. The reaction mixture was extracted with
ethyl ether (3£15 mL), washed with water and dried over
anhydrous magnesium sulfate. The recovery of the 1-decene
was determined by 1H NMR and found that 90% olefin was
recovered. The 11B NMR showed 3–4% formation of
alkyldichloroborane–dimethyl sulfide complex. A similar
procedure was used for the reduction of n-hexyl azide with
BHCl2·SMe2 in the presence of other olefins.
4.4. General procedure for the reduction of azides by
BHCl2·SMe2 in dichloromethane at RT
The following procedure for the reduction of 2-azidounde-
cane is representative. BHCl2·SMe2 in dichloromethane
(7.5 mL, 7.5 mmol) was added to a dry 25-mL flask
equipped with a magnetic stir bar, septum inlet and reflux
condenser connected to a gas buret through a dry ice–
acetone trap to measure the evolved nitrogen. To this,
2-azidoundecane (0.985 g, 5 mmol) was added slowly at RT
and the reaction was monitored by the nitrogen evolved
during the reduction (no hydrogen is evolved). The addition
of the azide is completed in 35–40 min. During this time,
the reaction is ,75% complete and the reaction mixture was
refluxed for 1 h to achieve complete reduction. The solvent
was removed from the reaction mixture under vacuum and
the intermediate was hydrolyzed with conc. HCl at 808C for
35–40 min. The mixture was then cooled to RT, made
strongly alkaline with aqueous potassium hydroxide,
4.7. General procedure for the hydroboration of olefins
with BH3·THF in the presence of n-hexyl azide in
tetrahydrofuran at 08C
The hydroboration of 1-hexene is representative. 1-Hexene
(15 mmol, 1.88 mL) and n-hexyl azide (5 mmol, 0.635 g)
was placed in 2.4 mL of anhydrous THF in a 50 mL R. B.

10064
A. M. Salunkhe et al. / Tetrahedron 58 (2002) 10059–10064
Chem. Lett. 2001, 12, 659. (b) Malanga, C.; Mannucci, S.;
Lardicci, L. J. Chem. Res. S 2000, 256. (c) Pathak, D.; Laskar,
D. D.; Prajapati, D.; Sandhu, J. S. Chem. Lett. 2000, 816.
(d) Wu, H. Y.; Chen, R.; Zhang, Y. M. J. Chem. Res. S 2000,
248. (e) Fringuelli, F.; Pizzo, F.; Vaccaro, L. Synthesis 2000,
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flask equipped with rubber septum and magnetic stir bar and
cooled to 08C. To this BH3·THF (5 mL of 1.0 M solution,
5 mmol) was added slowly with stirring and the reaction
was monitored by 11B NMR spectroscopy. When all
BH3·THF was consumed (0.5 h) and trialkylborane was
formed, the mixture was oxidized with hydrogen peroxide
and 3 M sodium acetate by stirring overnight. Biphenyl was
added as an internal standard and the recovered azide was
estimated using 1H NMR spectrum, which revealed
quantitative recovery. A similar procedure was used for
the hydroboration of other olefins in the presence of n-hexyl
azide with BH3·THF or BH3·SMe2. In the case of
BH3·SMe2, diethyl ether was used as the solvent.
5. (a) Boyer, J. H. J. Am. Chem. Soc. 1951, 73, 5865. (b) Boyer,
J. H.; Canter, F. C. Chem. Rev. 1954, 54, 1. (c) Hojo, H.;
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Acknowledgements
9. Salunkhe, A. M.; Brown, H. C. Tetrahedron Lett. 1995, 36,
7987.
We gratefully acknowledge financial support from the
United States Army Research Office (DAAG55-98-1-0405)
and the Herbert C. Brown Center for Borane Research
(Contribution No. 21).
10. Fowler, F. W.; Hassner, A.; Levy, L. A. J. Am. Chem. Soc.
1967, 89, 2077.
11. Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M.
Organic Synthesis via Boranes; Wiley Interscience: New
York, 1975; Reprinted as Vol. 1 by Aldrich Chemical Co.,
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