Chemoselective three-component synthesis of homoallylic azides using an FeCl3 catalyst

Article abstract of DOI:10.1039/c3ra42821d

A one-pot, three-component synthesis of homoallylic azides from corresponding aldehydes, TMS-allyl, and TMS-N₃ has been developed for the first time using an FeCl₃ catalyst. The aromatic and hetero-aromatic aldehydes provided the cor

Full text of DOI:10.1039/c3ra42821d

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Chemoselective three-component synthesis of
homoallylic azides using an FeCl3 catalyst†
Cite this: RSC Adv., 2013, 3, 23157
*
Suman Pramanik and Prasanta Ghorai
A one-pot, three-component synthesis of homoallylic azides from corresponding aldehydes, TMS-allyl, and
TMS-N3 has been developed for the first time using an FeCl3 catalyst. The aromatic and hetero-aromatic
aldehydes provided the corresponding homoallylic azides with excellent chemoselectivity. This direct
azido-allylation process is also readily scalable (1–28 mmol). The mechanism of the process is proposed.
Finally, the selective as well as simultaneous functionalization of homoallylic azides has also been
exemplified.
Received 7th June 2013
Accepted 17th September 2013
DOI: 10.1039/c3ra42821d
www.rsc.org/advances
Introductions
Homoallylic azides are very important and versatile building
blocks for the synthesis of various therapeutic agents and
natural products. For example, they are used for the synthesis of
alkaloid natural products containing a piperidine1 core such as
aza-(ꢀ)-diospongin A2 (Scheme 1). It has also been used to
synthesize the pyrrolidine core.3 Azides are useful precursors for
the corresponding primary amines, nitrenes and isocyanates.4
Moreover, the azides are also potential ‘click’ partners in the
Huisgen 1,3-dipolar cycloaddition5 to provide 1,2,3-triazolo-
heterocyclic compounds which have recently attracted signi-
cant attention in medicinal and pharmaceutical chemistry6 as
well as in material sciences.7 Thus, the co-existence of these two
functionalities provide various complex molecular architectures
in a simplied manner.1–3,8
Scheme 1 Versatility of homoallylic azide building block.
In general, the homoallylic azides are synthesized from the
corresponding homoallylic alcohols (which are commonly
prepared from the corresponding aldehydes and allyl anion) via
SN2-type reaction pathway. This is proceeded either via the
conversion of alcohol to a better leaving group (such as tosylate,
halide, phosphate, etc.) followed by azidation reaction1a,2,9 or
under Mitsunobu-type of reaction conditions (see Scheme 2).10
Nevertheless, these reactions require stoichiometric reagents.
In recent years much attention was focused in such bond
formation via SN1-type reaction pathway with the aid of catalysts
such as BF3$OEt2,11a Fe(OTf)3,11b and AgOTf.11c,12 However, in
some cases, electron-rich (o-MeO–) benzyl alcohols11a or acetal
derivative11b of the corresponding alcohols are necessary to
make the reaction possible. Despite a large number of reports
for the direct catalytic allylic amination of aldehydes,13,14 the
Scheme 2 Synthesis of homoallylic azides.
related azidation still remains to be developed. Therefore, the
development of a concise and an efficient catalytic method for
the synthesis of such homoallylic azides, meeting the criteria of
atom and step economy, would be of high signicance.
Following our interest in the synthesis of homoallylic amines by
three-component reactions,14 we envisioned the catalytic one-
pot, chemoselective synthesis of the above-mentioned homo-
allylic azides, starting from aldehyde, TMS-N3, and allylsilane.
Results and discussions
Department of Chemistry, Indian Institute of Science Education and Research (IISER)
Bhopal, Indore By-pass Road, Bhouri, Bhopal, 462066, India. E-mail: pghorai@iiserb.
ac.in; Fax: +91 7554092329; Tel: +91 7556692330
† Electronic supplementary information (ESI) available: For, 1H and 13C spectra.
In our initial investigation, benzaldehyde (1a), allylsilane (2a)
and TMS-azide, with 1 : 1 : 1 molar ratios, were chosen as model
substrates. Various catalysts (10 mol%) such as Sc(OTf)3,
In(OTf)3, Cu(OTf)2, Bi(OTf)3, FeCl3 were screened for the current
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Table 2 Scope of aryl- and hetero-aryl aldehydesa
process (summarized in Table 1). These experiments indicate
that FeCl3 is the best catalyst in terms of conversion as well as
chemoselective formation of homoallylic azide (3a) over diazide
(4) and diallyl (5). However, the conversion as well as the iso-
lated yield increased when a mixture of TMS-N3 and TMS-allyl
were added over a period of 20 min (entry 8). Moreover, it is
noteworthy that iron salts have low toxicity, are naturally
abundant, cheap, and are also easy to handle.15
Entry Ar-CHO
Product
t/h
[%]b
63
Under the above-mentioned optimized reaction conditions a
wide range of aromatic and hetero-aromatic aldehydes were
investigated to examine the scope of the reaction. The results
are summarized in Table 2. In general various substituted
benzaldehydes such as p-Me-, p-Cl-, p-F-, p-MeO-, o-MeO-, p-Ph-,
p-tBu-, o-TBSO-(1b–i, respectively) reacted smoothly to provide
the corresponding homoallylic azides (3b–i, respectively) in a
highly chemoselective manner (entries 1–9). Other aromatic
aldehydes such as a-naphthaldehyde, b-naphthaldehyde, 9H-
uorene-2-carbaldehyde (1j–l, respectively) provided the corre-
sponding products 3j–l in excellent yields (entries 10–12).
Furthermore, the reactions of heteroaromatic aldehydes,
such as N-Boc-3-indole- (1m), N-Boc-2-pyrrole- (1n), 2-fural- (1o),
2-thiophene- (1p), 1-phenyl-1H-pyrazole-4-(1q) carbaldehyde
also proceeded smoothly without any complication (entries 13–
17, respectively). Even, the sensitive 4-oxo-4H-chromene-3-car-
baldehyde (1r) provided the corresponding homoallylic azide
(3r, entry 18). Interestingly, the o-phthalaldehyde (1s) in pres-
ence of excess allylsilane and TMS-N3 gave the corresponding
di-homoallylic azide (3q) in good yield (entry 19).
1
1
2
1.5
75
3
4
1
1
72
50
Other allyl source such as methallyltrimethylsilane also
provided the corresponding homoallylic azide (3t, entry 20).
Unfortunately, electron-decient aldehydes such as p-NO2
benzaldehyde (1t) did not proceed to provide the corresponding
desired product (entry 21). Even, using Fe(OTf)3 (a mixture of
FeCl3 and AgOTf) as catalyst, a successful catalyst for the
5
6
2
75
70
0.3
Table 1 Screening of catalysts
7
8
0.5
0.5
84
88
No
Catalyst
TMS-N3
Yield of 3aa (%)
1a/3a/4b [%]
1
2
3
4
5
6
7
8
Sc(OTf)3
In(OTf)3
Cu(OTf)2
Bi(OTf)3
FeCl3
Fe(acac)3
FeCl3
FeCl3
1
1
1
1
1
1
39
12
4
12
68
0
11/89/0
50/50/0
10/5/85
66/34/0
4/96/0
100/0/0
3/97/0
0/100/0
9
1
1
68
90
1.5
93
1.5c
100 (63)d
a 1H NMR yield of reaction mixture using acetophenone as internal
standard. Ratios was determined using 1H NMR of the reaction
b
c
10
mixture. A solution of TMS-allyl and TMS-N3 (1.2 : 1.0 respectively)
was added dropwise for 20 min, followed by addition of 0.5 equiv. of
d
TMS-N3. In parenthesis, the isolated yield of 3a.
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Table 2 (Contd. )
Table 2 (Contd. )
Entry Ar-CHO
Product
t/h
[%]b Entry Ar-CHO
Product
t/h
[%]b
1f
54
11
1
92
20
1a
—
21
2h/12i
0
12
1
83
a
Reaction conditions: aldehydes (1.0 mmol), TMS-allyl (1.2 equiv.) and
b
TMS-N3c(1.5 equiv.) and FeCl3 (10 mol%) in CH2Cl2 at 0 ꢁC. Isolated
yields. Decompositions observed during column chromatography.
d
TMS-allyl (2.5 equiv.) and TMS-N3 (1.5 equiv.) were used (see ESI).
e
TMS-allyl (2.4 equiv.) and TMS-N3 (3 equiv.) were used.
13
14
1
73
f
g
Methallyltrimethylsilane was used instead of TMS-allyl. Reaction
h
i
was carried out at rt. Using standard reaction conditions. The
reaction was also performed using Fe(OTf)3 (mixture of 5 mol% FeCl3
and 15 mol% AgOTf) at rt.
1.5
37c
activation of benzylic acetates,11b the situation remained the
same. Nevertheless, none of the previous reports, proceeding
via SN1-pathway, attempted on such electron-withdrawing
functionalities on the aryl ring.11,12
Further, the reaction was also developed in a relatively large
scale for aldehyde 3a (3 g scale) as described in Scheme 3.
The aliphatic aldehydes were examined (see Scheme 4). To
our disappointment, the reaction of heptaldehyde (1u) and
cyclohexaldehyde (1v) with allyl-TMS (1.2 equiv.) and TMS-N3
(1.5 equiv.) under standard reaction conditions did not provide
any corresponding homoallylic azide. Instead, a mixture of
15
16
1c
58c
77
0.6
17
18
16d,g 47
24d,g 64
Scheme 3 Large scale preparation of homoallylic azide.
68
19
0.5e
Scheme 4 Allylic azidation of aliphatic aldehydes.
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compounds containing a single diastereomer of cyclic product
6, a result of Prins-type cyclization16 of allyl-alcohol interme-
diate, an a-azido-silylated alcohol (7), and a small amount of
diazide (8) were obtained.
Eventually, the selective functionalizations of synthesized
homoallylic azides were explored for broader synthetic utility
(see Scheme 5). For example, selective aziridination and epoxi-
dation provided the corresponding 4-azido-1,2-aziridine (9) and
4-azido-1,2-epoxide (10), respectively. The azide functionality in
the synthesized homoallylic azide was reacted under ‘click’
condition with phenyl-acetylene to provide the corresponding
1,2,3-triazole (11). On the other hand, reduction of the azido
group was easily achieved to provide the corresponding primary
amine (12). Finally, the compatibility of azido-functionality in
metathesis as well as Heck-coupling conditions was tested and
interestingly, the respective products (13 and 14, respectively)
were obtained in good yields. To demonstrate the further
synthetic utility of homoallylic azides, we envisioned the
synthesis of 2-arylpyrrolidine (15) from corresponding homo-
allylic azide 3a via a simultaneous functionalization of the azide
as well as the C]C bond.
Scheme
7
Proposed mechanistic for FeCl3 catalyzed current “one-pot”
reactions.
In order to understand the mechanism of the current
process, control experiments were performed (see Scheme 6). It
revealed that the allylation of aldehyde (1a) initially provided a
mixture of silyl ether and alcohol intermediates, followed by
azidation to form the homoallylic azide 3a. However, the pre-
formed 1,1-diazide (4) did not provide the corresponding
homoallylic azide (3a) in presence of TMS-allyl under similar
reaction conditions.
Based on these observations, the mechanism of the current
process is suggested in Scheme 7. In case of aromatic and
hetero-aromatic aldehydes, the activation of the aldehyde as
well as TMS-allyl by FeCl3 to form the allylic alcohol interme-
diate I, which in the presence of TMS-N3 further deoxygenates
(via SN1 type) to form the benzylic cation II (Scheme 7). Its
trapping with azide anion provides the corresponding homo-
allylic azide (3). However, in case of aliphatic aldehydes, the
allylic alcohol intermediate (I) quickly reacts with the second
equivalent of aldehyde, probably because of its high reactivity,
to provide the acetal intermediate (III) which gives the Prins
cyclization product (6) via oxo-carbenium ion intermediate (IV).
Scheme
5
Selected functionalization of homoallylic azides. Reagents and
conditions: (i) PhI]Ns (1.5 equiv.), Cu(OTf)2 (0.1 equiv.), CH3CN, rt, 4 h; (ii) mCPBA,
CH2Cl2, rt, 6 h; (iii) PhC^CH (2.5 equiv.), CuI (20 mol%), tBuOH: 1,4-dioxane
(1 : 20), 78 ꢁC, 24 h; (iv) Ph3P (1.2 equiv.), THF : H2O (1 : 1), rt, 12 h; (v) but-2-ene-
1,4-diol (4 equiv.), Grubbs-II (5 mol%), CH2Cl2, 50 ꢁC, 24 h; (vi) PhI (1.8 equiv.),
Pd(OAc)2 (10 mol%), Bu4NBr (1.5 equiv.), LiCl (1.5 eq), K2CO3 (2 equiv.), DMF, 100
ꢁC, 12 h; (vii) Cy2B–H (3 equiv.), CH2Cl2, 0 ꢁC, rt, 4 h.
Conclusions
In summary, we have developed an efficient and mild FeCl3-
catalyzed one-pot, three-component synthesis of homoallylic
azides starting from either aromatic or hetero-aromatic alde-
hydes, TMS-allyl, and TMS-N3 with excellent chemoselectivity.
The probable mechanism for such processes have also been
provided. Finally, the selective functionalizations of homoallylic
azides have been exemplied. Further studies aimed towards
Scheme 6 Allylic alcohol/ether formation followed by azidation.
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the utilization of homoallylic azides in the synthesis of complex over a period of 30 minutes. Aer stirring for further 30 minutes
molecular architectures is our current focus.
at the same temperature, the reaction mixture was extracted
with brine solution and CH2Cl2 (3 ꢂ 180 mL). The organic layers
were combined, washed with water and dried over anhydrous
Na2SO4. The solvent was removed under vacuum and the crude
was puried by ash column chromatography (EtOAc–hexane)
Experimental section
General methods
All reagents and solvents were used as supplied commercially. on silica gel (3.57 g, 73% yield).
Analytical thin-layer chromatography (TLC) were performed on
(1-Azidobut-3-en-1-yl)benzene (3a).1a 0.109 g, 63% yield; Rf ¼
0.2 mm coated science silica gel (EM 60-F254) plates purchased 0.46 (100% n-hexane); colorless oil; IR (neat): 3315, 3081, 3032,
from Merck, Germany. Visualization was accomplished with UV 2096, 1643, 1454, 1246, 921 cmꢀ1; H NMR (400 MHz, CDCl3):
1
light (254 nm) and exposure to either ceric molybdate, ani- 7.50–7.30 (5H), 5.84–5.71 (m, 1H), 5.20–5.10 (2H), 4.56–4.48 (t,
saldehyde or KMnO4 solution followed by heating. Melting J ¼ 6.8 Hz, 1H), 2.68–2.50 (m, 2H); 13C NMR (100 MHz, CDCl3):
points are uncorrected. 1H NMR spectra were acquired on a 400 139.2, 133.7, 128.8, 128.3, 126.9, 118.2, 65.8, 40.6; HRMS (ESI,
MHz NMR spectrometer, and chemical shis are reported m/z): [M ꢀ N2 + H]+ calculated for C10H12N: 146.0970; found;
relative to the residual solvent peak. 13C NMR spectra were 146.0991.
acquired on a 100 MHz NMR spectrometer, and chemical shis
(Diazidomethyl)benzene (4).17 Rf ¼ 0.50 (100% n-hexane);
are reported in ppm relative to the residual solvent peak. Unless colorless oil; IR (neat): 3063, 3086, 2360, 2105, 1455, 1287, 1246,
noted, NMR spectra were acquired in CDCl3; individual peaks 1186, 900 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.56–7.50 (5H), 5.77
are reported as: multiplicity, integration, coupling constant in (s, 1H); 13C NMR (100 MHz, CDCl3): 134.6, 129.8, 128.9, 126.3,
Hz. All IR spectra were obtained as neat lms, and selected 78.8; HRMS (ESI, m/z): [M ꢀ 2N2 + H]+ calculated for C7H7N2,
absorbances are reported in cmꢀ1. Low resolution (LR) and 119.0609; found, 119.0624.
high-resolution (HR) mass spectrometry data were acquired
using a Q-TOF analyzer in CH3CN–H2O as solvent (unless yield; Rf ¼ 0.31 (100% n-hexane); colorless oil; IR (neat): 3317,
otherwise noted).
2981, 2923, 2360, 2096, 1642, 1515, 1436, 1248, 920, 815 cmꢀ1
1-(1-Azidobut-3-en-1-yl)-4-methylbenzene (3b). 0.140 g, 75%
;
Standard procedure for one-pot homoallylic azide synthesis. 1H NMR (400 MHz, CDCl3): 7.27–7.20 (4H), 5.85–5.70 (m, 1H),
To a stirred solution of aldehyde (1.00 mmol) and anhydrous 5.20–5.10 (2H), 4.55–4.40 (t, J ¼ 6.6 Hz, 1H), 2.68–2.47 (m, 2H),
FeCl3 (0.10 mmol, 10 mol%) in dry CH2Cl2 (2.0 mL), a solution 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): 138.1, 136.2, 133.9,
of allyltrimethylsilane (1.20 mmol) and azidotrimethylsilane 129.5, 126.9, 118.1, 65.6, 40.5, 21.2; HRMS (ESI, m/z): [M ꢀ N2 +
(1.00 mmol) in dry CH2Cl2 (0.5 mL) was added dropwise over 20 H]+ calculated for C11H14N, 160.1126; found, 160.1137.
minutes at 0 ꢁC. The solution was stirred for 30 min at the same
1-(1-Azidobut-3-en-1-yl)-4-chlorobenzene (3c). 0.149 g, 72%
temperature. Then an excess solution of azidotrimethylsilane yield; Rf ¼ 0.44 (100% n-hexane); colorless oil; IR (neat): 3320,
(0.50 mmol) was added dropwise over a period of 15 minutes. 3081, 2982, 2913, 2360, 2098, 1643, 1493, 1246, 1092, 922,
Aer stirring for given time on Table 2, the reaction mixture was 827 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.34 (d, J ¼ 8.4 Hz, 2H),
passed through a plug of silica, eluting with CH2Cl2. The solvent 7.22 (d, J ¼ 8.4 Hz, 2H), 5.80–5.60 (m, 1H), 5.18–5.00 (2H), 4.55–
was removed under vacuum and the crude was puried by ash 4.30 (t, J ¼ 7.0 Hz, 1H), 2.64–2.38 (m, 2H); 13C NMR (100 MHz,
column chromatography (EtOAc–hexane) on silica gel.
CDCl3): 137.7, 134.0, 133.2, 128.9, 128.2, 118.6, 65.0, 40.5;
Alternative procedure for one-pot homoallylic azide HRMS (ESI, m/z): [M ꢀ N2 + H]+ calculated for C10H11ClN,
synthesis (for the compounds 1o, 1q, 1r). To a stirred solution 180.0580; found: 180.0587.
of aldehyde (1.00 mmol), allyltrimethylsilane (2.50 mmol) and
1-(1-Azidobut-3-en-1-yl)-4-uorobenzene (3d). 0.096 g, 50%
azidotrimethylsilane (1.50 mmol) in dry CH2Cl2 (3.0 mL), yield; Rf ¼ 0.37 (100% n-hexane); colorless oil; IR (neat): 3318,
anhydrous FeCl3 (0.10 mmol, 10 mol%) was added carefully in 3082, 2914, 2360, 2099, 1643, 1605, 1511, 1229, 922, 835 cmꢀ1; 1H
one portion at 0 ꢁC. Aer stirring for given time on Table 2, the NMR (400 MHz, CDCl3): 7.31 (t, J ¼ 8.4 Hz, 2H), 7.09 (t, J ¼ 8.4 Hz,
reaction mixture was passed through a plug of silica, eluting 2H), 5.86–5.62 (1H), 5.22–5.06 (2H), 4.51 (t, J ¼ 6.8 Hz, 1H), 2.70–
with CH2Cl2. The solvent was removed under reduced pressure 2.45 (2H); 13C NMR (100 MHz, CDCl3): two signals: 163.7 & 161.3
(maintaining the temperature of heating bath at 25 ꢁC) and the (d, J ¼ 246 Hz), two signals: 135.05 & 135.02 (d, J ¼ 3 Hz), 133.4,
crude was puried by ash column chromatography (EtOAc– two signals: 128.67 & 128.59 (d, J ¼ 8 Hz), 118.4, two signals:
hexane) on silica gel. 115.80 & 115.59 (d, J ¼ 21 Hz), 65.0, 40.6; HRMS (ESI, m/z): [M ꢀ
Representative large scale procedure for one-pot homoallylic N2 + H]+ calculated for C10H11FN, 164.0876; found, 164.0881.
azide synthesis. To a stirred solution of benzaldehyde (3.0 g, 1-(1-Azidobut-3-en-1-yl)-4-methoxybenzene (3e). 0.153 g,
28.3 mmol, 2.88 mL, 1.00 equiv.), allyltrimethylsilane 75% yield; Rf ¼ 0.29 (2 : 98 ¼ EtOAc–n-hexane); colorless oil; IR
(1.20 equiv., 34.0 mmol, 5.43 mL) and azidotrimethylsilane (neat): 3313, 3004, 2936, 2838, 2360, 2097, 1613, 1514, 1305,
1
(1.50 equiv., 42.45 mmol, 4.25 mL) in dry CH2Cl2 (65.0 mL), 1250, 1177, 1035, 921, 831 cmꢀ1; H NMR (400 MHz, CDCl3):
ꢁ
anhydrous FeCl3 (0.10 equiv., 10 mol%) was added at ꢀ30 C. 7.22 (d, J ¼ 8.4 Hz, 2H), 6.90 (d, J ¼ 8.4 Hz, 2H), 5.82–5.58 (1H),
ꢁ
The temperature was increased to 0 C over 2 hours, the solu- 5.20–5.00 (2H), 4.43 (t, J ¼ 7.2 Hz, 1H), 3.80 (s, 3H), 2.66–2.36
tion was stirred for 30 min at the same temperature. Then an (2H); 13C NMR (100 MHz, CDCl3): 159.5, 133.9, 131.2, 128.1,
excess solution of azidotrimethylsilane (0.15 equiv., 4.24 mmol, 118.0, 114.1, 65.3, 55.2, 40.4; HRMS (ESI, m/z): [M ꢀ N2 + H]+
ꢁ
0.56 mL) was added. The temperature was increased to 25 C calculated for C11H14NO, 176.1075; found: 176.1082.
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1-(1-Azidobut-3-en-1-yl)-2-methoxybenzene (3f). 0.142 g, 70%
2-(1-Azidobut-3-en-1-yl)-9H-uorene (3l). 0.217 g, 83% yield;
yield; Rf ¼ 0.38 (2 : 98 ¼ EtOAc–n-hexane); colorless oil; IR Rf ¼ 0.35 (2 : 98 ¼ EtOAc–n-hexane); colorless solid; M.P. ¼ 30 –
(neat): 3324, 3079, 3007, 2940, 2360, 2097, 1602, 1493, 1246, 32 ꢁC; IR (neat): 3313, 3074, 3014, 2910, 2480, 2360, 2093, 1642,
1029, 920 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.40–7.20 (2H), 6.98 1426, 1247, 920 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.81 (d, J ¼ 8
(t, J ¼ 7.2 Hz, 1H), 6.90 (d, J ¼ 8.0 Hz, 1H), 5.90–5.70 (1H), 5.20– Hz, 2H), 7.58 (d, J ¼ 7.2 Hz, 1H), 7.53 (s, 1H), 7.42 (t, J ¼ 7.2 Hz,
5.05 (2H), 4.99 (t, J ¼ 7.2 Hz, 1H), 3.84 (s, 3H), 2.56 (2H); 13C 1H), 7.39–7.32 (2H), 5.89–5.75 (1H), 5.26–5.10 (2H), 4.60 (t, J ¼
NMR (100 MHz, CDCl3): 156.6, 134.3, 129.1, 127.5, 127.2, 120.7, 6.8 Hz, 1H), 3.95 (s, 2H), 2.75–2.55 (2H); 13C NMR (100 MHz,
117.7, 110.6, 59.3, 55.4, 38.9; HRMS (ESI, m/z): [M ꢀ N2 + H]+ CDCl3): 143.8, 143.4, 141.9, 141.1, 137.7, 133.8, 126.9, 126.8,
calculated for C11H14NO, 176.1075; found: 176.1070.
125.7. 125.0, 123.5, 120.05, 120.02, 118.2, 66.1, 40.7, 36.9; HRMS
4-(1-Azidobut-3-en-1-yl)-1,10-biphenyl (3g). 0.209 g, 84% (ESI, m/z): [M ꢀ N2 + H]+ calculated for C17H16N, 234.1283;
yield; Rf ¼ 0.28 (1 : 99 ¼ EtOAc–n-hexane); colorless oil; IR found: 234.1260.
(neat): 3316, 3079, 3031, 2912, 2096, 1642, 1487, 1307, 1248,
tert-Butyl-3-(1-azidobut-3-en-1-yl)-1H-indole-1-carboxylate
995 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.70–7.60 (4H), 7.52–7.36 (3m). 0.228 g, 73% yield; Rf ¼ 0.38 (2 : 98 ¼ EtOAc–n-hexane);
(5H), 5.92–5.75 (1H), 5.25–5.11 (2H), 4.57 (t, J ¼ 7.6 Hz, 1H), colorless oil; IR (neat): 3312, 2981, 2485, 2360, 2100, 1732, 1568,
2.74–2.53 (2H); 13C NMR (100 MHz, CDCl3): 141.2, 140.5, 138.2, 1455, 1373, 1084, 1020, 921 cmꢀ1; H NMR (400 MHz, CDCl3):
1
133.7, 128.8, 127.5, 127.3, 127.1, 118.3, 65.5, 40.5; HRMS (ESI, 8.35–8.05 (1H), 7.68 (d, J ¼ 7.6 Hz, 1H), 7.62 (s, 1H), 7.45–7.25
m/z): [M ꢀ N2 + H]+ calculated for C16H16N, 222.1277; found: (2H), 5.96–5.25 (1H), 5.30–5.10 (2H), 4.74 (t, J ¼ 7.2 Hz, 1H),
222.1261.
2.82–2.72 (2H), 1.71 (s, 9H); 13C NMR (100 MHz, CDCl3): 149.5,
1-(1-Azidobut-3-en-1-yl)-4-(tert-butyl)benzene (3h). 0.202 g, 135.7, 133.8, 128.4, 124.9, 123.7, 122.8, 119.5, 118.6, 118.3,
88% yield; Rf ¼ 0.48 (1 : 99 ¼ EtOAc–n-hexane); colorless oil; IR 115.5, 84.1, 58.6, 38.7, 28.2; HRMS (ESI, m/z): [M ꢀ N2 + H]+
(neat): 3315, 3080, 2965, 2906, 2097, 1643, 1508, 1364, 1248, calculated for C17H21N2O2, 285.1603; found: 285.1600.
1109, 995 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.43 (d, J ¼ 8.0 Hz,
tert-Butyl-2-(1-azidobut-3-en-1-yl)-1H-pyrrole-1-carboxylate
2H), 7.27 (d, J ¼ 8.0 Hz, 2H), 5.89–5.71 (1H), 5.26–5.08 (2H), 4.49 (3n). Following the standard procedure for one pot homoallylic
(t, J ¼ 6.8 Hz, 1H), 2.70–2.45 (2H), 1.36 (s, 9H); 13C NMR (100 azide synthesis described above, the compound was puried by
MHz, CDCl3): 151.2, 136.2, 134.0, 126.5, 125.6, 118.0, 65.6, 40.4, ash chromatography (EtOAc–n-hexane) on neural Al2O3. 0.097
34.6, 31.3; HRMS (ESI, m/z): [M ꢀ N2 + H]+ calculated for g, 37% yield; Rf ¼ 0.29 (100% n-hexane); colorless oil; IR (neat):
C
14H20N, 202.1596; found: 202.1593.
2982, 2099, 1747, 1485, 1324, 1163, 1130, 847, 728 cmꢀ1 1H
;
(2-(1-Azidobut-3-en-1-yl)phenoxy)(tert-butyl) dimethylsilane NMR (400 MHz, CDCl3): 7.30–7.23 (1H), 6.40–6.30 (1H), 6.17 (t,
(3i). 0.206 g, 68% yield; Rf ¼ 0.52 (1 : 99 ¼ EtOAc–n-hexane); J ¼ 3.4 Hz, 1H), 5.96–5.76 (m, 1H) 5.31–5.25 (1H), 5.25–5.11
colorless oil; IR (neat): 3319, 2957, 2932, 2860, 2097, 1601, 1488, (2H), 2.80–2.48 (2H), 1.67–1.58 (9H); 13C NMR (100 MHz,
1453, 1340, 1261, 1098, 1045, 995 cmꢀ1 1H NMR (400 MHz, CDCl3): 149.1, 134.1, 132.6, 122.6, 118.0, 112.5, 110.1, 84.4, 57.7,
;
CDCl3): 7.36 (dd, J ¼ 2 & 8 Hz, 1H), 7.20 (ddd, J ¼ 1.6, 7.2 & 38.4, 27.9; HRMS (ESI, m/z): [M ꢀ N2 + H]+ calculated for
9.2 Hz, 1H), 7.02 (dt, J ¼ 1.2 & 7.6 Hz, 1H), 6.86 (dd, J ¼ 1.2 &
8 Hz, 1H), 5.90–5.74 (1H), 5.25–5.06 (2H), 5.02 (t, J ¼ 7.2 Hz, 1H),
C
13H19N2O2, 235.1447; found: 235.1447.
2-(1-Azidobut-3-en-1-yl)furan (3o).1a Following the standard
2.54 (t, J ¼ 6.8 Hz, 2H), 1.05 (s, 9H), 0.30 (s, 6H); 13C NMR procedure for one pot homoallylic azide synthesis described
(100 MHz, CDCl3): 152.7, 134.1, 127.3, 121.3, 118.4, 117.8, 59.3, above, the reaction mixture was passed two times through a
39.5, 25.8, 18.3, ꢀ4.0, ꢀ4.2; HRMS (APCI, m/z): [M ꢀ N2 + H]+ plug of silica, eluting with CH2Cl2 to remove iron catalyst
calculated for C16H26NOSi, 276.1784; found: 276.1794.
completely from the reaction mixture before making silica
1-(1-Azidobut-3-en-1-yl)naphthalene (3j). 0.201 g, 90% yield; slurry for ash column chromatography on silica gel. 0.095 g,
Rf ¼ 0.36 (100% n-hexane); colorless oil; IR (neat): 3316, 3065, 58% yield; Rf ¼ 0.54 (100% n-hexane); colorless oil; IR (neat):
1
2920, 2360, 2099, 1642, 1598, 1511, 1325, 1258, 994 cmꢀ1; H 2105, 1317, 1247, 1013, 924, 742, 597 cmꢀ1; 1H NMR (400 MHz,
NMR (400 MHz, CDCl3): 8.12 (d, J ¼ 8.4 Hz, 1H), 7.93 (d, J ¼ CDCl3): 7.45–7.36 (d, 1H), 6.42–6.25 (m, 2H), 5.84–5.68 (m, 1H),
8.4 Hz, 1H), 7.87 (d, J ¼ 8 Hz, 1H), 7.66–7.46 (4H), 5.97–5.83 5.24–5.00 (2H), 4.45 (t, J ¼ 7.3 Hz, 1H), 2.71–2.55 (2H); 13C NMR
(1H), 5.304 (t, J ¼ 7.2 Hz, 1H), 5.26–5.12 (2H), 2.79 (2H); 13C (100 MHz, CDCl3): 151.9, 142.8, 133.2, 118.4, 110.2, 107.9, 58.4,
NMR (100 MHz, CDCl3): 134.7, 134.0, 130.6, 129.1, 128.8, 126.5, 37.0; HRMS (ESI, m/z): [M ꢀ N2 + H]+ calculated for C8H10NO,
125.8, 125.3, 124.4, 122.9, 118.2, 62.3, 39.8; HRMS (ESI, m/z): 136.0762; found: 136.0762.
[M ꢀ N2 + H]+ calculated for C14H14N, 196.1126; found: 196.1133.
2-(1-Azidobut-3-en-1-yl)thiophene (3p). 0.138 g, 77% yield; Rf
2-(1-Azidobut-3-en-1-yl)naphthalene (3k). 0.205 g, 92% yield; ¼ 0.56 (100% n-hexane); colorless oil; IR (neat): 3080, 2101,
Rf ¼ 0.46 (2 : 98 ¼ EtOAc–n-hexane); colorless oil; IR (neat): 1644, 1436, 1307, 1245, 923, 704 cmꢀ1
;
1H NMR (400 MHz,
3319, 3059, 2911, 2360, 2098, 1642, 1508, 1315, 1249, 994 cmꢀ1
;
CDCl3): 7.35–7.25 (dd, 1H), 7.08–6.95 (m, 2H), 5.88–5.69 (m,
1H NMR (400 MHz, CDCl3): 7.98–7.86 (3H), 7.80 (d, J ¼ 0.8 Hz, 1H), 5.25–5.05 (2H), 4.72 (t, J ¼ 7.2 Hz, 1H), 2.71–2.55 (2H); 13
C
1H), 7.60–7.40 (3H), 5.91–5.71 (1H), 5.25–5.10 (2H), 4.70 (t, J ¼ NMR (100 MHz, CDCl3): 142.1, 133.3, 126.8, 125.7, 125.6, 118.6,
6.8 Hz, 1H), 2.82–2.58 (2H); 13C NMR (100 MHz, CDCl3): 136.6, 61.0, 40.8; HRMS (ESI, m/z): [M ꢀ N2 + H]+ calculated for
133.7, 133.2, 133.1, 128.8, 128.0, 127.7, 126.4, 126.3, 126.2, C8H10NS, 152.0534; found: 152.0539.
124.4, 118.3, 66.0, 40.5; HRMS (ESI, m/z): [M ꢀ N2 + H]+ calcu-
4-(1-Azidobut-3-en-1-yl)-1-phenyl-1H-pyrazole (3q). 0.112 g,
47% yield; Rf ¼ 0.33 (5 : 95 ¼ EtOAc–n-hexane); colorless oil; IR
lated for C14H14N, 196.1126; found: 196.1131.
23162 | RSC Adv., 2013, 3, 23157–23165
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(neat): 3080, 2100, 1600, 1505, 1403, 1247, 955, 923, 757, 690 cmꢀ1
RSC Advances
;
M.P. 69–71; IR (neat): 2924, 2852, 1449, 1315, 1148, 1069,
1H NMR (400 MHz, CDCl3): 7.92–7.87 (s,1H), 7.71–7.62 (3H), 889 cmꢀ1; 1H NMR (400 MHz, CDCl3): 4.0 (m, 1H), 3.01–2.90 (m,
7.49–7.40 (2H), 7.33–7.23 (1H), 5.88–5.74 (1H), 5.23–5.06 (2H), 2H), 2.22–1.90 (dd, J ¼ 12.6 Hz, 4H), 1.85–0.85 (m, 22H); 13C
4.54 (t, J ¼ 7.0 Hz, 1H), 2.70–2.52 (2H); 13C NMR (100 MHz, NMR (100 MHz, CDCl3): 81.0, 57.6, 42.9, 40.0, 29.0, 28.8, 26.5;
CDCl3): 139.9, 139.4, 133.5, 129.5, 126.8, 125.1, 121.9, 119.2, LRMS (EI, m/z): 248.2 [M ꢀ HCl], 201.1 [M-cyclohexyl], 183.1,
118.6, 57.2, 39.9; HRMS (ESI, m/z): [M ꢀ N2 + H]+ calculated for 165.1, 147.1, 81.1, 55.1.
C
13H14N3, 212.1188; found: 212.1188.
3-(1-Azidobut-3-en-1-yl)-4H-chromen-4-one (3r). 0.154 g, 30% (100% n-hexane); colorless oil; IR (neat): 3320, 2931, 2856, 2103,
(Azido(cyclohexyl)methoxy)trimethylsilane (7b). Rf ¼ 0.53
yield; Rf ¼ 0.39 (100% n-hexane); yellow oil; IR (neat): 3076, 1451, 1252, 1113, 844 cmꢀ1; H NMR (400 MHz, CDCl3): 4.47–
2356, 1640, 1478, 1147, 1005, 757, 702 cmꢀ1; 1H NMR (400 MHz, 4.46 (d, J ¼ 4.3 Hz, 1H), 1.90–0.90 (m, 11H), 0.21 (s, 9H); 13C
CDCl3): 7.88 (s, 1H), 7.86–7.80 (dd, J ¼ 1.6 Hz, 7.8 Hz, 1H), 7.48– NMR (100 MHz, CDCl3): 89.9, 44.6, 27.93, 27.89, 26.2, 25.70,
7.39 (m, 1H), 7.07–6.98 (m, 1H), 6.95–6.88 (d, J ¼ 8.3 Hz, 1H), 25.66, 0.13; HRMS (APCI, m/z): [M ꢀ N2 + H]+ calculated for
1
5.90–5.70 (1H), 5.17–5.04 (2H), 5.03–4.95 (t, J ¼ 6.7 Hz, 1H),
C
10H22NOSi, 200.1471; found: 200.1445.
(Diazidomethyl)cyclohexane (8b). Rf ¼ 0.63 (100% n-hexane);
2.70–2.38 (2H); 13C NMR (100 MHz, CDCl3): 180.5, 171.8, 158.2,
135.7, 132.5, 126.3, 121.7, 119.8, 119.0, 118.0, 108.4, 75.5, 39.7; colorless oil; IR (neat): 3310, 2932, 2857, 2360, 2102, 1452, 1322,
HRMS (ESI, positive, CH3COONH4, m/z): [M ꢀ HN3 + H]+ 1242, 949 cmꢀ1; 1H NMR (400 MHz, CDCl3): 4.44 (d, J ¼ 7.2 Hz,
calculated for C13H11O2, 199.0759; found: 199.0760.
1H), 1.95–1.75 (4H), 1.74–1.66 (1H), 1.64–1.52 (1H), 1.34–0.98
1,2-Bis(1-azidobut-3-en-1-yl)benzene (3s). 0.182 g, 68% yield; (5H); 13C NMR (100 MHz, CDCl3): 82.7, 42.4, 28.3, 25.9, 25.4;
Rf ¼ 0.27 (2 : 98 ¼ EtOAc–n-hexane); colorless oil; IR (neat): HRMS (APCI, m/z): [M ꢀ N2 + H]+ calculated for C7H13N4,
3316, 3076, 2902, 2360, 2105, 1641, 1430, 1349, 1228, 1045, 997, 153.1140; found: 153.1149.
916 cmꢀ1; H NMR (400 MHz, CDCl3): 7.28 (bs, 2H), 7.21 (bs,
Synthesis of 2-(2-azido-2-phenylethyl)-1-((4-nitrophenyl)-
1
2H), 6.02–5.74 (2H), 5.35 (bs, 2H), 5.25–5.00 (4H), 2.75–2.45 sulfonyl)aziridine (9). To a stirring solution of 3a (0.5 mmol,
(4H); 13C NMR (100 MHz, CDCl3): 141.8, 134.0, 127.4, 121.3, 1.0 equiv.) and N-(p-nosylsulfonyl)imino]phenyliodinane
117.6, 82.3, 40.9; HRMS (ESI, m/z): [M ꢀ 2(N2 + 2H)]+ calculated (0.75 mmol, 1.5 equiv.) in CH3CN (2.0 mL), Cu(OTf)2 (0.05 mmol,
for C14H20N2, 216.1626; found: 216.1382.
10 mol%) was added and stirred at ambient temperature. Aer
(1-Azido-3-methylbut-3-en-1-yl)benzene (3t). 0.101 g, 54% 4 hours of reaction time the crude reaction mixture was passed
yield; Rf ¼ 0.47 (1 : 99 ¼ EtOAc–n-hexane); colorless oil; IR through a plug of silica, eluted with dichloromethane. The
(neat): 3318, 3078, 3032, 2920, 2098, 1651, 1455, 1247, 895 cmꢀ1
;
solvent was removed under vacuum and the crude was puried
1H NMR (400 MHz, CDCl3): 7.50–7.30 (5H), 4.89 (s, 1H), 4.82 (s, by ash column chromatography (6% to 12% EtOAc–n-hexane)
1H), 4.62 (t, J ¼ 6.4 Hz, 1H), 2.70–2.38 (2H), 1.78 (3H); 13C NMR on silica gel.
(100 MHz, CDCl3): 141.2, 139.5, 128.7, 128.2, 126.8, 113.9, 64.4,
0.064 g, 34% yield; dr ¼ 1 : 1; Rf ¼ 0.33 (20 : 80 ¼ EtOAc–n-
44.3, 22.4; HRMS (ESI, m/z): [M ꢀ N2 + H]+ calculated for hexane); colorless oil; IR (neat): 3106, 2926, 2102, 1607, 1532,
C
11H14N, 160.1126; found: 160.1138.
1350, 1310, 1237, 1166, 1091, 930 cmꢀ1 1H NMR (400 MHz,
;
All cis-4-chloro-2,6-dihexyltetrahydro-2H-pyran (6a).16b 0.075 CDCl3): 8.50–8.10 (m, 4H), 7.50–7.20 (m, 5H), 4.62–4.53 (t, J ¼
g, 49% yield; Rf ¼ 0.38 (100% n-hexane); colorless solid; M.P. 7.2 Hz, 0.48H), 4.43–4.35 (dd, J ¼ 3.6, 10.2 Hz, 0.52H), 3.18–3.08
38–40 ꢁC; IR (neat): 2927, 2848, 1467, 1449, 1274, 1072, 921 (m, 0.51H), 2.91–2.77 (m, 0.49H), 2.91–2.77 (d, J ¼ 7.0 Hz,
cmꢀ1; 1H NMR (400 MHz, CDCl3): 4.0 (tt, J ¼ 4.5, 11.8, 23.5 Hz, 0.50H), 2.70–2.63 (d, J ¼ 7.0 Hz, 0.50H), 2.25–2.19 (d, J ¼ 4.6 Hz,
1H), 3.22 (m, 2H), 2.15–2.03 (dd, J ¼ 4.4, 12.4 Hz, 2H), 1.60–1.18 0.52H), 2.18–2.14 (d, J ¼ 4.6 Hz, 0.48H), 2.14–1.60 (m, 2H); 13C
(m, 22H), 0.94–0.76 (t, J ¼ 6.7 Hz, 6H); 13C NMR (100 MHz, NMR (100 MHz, CDCl3): 150.8, 150.7, 143.68, 143.66, 138.3,
CDCl3): 76.7, 56.3, 42.7, 35.9, 31.8, 29.2, 25.5, 22.6, 14.1; LRMS 137.8, 129.5, 129.4, 129.1, 129.0, 128.8, 127.1, 126.6, 124.30,
(EI, m/z): 252.2 [M ꢀ HCl], 203.1 [M-hexyl], 149.1, 83.1, 55.1.
124.29, 64.2, 63.7, 38.4, 38.2, 37.9, 37.7, 34.7, 34.2; HRMS (ESI,
((1-Azidoheptyl)oxy)trimethylsilane (7a). Rf ¼ 0.52 (100% n- m/z): [M ꢀ N2 + H]+ calculated for C16H16N3O4S, 346.0862;
hexane); colorless oil; IR (neat): 2930, 2106, 1458, 1253, 1101, found: 346.0858.
1
845 cmꢀ1; H NMR (400 MHz, CDCl3): 4.70 (t, J ¼ 5.8 Hz, 1H),
Synthesis of 2-(2-azido-2-phenylethyl)oxirane (10). mCPBA
1.71–1.59 (m, 2H), 1.40–1.22 (m, 8H), 0.90–0.84 (t, J ¼ 7 Hz, 3H), (0.65 mmol, 1.3 equiv.) was added at ambient temperature to a
0.17 (s, 9H); 13C NMR (100 MHz, CDCl3): 86.2, 37.3, 31.7, 28.8, solution of 3a (0.5 mmol, 1 equiv.) in CH2Cl2 (2.0 mL). Aer 6
24.6, 22.5, 14.0, 0.1; HRMS (APCI, m/z): [M ꢀ N2 + H]+ calculated hours of reaction time the crude reaction mixture was extracted
for C10H24NOSi, 202.1627; found: 202.1628.
with NaHCO3 and CH2Cl2. The organic layer was separated and
1,1-Diazidoheptane (8a). Rf ¼ 0.65 (100% n-hexane); color- dried over anhydrous Na2SO4. The solvent was removed under
less oil; IR (neat): 3309, 2931, 2861, 2100, 1467, 1237, 1208, 921 vacuum and the crude was puried by ash column chroma-
cmꢀ1; 1H NMR (400 MHz, CDCl3): 4.62 (t, J ¼ 6.8 Hz, 1H), 1.79– tography (2% EtOAc–hexane) on silica gel.
1.67 (2H), 1.55–1.20 (8H), 0.91 (t, J ¼ 6.8 Hz, 3H); 13C NMR
0.079 g, 83% yield; dr ¼ 1 : 1; Rf ¼ 0.43 (10 : 90 ¼ EtOAc–n-
(100 MHz, CDCl3): 78.1, 33.9, 31.5, 28.5, 24.8, 22.4, 13.9; HRMS hexane); colorless oil; IR (neat): 3323, 3033, 2998, 2924, 2360,
(APCI, m/z): [M ꢀ N2 + H]+ calculated for C7H15N4, 155.1297; 2098, 1455, 1246, 913 cmꢀ1; H NMR (400 MHz, CDCl3): 7.54–
1
found: 155.1300.
7.30 (5H), 4.74 (d, J ¼ 9.6 Hz, 0.5H), 4.69 (t, J ¼ 7.2 Hz, 0.5H),
All cis-4-chloro-2,6-dicyclohexyltetrahydro-2H-pyran (6b).16c 3.12 (s, 0.5H), 2.85 (s, 1H), 2.75 (s, 0.5H), 2.53 (d, J ¼ 12.4 Hz,
0.060 g, 42% yield; Rf ¼ 0.44 (100% n-hexane); colorless solid; 1H), 2.22–1.96 (1.5H), 1.88–1.72 (0.5H); 13C NMR (100 MHz,
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CDCl3): 139.1, 138.6, 128.98, 128.95, 128.6, 128.5, 126.9, 126.7, (d, J ¼ 5.2 Hz, 2H), 2.75–2.40 (2H), 1.44 (bs, 1H); 13C NMR (100
63.8, 63.7, 49.4, 49.2, 47.5, 46.9, 39.7, 39.2; HRMS (ESI, m/z): MHz, CDCl3): 139.1, 132.8, 128.8, 128.3, 127.3, 126.8, 65.8, 63.3,
[M ꢀ N2 + H]+ calculated for C10H12NO, 162.0919; found: 39.1; HRMS (ESI, m/z): [M ꢀ N2 + H]+ calculated for C11H14NO,
162.0922.
4-Phenyl-1-(1-phenylbut-3-en-1-yl)-1H-1,2,3-triazole (11). To
176.1075; found: 176.1081.
(E)-(4-Azidobut-1-ene-1,4-diyl)dibenzene (14). To a solution
a solution of 3a (0.5 mmol, 1.0 equiv.) in 1,4-dioxane : tBuOH of 3a (0.5 mmol, 1.0 equiv.) in dry DMF, iodobenzene (0.9 mmol,
(20 : 1), phenylacetylene (1.25 mmol, 2.5 equiv.) and CuI 1.8 equiv.), tetrabutylammoniumbromide (0.75 mmol, 1.5
(0.1 mmol, 20 mol%) were added and heated at 78 ꢁC. Aer equiv.), LiCl (0.75 mmol, 1.0 equiv.), K2CO3 (1 mmol, 2.0 equiv.)
being stirred for 24 hours, the reaction mixture was passed were added followed by addition of Pd(OAc)2 (0.05 mmol, 10
through a plug of silica, eluted with CH2Cl2. The solvent was mol%). The reaction mixture was heated at 100 ꢁC. Aer stirring
removed under reduced pressure and the residue was puried for 12 hours, the reaction mixture was quenched with saturated
by ash column chromatography (5% to 10% EtOAc–hexane) on aq. NH4Cl solution and extracted 4 times with EtOAc. The
silica gel to get the desired product.
organic layers were combined, washed with water and dried
0.044 g, 32% yield; Rf ¼ 0.41 (15 : 85 ¼ EtOAc–n-hexane); over anhydrous Na2SO4. The solvent was removed under
ꢁ
colorless solid; M.P. ¼ 99–101 C; IR (neat): 3082, 2919, 2358, reduced pressure and the residue was puried by column
1
1456, 1227, 1077, 923 cmꢀ1; H NMR (400 MHz, CDCl3): 7.88– chromatography (0.2% to 0.5% EtOAc–n-hexane) to get the
7.79 (2H), 7.71 (s, 1H), 7.50–7.25 (8H), 5.85–5.65 (2H), 5.25–4.95 desired product.
(2H), 3.40–3.00 (2H); 13C NMR (100 MHz, CDCl3): 147.6, 138.4,
0.071 g, 57% yield; E/Z > 99 : 1; Rf ¼ 0.30 (100% n-hexane);
132.8, 130.6, 128.7, 128.6, 128.1, 127.0, 125.6, 118.9, 118.7, 64.9, colorless oil; IR (neat): 3318, 3029, 2927, 2096, 1599, 1493, 1453,
39.4; HRMS (ESI, m/z): [M + H]+ calculated for C18H18N3, 1243, 965 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.55–7.15 (10H), 6.50
276.1501; found: 276.1509.
(d, J ¼ 16 Hz, 1H), 6.25–6.05 (1H), 4.60 (s, 1H), 2.85–2.60 (2H); 13
C
1-Phenylbut-3-en-1-amine (12).18 To a stirred solution of 3a NMR (100 MHz, CDCl3): 139.2, 137.1, 133.3, 128.8, 128.5, 128.3,
(0.5 mmol, 1.0 equiv.) in 1 : 1 (THF : H2O), PPh3 (0.75 mmol, 127.4, 126.9, 126.2, 125.2, 66.2, 39.9; HRMS (ESI, m/z): [M ꢀ N2 +
1.5 equiv.) was added at ambient temperature. Aer stirring for H]+ calculated for C16H16N, 222.1283; found: 222.1288.
12 hours, the reaction mixture was extracted with CHCl3
2-Phenylpyrrolidine (15). To a suspension of (6 mmol, 3
(3 times). The combined organic layer was dried over anhydrous equiv.) of dicyclohexylborane in 7.0 mL of CH2Cl2 was added a
Na2SO4 and solvent was removed under reduced pressure. The 0 ꢁC solution of azido olen (3a) (2.0 mmol, 1 equiv.) in 3.5 mL of
residue was puried by ash column chromatography (25% to CH2Cl2. The cooling bath was removed and the reaction mixture
35% EtOAc–n-hexane) on silica gel to get the desired product was stirred for 4 h at room temperature. The resultant solution
1
(0.063 g, 85% yield; >95% pure by H NMR).
was partitioned between 35 mL of CH2Cl2 and 35 mL of 1 (N)
Further, the same reaction was worked up without column aqueous HCl. The aqueous phase was concentrated to give a
chromatography: The above reaction mixture was treated with 1 N white solid. The solid was treated with 6 (M) KOH to bring it to pH
HCl to reach pH 1, followed by extraction with Et2O (3 ꢂ 10 mL). 10. The aqueous phase was extracted with CH2Cl2 (3 ꢂ 30 mL).
The organic layer was discarded. The aqueous layer was further The organic part was dried over anh. Na2SO4. The solvent was
basied to pH 10 using 6 N KOH solution. Thereaer, aqueous removed under reduced pressure to give the pure desired product.
layer was extracted with CH2Cl2 (3 ꢂ 10 mL). The organic layer
0.211 g, 72% yield; Rf ¼ 0.26 (60% MeOH in EtOAc); colorless
was dried over sodium carbonate, ltered, and removed by rotary oil; IR (neat): 3336 (br), 3028, 2963, 1394, 1210, 903, 755, 700
evaporator to provide analytical pure amine (90% yield).
cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.50–7.00 (5H), 4.10 (t, J ¼ 7.7
Rf ¼ 0.18 (100% EtOAc); colorless oil; IR (neat): 3371, 3076, Hz, 1H), 3.25–3.10 (1H), 3.10–2.90 (1H), 2.28 (s, br, 1H), 2.22–
3028, 2925, 2854, 2360, 1640, 1603, 1493, 1453, 998, 916 cmꢀ1
;
2.10 (1H), 2.00–1.75 (2H), 1.74–1.58 (1H); 13C NMR (100 MHz,
1H NMR (400 MHz, CDCl3): 7.46–7.18 (5H), 5.92–5.64 (1H), 5.26– CDCl3): 144.7, 128.4, 126.8, 126.6, 62.6, 47.0, 34.3, 25.6; HRMS
4.96 (2H), 4.02 (t, J ¼ 5.6 Hz, 1H), 2.59–2.25 (2H), 1.68 (bs, 2H); (ESI, m/z): [M + H]+ calculated for C10H14N, 148.1126; found:
13C NMR (100 MHz, CDCl3): 145.8, 135.4, 128.4, 126.9, 126.3, 148.1129.
117.6, 55.3, 44.2; HRMS (ESI, m/z): [M + H]+ calculated for
C
10H14N, 148.1126; found: 148.1132.
(E)-5-Azido-5-phenylpent-2-en-1-ol (13). To a solution of 3a
Acknowledgements
(0.5 mmol, 1.0 equiv.) in CH2Cl2, but-2-ene-1,4-diol (2.0 mmol, 4 We thankfully acknowledge BRNS, DAE, India for DAE Young
equiv.) was added via syringe followed by addition of Grubbs II Scientist Research Award Grant and IISER Bhopal for nancial
catalyst (0.025 mmol, 5 mol%). The reaction mixture was heated support. We are thankful to Dr Deepak Chopra, Assist. Prof.,
ꢁ
at 50 C. Aer stirring for 24 hours, the solvent was removed IISER Bhopal for his assistance. S. P. thanks the CSIR, New
under reduced pressure and the residue was directly loaded on Delhi, for a fellowship.
silica column and the product was puried by column chro-
matography (10% EtOAc–n-hexane).
Notes and references
0.054 g, 53% yield; E/Z ¼ 16 : 1; Rf ¼ 0.27 (20 : 80 ¼ EtOAc–n-
hexane); colorless oil; IR (neat): 3392, 2915, 2360, 2095, 1670,
1 (a) T. Spangenberg, B. Breit and A. Mann, Org. Lett., 2009, 11,
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1494, 1455, 1243, 1085, 972 cmꢀ1; H NMR (400 MHz, CDCl3):
7.49–7.29 (5H), 5.85–5.50 (2H), 4.51 (dd, J ¼ 6.4 & 8 Hz, 1H), 4.11
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