Indium-mediated allylation/propargylation of α-diazoketones: a facile synthesis of 1-bromo-2-alkyl- or 2-arylpent-4-en-2-ols

Article abstract of DOI:10.1016/j.tetlet.2007.07.136

α-Diazoketones undergo smooth allylation with successive bromide insertion with allylindium bromide generated in situ from allyl bromide and indium metal to produce 1-bromo-2-alkyl- or 2-arylpent-4-en-2-ols in high yields. Addition of propargylindium brom

Full text of DOI:10.1016/j.tetlet.2007.07.136

Tetrahedron Letters 48 (2007) 6641–6643
Indium-mediated allylation/propargylation of a-diazoketones:
a facile synthesis of 1-bromo-2-alkyl- or 2-arylpent-4-en-2-ols
J. S. Yadav,* B. V. Subba Reddy, P. Vishnumurthy and Swapan Kr. Biswas
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 23 April 2007; revised 11 July 2007; accepted 20 July 2007
Available online 27 July 2007
Abstract—a-Diazoketones undergo smooth allylation with successive bromide insertion with allylindium bromide generated in situ
from allyl bromide and indium metal to produce 1-bromo-2-alkyl- or 2-arylpent-4-en-2-ols in high yields. Addition of propargylin-
dium bromide produces 1-bromo-2-alkyl-or 2-arylpent-4-yn-2-ols under similar conditions.
ꢀ 2007 Published by Elsevier Ltd.
a-Diazocarbonyl compounds find widespread applica-
tions in organic synthesis especially in natural product
synthesis.1 The ready availability and facile decomposi-
tion of a-diazocarbonyl compounds under thermal, pho-
tochemical, acid, base and transition metal catalysis
conditions make them useful intermediates in organic
synthesis.2 Since the successful introduction of magne-
sium metal in Grignard reactions for carbon–carbon
bond formation, the utilization of other metals of the
periodic system for organic synthesis has received wide-
spread attention and one of the recent additions is in-
dium. Indium has emerged as a metal of high potential
in organic synthesis because it possesses certain unique
properties. Indium metal is unaffected by air or oxygen
at ambient temperatures and can be handled safely with-
out any apparent toxicity. In addition, indium exhibits
low heterophilicity in organic reactions and thus
oxygen- and nitrogen-containing functional groups are
usually well tolerated by organoindium reagents.3 More-
over, indium-assisted reactions display low nucleophilic-
ity thus permitting chemoselective transformations of
groups of similar reactivity.4 However, there have been
no reports on the allylation of a-diazoketones using ally-
lindium/propargylindium bromide.
In this report, we describe a novel and efficient protocol
for the allylation/propargylation of a-diazoketones
using allyl/propargyl bromide and indium metal. Ini-
tially, we attempted the allylation of diazoacetophenone
(1) with allyl bromide (2) in the presence of indium
metal. The reaction proceeded smoothly in THF at
room temperature to produce 1-bromo-2-phenylpent-4-
en-2-ol 3a in 90% yield (Scheme 1).
A variety of a-diazoketones, such as p-methoxy-, p-
methyl-, p-fluoro-, o-fluoro- and p-chlorophenyl deriva-
tives, reacted efficiently with allylindium bromide to give
the corresponding 1-bromo-2-aryl-pent-4-en-2-ols in
satisfactory yields. Both aryl and alkyl substituted dia-
zoketones worked well under the reaction conditions
(Table 1). The cis-cyhalothric acid derived diazoketone
gave similar results (Table 1, entry j). In addition, the
OH
O
Indium
N2
Br
+
THF
Br
1
3a
2
Scheme 1.
Keywords: Indium metal; a-Diazoketones; Bromo-insertion; Allylation/propargylation.
*
Corresponding author. Tel.: +91 40 27193030; fax: +91 40 27160512; e-mail: yadavpub@iict.res.in
0040-4039/$ - see front matter ꢀ 2007 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2007.07.136

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J. S. Yadav et al. / Tetrahedron Letters 48 (2007) 6641–6643
Table 1. Indium-mediated allylation/propargylation of a-diazoketones
Entry
a-Diazoketone
Allylbromide/propargyl bromide
Producta
OH
Time (h)
46
Yieldb (%)
90
O
N2
a
Br
Br
OH
O
N2
b
c
51
42
82
75
Br
Br
Br
O
OH
Br
OH
Br
N2
N2
MeO
MeO
MeO
MeO
O
d
44
70
Br
O
OH
N2
e
f
Br
Br
Br
Br
Br
Br
45
48
46
47
45
46
80
72
89
87
90
79c
Br
OH
Me
Me
Me
Me
O
N2
Br
O
OH
N2
g
h
i
Br
F
F
O
NO
NO2
2 OH
N2
Br
OH
O
N2
Br
OH
Cl
Cl
Cl
Cl
O
N2
N2
j
CF3
Br
OH
Br
CF3
O
71c
90c
Cl
Cl
k
l
48
45
Br
Br
CF3
CF3
N
N
N2
OH
O
CBz
CBz
Br
a Products were characterized by NMR, IR and mass spectroscopy.
b Yield refers to pure products after column chromatography.
c Diastereomeric ratio of the crude product was 2:1 as confirmed by 1H NMR spectroscopy.
Cbz-protected L-proline derived diazoketone also under-
went smooth allylation under the present conditions
(Table 1, entry l). The method is clean and the products
were obtained in high yields with high selectivity. No
side products arising from Wolff rearrangement or car-
bene dimerization were observed under these conditions.
As solvent, THF gave the best results over acetonitrile
and dichloromethane. Activated zinc was also equally
effective for this conversion. Similarly, a-diazoketones
underwent propargylation with propargyl bromide un-
der identical conditions. For example, treatment of the
cis-cyhalothric acid derived diazoketone with propargyl
bromide in the presence of indium in THF gave the
propargylated product in 71% yield (Table 1, entry k,
Scheme 2).
In situ generated allyl/propargylindium bromide pre-
pared from 1.2 equiv of indium and 1.5 equiv of allyl/
propargyl bromide was effective for the allylation/prop-
argylation of a-diazoketones.5 Mechanistically, it is pos-

J. S. Yadav et al. / Tetrahedron Letters 48 (2007) 6641–6643
6643
OH
Br
O
Indium
Cl
Br
Cl
N2
+
THF
CF3
CF3
Scheme 2.
O
OH
OInBr
In
N2
HBr
Br
N2
+
THF
Br
1
3a
Scheme 3. A possible reaction mechanism.
2001, 42, 6385–6388; (d) Yadav, J. S.; Anjaneyulu, S.;
Moinuddin Ahmed, Md.; Subba Reddy, B. V. Tetrahedron
Lett. 2001, 42, 2557–2559; (e) Yadav, J. S.; Bandyopadh-
yay, A.; Reddy, B. V. S. Synlett 2001, 1608–1610.
sible that allylation occurs initially, followed by decom-
position of the allyl or propargyl diazo complex with
HBr to afford the quaternary bromohydrin. A tentative
reaction mechanism is shown in Scheme 3.
5. Yasuda, M.; Tsuchida, M.; Baba, A. Chem. Commun. 1998,
563–564.
The scope of this method is illustrated with respect to
various a-diazoketones and allyl/propargylindium bro-
mide and the results are presented in Table 1.6
6. General procedure: A mixture of a-diazoketone (1 mmol),
allyl bromide/propargyl bromide (1.5 mmol) and indium
metal (1.2 mmol) was stirred in THF at room temperature
for the appropriate time (Table 1). After complete conver-
sion as indicated by TLC, the reaction mixture was
quenched with aqueous saturated ammonium chloride
(10 mL) and extracted with ethyl acetate (2 · 10 mL). The
combined organic extracts were dried over anhydrous
Na2SO4, and concentrated in vacuo. The resulting product
was purified by column chromatography on silica gel
(Merck, 100–200 mesh, ethyl acetate–hexane) to afford the
pure product. Products 3a, 3c, 3e, 3h and 3i are reported in
the literature.5 Spectral data for selected products: 1-Bromo-
2-(4-methoxyphenyl)-4-pentyn-2-ol (3d): Liquid, IR (KBr):
In conclusion, we have described an efficient protocol
for the allylation/propargylation of a-diazoketones
using allyl/propargyl bromide and indium metal. The
use of indium makes this procedure quite simple and
more convenient for scale-up. The products are poten-
tially very useful precursors for the preparation of
homoallyl epoxides, which are important building
blocks in organic synthesis.
1
m 3496, 2961, 2052, 1706, 1609, 1511, 1178, 695 cmÀ1; H
NMR (200 MHz, CDCl3): d 7.98 (d, 2H, J = 8.4 Hz), 7.25
(d, 2H, J = 8.4 Hz), 3.98 (dd, 2H, J = 3.2, 11.0 Hz), 3.91 (s,
3H), 2.68 (s, 2H), 2.48 (s, 1H), 1.76 (br, 1H); 13C NMR
(75 MHz, proton decoupled CDCl3): d 31.2, 41.8, 54.2,
74.4, 80.2, 84.7, 119.2, 126.9, 139.1, 158.8; EIMS: m/z (%):
272 (M+3), 271 (M+1), 187, 185, 152, 77, 64; CHN analysis
for C12H13BrO2, Calcd C, 53.55; H, 4.87. Found: C, 53.42;
H, 4.95. 1-Bromo-2-(4-fluorophenyl)-4-penten-2-ol (3g):
Liquid, IR (KBr): m 3569, 3019, 2952, 1640, 1452, 1354,
Acknowledgement
P.V.M. and S.K.B. thank the CSIR, New Delhi, for the
award of fellowships.
References and notes
1
1285, 1159, 865, 711 cmÀ1; H NMR (300 MHz, CDCl3): d
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7.38 (t, 2H, J = 7.5 Hz), 7.01 (t, 2H, J = 7.5 Hz), 5.72–5.61
(m, 1H), 5.09 (t, 2H, J = 9.0 Hz), 3.92 (dd, 2H, J = 3.0,
11.2 Hz), 3.81 (br, 1H), 2.65 (d, 2H, J = 7.5 Hz), 13C NMR
(75 MHz, proton decoupled CDCl3): d 43.2, 49.7, 74.5,
115.8, 119.8, 128.3, 134.9, 142.3, 162.4; LC-MSD-Trap-SL:
m/z: 282 (M+23); CHN analysis for C11H12BrFO, Calcd C,
50.98; H, 4.66. Found: C, 51.07; H, 4.61. (2S)-1-bromo-
2-(1S,3S)-3-[(E)-2-chloro-3,3,3-trifluoro-1-propenyl]-2,2-
dimethyl-cyclopropyl-4-pentyn-2-ol (3k): Liquid, IR (KBr):
1
m 3456, 2924, 1729, 1591, 1447, 1263, 767 cmÀ1; H NMR
(300 MHz, CDCl3): d 6.98 (d, 1H, J = 8.5 Hz), 3.63 (dd,
2H, J = 3.1, 11.2 Hz), 2.81 (br, 1H), 2.62 (s, 2H), 2.53 (s,
1H), 1.56 (m, 1H), 1.24 (m, 1H), 1.05 (s, 3H), 1.02 (s, 3H);
EIMS: m/z (%): 361 (M+3), 267, 265, 221, 207, 73, 55;
CHN analysis for C13H15ClBrF3O, Calcd C, 43.41; H, 4.20.
Found: C, 43.35; H, 4.28.
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