An expedient stereoselective synthesis of (Z)- and (E)-allyl iodides from Baylis-Hillman adducts along with selective iodination of benzylic alcohols using the polymethylhydrosiloxane-iodine system

Article abstract of DOI:10.1016/j.tetlet.2007.03.050

A stereoselective method has been developed for the synthesis of (Z)- and (E)-allyl iodides from Baylis-Hillman adducts using polymethylhydrosiloxane (PMHS) and iodine in chloroform at room temperature. In addition, the reagent system has been utilized for the iodination of benzylic alcohols selectively.

Full text of DOI:10.1016/j.tetlet.2007.03.050

Tetrahedron Letters 48 (2007) 3201–3204
An expedient stereoselective synthesis of (Z)- and
E)-allyl iodides from Baylis–Hillman adducts along
with selective iodination of benzylic alcohols using
(
I
the polymethylhydrosiloxane–iodine system
a,
a
a
a
*
Biswanath Das, Harish Holla, Yallamalla Srinivas, Nikhil Chowdhury and
b
B. P. Bandgar
a
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
b
Organic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth Marathwada University,
Vishnupuri, Nanded 431 606, India
Received 20 January 2007; revised 28 February 2007; accepted 7 March 2007
Available online 12 March 2007
Abstract—A stereoselective method has been developed for the synthesis of (Z)- and (E)-allyl iodides from Baylis–Hillman adducts
using polymethylhydrosiloxane (PMHS) and iodine in chloroform at room temperature. In addition, the reagent system has been
utilized for the iodination of benzylic alcohols selectively.
Ó 2007 Elsevier Ltd. All rights reserved.
PBr33f and Lewis acids (FeCl , InCl ).
3g,h
On the other
The Baylis–Hillman reaction is widely utilized as a use-
ful carbon–carbon bond forming reaction in organic
synthesis. The Baylis–Hillman adducts, 3-hydroxy-2-
3
3
hand, methods for the preparation of allyl iodides from
1
4
Baylis–Hillman adducts are limited and most of
methylene-alkanoates (derived from acrylate esters) or
the reported methods suffer from disadvantages includ-
ing the use of strong acids, low stereoselectivity, unsatis-
factory yields for some substrates, long reaction times
and complex experimental procedures. Recently, a
method utilizing TMSCl/NaI was reported for the
preparation of (Z)-allyl iodides containing only an aryl
group.
3
-hydroxy-2-methylene-alkanenitriles (derived from
acrylonitrile) are precursors for stereoselective syntheses
1
b,2
of various multifunctional molecules.
The develop-
4
e
ment of efficient and stereoselective methods for the
preparation of substituted allyl iodides from these
adducts is highly desirable, as they are utilized for the
construction of different naturally occurring bioactive
compounds and their analogues, for example, a-alkylid-
In continuation of our work3g,4d,5a–c on the conversion
of Baylis–Hillman adducts into trisubstituted alkenes,
along with our interest in the catalytic application of
2
a
2b
ene-b-lactams,
a-methylene-c-butyrolactones
and
2
c
3
flavonoids. Different reagents have been reported
for the synthesis of allyl halides directly from Baylis–
Hillman adducts such as hydrogen halides with strong
acids (HBr–H SO , HI–H PO ),
halides (oxalyl chloride, MsCl),
5
d–f
molecular iodine,
we have discovered that treatment
of Baylis–Hillman adducts with iodine and poly-
methylhydrosiloxane (PMHS) in chloroform at room
temperature afforded the corresponding allyl iodides
in high yields and stereoselectivities, as depicted in
Scheme 1.
2
a,4a
organic acid
NCS/NBS–Me S,
2
4
3
4
a,b
3
3c,e
2
Keywords: Baylis–Hillman adduct; (Z)- and (E)-Allyl iodides; Poly-
methylhydrosiloxane (PMHS); Iodine; Benzylic iodide.
q
Part 137 in the series, ‘Studies on novel synthetic methodologies.’
Baylis–Hillman adducts possessing ester and nitrile moi-
eties underwent the conversion readily and allyl iodides
containing aryl as well as alkyl groups were obtained in
high yields (Table 1). Aryl groups substituted with elec-
tron-donating or electron-withdrawing functionalities
IICT Communication No. 070220.
*
Corresponding author. Tel./fax: +91 40 7160512; e-mail:
biswanathdas@yahoo.com
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.03.050

3202
B. Das et al. / Tetrahedron Letters 48 (2007) 3201–3204
6
OH
H
tra of the products were used to establish their struc-
tures and stereochemistry by comparison with reported
PMHS/ I2
EWG
EWG
I
4
d
R
R
data for known compounds.
CHCl , r.t.
3
20-30 min
The utility of polymethylhydrosiloxane (PMHS), a co-
product of the silicone industry, as an attractive, inert
reducing agent for environmentally benign processes is
well documented. However, to our knowledge its use
in combination with iodine for the synthesis of allyl iod-
ides has not previously been explored.
1
2
8
4-96%
R= alkyl, aryl
7
EWG= -COOMe, -CN
Scheme 1.
did not alter the rate of the reaction. Allyl iodides
containing an ester moiety were formed with (Z)-config-
uration while those possessing a nitrile moiety gave
A possible reaction mechanism is shown in Scheme 2.
Iodine may react initially with PMHS to produce tri-
methylsilyliodide and the unstable intermediate 3,
7
c
1
exclusively (E)-configured products. The H NMR spec-
which then leads to in situ formation of hydroiodic acid
a
2
Table 1. Preparation of (Z)- and (E)-allyl iodides from Baylis–Hillman adducts using PMHS/I
Entry
Adduct 1
OH
Product 2
Time (min)
30
Isolated yield (%)
96
COOCH3
I
COOCH3
a
OH
COOCH3
COOCH3
b
25
94
Cl
I
Cl
OH
COOCH CH
2
3
COOCH CH3
2
c
d
e
20
25
30
90
92
94
I
OH
COOCH3
I
COOCH3
OH
O N
COOCH3
2
O N
COOCH3
2
I
OH
COOCH3
I
f
COOCH3
5
30
87
5
OH
I
CN
g
25
25
86
88
CN
OH
I
CN
h
CN
MeO
Cl
MeO
Cl
OH
I
CN
i
j
30
30
92
84
CN
OH
I
CN
CN
a
1
The structures of the alkenes were determined from their spectral (IR, H NMR and MS) and analytical data. The allyl iodides in entries a–f were
formed with (Z)-configuration while those of entries g–j were formed with (E)-configuration.

B. Das et al. / Tetrahedron Letters 48 (2007) 3201–3204
3203
Me
Me
Si
Me
SiMe
Me
3
SiI
+
I
O
Si
H
O
Si
H
O
SiMe3
I2 + Me SiO
O
3
3
H
n-1
n
3
-
HI
Me
Si
Me
Si
O
O
SiMe
3
O
H
n-1
Me Si
I
3
H
O
H
EWG
EWG
I
+
H O
2
R
R
+
Me
3
SiI
I
H
Scheme 2.
R
R
Table 2. Conversion of primary and secondary benzylic alcohols to
a
PMHS / I 2
iodides using PMHS/I
2
OH
I
Entry Alcohol
Iodide
5
Time Isolated
(min) yield (%)
CHCl3 , r.t.
4
X
X
20-30 min
4
5
OH
I
a
20
30
96
94
X = Br, NO2, OCH3
90-96%
R = H, CH
3
Cl
Cl
Scheme 3.
b
OH
I
Cl
Cl
which might react with the Baylis–Hillman adduct to
give the corresponding allyl iodide.
OH
I
c
20
94
MeO
MeO
Encouraged by the successful results obtained with the
Baylis–Hillman adducts we further studied the effect of
the PMHS–I system on other types of alcohols. The
OH
I
2
reaction was found to be highly efficient with primary
and secondary benzylic alcohols leading to the corre-
sponding benzylic iodides in high yields (Scheme 3).
Electron-donating as well as electron-withdrawing sub-
stituents on the aromatic rings of the benzylic alcohols
did not show any significant effect on the yields of the
products.
d
e
f
25
30
25
93
92
90
O N
O N
2
2
OH
I
OH
I
The reaction was unsuccessful with aliphatic alcohols
and phenols (Table 2). Even with allylic alcohols no
monoiodinated unsaturated compounds were obtained.
Thus the present method seems to be chemoselective
towards iodination of benzylic alcohols.
Br
Br
OH
I
g
25
94
O N
O N
In conclusion, the PMHS–I system has been utilized for
2
2
2
the synthesis of both (Z)- and (E)-allyl iodides from
(continued on next page)

3
204
B. Das et al. / Tetrahedron Letters 48 (2007) 3201–3204
Banerjee, J.; Ravindranath, N. Tetrahedron 2004, 60,
Table 2 (continued)
8
1
357–8361; (e) Li, J.; Wang, X.; Zhang, Y. Synlett 2005,
039–1041.
Entry
h
Alcohol
4
Iodide
5
Time
(min)
Isolated
yield (%)
5
. (a) Das, B.; Banerjee, J.; Mahender, G.; Majhi, A. Org.
Lett. 2004, 6, 3349–3352; (b) Das, B.; Banerjee, J.; Majhi,
A.; Mahender, G. Tetrahedron Lett. 2004, 45, 9225–9227;
OH
I
30
88
—
(
c) Das, B.; Mahender, G.; Chowdhury, N.; Banerjee, J.
Synlett 2005, 1000–1002; (d) Das, B.; Banerjee, J.; Ramu,
R.; Pal, P. M.; Ravindranath, N.; Ramesh, C. Tetrahedron
Lett. 2002, 44, 5465–5468; (e) Das, B.; Reddy, K. R.;
Ramu, R.; Tirupathi, P.; Ravikanth, B. Synlett 2006, 1756–
OH
i
No reaction
No reaction
120
1
758; (f) Das, B.; Ravikanth, B.; Ramu, R.; Laxminara-
yana, K.; Vittal Rao, B. J. Mol. Catal. A: Chem. 2006, 255,
74–77.
. General procedure for the preparation of allyl iodides and
benzylic iodides: To a solution of Baylis–Hillman adduct
OH
j
120
120
—
—
6
k
3 2 7
CH –(CH ) OH No reaction
(
(
0.5 mmol) or benzylic alcohol (0.5 mmol) and PMHS
0.75 mmol) in chloroform (5 mL), iodine (0.5 mmol) was
a
The structures of the iodides were determined from their spectral (IR,
H NMR and MS) and analytical data.
1
added. The reaction was allowed to stir at room temper-
ature for 20–30 min. The reaction was monitored by TLC.
On completion of the reaction, the solvent was evaporated
under vacuum and the reaction mixture was dissolved in
hexane and passed through a silica gel column using
hexane–ethyl acetate as eluent. Evaporation of the solvent
afforded the iodinated product in pure form. Spectral and
analytical data of novel allyl iodides and benzyl iodides are
given below.
Baylis–Hillman adducts and benzylic iodides from benz-
ylic alcohols in excellent yields at room temperature.
Operational simplicity, short reaction times, high yields
and impressive stereo- and chemoselectivities are advan-
tages of this method.
Compound 2c: IR (KBr): 1709, 1606, 1509, 1462,
À1
1
1
263 cm ; H NMR (CDCl , 200 MHz): d 7.62 (1H, s),
3
Acknowledgement
7
.42 (2H, d, J = 8.0 Hz), 7.22 (2H, d, J = 8.0 Hz), 4.28
(
2H, s), 4.22 (2H, q, J = 7.0 Hz), 2.85 (1H, m), 1.33 (3H, t,
The authors thank the UGC and CSIR, New Delhi, for
financial assistance.
J = 7.0 Hz), 1.25 (6H, d, J = 7.0 Hz); EIMS: m/z 231
+
Å
(M ÀI); Anal. Calcd for C15
H19IO : C, 50.28; H, 5.28.
2
Found: C, 50.18; H, 5.31.
Compound 2h: IR (KBr): 2210, 1686, 1599, 1509, 1261,
À1
; H NMR (CDCl , 200 MHz): d 7.72 (2H, d,
3
1
1
176 cm
References and notes
J = 8.0 Hz), 7.14 (1H, s), 6.88 (2H, d, J = 8.0 Hz), 4.14 (2H,
+
Å
s), 3.82 (3H, s); EIMS: m/z 172 (M ÀI); Anal. Calcd for
10ION: C, 44.15; H, 3.34. Found: C, 44.22; H, 3.26.
Compound 2j: IR (KBr): 2225, 1634, 1460, 1163,
1
. (a) Baylis, A. B.; Hillman, M. E. D. German Patent
155113, 1972; Chem. Abstr. 1972, 77, 34174q; (b) Basava-
iah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003,
03, 811–891, and references cited therein.
. (a) Buchholz, R.; Hoffmann, H. M. R. Helv. Chim. Acta
991, 74, 1213–1220; (b) Hoffmann, H. M. R.; Rabe, J.
Angew. Chem., Int. Ed. Engl. 1985, 24, 94–110; (c) Basa-
vaiah, D.; Bakthadoss, M.; Pandiaraju, S. J. Chem. Soc,
Chem. Commun. 1998, 1639–1640.
11
C H
2
À1
1
1
114 cm
J = 7.0 Hz), 3.91 (2H, s), 2.35 (2H, q, J = 7.0 Hz), 1.62–
.47 (2H, m), 0.90 (3H, t, J = 7.0 Hz); EIMS: m/z 108
; H NMR (CDCl , 200 MHz): d 6.42 (1H, t,
3
1
2
1
(
1
+
Å
M ÀI); Anal. Calcd for C H IN: C, 35.74; H, 4.26.
7
10
Found: C, 35.62; H, 4.24.
Compound 5b: IR (KBr): 3012, 2910, 1594, 1507, 1410,
À1
1
1
7
(
(
172, 1150, 810, 718 cm ; H NMR (CDCl , 200 MHz): d
3
3
. (a) McFadden, H. G.; Harris, R. L. N.; Jenkins, C. L. D.
Aust. J. Chem. 1989, 42, 301–314; (b) Chavan, S. P.;
Ethiraj, K. S.; Kamat, S. K. Tetrahedron Lett. 1997, 38,
.32 (1H, d, J = 2.0 Hz), 7.20 (1H, dd, J = 8.0, 2.0 Hz), 7.08
1H, d, J = 8.0 Hz), 4.44 (2H, s); EIMS: m/z 160, 162, 164
+
Å
M ÀI); Anal. Calcd for C
7 5 2
H Cl I: C, 29.27; H, 1.74.
Found: C, 29.34; H, 1.78.
Compound 5g: IR (KBr): 3062, 2986, 1595, 1521, 1416,
7
415–7416; (c) Goldberg, O.; Dreiding, A. S. Helv. Chim.
Acta 1976, 59, 1904–1910; (d) Hoffmann, H. M. R.; Rabe,
J. Angew. Chem., Int. Ed. Engl. 1983, 22, 795–796; (e)
Hoffmann, H. M. R.; Rabe, J. J. Org. Chem. 1985, 50,
849–3859; (f) Semmelhack, M. F.; Wu, E. S. C. J. Am.
Chem. Soc. 1976, 98, 3384–3386; (g) Das, B.; Banerjee, J.;
Ravindranath, N.; Venkataiah, B. Tetrahedron Lett. 2004,
À1
1
1
8
212, 1112, 838, 675 cm ; H NMR (CDCl
3
, 200 MHz): d
.12 (2H, d, J = 8.0 Hz), 7.50 (2H, d, J = 8.0 Hz), 5.28 (1H,
q, J = 7.0 Hz), 2.16 (3H, d, J = 7.0 Hz); EIMS: m/z 150
3
+
Å
(
M ÀI); Anal. Calcd for C
8 8 2
H IO N: C, 34.66; H, 2.89.
Found: C, 34.58; H, 2.84.
4
5, 2425–2426; (h) Guriec, A.; Goucaud, A. New J. Chem.
7
. (a) Lawrence, N. J.; Drew, M. D.; Bushell, S. M. J. Chem.
Soc., Perkin Trans. 1 1999, 3381–3391; (b) Chandrasekhar,
S.; Chandrasekhar, G.; Reddy, M. S.; Srihari, P. Org.
Biomol. Chem. 2006, 4, 1650–1652; (c) Yadav, J. S.; Subba
Reddy, B. V.; Premalatha, K.; Swamy, T. Tetrahedron Lett.
1991, 15, 943.
4
. (a) Ameer, F.; Drewes, S. E.; Houston-McMillan, M. S.;
Kaye, P. T. J. Chem. Soc., Perkin Trans. 1 1985, 1143–1145;
b) Yadav, J. S.; Reddy, B. V. S.; Madan, C. New J. Chem.
001, 25, 1114–1117; (c) Li, J.; Xu, H.; Zhang, Y.
Tetrahedron Lett. 2005, 46, 1931–1934; (d) Das, B.;
(
2
2
005, 46, 2687–2690.