First example of molecular iodine-catalyzed allylation and alkynylation of cyclic allylic acetates

Article abstract of DOI:10.1016/j.tetlet.2004.06.116

Cyclic allylic acetates undergo smooth allylation and alkynylation with allyltrimethylsilane and alkynyl silanes in the presence of molecular iodine under mild conditions to afford the corresponding allylated and alkynylated cyclohexene derivatives in goo

Full text of DOI:10.1016/j.tetlet.2004.06.116

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6505–6507
First example of molecular iodine-catalyzed allylation and
alkynylation of cyclic allylic acetates
a
a
a
J. S. Yadav,a, B. V. S. Reddy, K. Vishweshwar Rao, K. Sarita Raj,
*
P. Purushothama Rao,a A. R. Prasada and D. Gunasekarb
aDivision of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
bDepartment of Chemistry, S.V. University, Tirupati 517502, India
Received 25 May 2004; revised 11 June 2004; accepted 18 June 2004
Available online 20 July 2004
Abstract—Cyclic allylic acetates undergo smooth allylation and alkynylation with allyltrimethylsilane and alkynyl silanes in the
presence of molecular iodine under mild conditions to afford the corresponding allylated and alkynylated cyclohexene derivatives
in good yields with high selectivity.
ꢀ 2004 Elsevier Ltd. All rights reserved.
The stereoselective addition of allylsilanes to aldehydes,
referred to as the Sakurai–Hosomi reaction has been
recognized as a particularly efficient method of car-
bon–carbon bond formation and has been extensively
applied in organic synthesis, especially in natural prod-
uct synthesis.1,2 Acid catalyzed carbon–carbon bond
forming reactions are of great significance in organic
synthesis because of their high reactivity, selectivity
and mild reaction conditions.3 Allylic acetates are well-
known carbon electrophiles capable of reacting with
various nucleophiles and their ability to undergo nucle-
ophilic substitution reactions contributes to their syn-
thetic value.4,5 However, there have been no reports
on the allylation and alkynylation of allylic acetates with
allyl/alkynyl silanes. Owing to its unique catalytic prop-
erties, iodine has been extensively used as a catalyst for a
plethora of organic transformations.6
I2
OAc
Si
+
EtOOC
CH2Cl2, r.t.
EtOOC
3a
1a
2
Scheme 1.
lane 2 in the presence of 5mol% of molecular iodine re-
sulted in the formation of ethyl 4-allyl-2-methyl-2-
cyclohexene-1-carboxylate 3a in 86% yield (Scheme 1).
Similarly, various cyclohexenyl acetates underwent
smooth allylation with allyltrimethylsilane to afford
the corresponding allylated cyclohexenyl derivatives in
high yields (Table 1, entries d, f, i and l). In all cases,
the reactions proceeded smoothly at room temperature
and were complete within 30–40min. No c-substitution
was observed (as a result of allylic rearrangement,
SN20 type substitution) under the reaction conditions.
The acetate group was simply replaced by the allylic
functionality in a SN2 manner. Further, treatment of
2-ethyl-4-ethoxycarbonyl-3-methyl-2-cyclohexenyl ace-
tate 1d with 2-[(trimethylsilyl)ethynyl]benzene 4 gave
ethyl 3-ethyl-2-methyl-4-(2-phenyl-1-ethynyl)-2-cyclo-
hexene-1-carboxylate 3j in 75% yield (Scheme 2).
In continuation of our interest on the catalytic applica-
tions of elemental iodine for various organic transfor-
mations,7 we report herein a novel and efficient
protocol for the allylation and alkynylation of cyclic al-
lylic acetates with allyl and alkynyl silanes using iodine
as the catalyst. Thus treatment of 4-ethoxycarbonyl-3-
methyl-2-cyclohexenyl acetate 1a with allyltrimethylsi-
Keywords: Allyl/alkynyl silanes; Molecular iodine; Cyclic allylic ace-
tates.
Analogous to 2-[(trimethylsilyl)ethynyl]benzene, 1-tri-
methylsilyl-1-hexyne also reacted efficiently with various
cyclic allylic acetates to give the respective alkynylated
*
Corresponding author. Tel.: +91-40-27193030; fax: +91-40-
27160512; e-mail: yadav@iict.res.in
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.06.116

6506
J.S.Yadav et al./ Tetrahedron Letters 45 (2004) 6505–6507
Table 1. Iodine-catalyzed allylation and alkynylation of cyclic allylic acetates
Entry
Allylic acetate
OAc
Producta
Time (min)
40
Yield (%)b
86
a
EtO2C
EtO2C
Ph
OAc
OAc
b
45
72
EtO2C
EtO2C
EtO2C
c
d
e
f
50
30
35
35
40
45
70
82
75
90
80
78
EtO2C
OAc
Ph
OAc
OAc
Ph
OAc
OAc
g
h
OAc
OAc
OAc
i
35
50
60
87
75
72
EtO2C
EtO2C
EtO2C
EtO2C
EtO2C
EtO2C
Ph
j
k
OAc
l
30
40
89
82
Ph
OAc
OAc
m
n
45
80
a All products were characterized by 1H NMR, IR and mass spectroscopy.
b Yield refers to the isolated pure products after column chromatography.
Ph
present in the starting materials. Simple cyclohexyl ace-
tates failed to undergo either allylation or alkynylation
under the reaction conditions. Similarly, acyclic allylic
acetates such as 3-phenyl-(E)-2-propenyl acetate and
(E)-2-butenyl acetate did not give the desired products.
This method was only successful with cyclic allylic ace-
tates. As solvent, dichloromethane appeared to give
the best results. In the absence of catalyst, the reaction
did not yield any product even after a long reaction
time. All products were characterized by 1H, 13C
NMR, IR and mass spectroscopy.
I2
OAc
Si
Ph
+
EtOOC
EtOOC
CH2Cl2, r.t.
1d
4
3j
Scheme 2.
cyclohexenyl derivatives. However, alkynylsilanes af-
forded lower yields compared to allylsilanes. This meth-
od is compatible with the ester and alkene moieties

J.S.Yadav et al./ Tetrahedron Letters 45 (2004) 6505–6507
6507
Oxford; (b) Trost, B. M. Angew.Chem., Int.Ed.Engl. 1989,
28, 1173–1180; (c) Dawson, G. J.; Williams, J. M. J.; Coote,
S. J. Tetrahedron: Asymmetry, 1995, 2535–2546, and
references therein.
Interestingly, a catalytic amount of TMSI was also
found to be equally effective for this conversion. How-
ever, the use of allyltri-n-butyltin in place of allyltri-
methylsilane did not yield any product under these
reaction conditions, perhaps because iodine does not
interact with allyltri-n-butyltin. No additives or acidic
promoters were required for the reaction to proceed.
The catalyst is readily available at low cost and is highly
efficient in promoting allylations and alkynylations. The
scope and generality of this process is illustrated with re-
spect to various allylic acetates and the results are pre-
sented in Table 1.8
6. (a) Deka, N.; Kalita, D. J.; Borah, R.; Sharma, J. C. J.Org.
Chem. 1997, 62, 1563; (b) Vaino, A. R.; Szarek, W. A.
Synlett 1995, 1157; (c) Lipshutz, B. H.; Keith, J. Tetrahe-
dron Lett. 1998, 39, 2495.
7. (a) Yadav, J. S.; Reddy, B. V. S.; Hashim, S. R. J.Chem.
Soc., Perkin Trans. 1, 2000, 3025; (b) Yadav, J. S.; Reddy,
B. V. S.; Sabitha, G.; Reddy, G. S. K. K. Synthesis, 2000,
1532; (c) Kumar, H. M. S.; Reddy, B. V. S.; Reddy, E. J.;
Yadav, J. S. Chem.Lett. 1999, 857; (d) Yadav, J. S.; Reddy,
B. V. S.; Rao, C. V.; Chand, P. K.; Prasad, A. R. Synlett
2001, 1638.
In summary, we have described a novel and efficient
protocol for the allylation and alkynylation of cyclic al-
lylic acetates using cheap and readily available elemental
iodine as catalyst. In addition to its efficiency, simplicity
and mild reaction conditions, this method provides high
yields of products with high selectivity, which makes it a
useful and attractive process for the synthesis of allylat-
ed and alkynylated cyclohexenyl acetates.
8. General procedure: To a stirred solution of the allylic
acetate (1mmol) and iodine (5mol%) in dichloromethane
(10mL), allyl- or alkynyl-trimethylsilane (2mmol) was
added slowly dropwise at 0ꢁC and the mixture allowed to
stir at room temperature for the appropriate time (Table 1).
After complete conversion as indicated by TLC, the
reaction mixture was quenched with water (15mL) and
extracted with dichloromethane (2·15mL). The combined
organic extracts were washed with a 15% solution of aq
sodium thiosulfate, 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, 1:9) to afford the pure allyl or
Acknowledgements
BVS, KVR and KSR thank CSIR, New Delhi, for the
award of fellowships.
1
alkynyl derivative (Table 1, entry 3h): H NMR (200MHz,
CDCl3): d 5.31 (d, 1H, J=3.6Hz), 2.95 (m, 1H), 2.13 (m,
4H), 1.84 (t, 2H, J=7.2Hz), 1.76 (t, 2H, J=8.0Hz), 1.64 (s,
3H), 1.44 (m, 4H), 0.96 (t, 3H, J=6.8Hz). EIMS:m/z: 176
[M+], 134, 95, 91, 43. HRMS (LSIMS): calcd for C13H20
[M+]: 176.1565, found: 176.1563. (entry 3l): IR (KBr): t
3055, 3027, 2907, 1597, 1440, 1108, 967cmꢀ1 1H NMR
(200MHz, CDCl3): d 5.76 (m, 1H), 5.38 (brs, 1H), 4.98 (dd,
2H, J=2.0, 4.2Hz), 4.67 (s, 2H), 2.35 (m, 1H), 2.18 (m, 1H),
2.02 (m, 3H), 1.87 (m, 1H), 1.71 (s, 3H), 1.69 (s, 3H), 1.42
(m, 1H). 13C NMR (50MHz, proton decoupled): 20.5, 21.6,
30.4, 35.4, 36.9, 38.6, 76.2, 108.1, 115.5, 121.7, 137.8, 149.9,
216.1. EIMS: m/z: 176 [M+], 174, 134, 107, 93, 91, 69, 54,
42. HRMS (LSIMS): calcd for C13H20 [M+]: 176.1565,
found: 176.1562. [a]25 ꢀ2.27 (c 0.55 CHCl3). (entry 3m): 1H
NMR (200MHz, CDCl3): d 7.36–7.25 (m, 5H), 5.46 (brs,
1H), 4.72 (s, 2H), 3.14 (brs, 1H), 2.49 (m, 1H), 2.32 (m, 2H),
2.15 (m, 2H), 1.78 (s, 3H) 1.85 (s, 3H). EIMS: m/z: 236
[M+], 194, 160, 119, 92, 41. HRMS (LSIMS): calcd for
C18H20 [M+]: 236.1565, found: 236.1560. [a]25 ꢀ5.5 (c 0.50
CHCl3).
References and notes
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Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: