Direct and highly efficient synthesis of (Z)-allyl iodides from Baylis-Hillman adducts promoted by TMSCl/NaI system

Article abstract of DOI:10.1055/s-2005-863750

Direct and efficient transformation of Baylis-Hillman adducts into corresponding (Z)-allyl iodides has been achieved by treatment with TMSCl/NaI in THF at room temperature. The readily available reagents, mild conditions together with its generality make

Full text of DOI:10.1055/s-2005-863750

1039
LETTER
Direct and Highly Efficient Synthesis of (Z)-Allyl Iodides from Baylis–Hillman
Adducts Promoted by TMSCl/NaI System
Synthesis
i
of
(
Z
)
-A
a
llylIodide
n
s
fromBaylis–Hill
L
m
an
A
dducts i,a Xiaoxia Wang,b Yongmin Zhang*a,c
a
Department of Chemistry, Zhejiang University, Xi-xi Campus, Hangzhou, 310028, P. R. China
Fax +86(571)88807077; E-mail: yminzhang@mail.hz.zj.cn
b
c
College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua, Zhejiang, 321004, P. R. China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai, 200032, P. R. China
Received 12 January 2005
interest in the Baylis–Hillman reaction,9 herein we wish to
report that TMSCl in the presence of NaI can efficiently
promote the conversion of Baylis–Hillman adducts 1 into
the corresponding (Z)-allylic iodides 2 in THF at room
temperature (Scheme 1).
Abstract: Direct and efficient transformation of Baylis–Hillman
adducts into corresponding (Z)-allyl iodides has been achieved by
treatment with TMSCl/NaI in THF at room temperature. The readi-
ly available reagents, mild conditions together with its generality
make this procedure quite attractive.
Key words: Baylis–Hillman adduct, (Z)-allyl iodide, TMSCl/NaI
OR1
TMSCl/NaI
THF, r.t.
COOR
I
COOR
Ar
The Baylis–Hillman reaction is well known as one of the
powerful carbon-carbon bond-forming methods in organ-
ic synthesis.1 The adducts of the reactions, 3-hydroxy-2-
methylene-alkanoates (derived from acrylate esters), have
been utilized as important precursors for stereoselective
synthesis of different multifunctional molecules.2 Among
these transformations, the preparation of 2-(halometh-
yl)alk-2-enoates from Baylis–Hillman adducts has drawn
much attention as these compounds are usually employed
in the synthesis of various naturally occurring bioactive
compounds and their analogs such as a-methylene-g-
butyrolactone, a-alkylidene-b-lactam and flavanoid.3 Ac-
cordingly, synthesizing the corresponding allyl chlorides
and allyl bromides from Baylis–Hillman adducts are ex-
tensively studied and a variety of reagents including HBr/
H2SO4,3b NBS/Me2S,4a PBr3,4b CuBr2/silica gel,4c MsCl/
Et3N 5 have been developed. Toward this conversion, the
acetates of Baylis–Hillman adducts have also proved to be
applicable promoted by MgBr2 and AlCl3.6 However, the
preparation of corresponding allylic iodide analogs were
rarely investigated, which limited their application in or-
ganic synthesis to much extent. Moreover, the traditional
synthetic method obviously suffers from the use of strong
acid (HI/H3PO4) and long reaction time (4 d).7 Recently, a
new approach to allylic iodides has been achieved via the
aid of microwave.8 Although this procedure is attractive
in terms of the environmental compatibility and nontoxic-
ity, this method requires high temperature and clay, which
is not readily available. In addition, behavior of this ap-
proach was unsatisfactory under conventional reaction
conditions. As a result, to develop an alternative synthetic
method with more accessible reagents and operational/ex-
perimental simplicity is needed. As a continuation of our
Ar
1
2
Scheme 1
As shown by Scheme 1 and Table 1, blending of the
Baylis–Hillman adducts 1 with TMSCl in the presence of
NaI in THF at room temperature essentially afforded the
allyl iodides 2 in moderate to excellent yields. A variety
of substrates were used in this reaction to establish the
generality and efficiency, and most reactions proceeded
smoothly under the similar conditions. The experimental
results showed that the present method was effective for
substrates bearing either electron-donating or electron-
withdrawing groups, though reactions with the latter pro-
ceeded relatively slowly and afforded lower yields. In
fact, substrates with strong electron-withdrawing groups
(such as nitro group) attached to the aromatic rings result-
ed in poorer results (entry 10 and 12, Table 1). In such
cases, elevating temperature and prolonging reaction time
did not make improvement and products 2 were obtained
in lower yield and even no reaction occurred. When sub-
stitution of the OH group with OAc,10 a better leaving
group, the iodinization reaction proceeded smoothly and
the yields were dramatically improved (entry 11 and entry
13, Table 1). Besides of good yields, this process also
exhibits excellent stereoselectivity. The Z-stereoconfigu-
ration of the product was assigned by comparing the
chemical shifts in 1H NMR with reported ones8 and no E-
isomer was observed from the spectra. Though the Z-se-
lectivity has been observed elsewhere,1,3b,4–8 a satisfactory
explanation is still not available at present stage.
It has been documented that chlorosilanes in combination
with iodides anions converted alcohols to the iodides via
the in situ generation of iodosilanes.11 And TMSI was
SYNLETT 2005, No. 6, pp 1039–1041
Advanced online publication: 23.03.2005
DOI: 10.1055/s-2005-863750; Art ID: U01305ST
© Georg Thieme Verlag Stuttgart · New York
0
6.
0
4.
2
0
0
5

1040
J. Li et al.
LETTER
Table 1 Syntheses of (Z)-Allyl Iodides from Baylis–Hillman Adducts with TMSCl/NaI Systema
Entry
Ar
R1
H
H
H
H
H
H
R
Producta
2a
Time (h)
0.5
Yield (%)b
1
2
3
4
5
6
C6H5
Me
Me
Me
Me
Me
Me
73c
91
93
83
78
95
C6H5
2a
0.5
4-CH3-C6H4
2-Cl-C6H4
4-Cl-C6H4
2b
0.5
2c
1.5
2d
1.5
2e
0.5
O
O
7
8
9
2-CH3O-C6H4
H
H
H
Me
Me
Me
2f
0.5
0.5
1
92
87
85
4-CH3O-C6H4
2g
2h
O
10
11
12
13
14
15
16
3-NO2-C6H4
H
Me
Me
2i
2j
4
16
71
Ac
H
2
d
4-NO2-C6H4
4
–
Ac
H
2
61
86
79
84
C6H5
Et
Et
Et
2k
2l
1
2-Cl-C6H4
4-CH3-C6H4
H
2
H
2m
0.5
a All products were characterized by 1H NMR, Mass and IR spectroscopy.
b Isolated yields based on 2 equiv of TMSCl/NaI unless otherwise stated.
c One equiv of TMSCl/NaI was used.
d In such case, no reaction occurred.
completion of the reaction, the reaction was quenched with H2O and
extracted with Et2O (2 × 30 mL). The organic phase was successive-
ly washed with sat. Na2S2O3 (15 mL), sat. brine (10 mL), and dried
over anhyd Na2SO4. The solvents were removed under reduced
pressure to give the crude product, which were purified by prepara-
tive TLC using EtOAc and cyclohexane (1:5) as eluent.
reported to be effective in converting alcohols to the
corresponding iodides.12 It is reasonable to propose that
the iodinization reaction reported here proceeds via the in
situ generated TMSI. And the iodinization process may
follow similar patterns as in the preparation of allylic
chloride from Baylis–Himman adducts with the Lewis
acid FeCl3 and InCl3.13
Acknowledgment
In summary, we have described a new protocol for the
synthesis of (Z)-allyl iodides from Baylis–Hillman ad-
ducts in the presence of TMSCl/NaI. The advantages of
the method are good yields, excellent stereoselectivity,
mild reaction conditions, simple operational procedures
We are grateful to the National Natural Science Foundation of
China (Project No.20072033) and Specialized Research Fund for
the Doctoral Program of Higher Education of China.
as well as readily available reagents and starting
materials. As a result, it can be expected that the present
methodology may find its application in organic syn-
thesis.
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Typical Procedure for the Conversion of Baylis–Hillman
Adducts to their Allyl Iodides
To a solution of sodium iodide (0.3 g, 2 mmol) in THF (15 mL),
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were added and the resulting mixture was stirred at r.t. After
Synlett 2005, No. 6, 1039–1041 © Thieme Stuttgart · New York

LETTER
Synthesis of (Z)-Allyl Iodides from Baylis–Hillman Adducts
1041
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Synlett 2005, No. 6, 1039–1041 © Thieme Stuttgart · New York