512
Chemistry Letters Vol.37, No.5 (2008)
A Simple and Efficient Protocol for Chlorination of Baylis–Hillman Adducts
1
Using PPh3/CCl4
Biswanath Das,ꢀ Boddu Shashi Kanth, Kongara Ravinder Reddy,
Gandham Satyalakshmi, and Rathod Aravind Kumar
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500007, India
(Received February 12, 2008; CL-080155)
PPh3/CCl4 system has been employed for the stereoselec-
tive synthesis of (Z)- and (E)-allyl chlorides from Baylis–
Hillman adducts in excellent yields.
ester group was present in the adducts 1 the allyl chlorides with
(Z) stereochemistry 3 were the sole products. However, if –CN
group was present in the adducts 2 the allyl chlorides with (E)
stereochemistry 4 were the major products. The structures
and stereochemistries of 3 and 4 were easily settled from their
1
The conversions of primary and secondary alcohols into the
corresponding chlorides by treatment with PPh3/CCl4 proceed
with high efficiency.2 During our work3 on the Baylis–Hillman
adducts4 1 (3-hydroxy-2-methylene alkanoates) and 2 (3-hy-
droxy-2-methylene alkanenitriles), we have employed this
reagent for chlorination of these adducts. A mixture of 1 or 2
and PPh3/CCl4 was refluxed for 2–3 h to produce the
corresponding allyl chloride 3 or 4 in stereoselective manner
(Scheme 1).
The allyl halides prepared from Baylis–Hillman adducts are
utilized for the synthesis of different natural bioactive molecules
and their analogues such as ꢀ-methylene-ꢁ-butyrolactone, ꢀ-
alkylidene-ꢂ-lactam, and flavonoids.5 Generally, a strong acid
or a metal halide is used for the conversion of a Baylis–Hillman
adduct into the corresponding allyl halide.5a,6 However,
PPh3/CCl4 system has conveniently been utilized here for the
preparation of allyl chlorides 3 and 4 from the adducts 1 and 2
respectively in high yields (83–98%).
A series of allyl chlorides have been prepared7 from various
Baylis–Hillman adducts having both ester and nitrile moieties
(Table 1). Several functionalities such as halogen, nitro, ether,
and ester remained intact. The adducts containing electron-
donating as well as electron-withdrawing groups underwent
the conversion smoothly. The reaction when carried out at room
temperature afforded the products in poor yields even after 24 h.
CCl4 was used here both as a reagent and as a solvent. No
additional solvent and catalyst were required. Though previously
the halogenation of Baylis–Hillman adducts was performed6c,8
using a halogen carrier and trialkyl or triphenylphosphine no
systematic study on the preparation of allyl chloride from the
adducts has been reported there. Moreover, the chlorination
of the adducts with PPh3/HCA produced both normal and
rearranged products.6c
spectral (1H NMR and MS) data.9 In the H NMR spectrum the
ꢂ-vinylic proton cis and trans to the ester group is known to
resonate at ca. ꢃ 7.5 and 6.5, respectively, while the same proton
cis and trans to the nitrile group resonates at ca. ꢃ 7.5 and 7.0,
respectively.6e,10 These reported 1H NMR values were useful
to determine the stereochemistry of the products.
In the present reaction PPh3 reacts with CCl4 to form the
intermediate A which then reacts with a Baylis–Hillman adduct
to produce the alkenylphosphonium salt B.2 Chloride ion
subsequently attacks this salt to furnish the allyl chloride and
Ph3PO (Scheme 2).
The stereochemistry of the present conversion can be ex-
plained by considering the transition state models I, II, and III
(Scheme 3). Model I is more favoured than II when EWG is
an ester and (Z) products are produced predominantly. However,
model III is more favoured than I when EWG is –CN as it is
a linear group. The steric effect in III due to the proximity
of Ar and –CN is less compared to that in I resulting from the
proximity of Ar and –CH2Cl groups. Thus the (E) compounds
are the major products in this case.
+
-
Cl PPh3
+
CCl3
CCl4
PPh3
+
A
OH
EWG
Ar
+
PPh3
O
EWG
EWG
CHCl3
+
Ar
Ar
-
Cl
Cl
B
The present conversion was highly stereoselective. When an
Scheme 2.
OH
+
+
PPh3/CCl4
OPPh3
OPPh3
EWG
EWG
O
H
Ar
Ar
Ar
Reflux, 2−3 h
Cl
Cl
EWG
COOR
CN
Cl
Cl
Ar
Ar
EWG = COOR
EWG = CN
EWG = COOR
1
3
H
H
+
O
O
OPPh3
EWG = CN
4
2
83−98%
I
II
III
Scheme 1.
Scheme 3. Transition state models of the present reaction.
Copyright Ó 2008 The Chemical Society of Japan