R. N. Ram, R. K. Tittal / Tetrahedron Letters 55 (2014) 4342–4345
4343
O
extensively used for ATRA and the reaction became a broadly
applicable synthetic tool even in the case of highly polymerizable
olefins, like styrene, alkyl acrylates, and acrylonitrile.10 This proto-
col was then also extended for the construction of carbocycles and
heterocycles by atom transfer radical cyclization (ATRC) reactions.
Transition metals such as Cu, Ru, Fe, Ni, Cr, Mo, etc. in the form of
their salts or complexes have been used as catalysts in ATRC reac-
tions, of which copper(I) salts and complexes are the most popu-
lar.11 The transition metal in the higher oxidation state not only
controls the reactivity of the radical but also leads to the formation
of the products with retention of the valuable halogen functional-
ity for further transformations. The other advantages of transition
metal-complexes over classical Bu3SnH include its low cost, non-
hazardous nature, and easy work-up. The reaction can be per-
formed at relatively higher concentrations without the risk of
direct reduction of the carbonAhalogen bond. Solvents like DCE,
DCM, CH3CN, benzene, and toluene can be used.12
Our group has reported the generation of b-acyloxyalkyl radi-
cals from 2,2,2-trichloroethyl carboxylates under non-reducing
conditions of Cu(I)-complex which was rearranged by dechlorin-
ative 1,2-acyloxy migration to 1-acyloxy-1-chloroethenes. The
1,2-migration probably involves a copper-associated radical inter-
mediate.13 No reaction products arising by the reaction of the rad-
ical cation with methanol could be detected when the reaction was
conducted by us in a 1:1 v/v mixture of DCE and methanol. Only
1,2-acyloxy shift occurred providing no further insight.13
However, in our recent report, it was observed that an electron-
donating alkoxy substituent promoted the fragmentation of the
initially formed radical to the alkene radical cation–acetate anion
pair, as expected. An indication of this effect of the alkoxy substi-
tuent was forthcoming from the observation of the presence of
traces of 1-alkoxy-2,2-dichloroalkenes in the reaction mixture
even in a relatively less polar DCE solvent due to diffusion of the
radical cation and acetate ion out of the solvent cage. The forma-
tion of the contact radical cation–acetate anion pair has been fur-
ther supported by the formation of the alkoxydichloroalkene in
significantly higher isolated yield (65%) along with small amounts
of the rearranged products in more polar DCE/MeOH (1:1 v/v) sol-
vent.14 These results motivated us to further change the substitu-
tion at the alkyl group with a view to investigate the effect of the
migrating group from simple acyloxy to some more nucleofugal
groups. At this point of investigation, it was observed that the lit-
erature was silent on the reaction of the alkyl radicals substituted
by an alkoxy–carbonyloxy group (carbonate group) at the b-posi-
tion. A carbonate group has been reported to be more nucleofugal
than simple acyloxy groups but less nucleofugal than trifluoroacet-
oxy group.15 It was therefore considered worthwhile to investigate
the behavior of a b-alkoxy-carbonyloxyalkyl radical with respect to
migration of the carbonate group and/or its fragmentation. This
study would also fill the gap in the spectrum of the migrating
groups in the rearrangement of b-(ester)alkyl radicals. In this spec-
trum of migrating groups, the carbonatoxy group is conspicuous by
its absence.
O
R
O
R
CuCl/bpy
3 dry DCE
reflux
O
OEt
Cl
Cl
5 (CIP)
EtO
O CCl2
EtO
O CCl
R
4a-t
R = alkyl, aryl, heteroaryl etc.
Cl
H
Cl
OCOOEt
6
R
Cl
R
7a-t
Scheme 2.
(1:1 mol ratio) in DCE at reflux under a nitrogen atmosphere con-
verted them to the corresponding dichloroalkenes 7 in 4–6 h.
The reaction mixture was filtered through celite pad to remove
the solid inorganic copper-complex and the filtrate was easily puri-
fied by column chromatography using a short band of silica gel
(60–120 mesh) and n-hexane as the solvent for elution. The prod-
ucts 7a–t were obtained in good to excellent yield (65–90%) as col-
orless and free flowing thin liquids. In the case of some volatile
products, such as 7m,n the loss during workup of the reaction mix-
ture in DCE as solvent was reduced considerably by performing the
reaction in low boiling solvent DCM at the expense of 2 h addi-
tional reaction time. The results of the reactions are summarized
in Table 1.
Many functional groups such as alkyl and aryl halo, vic-
dibromo, nitro, alkoxy, carbonAcarbon double bond, and an addi-
tional carbonate group at a different location remained unaffected
under the reaction conditions. In this context, it is noteworthy that
many reported methods for the synthesis of dichloroalkenes
involving similar b-eliminations of trichloro methyl carbinol deriv-
atives used stronger reducing agents with the associated risk of
reduction of easily reducible groups such as nitro, halo, and vic-
dibromo functionality.
The dichloroalkenes are versatile intermediates in organic syn-
thesis18 and are anti-HIV chemicals.19 The 1,1-dichloroalkenes are
very frequently prepared by employing Wittig reaction condi-
tions.20 However, toxicity, exothermicity, and volume of phospho-
rous waste streams generated limit the attractiveness of this
method. Other methods include the synthesis from trichloroethyl
Table 1
Reaction of ethyl 2,2,2-trichloroethyl carbonates (4a–t) with CuCl/bpya
Entry
4
R
Time (h)
Yieldb 7 (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
a
b
c
d
e
f
C6H5
o-MeC6H4
p-MeC6H4
o-MeOC6H4
p-MeOC6H4
o-ClC6H4
p-ClC6H4
m-ClC6H4
p-BrC6H4
m-BrC6H4
p-O2NC6H4
p-Me2NC6H4
2-Pyridyl
2-Furanyl
Cinnamyl
C6H5CH(CH3)
C7H15
4
4
4
4
4
4
5
4
5
4
4
4
6
6
5
4
4
4
4
5
85
87
81
80
87
82
80
75
83
85
87
90
76c
75c
86
84
65
86
90
81
g
h
i
j
k
l
Thus, the 1-substituted 2,2,2-trichloroethyl carbonates
4
(Scheme 2) were prepared in one-pot two-step reaction involving
addition of CHCl3 to aldehydes in the presence of DBU16 under a
N2 atmosphere followed by reaction with ethyl chloroformate in
the presence of Et3N as a base and CHCl3 as a solvent at 25 °C. Some
special functional groups bearing carbonates 4r–t were also pre-
pared from salicylaldehyde by first protecting the phenolic group
as ethyl carbonate and allyl ether by the reaction with ethyl chlo-
roformate and allyl bromide, respectively, followed by CHCl3 addi-
tion and reaction with ethyl chloroformate. The vic-dibromo
derivative 4t was prepared from 4s by addition of molecular bro-
mine to the allyl group in CCl4 at À5 to 0 °C.17 The reaction of
2,2,2-trichloroethyl carbonates 4a–t with 2 mol equiv of CuCl/bpy
m
n
o
p
q
r
o-EtO2COC6H4
o-(CH2@CHCH2O)C6H4
o-(BrCH2CHBrCH2O)C6H4
s
t
a
All the reactions were performed with 0.003 mol of 4 and 0.006 mol each of
CuCl and bpy in 15 mL DCE at reflux under a nitrogen atmosphere.
b
Isolated yields after purification by column chromatography.
c
Volatile compound, reaction was performed in dry DCM.