TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2055–2058
Mild and efficient synthesis of thiocarbonates and
thiocarbamates via a three-component coupling utilizing Cs2CO3
and TBAI
Ralph N. Salvatore,a Suma Sahaba and Kyung Woon Junga,b,
*
aDepartment of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620-5250, USA
bDrug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612-9497, USA
Received 12 December 2000; accepted 22 January 2001
Abstract—The presence of cesium carbonate and tetrabutylammonium iodide (TBAI) facilitated efficient thiocarbonylation of
alcohols, and thiocarbamation of amines, using carbon disulfide with alkyl halides. This protocol was mild, chemoselective, and
efficient, compared to the existing methods. © 2001 Published by Elsevier Science Ltd.
Thiocarbonates (xanthates) and thiocarbamates1 have
received much attention due to their interesting techno-
logical,2 biological,3 and synthetic applications.4 Typi-
cally, the thiocarbonyl moiety has been utilized
ubiquitously as a protecting group,5 and as an interme-
diate in further synthesis.6 Their formation employs
harsh reaction conditions such as the use of strong
bases, high temperatures, and long reaction times.7 In
addition, modifications have been reported to use thio-
phosgene,8 chlorothioformates,1c and isothiocyanates,1c
which are costly and toxic reagents. Thus, we were
prompted to embark on improved procedures.
Recently, we reported a highly efficient cesium base-
promoted solution phase synthesis of alkyl carbonates
and carbamates,9 which utilizes non-toxic reagents under
mild conditions. This protocol has been successfully
applied to peptidomimetic synthesis as well as solid
phase synthesis.10 As a complementary approach, this
procedure has been extended to the formation of thio-
carbonates and thiocarbamates using carbon disulfide.
sively produces thiocarbonate 3 or thiocarbamate 5,
respectively, upon gentle warming to room temperature
(Scheme 1).
Under the explored standard conditions (Table 1), vari-
ous primary alcohols were found to react efficiently
with active halides such as methyl iodide to provide the
corresponding methyl thiocarbonates in high yields
(entries 1–3). However, the thiocarbonate analog of
tertiary alcohol 10 offered low yield (entry 4). Sterically
hindered secondary alcohols, including pantolactone 11
and menthol 12, underwent three way couplings with
carbon disulfide and methyl iodide, delivering the
methyl xanthates in high yields. A noteworthy feature is
that our developed protocol averts common side reac-
tions such as elimination (Chugaev reaction), permit-
ting a wide range of applications.
As representatively depicted in Scheme 2, unreactive
bromides including 13 were compatible with the reac-
In the presence of cesium carbonate and tetra-
butylammonium iodide (TBAI), various alcohols and
amines smoothly coupled with carbon disulfide at ambi-
ent temperatures to produce the incipient thiocarbonate
(or thiocarbamate) anions in N,N-dimethylformamide.
Subsequent addition of an alkyl halide at 0°C exclu-
S
CS2, Cs2CO3, TBAI
+
+
R
R
R'
R'
ROH
R'X
O
S
S
DMF, 0 °C-rt
3
1
2
S
CS2, Cs2CO3, TBAI
DMF, 0 °C-rt
RNH2
R'X
N
H
4
2
5
* Corresponding author.
Scheme 1.
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00132-0