Deprotonation of aryl methanedithioate by lithium amides: Formation of lithium arylthio(thioxo)methanide having unique reactivity

Article abstract of DOI:10.1246/cl.2005.1674

Deprotonation of aryl methanedithioate 5 bearing a bowl-type bulky subsituent with lithium tetramethylpiperidide at low temperature gave organolithium species 9 which was in equilibrium with a dimeric species 10; 9 extruded C=S at higher temperatures, thu

Full text of DOI:10.1246/cl.2005.1674

1674
Chemistry Letters Vol.34, No.12 (2005)
Deprotonation of Aryl Methanedithioate by Lithium Amides:
Formation of Lithium Arylthio(thioxo)methanide Having Unique Reactivity
Kaori Mogi, Keiko Takenaka, and Renji Okazakiꢀ
Department of Chemical and Biological Sciences, Faculty of Science, Japan Women’s University,
2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681
(Received September 12, 2005; CL-051164)
Table 1. Deprotonation of 5 with LiTMP followed by quench-
ing with CH3Ia
Deprotonation of aryl methanedithioate 5 bearing a bowl-
type bulky subsituent with lithium tetramethylpiperidide at low
temperature gave organolithium species 9 which was in equilib-
rium with a dimeric species 10; 9 extruded C=S at higher tem-
peratures, thus representing a new, convenient source of C=S.
Yield/%
7
Entry React. conditionsb CH3I/equiv.
6
8
11
1
2
3
4
5
ꢁ98 ꢂC, 5 min
ꢁ98 ꢂC, 5 minc
ꢁ78 ꢂC, 1 h
1.2
1.0
1.2
1.2
1.2
79 20
—
7
14
—
—
—
—
—
41
74
69
76
33
—
—
7
—
—
Acyllithiums 11 and carbamoyllithiums 22 are important re-
agents in organic synthesis and their chemistry has been relative-
ly well established. The corresponding sulfur analogues, howev-
er, have been much less studied. Seebach and his co-workers re-
ported the formation of thiocarbamoyllithiums 3 by deprotona-
tion of thioformamides with lithium diisopropylamide and
their reactions with some electrophiles.3 The intermediacy of 4
(R = Mesꢀ; Mesꢀ = 2,4,6-tri-t-butylphenyl) was proposed by
us in the reaction of MesꢀLi with carbon disulfide (Chart 1).4
We now wish to describe a new and straightforward approach
to lithium arylthio(thioxo)methanide 4 and its unique reactivity.
ꢁ50 ꢂC, 1 h
ꢁ30 ꢂC, 1 h
aDeprotonation in all reactions was carried out at ꢁ98 ꢂC.
bThe reaction conditions indicate temperature and time be-
fore treatment with CH3I. cThe starting material 5 was recov-
ered in 7%.
Chart 1.
Methanedithioate 55 bearing a bowl-type bulky substituent,
4-t-butyl-2,6-bis[(2,200,6,600-tetramethyl-m-terphenyl-20-yl)-
methyl]phenyl6 (denoted as Bmt hereafter) was allowed to react
with lithium 2,2,6,6-tetramethylpiperidide (LiTMP, 1.2 equiv.)
in THF at ꢁ98 ꢂC for 5 min and then to this solution was added
methyl iodide (1.2 equiv.) at the same temperature. After
quenching with aq ammonium chloride at ꢁ30 ꢂC and chromato-
graphic purification (gel permeation liquid chromatography and
TLC), alkenes 6 and 7 were obtained in 79 and 20%, respectively
(Scheme 1 and Table 1, Entry 1).7 The cis-configuration of 6 was
established by X-ray crystallography. The use of 1.0 equiv. each
of LiTMP and methyl iodide resulted in 6 (69%) and 8 (7%)
(Entry 2), showing that 7 was formed via 8.
Scheme 2.
of 9 with a carbene character as shown in a canonical structure
9b giving a dimeric species 10, followed by reaction with methyl
iodide. The exclusive formation of cis-isomer 6 is considered to
be due to the stabilization of 10 by chelation of a lithium cation
with thiolate anions. Dithioate 8 is most likely formed by reac-
tion of 9 bearing a carbanionic character 9a with methyl iodide
and then converted into 7 with excess LiTMP and methyl iodide.
Essentially the same results were obtained in Entry 3 where
methyl iodide was added after the reaction solution was warmed
to ꢁ78 ꢂC and stirred for 1 h. Quenching with methyl iodide at
ꢁ50 ꢂC under otherwise similar conditions (Entry 4), however,
led to the formation of sulfide 11 (41%) as a major product along
with 6 (33%), indicating that the loss of carbon monosulfide (CS)
from 9 took place partially at ꢁ50 ꢂC (see Scheme 2). Com-
pound 11 was a sole product (74%) in the reaction at ꢁ30 ꢂC.
These observations clearly show that dissociation of 10 to 9
The plausible mechanisim for the formation of 6–8 is shown
in Scheme 2. Alkene 6 is most likely produced by dimerization8,9
Scheme 1.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.12 (2005)
1675
(a backward reaction of dimerization of 9 to 10) occurs in the
reaction solution. Compound 9 is unstable even around
ꢁ50 ꢂC decomposing into CS and BmtSLi, the latter of which
reacts with methyl iodide to afford 11.
for Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
References and Notes
In order to confirm the formation of CS in the present reac-
tions, morpholine (2 equiv.) was added to a solution of 9 gener-
ated at ꢁ78 ꢂC. The temperature of the reaction solution was
raised stepwise to ꢁ30 ꢂC (ꢁ50 ꢂC, 30 min and ꢁ30 ꢂC,
30 min) and quenched with aq ammonium chloride at ꢁ30 ꢂC
to give thioamide 12 (83%, Chart 2) besides thiol BmtSH (83%).
1
K. Iwamoto, N. Chatani, and S. Murai, J. Org. Chem., 65,
7944 (2000), and references cited therein; For reviews, see:
C. Narayana and M. Periasamy, Synthesis, 1985, 253; C.
Najera and M. Yus, Org. Prep. Proced. Int., 27, 383 (1995);
P. Waner, in ‘‘Comprehensive Organic Functional Group
Transformations,’’ ed. by A. R. Katrizky, O. Meth-Cohn,
and C. W. Rees, Pergamon Press, Oxford (1995), Vol. 5,
p 435; S. Murai and K. Iwamoto, in ‘‘Modern Carbonyl Chem-
istry,’’ ed. by J. Otera, Willey-VCH, Weinheim (2000), p 131.
T. Mizuno, I. Nishiguchi, and T. Hirashima, Tetrahedron, 49,
2403 (1993), and references cited therein.
D. Seebach, W. Lubosch, and D. Enders, Chem. Ber., 109,
1309 (1976).
R. Okazaki, T. Fujii, and N. Inamoto, Chem. Commun., 1984,
1010; R. Okazaki, T. Fujii, and N. Inamoto, J. Phys. Org.
Chem., 1, 75 (1988).
Methanedithioate 5 was synthesized in 74% by the reaction of
BmtLi, generated by lithiation of BmtBr with t-BuLi at
ꢁ78 ꢂC, with carbon disulfide followed by quenching with tri-
fluoromethanesulfonic acid. The structure of 5 was establish-
ed by X-ray crystallography.
For the use of Bmt group in the synthesis of sulfur and sele-
nium compounds with unique reactivity, see: K. Goto, M.
Holler, and R. Okazaki, Tetrahedron Lett., 37, 3141 (1996);
K. Goto, M. Holler, and R. Okazaki, J. Am. Chem. Soc.,
119, 1460 (1997); K. Goto, M. Holler, and R. Okazaki, Chem.
Commun., 1998, 1915; K. Goto, Y. Hino, Y. Takahashi, T.
Kawashima, G. Yamamoto, N. Takagi, and S. Nagase, Chem.
Lett., 2001, 1204; M. Itoh, K. Takenaka, R. Okazaki, N.
Takeda, and N. Tokitoh, Chem. Lett., 2001, 1206; K. Goto,
M. Nagahama, T. Mizushima, K. Shimada, T. Kawashima,
and R. Okazaki, Org. Lett., 3, 3569 (2001).
2
3
4
Chart 2.
Carbon monosulfide is a useful building block of thiocar-
bonyl compounds and known to be highly reactive10 although
it is isoelectronic with carbon monoxide and isocyanides both
of which are stable. The practical preparative method of CS so
far known is decomposition of carbon disulfide vapor in a
high-voltage ac discharge which requires special equipment.11
Senning and Klabunde have reported the reaction of CS with
amines among which morpholine gave thioamide 12 in the high-
est yield (49%).11b In view of the experimental simplicity and the
higher yield of the product 12 in our procedure, the deprotona-
tion of dithioate 5 is a new and convenient method for the gen-
eration of CS in solution.
When the deprotonation of 5 was performed with LiTMP
at ꢁ98 ꢂC, TipCH2Br (Tip = 2,4,6-triisopropylphenyl) (1.2
equiv.) added at the same temperature, and then the reaction so-
lution quenched with aq ammonium chloride after the tempera-
ture of the solution was raised to ꢁ30 ꢂC over 3 h, dithioate 13
(68%) and alkene 14 (12%) were obtained without any forma-
tion of tetrathiasubstituted alkene 15 unlike in the reaction with
methyl iodide. As in the formation of 7 from 8, 14 is considered
to be produced from 13. The obtention of 13 and 14 instead of 15
indicates that bulky TipCH2Br cannot react with dianion 10 be-
cause of steric repulsion against Bmt group but reacts with more
reactive 9 in equilibrium with 10 to give 13 (Scheme 3).
5
6
7
8
The new compounds 6–8, 11, 13, and 14 were characterized
1
by H and 13C NMR and X-ray crystallography.
Dimerization of acyllithium 1 of a similar structure was postu-
lated to explain the formation of RC(=O)CHR(OH) and
RC(=O)CR(=O): L. S. Trzupek, T. L. Newirth, E. G. Kelly,
N. E. Sbarbati, and G. M. Whitesides, J. Am. Chem. Soc., 95,
8118 (1973); N. S. Nudelman and A. A. Vitale, J. Org. Chem.,
46, 4625 (1981).
9
An alternative pathway to 6 described below, i.e., the reaction
of 9 with 5 giving thiolate I followed by its deprotonation with
LiTMP, is considered to be unlikely, though not completely
excluded, because the reaction of BmtLi with carbon disulfide
followed by quenching with methyl iodide at ꢁ78 ꢂC also
gave 6 (55%). The detailed discussion of the reaction mecha-
nism will be reported elsewhere.
Scheme 3.
In conclusion, we have found that the deprotonation of
methanedithioate 5 with LiTMP affords lithium species 9 which
is in equilibrium with dimeric species 10 at low temperatures
(ꢁ78– ꢁ98 ꢂC) and extrudes CS at higher temperatures (ꢁ50–
ꢁ30 ꢂC). This reaction provides a new and convenient method
for the generation of CS.
10 For a review, see: E. K. Moltzen, K. J. Klabunde, and A.
Senning, Chem. Rev., 88, 391 (1988).
11 a) E. K. Moltzen, B. Jensen, and A. Senning, Acta Chem.
Scand., Ser. B, B40, 609 (1986). b) E. K. Moltzen, M. P.
Kramer, A. Senning, and K. J. Klabunde, J. Org. Chem., 52,
1156 (1987).
We thank Dr. M. Minoura of Kitasato University for X-ray
crystallography and Dr. N. Kano of the University of Tokyo for
13C NMR. This work was partially supported by a Grant-in-Aid
Published on the web (Advance View) November 19, 2005; DOI 10.1246/cl.2005.1674