Novel generation of (α-ketovinyl)thioketenes as intermediates through tandem [2,3]/[3,3] sigmatropic rearrangement of alkynyl propargyl sulfoxides

Article abstract of DOI:10.1016/j.tetlet.2007.04.055

Thermal reaction of alkynyl propargyl sulfoxides 1 afforded novel highly reactive (α-ketovinyl)thioketenes 3. Trapping experiments using a primary or secondary amine, formation of furanophane 4, through head-to-tail type dimerization, as well as direct ob

Full text of DOI:10.1016/j.tetlet.2007.04.055

Tetrahedron Letters 48 (2007) 4639–4642
Novel generation of (a-ketovinyl)thioketenes as
intermediates through tandem [2,3]/[3,3] sigmatropic
rearrangement of alkynyl propargyl sulfoxides
Shigenobu Aoyagi,a,* Muneyoshi Makabe,a Kazuaki Shimada,a
Yuji Takikawaa and Chizuko Kabutob
aDepartment of Chemical Engineering, Faculty of Engineering, Iwate University, 4-3-5 Ueda, Morioka 020-8551, Japan
bResearch and Analytical Center for Giant Molecules, Graduate School of Science, Tohoku University, Aramaki,
Aoba-ku, Sendai 980-8578, Japan
Received 20 February 2007; revised 31 March 2007; accepted 5 April 2007
Available online 19 April 2007
Abstract—Thermal reaction of alkynyl propargyl sulfoxides 1 afforded novel highly reactive (a-ketovinyl)thioketenes 3. Trapping
experiments using a primary or secondary amine, formation of furanophane 4, through head-to-tail type dimerization, as well as
direct observation using 1H NMR elucidated the generation pathway of 3 through sequential [2,3]/[3,3] sigmatropic rearrangement.
Ó 2007 Elsevier Ltd. All rights reserved.
In these decades, much attention has been focused on
generation of chalcogenoketenes because of their attrac-
tive reactivities intrinsic to the heterocumulene structure
as well as their potential in organic synthesis.1–5 Among
the research works concerning chalcogenoketenes, gen-
eration and trapping of allenylchalcogenoketenes
through [3,3] sigmatropic rearrangement of alkynyl
propargyl chalcogenides were widely studied,5 and syn-
thetic application of allenylthioketenes for natural prod-
ucts was also accomplished in our laboratory.5e,f
Moreover, we established generation and trapping of a
novel sulfene-type reactive species, allenylthioketene
S,S-dioxides, by thermal reaction of alkynyl propargyl
sulfones.6 As a part of our research works on generation
of highly reactive species from alkynyl propargyl chal-
cogenides and their oxidized forms, we were urged to
investigate thermal reaction of alkynyl propargyl sulfox-
ides, which are assumed to undergo in two possible reac-
tion modes, that is, [3,3] sigmatropic rearrangement7 to
give allenylthioketene S-oxides and [2,3] sigmatropic
rearrangement8 to give alkynesulfenates. Generally,
[2,3] sigmatropic rearrangement of sulfoxide proceeds
smoothly at relatively low temperature and in thermal
reaction of alkynyl propargyl sulfoxide the latter reac-
tion mode to give 2 is assumed to be preferable. Actu-
ally, tandem [2,3]/[3,3] sigmatropic rearrangement of
aryl propargyl sulfoxides to give benzothiophene deriv-
atives was reported by Majumdar.9 On the basis of these
results, alkynyl propargyl sulfoxides 1 were expected to
undergo similar sequential rearrangements to give (a-
ketovinyl)thioketene 3 as shown in Eq. 1. In this Letter,
we wish to describe thermal reaction of alkynyl proparg-
yl sulfoxides 1 to generate (a-ketovinyl)thioketenes 3.
Trapping and direct observation of reactive species 3,
as well as dimerization of 3 bearing silyl substituents
to form furanophanes 4 are also reported.
Alkynyl propargyl sulfoxides 1 were prepared by treat-
ment of alkynyl propargyl sulfides5d with mCPBA
(1.1 equiv) in CH2Cl2 at 0 °C for 30 min and were
S
R1
S
•
[2,3]
R1
R2
SO
[3,3]
R1
R2
O
O
ð1Þ
•
R2
1
2
3
*
Corresponding author. Tel.: +81 19 621 6324; e-mail: aoyagi@iwate-u.ac.jp
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.04.055

4640
S. Aoyagi et al. / Tetrahedron Letters 48 (2007) 4639–4642
S
R1
R2
SO
S
t-BuMe2Si
BnNH2 (20 equiv.)
1d
NBn
+
NHBn
ð4Þ
ð5Þ
Benzene, Reflux,
t-BuMe2Si
1a (R1= Me3Si, R2 = Me3Si); 79%
1b (R1= t-BuMe2Si, R2 = Me3Si); 88%
1c (R1= Me3Si, R2 = Ph); 88%
1d (R1= t-BuMe2Si, R2 =Ph); 85%
1e (R1= t-Bu, R2 = Me3Si); 66%
1f (R1= Ph, R2 = Me3Si); 78%
Ph
HO
6 h
7 (21%)
8 (33%)
S
S
t-BuMe2Si
BnNH2 (20 equiv.)
1b
+
Figure 1. Alkynyl propargyl sulfoxides 1.
NBn
NHBn
Benzene, Reflux,
6 h
t-BuMe2Si
O
7 (11%)
9 (35%)
purified by column chromatography on silica gel
(Fig. 1). Thermal reaction of 1 was carried out in hexane
at refluxing temperature for 24 h and the crude mixture
was subjected to column chromatography on silica gel.
When both R1 and R2 were silyl groups, novel furano-
phanes 4, which would be derived through dimerization
of (a-ketovinyl)thioketenes 3 in head-to-tail mode, were
afforded in good yields (Eq. 2). In contrast, thermal
reaction of 1c–f, bearing no silyl group as the R1 or
R2 substituent, only gave insoluble polymeric matter in
place of furanophanes 4. Therefore, silyl group at R1
stabilizing thioketene moiety of 33a,5d and silyl group
at R2, which induce nucleophilicity of oxygen atom
through interaction of Si–C r bond and carbonyl p orbi-
tal,10 would be essential for the formation of furano-
phanes 4. The structures of 4a and 4b were fully
in an NMR tube, a set of new signals assignable to 3c
emerged at d 0.36 (s, 9H; Me3Si), 5.42 (s, 1H; exo-meth-
ylene), 5.69 (s, 1H; exo-methylene), and 7.79 (d,
J = 8.6 Hz, 2H; o-H of phenyl group) along with those
of precursor 1c. However, the NMR signals became
complicated along with diminishing the signals of 3c
through further heating of the solution. In contrast to
thermal reaction of alkynyl propargyl sulfides,5d cyclo-
butenethione, a possible product through ring closure
of 3c, was not found at all in the resulting crude mixture.
Trapping of intermediary 3 was carried out using
primary and secondary amines. Heating of a solution
of 1d in the presence of diethylamine (20 equiv) in
refluxing benzene for 6 h afforded thioamide 5 and c-
keto-a,b-unsaturated thioamide 6 in 42% and 26%
yields, respectively (Eq. 3). The (E) geometry of 6 was
determined by NOE (25%) between the t-Bu of TBS
group and the methyl group. When a benzene solution
of 1d was heated to reflux in the presence of benzylamine
(20 equiv), thiolactam 8 was given in 33% yield along
with thioamide 7 in 21% yield (Eq. 4). The structure of
thiolactam 8 was confirmed by X-ray crystallographic
1
characterized by MS, IR, H NMR, 13C NMR and ele-
mental analysis.11 The dimeric structure of 4b was finally
determined by X-ray crystallographic analysis and an
ORTEP drawing of 4b is shown in Figure 2.12 Interest-
ingly, two furan rings tethered by –CH2S– moieties are
distorted. C(1), O(1), C(4) and C(3) atoms are located
almost on
a
same
plane
(C(1)–O(1)–C(4)–
C(3) = 1.5(3)°) and C(2) atom bearing a TBDMS group
is flipped to avoid the steric repulsion. Two double
bonds of furan rings are distorted (C(3)–C(2)–C(1)–
S(1) = 22.8(2)°;
C(5)*–C(3)–C(4)–O(1) = 19.6(3)°).
However, no significant change of line shape in 1H
NMR of 4b in benzene-d6 up to 100 °C suggests the rigid
structure of 4b, in spite of their plausible ring strain.
Direct observation of intermediate 3c was also success-
fully carried out by 1H NMR monitoring. When a
CDCl3 solution of 1c was heated at 60 °C for 15 min
S
SiMe3
R1
R1
n-Hexane
O
1a, 1b
Reflux, 24 h
O
ð2Þ
ð3Þ
Me3Si
S
4a (R1= Me3Si); 82%
4b (R1= t-BuMe2Si); 61%
S
S
t-BuMe2Si
Et2NH (20 equiv.)
NEt2
Ph
1d
+
NEt2
t-BuMe2Si
Benzene, Reflux,
6 h
O
5 (42%)
6 (26%)
Figure 2. ORTEP drawing of 4b.

S. Aoyagi et al. / Tetrahedron Letters 48 (2007) 4639–4642
4641
analysis (Fig. 3).13 Heating of a solution of 1b in the
presence of benzylamine (20 equiv) in refluxing benzene
for 6 h afforded thioamide 7 and monothiosuccinimide 9
in 11% and 35% yield, respectively (Eq. 5). Trans config-
uration of TBS and Me groups of 9 was determined by
the coupling constant (J = 1.9 Hz) of the protons at 3
and 4 positions as well as NOE (12%) between the
hydrogen at the 3-position and methyl group. Products
6, 8 and 9 were assumed to be trapping products of (a-
ketovinyl)thioketenes 3 generated through tandem [2,3]/
[3,3] sigmatropic rearrangement of 1. Thermal reaction
of 1e bearing t-Bu which would stabilize the thioketene
moiety in the presence of Et2NH (20 equiv) in refluxing
benzene for 6 h only gave N,N-diethyl-3,3-dimethy-
butanethioamide in 43% yield in place of a trapping
product of 3e. Analogous reaction of 1f in the presence
of Et2NH gave a complex mixture including an enamine
formed through Michael addition of amine to 1f. In
contrast, attempts for trapping of 3 using N-benzyl-
benzylideneimine, 2-methypyrroline, DMAD, DEAD
or azobenzene afforded neither [4+2] nor [2+2] cyclo-
adduct derived from (a-ketovinyl)thioketene 3.
Plausible formation pathway of all products are shown
in Scheme 1. Initially, [2,3] sigmatropic rearrangement
of 1 occurred to generate sulfenic ester 2. Then [3,3] sig-
matropic rearrangement of 2 via transition state A pro-
ceeded to give intermediary (a-ketovinyl)thioketenes 3.
In the absence of amine, dimerization of 3 having silyl
groups at both R1 and R2 proceeded to furnish furano-
phane 4. On the other hand, when the similar heating
was carried out in the presence of a primary or second-
ary amine, 3 reacted with amine to afford intermediary
thioamide B and following isomerization gave 6. Espe-
cially, in the case using a primary amine as a trapping
reagent, 6 underwent cyclization leading to thiolactam
8. Moreover, Brook-type rearrangement and isomeriza-
tion of olefin into silyl enol ether followed by desilyl-
ation would occur to afford monothiosuccinimide 9,
when R2 was silyl group. Low yields of trapping prod-
ucts 6, 8 and 9 were presumably due to competitive
attack of the amine to A of biradical character leading
to thioamide 5 and 7. In conclusion, thermal reaction
of alkynyl propargyl sulfoxides 1 afforded novel (a-keto-
vinyl)thioketenes 3 via tandem [2,3]/[3,3] sigmatropic
rearrangement. All the results of trapping experiments
using amine, formation of furanophanes 4 through
Figure 3. ORTEP drawing of 8.
4
5 or 7
R1 = R2 =
trialkylsilyl
dimerization
HNR3R4
S
R1
S
S
•
R1
R2
SO
[3,3]
[2,3]
O
R1
O
R1
R2
•
R2
R2
1
2
O
3
A
HNR3R4
S
S
S
S
R1
R1
R2 = Me3Si
NR3R4
R2
R4 = H
NR3R4
R2
NR3
NR3
R2
R1
R1
O
HO
O
O
9
8
6
B
Scheme 1. Plausible formation mechanism of products.

4642
S. Aoyagi et al. / Tetrahedron Letters 48 (2007) 4639–4642
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head-to-tail type dimerization, as well as direct NMR
observation elucidated the generation of 3. Further
investigation on synthetic aspect of 3 as key intermedi-
ates for heterocyclic compounds is in progress in our
laboratory.
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2002, 43, 2123–2125.
References and notes
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11. Compound 4a: Colorless prisms: mp 153.2 °C (dec). MS
(m/z): 512 (M+, 37%), 439 (M+ꢀMe3Si, 12%), 241 (M+/
2ꢀMe, 64%), 73 (Me3Si, bp). IR (KBr): 2958, 2897, 1423,
1248, 1114, 829, 633 cmꢀ1. 1H NMR (CDCl3, 400 MHz): d
0.23 (s, 18H), 0.34 (s, 18H), 3.81 (d, J = 10.8 Hz, 2H), 4.28
(d, J = 10.8 Hz, 2H). 13C NMR (CDCl3, 100 MHz): d 0.0
(q), 2.2 (q), 35.9 (t), 137.0 (s), 138.7 (s), 150.1 (s), 162.5 (s).
Anal. Calcd for C22H40O2S2Si4: C, 51.51; H, 7.86. Found:
C, 51.60; H, 7.98.
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Compound 4b: Colorless prisms: mp 166.9–168.3 °C (dec).
MS (m/z): 596 (M+, 5%), 73 (Me3Si, bp). IR (KBr): 2954,
1471, 1416, 1248, 1032, 782 cmꢀ1 1H NMR (CDCl3,
.
400 MHz): d 0.32 (s, 18H), 0.35 (s, 6H), 0.50 (s, 18H), 0.57
(s, 6H), 3.83 (d, J = 10.8 Hz, 2H), 4.26 (d, J = 10.8 Hz,
2H). 13C NMR (CDCl3, 100 MHz): d ꢀ4.6 (q), ꢀ2.8 (q),
ꢀ0.3 (q), 17.8 (s), 25.9 (q), 36.4 (q), 131.9 (s), 138.8 (s),
151.6 (s), 161.9 (s). Anal. Calcd for C28H52O2S2Si4: C,
56.32; H, 8.78. Found: C, 56.52; H, 8.83.
12. Crystal data for 4b: C28H52O2S2Si4, Mw = 597.18, color-
ꢀ
˚
less prism, triclinic, P1(#2), a = 11.062(3) A, b =
˚
˚
16.75(1) A, c = 9.986(3) A, a = 91.86(4)°, b = 106.12(2)°,
3
˚
c = 93.99(5)°, V = 1771(1) A , Z = 2, Dcalcd = 1.090 g/
cm3, l(Mo Ka) = 3.04 cmꢀ1
,
R = 0.043, Rw = 0.043.
Crystallographic data (excluding structure factors) for
this structure have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publica-
tion No. CCDC633770.
13. Crystal data for 8: C24H31NSiSOÆ0.5C6H6, Mw = 448.72,
˚
yellow needle, monoclinic, P21/c(#14), a = 10.5585(8) A,
˚
˚
b = 22.857(2) A, c = 11.938(1) A b = 106.933(3)°, V =
2756.2(4) A , Z = 4, Dcalcd = 1.081 g/cm3, l(Mo Ka) =
3
˚
1.78 cmꢀ1, R = 0.091, Rw = 0.089. Crystallographic data
(excluding structure factors) for this structure have
been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication No.
CCDC633771.