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Marcin Jasi n´ ski, Hans-Ulrich Reissig et al.
Table 2. Relative energies of model compounds and intermediates
according to DFT calculation (B3LYP/6-311+G ACHUNTGRNENGU( d,p) level) in the gas
phase.
In the first experiment tetracyanoethylene (TCNE) was
combined with 28. After two days at room temperature,
both in dichloromethane or in tetrahydrofuran, the conver-
sion was complete, and a single product was identified in
the crude reaction mixture. After filtration through a silica
gel pad, this compound was isolated as analytically pure
solid (87% yield, Scheme 10). The H NMR spectrum re-
vealed the presence of a methoxy signal along with a group
of three signals (dd and 1H each) at 4.43 (J=8.7, 11.1 Hz),
À1
À1
Compounds
kJmol
0
Compounds
kJmol
0
Methoxyallene
Methoxyallene
+Thioacetone
Primary Adduct
Vinylthiirane
+
Acetone
Primary Adduct
Vinyloxirane
Dihydrofuran
À14.2
À40.8
À112.0
À58.4
1
À120.0
À186.5
Dihydrothiophene
3
.46 (J=11.1, 12.2 Hz), and 3.09 (J=8.7, 12.2 Hz) ppm. In
1
3
energy gain by the addition of methoxyallene to thioacetone
the C NMR spectrum, two singlets attributed to C=C
(both i-C-atoms) were found at 142.7 and 136.0 ppm. These
data fit to alkenyl-substituted cyclobutane derivative 29. It
is well known that other 1,1-disubstituted buta-1,3-dienes
and TCNE produce cyclobutanes in step-wise thermal [2+2]
À1
(
(
À58.4 kJmol )
compared
to
that
to
acetone
À1
À14.2 kJmol ). The higher energy gain in this step can be
attributed to the higher energy level of the thiocarbonyl
group. For the next step, the rearrangement to a vinylthiirane
or a vinyloxirane, again a dramatically higher energy gain
was calculated for the sulfur system (À61.8 versus
[23]
cycloadditions.
No rearrangement of 29 into the corre-
sponding cyclohexene derivative was observed. Unexpected-
ly, the electron-deficient dimethyl dicyanofumarate, known
À1
À26.6 kJmol ). We can speculate that the more exothermic
[24a]
[24b]
reaction step also involves a lower energy barrier; however,
we should bear in mind that these steps are catalyzed pro-
cesses. Comparing finally the strained vinylthiiranes/oxir-
anes with the unstrained five-membered heterocycles re-
veals the last energy gain of the system, which is in the
as a reactive Michael acceptor
and dienophile,
did not
undergo the reaction with 28 even after seven days at room
temperature. Extremely reactive fluorinated alkenes such as
[
24c]
trans-1,2-bis(trifluoromethyl)-1,2-dicyanoethylene
1,1-bis(trifluoromethyl)-2,2-dicyanoethylene
and
[24d]
were also
À1
range of À65 kJmol for both series.
unreactive towards 1,3-diene 28. Very likely, steric hindrance
caused by the bulky adamantane moiety is the reason for
the observed inertness of 28.
Having the new thiirane 18 in hand, its desulfurization
[21]
with tris(diethylamino)phosphine was carried out in order
to prepare the hitherto unknown electron-rich 2-methoxy-
diene 28. This reaction occurred smoothly in refluxing tetra-
hydrofuran yielding the desired diene 28 in an excellent
yield of 94% (Scheme 10). The alternative thermal sulfur
extrusion by boiling of 18 in toluene also led to 28, but the
yield was considerably lower (35%). Because many ada-
mantane-derived compounds are known as biologically
Gratifyingly, the reaction of diene 28 with nitrosobenzene
occurred smoothly at room temperature, and after three
days a colorless solid was obtained as the major product.
The spectroscopic analysis confirmed the structure of the ex-
pected [4+2] cycloadduct. For example, the diagnostic sig-
nals of the enol ether moiety were found in the NMR spec-
tra: a pseudo-triplet (Jꢀ2.7 Hz) at 4.37 ppm attributed to 4-
[22]
1
active compounds, the new 1,3-diene 28 bearing an ada-
mantanylidene moiety could be an attractive building block
for the synthesis of complex molecules. For example, [4+2]
cycloadditions with active (hetero)dienophiles should offer
a straightforward method for the preparation of diverse six-
membered products. We therefore examined the reactions
of diene 28 with selected electron-deficient dienophiles.
H in the H NMR spectrum and signals of C-4 and C-5 at
1
3
89.9 and 160.5 ppm, respectively, in the C NMR spectrum.
The synthetic utility of diverse 1,2-oxazine derivatives lead-
ing to polyfunctionalized compounds of potentially biologi-
[25]
cal significance is well documented. For that reason, cy-
cloadduct 30 was treated with an excess of SmI to give un-
2
[26]
saturated amino alcohol 31 in 72% yield. A surprising re-
sistance of the 3,6-dihydro-1,2-oxazine 30 to undergo ex-
haustive hydrogenation was observed employing palladium
on charcoal as a catalyst. Amino alcohol 31 was obtained as
a sole product in comparable yield of 69% after 24 h. The
structure of the latter was unambiguously confirmed based
on spectroscopic data, for example, signals of the C=C bond
1
3
at 99.6 and 161.2 ppm in the C NMR spectrum.
Conclusions
The present study shows that lithiated methoxyallene easily
reacts with non-enolizable cycloaliphatic thioketones and
that in all cases carbophilic attack of the nucleophile occurs.
In the case of the enolizable thiocamphor 1d no addition
was observed, probably due to deprotonation of the thioke-
tone. The primary thiols formed by addition of the allenyl
Scheme 10. Synthesis and transformations of methoxy-substituted 1,3-
diene 28: a) P
1.0 mmol), CH
THF, 2 h; e) H
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(NEt
Cl
(balloon pressure), Pd/C, MeOH/AcOEt, rt, 24 h.
2
)
3
(1.2 equiv), THF, reflux, 1 h; b) tetracyanoethylene
(
2
2
, rt, 2 d; c) PhNO (1.3 equiv), CH Cl , rt, 3 d; d) SmI ,
2
2
2
2
Chem. Asian J. 2014, 9, 2641 – 2648
2646
ꢄ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim