Mechanistic Studies on Garratt-Braverman Cyclization: The Diradical-Cycloaddition Puzzle

Article abstract of DOI:10.1021/acs.joc.6b00490

In this work, we present the results of extensive multiprong studies involving the fate of deuterium-labeled substrates, EPR, trapping experiments, and LA-LDI mass spectrometry to sort out the controversies relating to the mechanism of Garratt-Braverman c

Full text of DOI:10.1021/acs.joc.6b00490

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Article
Mechanistic studies on Garratt-Braverman
Cyclization: The Diradical-Cycloaddition Puzzle
Joyee Das, Subhendu Sekhar Bag, and Amit Basak
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00490 • Publication Date (Web): 26 Apr 2016
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Mechanistic studies on Garratt-Braverman Cyclization: The
Diradical-Cycloaddition Puzzle
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Joyee Dasa, Subhendu Sekhar Bag*b and Amit Basak*a
a Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721 302, India
b Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India
*Corresponding author
Email: absk@chem.iitkgp.ernet.in, ssbag75@iitg.ernet.in,
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Abstract
In this work, we present the results of extensive multi prong studies involving fate of deuterium labeled
substrates, EPR, trapping experiments and LA-LDI mass spectrometry to sort out the controversies
relating to the mechanism of Garratt-Braverman cyclization in two systems, namely bis-propargyl
sulfones and ethers. The results are in conformity with a diradical mechamism for the sulfone, while for
the ether, the anionic [4+2] appears to be the preferred pathway. This shows that the mechanistic
pathway towards GB cyclization is dependent upon the nature of hetero atom (O or S in sulfone)
bridging the propargyl arms.
Key Words: Garratt-Braverman Cyclization, Bis-propargyl, sulfone, Ether, Bis-allene, Diradical,
EPR
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Introduction
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Cycloaromatization reactions1 have become an important research area because of their interesting
mechanistic possibilities2 which control the reactivity of molecules undergoing such reactions and the
extent of their interactions with biomolecules.3 Several cycloaromatization reactions are known starting
from the famous Bergman Cyclization reported first in 1971.4,5 Few years after Bergman’s paper,
Garratt and Braverman6.7 independently reported the reactivity of bis-propargyl systems (sulfide,
sulfone, ether, amine) under base mediated conditions. The final outcome of the reaction, now popularly
known as Garratt-Braverman (GB) Cyclization, was dependent upon the nature of substituent in the
propargyl arm as well as the reaction condition. For example, in case of an unsubstituted thioether, a
dimeric product was obtained in virtually quantitative yield via the bis-allene (path A).8a The reaction
was carried out in two stages: an initial treatment with KOtBu at -65 °C to get the bis-allene followed by
warming the latter in CHCl3 to 50 °C. For di-t-butyl propargyl thioether, the product was mainly the
cyclobutane-fused thiophene.8a Later on, Garratt et al. reported the isolation of similar products in low
yields from all the systems (thioether, ether and amine) using KOH/MeOH.8b For alkyl substituted
substrates, 3, 4-disubstitued 5-membered heterocycles were formed (path B).9 On the other hand, aryl
or vinyl substituted starting materials provides a new aromatic system via the participation of the aryl or
vinyl double bond, ultimately leading to the formation of a naphthalene or benzene fused heterocyclic
system (path C).10 All these possibilities are shown in Scheme 1
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H
R
R
C
R
R
X
X
X
X
R
R
C
III
II
I
R = alkyl
R = aryl/alkene
a
R = tBu
b
c
R = H
tBu
X
X
X
X
X
tBu
R
V
IV
R
VI
(major)
VII
X = S, O, NEt
X = S, O, SO2, NMe
Scheme 1: Garratt-Braverman Cyclization
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The generally accepted mechanism for the process as is depicted in pathways a-c (Scheme 1) involves
the formation of a diradical from a bis-alleneic intermediate8 (Scheme 2A). Support for this mechanism
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came from various experiments like successful trapping of the diradical with O2 to form the endo
peroxide11 (in case of sulfide), the non-perturbation of the rate upon varying solvent polarity12 as well as
the isolation XIII as an intermediate (Scheme 2A). In recent years, through a combination of
experiment and computations on the selectivity of aryl substituted bis-propargyl sulfones, the diradical
mechanism was shown to be the preferred pathway.13 Moreover, the complete GB selectivity of
substrates capable of undergoing multiple reactions could be successfully explained on the basis of
diradical mechanism.14
bisallene
diradical
formation
formation
X
C
X
X
X
R
H
C
R
R
R
VIII
IX
X
XI
X
H-shifts
X = SO2, O, N
R = Aryl or Alkyl
X
R
A possible intermediate
R
XII
XIII
Scheme 2A: The diradical mechanism
-
-
C
O
base
O
O
R
R
R
XV
XIV
XVI
-
Protonation
[4 + 2]
O
Isomerization
O
Cycloaddition
H
R
R
XVII
XVIII
Scheme 2B: The anionic IMDAR Mechanism
Some ambiguities still remain regarding the diradical mechanism for the GB process, especially for
reactions going through path c in view of the fact that the bis-allene, the progenitor of the diradical, is
generated only after double isomerization and also has multiple mechanistic options. In some of the
earlier experiments with sulfones by Braverman, 7a the bis-allene was directly generated and hence not
much of ambiguity existed for those cases. But in classical GB reaction, where bis-propargyl systems
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are the starting materials, bis-allene formation is an important issue which should be a sequential event.
If the mono to the bis-allene formation is slow,15 by the time it undergoes isomerization, it may give rise
to the same products via an alternate route. For example, one can draw a [4+2] cycloaddition
(Intramolecular Diels-Alder Reaction (IMDAR) mechanism) to arrive at the products from aryl
substituted systems. Such a mechanism has been originally proposed by Iwai and Ide10a and later on
reinforced by Kudoh et al.16 for rearrangement of bispropargyl ethers in presence of strong bases like
NaH or Triton B in DMSO involving a monoallenic anion followed by an intramolecular Diels-Alder
reaction and subsequent quenching of the resulting anion by DMSO (Scheme 2B). The final product
was obtained via a 1,5-migration of the anion generated at ring fusion carbon and subsequent
quenching. The mechanism was supported by labeling experiments with deuterated solvents and
computations. Recently, Balci et al.17 have reported the synthesis of Chromenopyridines exploiting the
IMDAR mechanism from an in situ generated azadiene and an alkyne system. Although Kudoh et al.16
synthesized several aryl naphthalenes using their protocol, for their mechanistic study involving
deuterium incorporation, the group used a system which can only isomerize to a monoallene as the other
arm was disubstituted at the propargyl position thus limiting the generality of such a pathway in systems
capable of undergoing isomerization to the bis-allene.
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Results and Discussion
With this backdrop, we undertook a detailed study to address these mechanistic issues. Specifically we
have the following questions in mind: i) do all these bis-propargyl systems (S, SO2, O, N) follow the
same mechanism or mechanisms are different for different systems considering the variations in the
reaction conditions employed for different propargyl systems? ii) if that be the case (different
mechanisms), will the selectivity pattern from unsymmetrical systems follow different trend? iii) will it
be possible to use appropriately deuterated substrates to discriminate between the mono-allene vs bis-
allene mechanism? and finally iv) will it be possible to capture any EPR signal during the course of the
reaction? The present work was aimed to address these issues and we have been able to provide
evidences for the reaction pathways for the ether and the sulfone which are presented in this paper.
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The selectivity issue was taken up first. Towards that end, we prepared several unsymmetrically
substituted bis-propargyl ethers/sulfones and treated them with a suitable base depending upon the
nature of substrate (KOtBu in DMSO for ethers and Et3N in CHCl3 for sulfones) to get an insight into
the outcome of GB reaction, the reaction was carried out at room temperature. The product ratio was
determined from the integrations for characteristic signals of the two isomers in the 1H−NMR spectrum
of the crude reaction mixture. The results of the GB reaction which showed opposite selectivity for the
ethers vis-a-vis sulfones are compiled in Table 1. Previously18 we have reported the product ratio for
the ether systems using different reaction condition (DBU/Toluene/reflux). The trend of selectivity
followed similar pattern. The structures of the products were confirmed mainly on the basis of
1H−NMR, 13C−NMR, DEPT-135 and correlation spectroscopy in some cases. For the sulfones, the
major product arises from the preferential participation of the more electron-rich aryl ring while for the
ether, the less electron -rich aryl ring predominantly participates. Prima facie, this contrast in selectivity
for the sulfone vis-à-vis ether, indicated different mechanism for the two reactions. The results fit well
with the anionic cycloaddition mechanism for the ether but not for the sulfone. However, we must keep
in mind the different electronic nature of sulfone (-R, -I effects) vis-à-vis the ether (+R, -I) which might
explain the different selectivity for the both the reactions even if they involve a common diradical
pathway (Figure 1). In case of sulfone, the radical benzylic to the electron donor aryl ring will be
captodatively stabilized while in case of ether it will just be the opposite with electron withdrawing aryl
group stabilizing the benzylic radical.13, 18
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X
For X = O, KOtBu/DMSO/rt/1 h; For
A
X
X
X= SO2, Et3N/CHCl3/rt/ 30 min
+
A
A
1a-d
2a-d
3a-d
5a-d
4a-d
6a-d
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SM
X
A
Yield
(%)
Product ratio
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9
O
O
2-naphthyl
97
94
95
94
95
90
85
87
1a
1b
1c
1d
2a
2b
2c
2d
3a:4a (2:1)
3b:4b (1:2)
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6-Methoxynaphthyl
4-Methoxyphenyl
2,4-Dimethoxy phenyl
2-naphthyl
O
3c:4c (1:8)
O
3d:4d (1:10)
5a:6a (3.16:1)
5b:6b (5.16:1)
5c:6c (2:1)
SO2
SO2
SO2
SO2
6-Methoxynaphthyl
4-Methoxyphenyl
2,4-Dimethoxy phenyl
5d:6d (5.16:1)
Table 1: Results of base mediated reaction of sulfones and ethers
.
.
.
.
O
O
S
O
..
D
A
.
A
D
.
D= Electron donating groups
A =Electron accepting groups
-
.
-
.
O
S
O
.
O
.
D
+
+
A
A
.
D
.
Figure 1: Differential Electronic nature of Sulfone and Ether
We next turned our attention to a more assertive experiment based on the outcome by carrying out the
reaction in deuterated solvents. Before carrying out these experiments, we wanted to check the
exchangeability of the heterocyclic methylenes in the GB products under basic conditions. Thus, the GB
products derived from both the sulfone and the ether were subjected to the respective reaction
conditions in presence of deuterated solvents. The phthalans derived from the ether was stirred in d6-
DMSO in presence of KOtBu whereas the counterpart dihydrothiophene 1,1-dioxide was treated with
Et3N in presence of CDCl3 (Scheme 3) to find out the level of deuterium incorporation, if any at C-1
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and C-3. The temperature was maintained at the room temperature of 30 °C in both the cases which is
also the GB reaction temperature. Interestingly but not unexpectedly, varying degrees of deuterium was
found at these positions in the phthalans, the extent of deuteration depends upon the amount of base.
With excess of KOtBu in d6-DMSO, 100% deuteration was observed at both the methylene positions.
Although lesser extent of deuterium incorporation occurs with 1.0 eq of base, any mechanistic study
based on deuterium incorporation at the methylene positions may not be reliable. For the
dihydrothiophene 1,1-dioxide, although no such exchange at the methylenes was observed, there was a
possibility of incorporation of D during propargyl-allene isomerization. Experimental results showed
that no deuterium was incorporated at any position of the product from the reaction of sulfone with Et3N
and CDCl3 thus ruling out any D exchange during propargyl-allene isomerization. This observation is
important as anionic [4+2] cyclization (IMDAR) suggests deuterium incorporation, especially at C-9.
This single observation rules out the anionic IMDAR mechanism for the rearrangement of sulfone, a
conclusion also supported by the results obtained from deuterated substrates (as discussed below). A
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general structure showing the numbering is included in Scheme 3 (Structure A)
D
H
D
H
9
O
8
O
100%
SO2
1
5.0 equiv
SO2 No D
H
D
KOtBu, DMSO-d6,
rt, 1 h
incorpoartion
5.0 equiv Et3N,
CDCl3, rt, 1 h
D
OMe
H
O
OMe
OMe
4d''
3
4
5
10b
OMe
4d
10b
1.0 equiv Et3N,
CHCl3, rt, 30 min
S
A
O2
8b
Scheme 3: Results of exchange reactions
For the rearrangement of labeled substrates having deuterium at both the ortho positions of the
phenyl ring, the possible outcome of the deuterium retention, loss or migration are shown in Scheme 4.
In case of diradical mechanism, the intermediate XXII has all the D intact. This will be followed by a
series of migrations involving H (D). If these migrations are concerted, then highest level of deuterium
is expected to be observed at the migrating position. If such migrations are non-concerted and follows in
a stepwise manner, less percentage of D incorporation is then expected. For the intermediate sulfone (X
= SO2), because of non-aromatic character of heterocycle, 1,5- D-shift (from C-11 to C1) along with a
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1,3-H shift from C-4 to C-3 are expected to lead to the creation of the new aromatic ring. The stability
of the anion  to the sulfone may also aid the 1,5 shift. 1,3-D migration from C-11 to C-9 was ruled out
because that still retains the nonaromatic thiophene dioxide ring. If these processes are concerted, D
incorporation at C-1 was expected to the extent of 50% in the final product. However, prima facie, the
transoid geometry of the diene framework should prohibit a concerted 1,5-sigmatropic shift thus raising
doubts on the expected level of deuteration. No deuterium is expected at C-9 for sulfone; however for
the ether, because of the aromaticity of furan, 1,3 shift from C-11 to C-9 can take place. Another 1,3
shift fromC-9 to C-1 will lead to the final product. The extent of deuterium at these positions (C-1 and
C-9) depends upon the concertedness of migration and possible exchange with the non-deuterated
solvent. For anionic IMDAR mechanism, if a concerted 1,3-H shift from C-11 to C-9 occurs, one can
expect high level of deuterium at C-9. Kudoh et al.16 has mentioned in their paper about such a
possibility of a concerted H migration via an anionic 1,3- sigmatropic shift from C-11 to C-9 although
no evidence to support this was proposed. The incorporation of deuterium at C-1 was explained on the
basis of migration of ring junction anion to C-1 through the π-network followed by quenching (d6-
DMSO). These possibilities are shown in Scheme 4 (numbering has been shown in structure XXVII).
With all these information in hand, the pentadeuterated phenyl based bis-propargyl ethers (1dʹ,
7bʹ and 11d´) and sulfones (2cʹ and 8bʹ) were prepared and subjected to the GB conditions in non-
deuterated solvents as mentioned earlier. The results for both ethers and sulfones are shown in Table 2.
In these cases, although there exist a possibility of exchange of deuterium at C-1 and C-3 positions,
presence of any extent of deuterium at these positions can only arise through migration and not through
exchange considering the fact that the reaction is carried out in non-deuteriated solvent which is used in
large excess.
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X
1,5 shift
X
X
1
Ar
6
7
8
9
H
D
D
C
C
D
D
X
Ar
Diradical
1,3 shift
D
D
D
D
D
Ar
D
Ar
11
D
D
D
D
D
D
XIX
D
D
D
D
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XXII
IMDAR
XX
XXI
1,5-D shift
C-11 to C-1
1,3-H shift
C-4 to C-3
D
D
D
C
X
H
D
D
D
D
X
D
D
Quenching
by solve nt
X
D
D
upto 50%
D
D
D
if concerted;
<50% in case of
stepwise/solvent
exchange
Ar
D
Ar
XXV
Ar
XXIV
upto 50%
if concerted;
<50% if
stepwise/solvent
exchange
H
1,3-D shift anionic
1,5-D shift
C-11 to C-1
X
D
Extent will depend upon
if concerted or stepwise
and competion from solvent quenching
C-9 D is not
expected in
case of
Ar
H(D?)
D
H
D
X
D
3
D (H)
sulfone
1
D
D
D
1,5-anion
D
D
D
Quenching
by solvent
9
4
migration
D
D
Ar
H(D?)
D
X
X
C-11 to C-1
D
D
XXIII
D
D
D
Ar
Ar
XXVII
D
XXVIII
XXVI
Scheme 4: Possible fate of deuterated substrate
Substrate
Condition
Product*
D
D
OMe
25%
D
O
O
14%
D
KOtBu (1 eq)/DMSO/rt/1h
OMe
D
D
D
OMe
D
D
1d'
D
OMe
D
4d'
D
D
D
16%
D
O
D
D
O
14%
D
D
D
KOtBu (1 eq)/DMSO/rt/1h
D
D
D
D
D
D
D
D
D
D
D
7b'
D
9b'
50%
D
S
D
D
O2
2c'
S
SO2
H
Et3N (1 eq), CHCl3, rt, 30
D
D
OMe
D
D
D
min
OMe
D
D
6c'
50%
D
D
D
SO2
D
D
D
O2
H
Et3N (1 eq), CHCl3, rt, 30
D
D
D
D
D
D
D
8b'
min
D
D
D
D
D
D
D
D
10b'
27%
D
O
O
D
D
18%
D
KOtBu (1 eq)/DMSO/rt/1h
D
OMe
D
11d'
OMe
12d'
*The % incorporations of Deuterium are approximate values within the limits of integration
Table 2: Experimental results on deuterated substrates
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Determination of extent of deuterium
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The extent of deuterium incorporation was determined from the integration of various proton signals in
the 1H-NMR spectra (See SI Page no 37). Comparison of intensities of the signals in the corresponding
13C-NMR spectra (See SI Page no 38) of deuterated product against the fully protiated compound also
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provided qualitative information about deuterium incorporation. The H-NMR spectrum of ether 4d´
(See SI Page no 40) showed the presence of deuterium at C-1 via the appearance of a broad singlet at 
5.43. The signal for D at C-9 was masked by the broad signals of D present in the other aromatic rings.
However, in the corresponding lactone 15d´, deshielding by the lactone carbonyl made it to appear at 
8.67 (See SI Page no 40). For the sulfone, we could clearly observe the signal at  4.59 due to the D at
C-1 (See SI Page no 40). The assignments of various signals were done from H-1H COSY NMR
1
experiments.
Inspection of the results of D-incorporation leads to some key differences between the reactions
of ether vis-à-vis sulfone. The level of deuterium incorporation at C-1 and C-9 are different in case of
ethers and sulfones thus pointing out different mechanisms for their pathways. In case of ethers, C-9
showed low but distinct presence of D (~14%). Similar observation was made for the dimethyl
propargyl ether 11d´ which can react only via the monoallene. The presence of deuterium at C-9 in case
of deuterated substrates confirms an intramolecular 1,3-shift which is, however, a minor pathway as
indicated by the low level of D incorporation, the major pathway being the quenching of the anion by
DMSO. Base mediated intramolecular 1,3-H shift have been reported by Mulzer et al.19 For the ethers,
varying degrees of D (16-27%) incorporation was observed at C-1 indicating possible exchange under
the reaction condition. However, the presence of D certainly proves the intramolecular nature of the 1,5-
migration. All these findings are in agreement with the anionic [4+2] mechanism involving the
monoallenide anion as proposed by Kudoh et al.16 The presence of deuterium at C-1 and C-9 can also be
explained on the basis of 1,3-prototropic shift for ethers. Deuteration at these positions can be achieved
after diradical cycloaromatization followed by 1,3-prototropic shift leading to rearomatization of the
phenyl. It may be noted that in case of ether, the intermediate has a furan ring which is aromatic. In the
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case of sulfone, due to the lack of aromaticity of the heterocyclic ring20 and relative stability of the
anion at C-1-position to the sulfone, base-catalyzed 1,5-H shift can occur immediately. A definitive
support for this mechanism was obtained when the monoallenic intermediate was successfully trapped
as evidenced from the formation of mono methoxy enol ether 16 [peak at m/z 417 (M+K+) in the LA-
LDI MS21] by carrying out the reaction of naphthyl propargyl ether with KOtBu in a mixture of DMSO
and MeOH. No double adduct of methanol (m/z at 449) could be detected (See SI Page no 39).22 In
case of labeled sulfones 2cʹ and 8bʹ, ~50% deuterium incorporation at C-1 was observed while C-9 had
no deuterium. The observed results ruled out the involvement of a 1,3-H(D) migration from C-11 to C-9
from the intermediate XXII (Scheme 3) formed during the GB process; only intramolecular 1,5-H(D)
migration occured from C-11 to C-1 as confirmed by the occurrence of ~50% D at C-1. The concerted
nature of 1,5-migration most likely involves deprotonation and reprotonation strictly through an
intramolecular fashion as sigmatropic shift may be ruled out because of geometric constraints pointed
earlier. This observation ruled out the involvement of intermediate XIII (Scheme 2A) which is also in
line with the observation by Feldman23 after their unsuccessful attempt to trap the intermediate in a
[4+2] fashion. No deuterium incorporation at C-9 from deuterated substrates as well as from the
reaction of unlabelled precursors in CDCl3 and Et3N ruled out the normal or anionic [4+2] cyclization
route for the sulfone and supported the diradical mechanism via the involvement of a bis-allene. The
involvement of latter (bis-allene) as an intermediate was also proven by the isolation of bis-enol ether
along with the GB product by carrying out the reaction in presence of methanol, confirmed by 1H NMR
and LA-LDI MS [peak for dimethanol adduct 19 at m/z 497 (M+K+), no peak at m/z 465 for the mono
methanol adduct and peak for GB product at m/z 433 (M+K+)] (See SI Page no 39). It may be
mentioned that Braverman et al.12 through a combination of 1H NMR and kinetic studies have reported
the involvement of bis-allene during rearrangement of sulfones. This is in line with the previously
reported involvement of bis-allene proven. Finally, EPR studies as discussed below, confirmed the
diradical nature of the intermediate only in case of rearrangement of sulfones and not for the ethers.
EPR studies
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The EPR spectra were then recorded by carrying out the reactions of sulfones 13 and 2b as well as
ethers 14 and 1d (Figure 2) under appropriate conditions after initially purging the solutions with Ar
gas for 5 min to remove the dissolved oxygen. Suitable bases or TEMPO or both were added as per the
requirement of the reaction. For the sulfones 13 and 2b, we did observe nice stable EPR signals at room
temperature (spectrum shown in Figure 3A and 3B respectively) with isotropic g value of 2.004. The g
value was found to be close to that for TEMPO (g = 2.00036) and is thus surely an indication for the
generation and presence of organic free radical in cases involving sulfones.24-26 This was also tested by
quenching experiment with molecular O2 in the triplet ground state. Thus, the EPR signal disappeared
when the spectrum was recorded while the reaction mixture was being purged with O2 gas for 2-4 mins
(Figure 3C).
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S
O
O
O
14
13
OMe
O
S
O
O
MeO
1d
MeO
2b
Figure 2: Compounds used in EPR study
Figure 3: X band (9.44 GHz) EPR spectra of a mixture of sulfone and Et3N in CH2Cl2 at room temperature. Condition: X-
band microwave frequency (GHz), 9.44; modulation frequency (kHz), 100; modulation amplitude (G), 140.0; and
microwave power, 0.998 [μW]. Spectra (A) is for bis-naphthyl-substituted bispropargyl sulfone 13; (B) is for sulfone 2b and
(C) is for a solution of sulfone 2b purging with O2 gas at room temperature. All the solutions of samples in dry CH2Cl2
contained Et3N as base. EXP and SIM represent experimental and simulation spectra, respectively.
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It is to be noted that a hyperfine splitting of the EPR signal is expected which is also clearly observed in
the experimental spectra of compound 13. However the spectral broadness did not allow us to calculate
the hyperfine splitting constant (A value) due to the strong spin delocalization within the aromatic core
and the benzylic proton24a-c as well as strong spin-spin exchange.24d-e The same is true for compound 2b
for which a broad signal was observed. The strong nucleophilic/electrophilic nature of the radical under
the influence of electron donor/acceptor substituent in the aromatic core may also be a probable reason
of weak hyperfine coupling of compound 2b. 24b However, the hyperfine splitting is resolved in the
simulated spectra. Thus, the best fit to the experimental data provided the parameters gav = 2.004 and
hyperfine coupling constant, Aav = 8 × 10−4 cm−1 for compound 13 and compound 2b shows same g
value with a slightly weaker hyperfine coupling constant Aav = 7 × 10−4 cm−1. Both the experimental
and simulated spectra of compound 13 showed the average triplet EPR signal for the two radicals under
the coupling influence of two separate hydrogens attached to the radical bearing carbons. However, at
this stage it is difficult to clearly explain the splitting pattern or the exact interactions with our available
experimental setup.24a
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To check whether the observed signal has any interaction with a stable organic radical like TEMPO we
monitored the signal intensity of a fixed concentration of TEMPO in presence of the reaction mixture of
compound 13. It is well known that TEMPO gives a triplet EPR signal with an isotropic hyperfine
splitting aN = 15.5 G and g0 = 2.0055 as was reported by Talsi et.al.24d, 26 However, in our experimental
condition at room temperature TEMPO exhibited a single line EPR spectrum with a center g value of
2.013 which possibly due to high concentration of the TEMPO. We observed a reduction of EPR signal
intensity by 17% of a solution containing the compound 13 (1.7 mM), Et3N and TEMPO (0.5/1.0 eq) in
CH2Cl2. This is in comparison to the signal intensity of a 0.5/1.0 mM of TEMPO in CH2Cl2. The effect
is more pronounced in case of compound 2b under similar condition. In this case, the signal intensity of
TEMPO was reduced by 41% (Figures 4A and 4B). (All these observations put in a tabulated form
(Table 3)) The results indicate there is an antiferromagnetic interaction between TEMPO and our GB
diradical in solution.27 It may be mentioned that at this stage we are unable to quantify the spin.
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EPR Absorbance
∆
% decrease in spin
concentration of
TEMPO
EPR Absorbance area
area
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8
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Tempo (1mM)
938
738
563
----
155
375
----
17%
41%
Tempo + 13 (1:1)
Tempo + 2b (1:1)
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Tempo (2mM)
1983
1635
1178
----
348
805
----
18%
41%
Tempo + 13 (1:1)
Tempo + 2b (1:1)
Table 3: Effect of Sample’s spin on the spin of Tempo.
However, a correlation could be made examining the area of absorbance (Integration of the first-
derivative EPR and integration again) of sample and that of TEMPO. This gave the relative spin
concentration which is mentioned in a tabular form in SI. As the sample would generate diradical,
understanding the exact spin state is not conclusive at this stage and need further study. In case of
bispropargyl ethers 1d and 14, no EPR signals could be observed during the reaction under standard
conditions (KOBut/DMSO) indicating that the GB pathway mainly follows a non-radical pathway.
Figure 4. (A) and (B): X band (9.44 GHz) EPR spectra of a mixture of TEMPO and sulfones 13 and 2b and Et3N in CH2Cl2,
Condition: X-band microwave frequency (GHz), 9.44; modulation frequency (KHz), 100; modulation amplitude (G), 140.0;
and microwave power, 0.998 [μW];
Conclusion
In summary, definitive evidences have been provided to confirm the mechanistic pathways followed by
bis-propargyl ethers and sulfones during their GB rearrangement to aryl naphthalene systems. A
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multiprong strategy involving fate of deuterium labeled substrates, trapping of possible intermediates
(mono or bis-allenes) with an external nucleophile (MeOH) and EPR experiments supported the anionic
[4+2] cycloaddition of the mono-allenide species for rearrangement of ethers, while the corresponding
cyclization of sulfones implicated a pathway involving the diradical generated from the bis-allene. All
the present studies are new and for the first time that EPR signals could be detected for reactions of
sulfones, the intermediates could be trapped by methanol as indicated by LA-LDI MS and deuterium
NMR recorded to know the fate of rearrangement of deuterium labeled substrates. Although issues like
intramolecular 1,5-H shift remains to be resolved, this study hopefully dispels some of the confusion
regarding the mechanism of GB cyclization which is definitely proved to be system (ether or sulfone)
dependent.
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Experimental Section
All the reactions were monitored by TLC using polygramR SILG/UV254 precoated (0.25 mm) silica gel
TLC plates. Column chomatography was done with silica gel (60-120 or 230-400 mesh). NMR data
were recorded at 200 MHz, 400 MHz and 600 MHz NMR instruments in CDCl3 unless mentioned
otherwise. For 2H NMR the compounds were dissolved in distilled CHCl3 with 1 drop of CD3CN (δ 2.1)
as internal standard. The following abbreviations are used to describe peak patterns where appropriate: s
= singlet, d = doublet, t = triplet, q = quartet, m = multiplet, app. = apparently, and b = broad signal. All
coupling constants (J) are given in Hz. Mass spectra were recorded in ESI+ mode (ion trap). The LA-
LDI experiments were carried out using MALDI-TOF Mass Spectrometer. UV laser: smart beam II
laser, 355 nm wavelength; laser rep rate 2000 Hz, reflector mode. The mass spectra were recorded in
positive ion mode.
All dry solvents used for reactions were purified according to the standard protocols. Dimethyl
sulfoxide (DMSO), N,N-dimethylformamide (DMF), and triethylamine (Et3N) were distilled from
calcium hydride and Chloroform (CHCl3) was distilled over anhydrous CaCl2. All the solvents for
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column chomatography were distilled prior to use. In most of the column chomatographic purifications,
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ethyl acetate (EA/EtOAc) and petroleum ether (PE) of boiling range 60−80 °C were used as eluents.
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General procedure for the synthesis of sulfones (2b-2d, 2c´, 8b, 8b´, 13)
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To an ice-cold solution of sulfide28 (0.1 mmol) in a mixture of THF (10 mL) and methanol (2 mL) was
added oxone (4.0 eq), a few drops of water and the reaction was allowed to stir at room temperature
overnight. The reaction was then quenched with water (20 mL) and extracted with ethyl acetate. The
organic layer was then dried over Na2SO4, evaporated and subjected to column chromatography [Si-gel,
pet ether-ethyl acetate (5:1) mixture as eluent]. For sulfone 2a see reference 29.
General procedure for the O-propargylation: Synthesis of bis-propargyl ethers (1a-1d, 1d´, 7b,
7b´, 11d´, 14)
To an ice-cold solution of alcohol derivatives (0.1 mmol) in dry DMF (10 mL) was added NaH (2 eq,
60% suspension in mineral oil) and was stirred for 30 min at ice-cold temperature under N2 atmosphere.
After the alkoxide was generated, the respective propargyl bromides (1.0 eq) diluted in dry DMF (10
mL) was added drop wise to the reaction mixture by maintaining the ice-cold temperature. The reaction
was then allowed to stir at room temperature for 1 h. It was quenched with saturated solution of NH4Cl
and partitioned between ethyl acetate and water. Organic layer was washed with brine, dried over
sodium sulfate, evaporated and subjected to column chromatography [Si-gel, pet ether-ethyl acetate
(10:1) mixture as eluent].
General procedure for the Garratt-Braverman Cyclization: Synthesis of aryl naphthalenes
For ethers (3-4 a, b, c, d, 4d´, 9b´, 12d´)
To a solution of ether (0.05 mmol) in dry DMSO (1 mL) was added 1.0 eq of KOtBu and the solution
was allowed to stir at room temperature for 1 h. It was then quenched with NH4Cl and extracted with
ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and evaporated to get the
crude product that was purified by column chromatography with hexane−ethyl acetate (10:1) mixture as
eluent.
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For sulfones (5-6 a, b, c, d, 5c´, 6c´, 10b, 10b´)
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8
To a solution of sulfone (0.05 mmol) in dry CHCl3 (1 mL) was added Et3N (1 eq) and the solution was
allowed to stir at room temperature for 30 min. It was then quenched with NH4Cl and extracted with
DCM. The organic layer was dried over anhydrous sodium sulfate and evaporated to get the crude
product that was purified by column chromatography with hexane−ethyl acetate mixture (5:1) as eluent.
Oxidation to the lactone: Synthesis of Compound (15d´)
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A DMSO (1 mL) solution of phthalan (10 mg, 0.025 mmol) was mixed with freshly prepared IBX (4.0
eq) and was stirred at 90 °C overnight under nitrogen. The solution was then filtered through celite and
was rinsed thoroughly with ethyl acetate several times. The organic layer was then washed with water,
dried over Na2SO4, concentrated in vacuo and the crude product was purified by column
chromatography with hexane-ethyl acetate mixture (4:1) as eluent.
EPR measurement
The samples solutions were prepared in dry dichloromethane and purged with Ar gas to free from any
dissolved oxygen for 5 min. Then base or TEMPO or both was added as per the requirement of the
reaction and preceded for recording the EPR spectra. The radical quenching experiment was performed
via purging O2 gas to a sample solution containing Et3N as base for 2 min and 4 minutes. Continuous-
wave EPR experiments at X band (9.44 GHz) were carried out using ESR spectrometer, at center field
330 mT with a sweep width 30 mT, and a modulation frequency (kHz), 100; modulation amplitude (G),
140.0; and microwave power, 0.998 [μW] at temperature, 22 °C.
Spectral data of new compounds
2,4-dimethoxy-1-(3-((3-(1,2,3,4,5-2H5) phenylprop-2-yn-1-yl)oxy)prop-1-yn-1-yl)benzene (1d´)
State: yellow liquid. Yield: 21 mg, 67%. 1H NMR (400 MHz, Chloroform-d) δ 7.36 (d, J = 8.0 Hz, 1H),
13
6.44 (d, J = 8.0 Hz, 1H), 6.43 (s, 1H), 4.58 (s, 2H), 4.56 (s, 2H), 3.85 (s, 3H), 3.81 (s, 3H); C NMR
(50 MHz, Chloroform-d) δ 161.6, 161.5, 134.7, 131.5 (t, J = 24.5 Hz) 127.9 (2C, s merged with t, J =
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24.4 Hz), 122.5, 104.9, 104.3, 98.5, 87.1, 86.7, 84.8, 83.4, 57.9, 57.4, 55.9, 55.5. HRMS: calcd for
C20H13D5O3 + H+, 312.1643; found, 312.1640.
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4-(2,4-dimethoxyphenyl)-1,3-dihydro(5,6,7,8-2H5) naphtho [2,3-c] furan (4d´)
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1
State: sticky mass. Yield: 11 mg, 74%. H NMR (600 MHz, Chloroform-d) δ 7.70 (s, 0.86H, 0.14D),
7.15 (d, J = 8.4 Hz, 1H), 6.66 (d, J = 2.4 Hz, 1H), 6.64 (dd, J = 8.4 Hz, 2.4 Hz, 1H), 5.32-5.31 (m, 1.5H,
0.5D), 5.04-4.96 (m, 2H), 3.92 (s, 3H), 3.71 (s, 3H); 13C NMR (150 MHz, Chloroform-d) δ 161.0,
158.2, 139.5, 138.1, 137.6, 137.5, 133.7, 132.5, 132.0, 129.0, 119.2, 118.8, 118.7, 114.3, 104.7, 99.2,
73.6, 73.3 (t, J = 25.8 Hz), 55.7, 55.6. HRMS: calcd for C20H13D5O3 + H+, 312.1643; found, 312.1628,
calcd for C20H14D4O3 + H+, 311.1580; found 311.1568.
1-Methoxy-4-[3-(3-(1,2,3,4,5-2H5) phenyl-prop-2-yn-1-sulfonyl) prop-1-ynyl]-benzene (2c´)
State: white solid. m.p. 119-120 °C; Yield: 23 mg, 70%. 1H NMR (400 MHz, Chloroform-d) δ 7.43 (d, J
13
= 8.0 Hz, 2H), 6.85 (d, J = 8.0 Hz, 2H), 4.32 (s, 2H), 4.31 (s, 2H), 3.82 (s, 3H); C NMR (100 MHz,
Chloroform-d) δ 160.6, 133.8, 131.9 (t, J = 24.0 Hz), 129.0 (t, J = 25.0 Hz), 128.1 (t, J = 25.0 Hz),
121.5, 114.3, 113.6, 88.3, 88.1, 76.2, 74.7, 55.6, 44.9, 44.7. HRMS: calcd for C19H11D5O3S + H+,
330.1207; found, 330.1194.
6-Methoxy-4-(1,2,3,4,5-2H5)phenyl-1,3-dihydro-naphtho [2,3-c] thiophene 2,2-dioxide (Major)
(5c´) + 4-(4-Methoxy-phenyl)-1,3-dihydro( 5,6,7,8-2H5) -naphtho [2,3-c] thiophene 2,2-dioxide
(Minor) (6c´) (2:1)
1
State: yellow sticky solid. Yield: 14 mg, 85%. H NMR (600 MHz, Chloroform-d) δ 7.81 (s, 1H,
minor), 7.77 (d, J = 9.0 Hz, 1H, major), 7.74 (s, 1H, major), 7.22 (d, J = 8.4 Hz, 2H, minor), 7.19 (dd, J
= 9.0 Hz, 2.4 Hz, 1H, major), 7.06 (d, J = 8.4 Hz, 2H, minor), 6.84 (d, J = 2.4 Hz, 1H, major), 4.56 (app
s, 2H major, 1H minor, 1D minor), 4.26 (s, 2H, minor), 4.20 (s, 2H, major), 3.91 (s, 3H, minor), 3.70 (s,
3H, major); 13C NMR (150 MHz, Chloroform-d) δ 159.7, 158.6, 138.0, 137.7, 136.8, 133.6, 133.4,
132.5, 130.9, 129.7, 129.6, 129.0, 128.6, 128.4, 126.2, 124.8, 124.7, 119.6, 114.6, 104.9, 57.3, 57.1 (t, J
= 21.6 Hz), 56.8, 56.7, 55.6, 55.4. HRMS: calcd for C19H11D5O3S + H+, 330.1207; found, 330.1213.
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6-Methoxy-4-phenyl-1,3-dihydro-naphtho [2,3-c] thiophene 2,2-dioxide (Major) (5c)+ 4-(4-
Methoxy-phenyl)-1,3-dihydro-naphtho [2,3-c] thiophene 2,2-dioxide (Minor) (6c) (2:1)
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State: yellow sticky solid. Yield: 14 mg, 85%. 1H NMR (400 MHz, Chloroform-d) δ 7.86 (d, J = 8.0 Hz,
1H, minor), 7.80 (s, 1H, minor), 7.76 (d, J = 8.8 Hz, 1H, major), 7.74 (s, 1H, major), 7.61 (d, J = 8.8 Hz,
1H, minor), 7.55-7.41 (m, 3H major, 2H minor), 7.30 (d, J = 6.8 Hz, 2H major), 7.21 (app t, J = 8.8 Hz,
1H major, 2H, minor), 7.06 (d, J = 8.8 Hz, 2H, minor), 6.83 (d, J = 2 Hz, 1H, major), 4.58 (s, 2H,
minor), 4.56 (s, 2H, major), 4.25 (s, 2H, minor), 4.20 (s, 2H, major), 3.90 (s, 3H, minor), 3.70 (s, 3H,
major); 13C NMR (100 MHz, Chloroform-d) δ 159.7, 158.5, 138.0, 137.9, 136.8, 133.6, 133.4, 132.6,
129.7, 129.6, 129.5, 129.2, 129.0, 128.7, 128.6, 128.4, 128.3, 128.1, 127.0, 126.9, 124.8, 124.7, 119.5,
114.5, 104.9, 57.4, 57.3, 56.8, 56.7, 55.6, 55.3. HRMS: calcd for C19H16O3S + H+, 325.0893; found,
325.0912.
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(Sulfonylbis(prop-1-yne-3,1-diyl))(2,3,4,5,6-2H5)dibenzene (8b´)
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State: pale yellow crystalline solid. m.p. 108-109 °C; Yield: 26 mg, 85%. H NMR (400 MHz,
13
Chloroform-d) δ 4.33; C NMR (50 MHz, Chloroform-d) δ 131.8 (t, J = 24.5 Hz), 129.0 (t, J = 24.5
Hz), 128.1 (t, J = 24.5 Hz), 121.4, 88.2, 76.1, 44.8. HRMS: calcd for C18H4D10O2S + H+, 305.1415;
found, 305.1423.
4-(2,3,4,5,6-2H5)Phenyl-1,3-dihydro-(5,6,7,8-2H5)naphtho[2,3-c]thiophene 2,2-dioxide (10b´)
State: White solid. m.p. 177-178 °C; Yield: 14 mg, 90%. 1H NMR (600 MHz, Chloroform-d) δ 7.85 (s,
1H), 4.6 (app s, 1H, 1D), 4.26 (s, 2H); 13C NMR (150 MHz, Chloroform-d) δ 138.2, 137.5, 133.3,
132.2, 129.2 (t, J = 25.0 Hz), 128.6 (t, J = 26.8 Hz), 128.6, 128.1, 127.8 (t, J = 24.1 Hz ), 127.7 (t, J =
25.2 Hz), 126.6 (t, J = 24.6 Hz), 126.5 (t, J = 24.0 Hz), 126.1 (t, J = 24.3 Hz), 125.0, 57.0 (t, J = 21.75
Hz), 56.7. HRMS: calcd for C18H4D10O2S + H+, 305.1415; found, 305.1402.
(Oxybis(prop-1-yne-3.1-diyl)) (2,3,4,5,6-2H5)dibenzene (7b´)
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State: yellow liquid. Yield: 17 mg, 65%. H NMR (400 MHz, Chloroform-d) δ 4.57 (s, 2H); C NMR
(50 MHz, Chloroform-d) δ 131.6 (t, J = 28.5 Hz), 128.1 (2×merged t, J = 24.0 Hz), 122.5, 86.9, 84.6,
57.6. HRMS: calcd for C18H4D10O + H+, 257.1745; found, 257.1740.
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4-phenyl-1,3-dihydro-(5,6,7,8-2H5)naphtho[2,3-c]furan (9b´)
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State: gummy mass. Yield: 9 mg, 70%. H NMR (600 MHz, Chloroform-d) δ 7.72 (s, 0.86H, 0.14D),
13
5.32 (s, 1.65H, 0.35D), 5.04 (s, 2H); C NMR (150 MHz, Chloroform-d) δ 138.1, 137.8, 137.0, 133.8,
132.7, 131.9, 129.2 (t, J = 24.1 Hz), 128.3 (t, J = 24.0 Hz), 125.6-125.1 (m), 118.9, 73.6, 73.1. HRMS:
calcd for C18H4D10O + H+, 257.1745; found, 257.1731, calcd for C18H5D9O + H+, 256.1683; found,
256.1675.
4-(2,4-dimethoxyphenyl)-(5,6,7,8-2H5)naphtho[2,3-c]furan-1(3H)-one (15d´)
1
State: Sticky solid. Yield: 4 mg, 50%. H NMR (600 MHz, Chloroform-d) δ 8.52 (s, 0.86H, 0.14D),
13
7.17 (d, J = 8.4 Hz, 1H), 6.69-6.67 (m, 2H), 5.24 (ABq, J = 15 Hz, 2H), 3.94 (s, 3H), 3.7 (s, 3H); C
NMR (150 MHz, Chloroform-d) δ 171.8, 161.6, 158.1, 139.9, 135.7, 133.8, 132.1, 130.8, 126.3, 123.1,
116.7, 105.1, 99.3, 70.2, 55.8, 55.7. HRMS: calcd for C20H12D4O4 + H+, 325.1374; found, 325.1358,
calcd for C20H11D5O4 + H+, 326.1436; found 326.1419.
1-Methoxy-4-[3-methyl-3-(3-(2,3,4,5,6-2H5)phenyl-prop-2-ynyloxy)-but-1-ynyl]-benzene (11d´)
1
State: yellow liquid. Yield: 21 mg, 67%. H NMR (600 MHz, Chloroform-d) δ 7.40 (d, J = 9 Hz, 2H),
6.86 (d, J = 8.4 Hz, 2H), 4.60 (s, 2H), 3.83 (s, 3H), 1.65 (s, 6H); 13C NMR (150 MHz, Chloroform-d) δ
159.8, 133.4, 114.9, 114.3, 114.1, 89.2, 86.6, 85.5, 85.2, 72.0, 55.5, 53.5, 29.3. HRMS: calcd for
C21H15D5O2 + H+, 310.1850; found, 310.1851.
9-(4-Methoxy-phenyl)1,1-dimethyl-1,3-dihydro-(5,6,7,8-2H5)naphtho[2,3-c]furan (12d´)
State: sticky mass. Yield: 9 mg, 60%. 1H NMR (400 MHz, Chloroform-d) δ 7.66 (s, 0.82H, 0.18D), 7.20
(d, J = 12.6 Hz, 2H), 7.02 (d, J = 12.6 Hz, 2H), 5.18 (app s, 1.73H, 0.27D), 3.90 (s, 3H), 2.17 (s, 6H);
13C NMR (100 MHz, Chloroform-d) δ 159.2, 143.3, 139.5, 138.4, 133.8, 133.2, 133.0, 132.0, 129.5,
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119.0, 114.3, 113.5, 86.4, 69.3, 55.5, 53.6, 31.1, 29.9. HRMS: calcd for C21H15D5O2 + H+, 310.1850;
found, 310.1833, calcd for C21H16D4O2 + H+, 309.1789; found, 309.1804.
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1-Methoxy-4-[3-(3-phenyl-prop-2-yne-1-sulfonyl)-prop-1-ynyl]-benzene (2c)
State: white solid, m.p. 110-111 °C; Yield: 23 mg, 72%. 1H NMR (400 MHz, Chloroform-d) δ 7.50 (d,
2H, J = 6.8 Hz, 2H), 7.43 (d, J = 8.4 Hz, 1H), 7.38-7.32 (m, 4H), 6.85 (d, J = 8.8 Hz, 2H), 4.31 (s, 2H),
4.30 (s, 2H), 3.82 (s, 3H); 13C NMR (50 MHz, Chloroform-d) δ 160.5, 133.8, 132.2, 129.4, 128.6,
121.6, 114.2, 113.6, 88.3, 88.1, 76.2, 74.7, 55.5, 44.9, 44.6. HRMS: calcd for C19H16O3S + H+,
325.0898; found, 325.0912.
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2,4-Dimethoxy-1-[3-(3-phenyl-prop-2-yne-1-sulfonyl)-prop-1-ynyl]-benzene (2d)
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State: pale yellow solid. m.p. 127-128 °C; Yield: 25 mg, 71%. H NMR (400 MHz, Chloroform-d) δ
7.49 (d, 2H, J = 7.6 Hz, 2H), 7.36-7.31 (m, 4H), 6.46-6.43 (bm, 2H), 4.40 (s, 2H), 4.33 (s, 2H), 3.82
(merged s, 6H). 13C NMR (100 MHz, Chloroform-d) δ 162.2, 162.1, 134.7, 132.3, 129.4, 128.6, 111.3,
105.1, 100.2, 98.6, 87.9, 85.1, 78.7, 76.4, 56.0, 55.7, 45.3, 44.2. HRMS: calcd for C20H18O4S + H+,
355.1004; found, 355.1003.
2-Methoxy-6-[3-(3-phenyl-prop-2-yne-1-sulfonyl)-prop-1-ynyl]-naphthalene (2b)
State: yellow solid. m.p. 109-110 °C; Yield: 28 mg, 76%. 1H NMR (600 MHz, Chloroform-d) δ 7.96 (s,
1H), 7.70 (d, J = 1.2 Hz, 2H), 7.53-7.49 (m, 3H), 7.40-7.34 (m, 3H), 7.19 (d, J = 11.4 Hz, 1H), 7.13 (s,
1H), 4.39-4.38 (merged s, 4H), 3.95 (s, 3H). 13C NMR (150 MHz, Chloroform-d) δ 158.9, 134.8, 132.4,
132.3, 129.6, 129.5, 129.0, 128.6, 128.4, 127.2, 121.6, 119.9, 116.4, 106.0, 88.8, 88.2, 76.2, 75.6, 55.6,
44.9, 44.8. HRMS: calcd for C23H18O3S + Na+, 397.0874; found, 397.0874.
3-methoxy-11-phenyl-8,10-dihydrophenanthro[2,3-c]thiophene 9,9-dioxide (Major) (5b) + 4-(6-
methoxynaphthalen-2-yl)-1,3-dihydronaphtho[2,3-c]thiophene 2,2-dioxide (Minor) (6b) (5.16:1)
1
State: yellow sticky solid. Yield: 17 mg, 90%. H NMR (400 MHz, Chloroform-d) δ 7.82 (s, 1H,
major), 7.70 (s, 2H, major), 7.58-7.52 (m, 3H, major), 7.42 (d, J = 9.6 Hz, 1H), 7.28 (app d, J = 8.0 Hz,
2H), 7.20 (d, J =2.8 Hz, 1H), 6.73 (dd, J = 9.6 Hz, 2.8 Hz, 1H), 4.62 (s, 2H major, 2H minor), 4.28 (dd,
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J = 16.8 Hz, 26.2 Hz, 2H minor), 4.15 (s, 2H, major), 3.99 (s, 3H,minor), 3.88 (s, 3H,major). 13C NMR
(100 MHz, Chloroform-d) δ 158.0, 142.3, 137.6, 135.6, 132.8, 130.9, 130.3, 129.3, 129.2, 128.7, 128.6,
128.4, 128.0, 127.6, 126.0, 124.6, 115.8, 109.3, 57.8, 57.7, 55.5. HRMS: calcd for C23H18O3S + H+,
375.1055; found, 375.1079.
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6,8-dimethoxy-4-phenyl-1,3-dihydronaphtho[2,3-c]thiophene 2,2-dioxide (Major) (5d) + 4-(2,4-
dimethoxyphenyl)-1,3-dihydronaphtho[2,3-c]thiophene 2,2-dioxide (Minor) (6d) (5.16:1)
1
State: sticky solid. Yield: 16 mg, 93%. H NMR (400 MHz, Chloroform-d) δ 8.15 (s, 1H, major),7.54-
7.46 (m, 3H, major), 7.29 (app d, J = 5.6 Hz, 2H, major), 6.53 (s, 1H, major), 6.39 (s, 1H, major), 4.56
(s, 2H major, 2H minor), 4.18 (s, 2H major, 2H minor), 3.99 (s, 3H major), 3.91 (s, 3H minor), 3.71 (s,
3H minor), 3.67 (s, 3H major). 13C NMR (100 MHz, Chloroform-d) δ 159.0, 156.6, 138.3, 136.4, 134.1,
129.6, 129.2, 128.3, 125.4, 122.0, 119.4, 98.4, 96.9, 57.6, 56.9, 56.0, 55.4. HRMS: calcd for C20H18O4S
+ H+, 355.1004; found, 355.0987.
Acknowledgement
Author A.B. is grateful to DST, Govt. of India, for funding (SB/S1/OC-94/2013). AB also thanks DST
for the JC Bose fellowship (SR/S2/JCB-11/2011). J. D. thanks CSIR, Govt. of India for a research
fellowship (NET). DST and IIT Kharagpur are also thanked for the funds for 400 MHz (IRPHA
program) and 600 MHz facilities respectively.
1
2
Supporting Information Available: The various H, 13C and H-NMR, HRMS, LA-LDI MS, EPR
spectra. This information is available free of charge via the Internet at http://pubs.acs.org.
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subsequent isomerization to the bis-allene: Braverman, S.; Zafrani, Y.; Gottlieb, H. E.
Tetrahedron 2001, 57, 9177.
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22. The formation of monomethoxy adduct was earlier shown by the appearance of a peak at m/z
417. This material was kept in CDCl3 containing trace HCl which was sufficient to convert the
enol ether to the ketone for which we see the peak at m/z 403 (For MS spectrum see SI).
Because of fast internal quenching through cyclization external addition of MeOH happens to a
very low extent. However, the high sensitivity of this LA-LDI MS technique was able show the
presence of methanol adduct. As a support experiment we have also treated the methoxy alkyne
t
I with BuOK in presence of DMSO:MeOH (7:1) in which case we could isolate the mono-OMe
addition product to the intermediate allene in decent yield.
From the intermediate diradical for sulfones we did not observe any H/D abstraction products
unlike Bergman cyclization in which case that is the major pathway as the radicals cannot self
quench.
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O
O
MeO
C
C
C
C
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m/z 417 (M + K+)
m/z 347 (M + H+)
O
8
9
OMe
OMe
OMe
CDCl3/ trace HCl
O
I
II
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m/z 403 (M + K+)
O
O
O
C
O
O
O
S
S
S
OMe
MeO
C
19
18
13
m/z 497 (M+K+)
23. Feldman. K. S.; Selfridge, B. R. Heterocycles 2010, 81, 117.
24. (a) Shultz, D. A.; Boal, A. K.; Lee, H.; Farmer, G. T. J. Org. Chem. 1999,64,4386. (b) Burton,
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Harrer, H. M.; Heim, C.; Nau, W. M.; Wang, D. J. Am. Chem. Soc. 1996, 118, 3974. (d)
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26. (a) Talsi, E.P.; Semikolenova, N.V.; Panchenko, V.N.; Sobolev, A.P.; Babushkin, D.E.; Shubin,
A.A.; Zakharov, V.A. J. Mol. Cat. A: Chemical 1999, 139, 131. (b) Gafurov, M.; Lyubenova, S.;
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28. The symmetrical sulfides were prepared by treating the corresponding bromides with Na2S in
MeOH while the unsymmetrical ones were prepared by S-propargylation of in situ generated
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Table of Contents
==========================================================================
Intramolecular
-
-
X = O
C
Diels Alder
pathway
This problem of diradical -Cycloaddition
puzzle has been tackled by a multiprong
sudies:
O
KOtBu
DMSO
O
X
R
(IMDAR)
H
Fate
Trapping of mono or bisallene with
methanol and EPR studies:
of
D-labelled
sustrates,
R
R
Et3N/CHCl3
X = SO2
Diradical
pathway
C
X
The mechanism is system dependent:
The nature of the bridging heteroatom (O
or S in SO2) connecting the propargyl
arms
O2S
O2S
C
R
R
R
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