Strain-promoted retro-Dieckmann-type condensation on [2.2.2]- and [2.2.1]bicyclic systems: A fragmentation reaction for the preparation of functionalized heterocycles and carbocycles

Article abstract of DOI:10.1039/c3ob41160e

The fragmentation reaction of differently functionalized [2.2.2]- and [2.2.1]bicyclic systems that leads to substituted five membered heterocycles and five/six membered carbocycles is broadly studied. This reaction is carried out through a retro-Dieckmann-type condensation on strained [2.2.1]bicyclic β-ketosulfones and their counterparts β-ketoesters under very mild catalytic acid or basic conditions and short reaction times. The same reaction is also achieved on [2.2.2]bicyclic β-ketosulfones requiring harsher reaction conditions.

Full text of DOI:10.1039/c3ob41160e

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Strain-promoted retro-Dieckmann-Type Condensation on [2.2.2]- and
[2.2.1]bicyclic Systems: a Fragmentation Reaction for the Preparation of
Functionalized Heterocycles and Carbocycles‡
Elena Moreno-Clavijo, Antonio J. Moreno-Vargas,* Ana T. Carmona and Inmaculada Robina*
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
The fragmentation reaction of differently functionalized [2.2.2]- and [2.2.1]bicyclic systems that leads to
substituted five membered heterocycles and five/six membered carbocycles is broadly studied. This
reaction is carried out through a retro-Dieckmann-type condensation on strained [2.2.1]bicyclic -
10 ketosulfones and their counterparts -ketoesters under very mild catalytic acid or basic conditions and
short reaction times. The same reaction is also achieved on [2.2.2]bicyclic -ketosulfones requiring
harder reaction conditions.
and (hetero)norbornane systems has been scarcely exploited in
45 the opening of the (hetero)bicyclic skeleton.6-14 In most of these
cases the ring opening was carried out through a basic promoted
Introduction
Fragmentation reactions, involving breaking of C-C bonds, are
15 difficult due to the strength and lack of polarization of this bond.
However, this reaction takes place very easily if the C-C bond is
polarized and the fragmentation releases the ring strain of a
system. In this regard, functionalized [2.2.1]bicyclic systems
bearing a β-ketosulfone/ester function, fulfill both requirements,
20 polarization of C-C bond and ring strain. For example,
norbornene ([2.2.1]bicyclic system) is more strained (ca. 100
kJ/mol) than the sum of cyclopentene (23.4 kJ/mol) and
cyclopentane (26.4 kJ/mol) and is comparable with those of
cyclobutane and cyclopropane (111 and 115 kJ/mol,
25 respectively).1
retro-Dieckmann type reaction of
a bicyclic -ketoester,
commonly with stoichiometric amount of bases such as Py-
H2O7,8 or K2CO3-MeOH9 at reflux and NaH in DMF at 0 ºC.11,13
50 In some of the cases, the opening was catalyzed by a specific
enzyme.10
A common approach for the synthesis of diastereomerically
pure substituted cyclopentanes is the use of conformationally
rigid norbornene derivatives as precursors.2 The substituents can
be introduced stereoselectively onto the rigid norbornene ring in
30 an easy manner, so the cleavage of a suitable bond in the bicyclic
skeleton should lead to cyclopentane derivatives with well-
defined configurations. This strategy has been also applied for the
preparation of functionalized tetrahydrofurans3 and pyrrolidines4
from 7-oxa- and 7-azanorbornenes, respectively. In the case of 7-
35 azanorbornenes, the strategy can also lead to functionalized
aminocyclohexene derivatives.5 All these synthetic pathways
require the ring opening of the functionalized bicyclic skeleton
through well-established reaction sequences, such as ozonolysis
and metathesis of double bonds or Baeyer-Villiger oxidation of
40 bicyclic ketones followed by lactone alcoholysis, among others.
In all these cases, the ring opening reaction requires specific
reagents and strong conditions.
Scheme 1. Retro-Dieckmann fragmentation on (7-hetero)norborn-5-en-2-
one derivatives.14
On our side, we have recently reported a very mild procedure
55 for the ring opening of norborn-5-en-2-one and 7-heteronorborn-
5-en-2-ones containing a -ketosulfone functionality (compounds
1-3) through
a
retro-Dieckmann-type reaction.14 In this
preliminary communication we have shown that the ring opening
can be induced by a catalytic amount of NaOMe in MeOH at
60 room temperature with quasi quantitative yield (compounds 1a-
3a, Scheme 1). Alternatively, the fragmentation of aza- and oxo-
norbornenone derivatives 1 and 2 was also successfully induced
by unusual acidic conditions affording pyrroline 1a and
dihydrofuran 2a, respectively. According to these results, we
65 concluded that (7-hetero)norborn-5-en-2-ones are readily
fragmented using catalytic basic conditions. We also observed
that for the ring opening under catalytic acid conditions the
However, the relatively high ring strain of (hetero)norbornene
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Organic & Biomolecular Chemistry
Page 2 of 9
bridgehead heteroatom is crucial, indeed, under these reaction
conditions, norborn-5-en-2-one (3) could not be opened.
fulvene, cyclohexadiene and anthracene, respectively. The
subsequent treatment with mixture of
30 triethylamine/diethylamine in acetonitrile foDllOoIw: 1e0d.1b0y39a/dCd3iOtioBn41o1f60E
a
View Article Online
10% HCl afforded the bicyclic ketones 6-8 as a mixture of
Results and discussion
epimers. This step implies
a three-reaction sequence: (i)
In order to establish the scope and limits of the proposed reaction,
the influence of different structural motifs was considered. For
that purpose different [2.2.1]- and [2.2.2]bicyclic systems
containing a -ketoester/ketosulfone functionality were prepared
(Fig. 1).
conjugate addition of diethylamine to the vinyl sulfone, (ii)
elimination of HBr promoted by triethylamine to afford the
35 enamine intermediate, (iii) acidic hydrolysis of the resulting
enamine to give the corresponding ketone.
5
With these substrates in hand, we decided to study the
fragmentation of the bicyclic system. For [2.2.1] bicyclic
derivatives, besides the influence on the retro-Dieckmann
40 reaction of the bridge-headed heteroatom (nitrogen and oxygen
versus carbon) already studied,14 we consider now the influence
of the electron-withdrawing group (EWG) and the influence of
the bridging C atom, C(sp2) versus a C(sp3) (Table 1).
Boc
O
N
O
O
O
Ts
EWG
EWG
3 (endo/exo = 2.6)
1, EWG = Ts
2, EWG = Ts
(endo/exo = 2.1)
4, EWG = COOMe
(endo/exo = 7.0)
(endo/exo = 1.0)
5, EWG = COOMe
(endo/exo = 1.9)
45 Table 1. Fragmentation on strained [2.2.1]bicyclic -ketosulfones/esters.
O
O
O
Ts
Ts
Ts
7 (a/b = 1.6)15
6 (exo/endo = 1.7)
8
Fig. 1. Strained -ketoesters/sulfones for the retro-Dieckmann reaction.
10
The synthesis of these compounds was carried out following
the methodology reported by Trudell and co-workers.16,17
Compounds 1-5 have been already described by Trudell, Leroy
and our research group,18 but [2.2.1]bicyclic ketone 6 and
15 [2.2.2]bicyclic ketone 8 are synthesized herein for the first time
starting from fulvene and anthracene, respectively. The synthesis
of 6-8 is outlined in Scheme 2. The preparation of [2.2.2]bicyclic
ketone 7 has been described previously by a different synthetic
strategy.19 A mixture of epimers was obtained in all the cases.20
entry
1b
substrate reaction conditionsa
product
1a
yield(%)
82c
NaOMe (0.1 eq.), rt, 1h
1
2b
2
4
5
1
2
4
4
5
3
3
3
6
6
6
2
2
NaOMe (0.1 eq.), rt, 1h
NaOMe (0.1 eq.), rt, 1h
NaOMe (0.1 eq.), rt, 1h
AcOH (0.1 eq.), rt, 1h
AcOH (0.1 eq.), rt, 1h
AcOH (0.1 eq.), rt, 10d
AcOH (0.1 eq.), 55ºC, 16h
AcOH (0.1 eq.), 55ºC, 16h
NaOMe (0.1 eq.), rt, 1h
Py (1 eq.), rt, 1h
2a
4a
quant.
quant.
quant.
quant.
quant.
quant.
90c
3
4
5a
5b
1a
6b
2a
7
4a
8
4a
9
5a/12d
3ae
3a
quant.
quant.
quant.
10b
11b
12b
13
14
15
16
17
f
AcOH (1 eq.), rt, 24h
Py (1 eq.), rt, 6d
-
-
6a
quant.
quant.
Et3N (0.1 eq.), rt, 48 h
AcOH (1 eq.), 55ºC, 30h
BnNH2 (1.2 eq.), rt, 1h
BnNH2 (1.0 eq.),g rt, 1h
6a
f
-
-
2a/2bd
quant.
quant.
2b
20
aGeneral conditions use MeOH as solvent (except when indicated); ratio
Scheme 2. Synthesis of strained β-ketosulfones 6-8. Reagents and
conditions: (a) Tol, 50 ºC, 4h, 83%; (b) Tol, 80 ºC, 4h, 87%; (c) Tol, 90
ºC, 10h, 62%; (d) 1. Et2NH, Et3N, MeCN, rt (50 ºC for 7); 2. 10%
HCl(aq), 80% for 6, 65% for 7, 90% for 8.
1
of the mixtures are given by H-NMR; all the products were obtained in
b
quant. yield (by NMR) except when indicated. These entries correspond
50 to the previous communication (ref. 14). cYield of isolated product by
purification. d Ratio 5a/12 = 2.3, ratio 2a/2b = 1.0. e Epimerization at C-2
25
f
g
2-Bromovinyl sulfones 9-11 were prepared through a Diels-
Alder reaction between p-tolyl 2-bromoethynyl sulfone21 and
was detected in a 1:1 ratio. Starting material was recovered. THF was
used as solvent.
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Organic & Biomolecular Chemistry
The study of the influence of the electron-withdrawing group
in the fragmentation of the bicyclic system was carried out by
changing the tosyl group in -ketosulfones 1 and 2 to a
methoxycarbonyl moiety. The fragmentation reaction of
[2.2.1]bicyclic β-ketoesters 4 and 5 under basic conditions
(NaOMe cat.) was similar to the reaction observed for 1 and 2
(Table 1, entries 1-4) affording the corresponding ring-opened
derivatives, pyrroline 4a and dihydrofuran 5a, in quant. yield.
However, the reaction under catalytic acid conditions was clearly
View Article Online
DOI: 10.1039/C3OB41160E
5
10 slower than with the corresponding tosyl analogues under similar
reaction conditions (entries 5-9). This indicates that the ester
function is less activating towards this fragmentation than the
tosyl one. The proposed mechanism for the unusual acid-
catalyzed retro-Dieckmann fragmentation is shown in Scheme 3.
15 Protonation of the carbonyl group promotes solvent nucleophilic
addition which evolves to the intermediate hemiacetal I. Ring
opening then takes place furnishing the corresponding five
membered functionalized ring.
Scheme 4. Proposed mechanism for the formation of diene 12.
40
ring strain in 6 compared to derivative 3. Attempts to accelerate
the reaction using a stronger base such as DBU provoked the
epimerization at C-2 (ratio 6:1 measured by 1H-NMR) in the ring
opened carbocycle 6a. A similar epimerization had already been
45 observed for the opening of 3 with NaOMe (entry 10). Finally,
the use of Et3N as catalyst, weaker base than DBU but stronger
than pyridine, afforded the best result (entry 14). As in the case of
norbornene 3, the opening of 6 under acidic conditions could not
be possible, even when 6 was treated with a stoichiometric
50 amount of the acid at 55 ºC (entries 12/15). We also explores the
opening of bicyclic systems with a primary amine as promoter in
order to obtain amides. The strained -ketosulfone 2 was chosen
for this purpose. Stoichiometric benzylamine was used in two
different solvents with different results (entries 16 and 17). When
55 MeOH was used, the benzylamine acts both as catalyst and
reagent to give a 1:1 mixture of methyl ester 2a and benzylamide
2b (Table 1). However, when the solvent was THF, benzylamine
provoked the fragmentation of the bicyclic system and the
exclusive formation of benzylamide derivative 2b in quantative
60 yield.
On the other hand, when the -CH2- group in 3 was changed by
a -CH2-CH2- moiety to give [2.2.2]bicyclic system 7 (Scheme 5),
a higher resistance to the opening under the usual basic
conditions was observed (see entry 10/Table 1 for comparison).
65 The fragmentation was finally achieved using NaOMe (0.2 eq.) in
MeOH at 60 ºC. These stronger reaction conditions provoked the
isomerization of the final product affording the ,-unsaturated
ester 7a after 48 h. The change of the -CH2-CH2- bridge in 7 to a
Scheme 3. Proposed mechanism for the acid-promoted retro-Dieckmann
20 type fragmentation.
In the particular case of the acid-promoted ring opening of
bicycle 5, the formation of diene 12 was also observed (Table 1,
entry 9). The formation of 12 can be explained through a
25 mechanism that implies protonation of the bridging oxygen in
intermediate I (X = O), as depicted in Scheme 4. The E-
configuration of the C2-C3 double bond in 12 clearly indicates
that only in the case of exo-5 both reactions (Schemes 3 and 4)
compete.
-CH=CH- (1,2-benzeno unit) in [2.2.2]bicyclic system
8
70 (C(sp3)C(sp2)) allowed the fragmentation reaction to take place
at room temperature what implies an increased ring strain of 8
with respect to 7.
30
In order to study the influence of the nature of the carbon
bridge atom in the ring opening reaction, the behaviour of
norbornenone 3 containing a C(sp3) center and derivative 6 with a
C(sp2) bridge atom was compared. The results of the
fragmentation of 3 and 6 are summarized in Table 1 (entries 10-
35 16). In general, bicycle 6 showed more resistance to the opening
reaction than norbornene 3. Under the same basic conditions
(pyridine in MeOH) compound 3 was opened in 1 hour and
bicycle 6 needed 6 days (entries 8/10), which indicates a lower
Scheme 5. Fragmentation on strained [2.2.2]bicyclic β-ketosulfones.
This journal is © The Royal Society of Chemistry [year]
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Organic & Biomolecular Chemistry
Page 4 of 9
The ability of (7-hetero)norbornenones to give the retro- 40 Table 2. Fragmentation on strained hydroxylated [2.2.1]bicyclic -
Dieckmann fragmentation led us to extend this reaction to highly
functionalized systems such as the new hydroxylated bicycles 19-
21 (Scheme 6). Attempts to prepare these compounds by direct
cis-dihydroxylation of (7-hetero)norbornenones 1-3 were
unsuccessful due to decomposition of the substrates under the
oxidative reaction conditions. Thus, we decided to use the known
(7-hetero)norbornadienes 13-1514 as substrates for the
dihydroxylation/diol protection sequence, giving the new vinyl
10 sulfones 16-18 in good overall yield with total and unambiguous
control of the stereoselectivity. Further transformation into the
new -ketosulfones 19-21 was carried out following the same
procedure as that described for the synthesis of derivatives 6-8.
ketosulfones.
View Article Online
DOI: 10.1039/C3OB41160E
X
retro-Dieckmann
conditions
COOMe
X
O
5
Ts
O
O
(see Table 2)
O
O
Ts
19, X = NBoc
20, X = O
21, X = CH2
19a, X = NBoc
20a, X = O
21a, X = CH2
entry
substrate reaction conditionsa
product
yield(%)
quant.
NaOMe (0.1 equiv.), rt, 1h
19
19a
1
2
3
4
5
19
20
20
21
AcOH (0.1 equiv.), 55ºC,2h
19a
20a
20a
21a
quant.
quant.
70c
NaOMe (0.1 equiv.),b rt, 1h
AcOH (0.1 equiv.),b rt, 9h
Py (0.1 equiv.),b rt, 3h
1. OsO4 (cat.), NMO
acetone-H2O (9:1)
2. 2,2-DMP, PTSA,
acetone
X
X
O
Br
Br
O
quant.
aGeneral conditions use MeOH as solvent (except when indicated); ratio
72-55%
Ts
Ts
1
of the mixtures are given by H-NMR; all the products were obtained in
13, X = NBoc
14, X = O
15, X = CH2
16, X = NBoc
17, X = O
18, X = CH2
quant. yield (by NMR) except when indicated. bCH2Cl2 was used as co-
45 solvent. c Yield of isolated product by purification.
1. Et2NH, Et3N
MeCN
Conclusions
93-76%
2. HClaq (10%)
The high ring strain of (7-hetero)norbornene and (7-
hetero)norbornane systems has been exploited in the opening of
X
O
O
(7-hetero)bicyclic skeletons containing
a -ketosulfone/ester
O
50 functionality through a retro-Dieckmann type reaction. The scope
and limits of this reaction have been established using differently
strained bicyclic systems. In most of the cases (especially in 7-
oxa- and 7-azanorbornene series), we have found that this
reaction occurs under mild basic conditions and even under acidic
55 conditions, which are unusual in this type of reactions. When
using primary amines as base, amides are readily obtained. This
result opens the possibility to the easy ligation of these systems to
amine containing molecules through a stable amide link in a
reagent-free click amidation.
Ts
19, X = NBoc
20, X = O
21, X = CH2
Scheme 6. Synthesis of ring strained hydroxylated (7-hetero)norbornan-
15 2-ones.
The retro-Dieckmann fragmentations of 19-21 were achieved
in an efficient manner (Table 2). The rate of this reaction under
catalytic basic conditions was comparable to the opening of the
20 corresponding unsaturated analogues 1-3. In the case of the
norbornane system 21, the ring opening was carried out using
pyridine instead of NaOMe in order to avoid the epimerization at
C-2 in the corresponding opened product 21a. When using
catalytic acid conditions, the resistance to the retro-Dieckmann
25 reaction was higher than with the unsaturated analogues, and
longer reaction times and/or higher temperatures were needed
(Table 2, entries 2 and 4). This result indicates that the strain
induced to the (7-hetero)norbornan-2-one system by the exo-5,6-
(2,2-dimethyldioxolane) moiety is lower than the strain induced
30 by the endocyclic double bond. Nevertheless the aforementioned
strain is enough to carry out the corresponding fragmentation in
an efficient manner under mild catalytic basic conditions. The
formation of 20 was accomplished with a by-product that could
not be isolated under chromatography column. The analysis of
35 the NMR data of the mixture indicates presumably that the by-
product is an alkene which results by a similar mechanistic
pathway that affords diene 12 from 5 (Scheme 4).
60
The known high exofacial stereoselectivity and regioselectivity
of the reactions on the norbornene double bond skeleton, together
with the ease of the ring opening, the mild conditions in which it
takes place and the high yields obtained, makes the method very
advantageous for the preparation of substituted five-membered
65 heterocycles and five/six membered carbocycles.
Experimental section
General experimental methods.
1H and 13C NMR spectra were obtained for solutions in CDCl3
and [d6]DMSO.  are given in ppm and J in Hz. All the
70 assignments were confirmed by two-dimensional NMR
experiments. The LSI mass spectra were obtained using
thioglycerol and NaI as the matrix. TLC was performed on silica
gel HF254 (Merck), with detection by UV light charring with
H2SO4, vanillin, ninhydrin or with Pancaldi reagent
75 [(NH4)6MoO4, Ce(SO4)2, H2SO4, H2O]. Silica gel 60 (Merck, 230
mesh) was used for preparative chromatography.
General strategy for the synthesis of bicyclic 2-bromovinyl
sulfones 9-11. To a stirred solution of p-tolyl-2-bromoethynyl
sulfone21 (1.5 mmol) in anhydrous toluene (5 mL) the
4
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Organic & Biomolecular Chemistry
corresponding diene (5 equiv. of 6,6-dimethylfulvene or 10
chromatography column on silica gel (ether/cyclohexane, 1/10) to
equiv. of cyclohexa-1,3-diene or 3.3 equiv. of anthracene) was 60 give the corresponding bicyclic bromovinyl ester (598 mg, 45%)
added. The mixture was heated (50 ºC for 9, 80 ºC for 10 and 90
ºC for 11) until the reaction was completed (4-10 h). The solvent
was removed and the residue purified by chromatography column
on silica gel.
(±)-2-Bromo-7-(propan-2-ylidene)-3-(p-toluenesulfonyl)-
bicyclo[2.2.1]hepta-2,5-diene (9). Following the general
procedure and after chromatographic purification (toluene),
as a dark yellowish liquid. To a solution of the VbieicwyAcrltiicclevOinnlyinle
DOI: 10.1039/C3OB41160E
ester (158 mg, 0.684 mmol) in anhydrous CH3CN (4.9 mL) was
added Et3N (0.51 mL) and Et2NH (81 µL). The reaction was
stirred for 5 h. at at room temperature. An aqueous solution of
65 HCl (10 %, 2.5 mL) was added and the mixture was stirred for
1.5 h. at r.t. The solution was diluted with CH2Cl2 and washed
with water. The aqueous phase was extracted with CH2Cl2 and
dried over Na2SO4, concentrated and purified by chromatography
column on silica gel (EtOAc/cyclohexane, 1/2) to give (±)-5 (74.6
5
10 compound 9 was obtained in 83% yield as an amorphous yellow
solid. IR: 3021, 2972, 2914, 2854, 1594, 157, 1546, 1316, 1298,
1289, 1147, 1088, 810, 754, 700, 671 cm-1. 1H NMR (300 MHz, 70 mg, 65%) as a mixture of isomers (endo/exo = 1.9) as a yellowish
CDCl3, ): 7.77-7.73 (m, 2H, H-Ts), 7.33-7.29 (m, 2H, H-Ts),
6.79 (ddd, 1H, J = 5.2, J = 3.2, J = 1.0, H-5 or H-6 ), 6.73 (ddd,
15 1H, J = 5.2, J = 3.0, J = 0.8, H-5 or H-6 ), 4.39 (m, 1H, H-1 or H-
4), 4.16 (m, 1H, H-1 or H-4), 2.42 (s, 3H, CH3 of Ts), 1.45, 1.39
oil. The characterization data match with those reported in the
literature.18
(±)-3-endo
and
3-exo-7-(Propan-2-ylidene)-3-(p-
To
toluenesulfonyl)bicyclo[2.2.1]hepta-5-en-2-one (6).
a
(2s, 3H each one, 2 CH3). 13C NMR (75.4 MHz, CDCl3): 159.1 75 solution of 9 (206 mg, 0.563 mmol) in anhydrous CH3CN (2.5
(C-7), 149.4, 144.6, 143.9 (C-Ar, C-2, C-3), 142.1, 139.7 (C-5,
C-6), 137.0, 129.9, 127.7 (C-Ar), 101.2 (C-2’), 62.3, 53.8 (C-1,
20 C-4), 21.8 (CH3 of Ts), 18.5, 18.4 (2 CH3). MS(CI) m/z: 367
(34%, [M+H]+), 366 (40%, [M]+), 365 (41%, [M+H]+), 364
mL) was added Et3N (0.41 mL) followed by a slowly addition of
a solution of Et2NH (65 μL) in anhydrous CH3CN (1.4 mL). The
reaction was stirred for 20 h at rt. Then HCl(aq) (10 %, 2.1 mL)
was added and the mixture was stirred for 3.5 h at rt. The solution
(30%, [M]+), 285 (33%, [M-Br]+), 211 (56%, [M+H-HTs]+), 209 80 was diluted with DCM and washed with water. The aqueous
(59%, [M+H-HTs]+). HRMS(CI)
m/z: [M]+ Calcd for
phase was extracted with DCM and dried over Na2SO4,
concentrated and purified by chromatography column on silica
gel (cyclohexane/EtOAc, 5/1) to give 6 (137 mg, 80%) as a
mixture of isomers (exo/endo = 1.7) and as a yellowish oil. IR:
C17H17O2S79Br 364.0133; Found 364.0124.
25
(±)-2-Bromo-3-(p-toluenesulfonyl)bicyclo[2.2.2]octa-2,5-
diene (10).22 Following the general procedure and after
chromatographic purification (toluene), compound 10 was 85 2918, 1747, 1596, 1446, 1317, 1303 1145, 1083, 1046, 814, 748,
obtained in 87% yield as an amorphous white solid. IR: 3052,
2980, 2944, 2875, 1610, 1593, 1574, 1318, 1300, 1147, 1108,
705, 665 cm-1. 1H NMR (300 MHz, CDCl3, , mixture of isomers
a/b: 1/1.7): 7.82-7.78 (m, 2H, H-Ts(a)), 7.77-7.72 (m, 2H, J =
8.3, H-Ts(b)), 7.36-7.31 (m, 4H, H-Ts(a), H-Ts(b)), 6.83 (ddd,
1H, J6,5 = 5.6, J = 2.8, J = 0.4, H-5a), 6.66 (ddd, 1H, J5,6 = 5.7, J
30 1088, 814, 759, 709, 675, 654 cm-1. 1H NMR (300 MHz, CDCl3,
): 7.81-7.77 (m, 2H, H-Ts), 7.33-7.28 (m, 2H, H-Ts), 6.32-6.23
(m, 2H, H-5, H-6 ), 4.35 (m, 1H, H-1 or H-4), 3.90 (m, 1H, H-1 90 = 3.1, J = 0.4, H-5b), 6.37 (ddd, 1H, J = 3.4, J = 1.1, H-6b), 6.22
or H-4), 2.43 (s, 3H, CH3 of Ts), 1.57-1.29 (m, 4H, H-7, H-8).
13C NMR (75.4 MHz, CDCl3, ): 144.5, 142.4, 138.0, 134.2 (C-
35 Ar, C-2, C-3), 133.8, 132.7 (C-5, C-6), 129.8, 127.7 (C-Ar), 51.6,
41.1 (C-1, C-4), 25.6, 24.7 (C-7, C-8), 21.8 (CH3 of Ts). MS(CI)
(m, 1H, H-6a), 4.22 (m, 1H, H-4b), 4.07 (m, 1H, H-4a), 3.89 (br
dd, 1H, J = 3.2, J = 0.4, H-3a), 3.73 (br dd, 1H, J = 3.5, J = 1.7,
H-1a), 3.67 (br dd, 1H, J = 3.2, J = 1.9, H-1b), 3.62 (br s, 1H, H-
3b), 2.44 (s, 6H, CH3 of Ts (a), CH3 of Ts (b)), 1.79 (s, 3H,
m/z: 341 (88%, [M+H]+), 339 (100%, [M+H]+). HRMS(CI) m/z: 95 CH3(b)), 1.67 (s, 3H, CH3 (a)), 1.59 (s, 3H, CH3(a)), 1.58 (s, 3H,
[M+H]+ Calcd C15H16O2S79Br 339.0054; Found 339.0055.
11-Bromo-12-(p-toluenesulfonyl)-9,10-dihydro-9,10-
CH3(b)). 13C NMR (75.4 MHz, CDCl3, ): 197.8, 196.6 (CO(a),
CO(b)), 145.1, 145.0 (C-7a, C-7b), 141.9 (C-5b), 140.4, 140.2
(C-Ar), 139.8 (C-5a), 136.8, 136.7 (C-Ar), 135.1 (C-6b), 129.8,
129.7, 129.4, 129.0, 128.9 (C-Ar, C-6a), 121.7, 119.5 (C-2’a, C-
40 ethenoanthracene (11). Following the general procedure and
after
chromatographic
purification
(EtOAc/cyclohexane,
1/100→1/10), compound 11 was obtained in 62% as an 100 2’b), 70.8 (C-3a), 69.8 (C-3b), 58.6 (C-1a), 57.4 (C-1a), 44.9 (C-
amorphous yellow solid. IR: 1593, 1575, 1458, 1317, 1302, 1148,
1090, 1070, 812, 769, 750, 688 cm-1. 1H NMR (300 MHz, CDCl3,
45 ): 7.72-7.67 (m, 2H, H-Ts), 7.36-7.25 (m, 4H, H-Ar), 7.24-7.19
(m, 2H, H-Ts), 7.04-6.98 (m, 4H, H-Ar), 5.77 (s, 1H, H-9 or H-
4a, C-4b), 21.80, 21.78 (CH3 of Ts (a), CH3 of Ts (b)), 20.3, 20.1,
19.8 (2 CH3(a), 2 CH3(b)). MS(LIS) m/z: 325 (100%, [M+Na]+).
HRMS(LSI) m/z: [M+Na]+ Calcd. for C17H18O3SNa 325.0874;
Found 325.0873.
10), 5.29 (s, 1H, H-9 or H-10), 2.37 (s, 3H, CH3 of Ts). 13C NMR 105 (±)-3-endo
and
3-exo-3-(p-Toluenesulfonyl)-
(75.4 MHz, CDCl3, ): 147.0, 144.7, 142.9, 142.4, 140.6, 137.2
(C-Ar, C-11, C-12), 129.7, 127.6, 126.1, 125.6, 123.9, 123.5 (C-
50 Ar), 64.0, 53.8 (C-9, C-10), 21.7 (CH3 of Ts). MS(LSI) m/z: 461
(38%, [M+Na]+), 459 (38%, [M+Na]+). HRMS(LSI) m/z:
bicyclo[2.2.2]octa-5-en-2-one (7).19 This compound was
prepared as described for 6, except that pure 10 (212 mg, 0.625
mmol) was used as starting material and that the reaction with
Et3N (0.47 mL)/Et2NH (0.3 mL) was stirred for 30 h at 50 ºC.
[M+Na]+ Calcd for C23H17O2S79BrNa 459.0030; Found 459.0023. 110 Crude 7 was purified by chromatography column on silica gel
(±)-3-endo
and
3-exo-(Methoxycarbonyl)-7-
(EtOAc/cyclohexane, 1/6) to give 7 (112 mg, 65%) as a mixture
of isomers (a/b: 1.6)15 and as an amorphous white solid. IR: 2975,
2935, 2916, 2874, 1730, 1596, 1301, 1287, 1142, 1081, 1048,
812, 727, 706, 671 cm-1. 1H NMR (300 MHz, CDCl3, , mixture
oxabicyclo[2.2.1]hepta-5-en-2-one (5). To a stirred solution of
55 methyl 3-bromopropiolate23 (946 mg, 5.80 mmol) in anhydrous
toluene (18 mL), furan (4.75 mL, 65.4 mmol) was added in four
portions, one each 2 hours. The mixture was heated at 90 ºC for 115 of isomers a/b: 1.6/1): 7.79 (d, 2H, J = 8.2, H-Ts (a)), 7.74 (d, 2H,
24 h. The solvent was removed and the residue purified by
J = 8.2, H-Ts(b)), 7.35-7.29 (m, 4H, H-Ts(a), H-Ts(b)), 6.54 (m,
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5

Organic & Biomolecular Chemistry
Page 6 of 9
1H, H-5a or H-6a), 6.47 (m, 1H, H-5b or H-6b), 6.22 (m, 1H, H-
hydroxyhepta-2,4-dienedioate (12). In basic conditions:
5a or H-6a), 6.09 (m, 1H, H-5b or H-6b), 3.68-3.53 (m, 4H), 60 Compound 5a was prepared as described for 4a (Method a),
View Article Online
3.25-3.18 (m, 2H), 2.55-2.39 (m, 1H), 2.43 (s, 6H, CH3 of Ts(a),
CH3 of Ts(a)), 2.22-2.08 (m, 1H), 1.85-1.37 (m, 6H). 13C NMR
(75.4 MHz, CDCl3, ): 200.6, 199.8 (CO(a), CO(b)), 145.0,
144.9, 137.4 (C-Ar), 136.7 (C-5a or C-6a), 136.3 (C-Ar), 134.6
except that pure 5 (22 mg, 0.131 mmol) DwOaIs: 1u0s.1e0d39a/sC3sOtaBr4ti1n1g60E
material. Pure 5a (26 mg, quant.) was obtained as a yellowish oil.
In acidic conditions: To a solution of ketoester 5 (25 mg, 0.149
mmol) in MeOH (1 mL), a solution of AcOH (glacial)/MeOH
5
(C-5b or C-6b), 130.2 (C-5a or C-6a), 129.7, 129.6, 129.3, 129.1 65 (0.1 equiv.) was added and the mixture was stirred for 16 h at 55
(C-Ar), 126.5 (C-5b or C-6b), 70.3, 68.5, 48.4, 48.3, 33.8, 33.6,
24.1, 22.0, 21.8, 20.8, 20.7 (C-1a, C-1b, C-4a, C-4b, C-3a, C-3b,
10 2 CH2 (a), 2 CH2 (b), CH3 of Ts (a), CH3 of Ts (b)). MS(CI) m/z:
277 (100%, [M+H]+). HRMS(CI) m/z: [M+H]+ Calcd for
C15H17O3S 277.0898; Found 277.0892.
12-endo and 12-exo-(p-Toluenesulfonyl)-9,10-dihydro-9,10-
ethenoanthracen-11-one (8). This compound was prepared as
15 described for 6, except that pure 11 (172 mg, 0.393 mmol) was
used as starting material and that the reaction with Et3N/Et2NH
ºC. Then, the solution was evaporated to give a mixture of 5a and
12 (30 mg, quant., 5a/12 = 2.3 measured by 1H NMR). The
mixture was purified by column chromatography on silica gel
(CH2Cl2/Acetone, 50/1) to give first 5a as a yellowish oil and
70 second 12 as a colourless oil. Data for 5a: IR: 2955, 1731, 1436,
1274, 1202, 1171, 1089, 1006, 754, 698 cm-1. 1H NMR (300
MHz, CDCl3, ): 6.04 (ddd, 1H, J = 6.1, J = 2.5, J = 1.5, H-3 or
H-4), 5.89 (dt, 1H, J = 6.1, J = 1.9, H-3 or H-4), 5.31 (m, 1H, H-
5), 5.24 (m, 1H, H-2), 3.73 (s, 3H, COOCH3), 3.70 (s, 3H,
was stirred for 48 h at rt. Crude 8 purified by chromatography 75 COOCH3), 2.84 (dd, 1H, JH,H = 15.9, JH,5 = 7.1, CHHCOOMe),
column on silica gel (EtOAc/cyclohexane, 1/4→1/1) to give 8
(133 mg, 90%) as an amorphous yellow solid. IR: 2921, 2899,
20 1727, 1594, 1457, 1314, 1302, 1289, 1176, 1129, 1092, 1077,
811, 754, 705, 669 cm-1. 1H NMR (300 MHz, CDCl3, ): 7.61 (d,
2.61 (dd, 1H, JH,5 = 6.2, CHHCOOMe). 13C NMR (75.4 MHz,
CDCl3, ): 171.5 (COOCH3), 171.3 (COOCH3), 131.8, 125.9 (C-
3, C-4), 84.6 (C-2), 84.0 (C-5), 52.4 (COOCH3), 51.9 (COOCH3),
41.2 (CH2COOMe). MS(CI) m/z: 201 (40%, [M+H]+).
1H, J = 7.4, H-Ar), 7.50 (d, 2H, J = 8.4, H-Ar), 7.45 (d, 1H, J = 80 HRMS(CI) m/z: [M+H]+ Calcd for C9H13O5 201.0763; Found
7.2, H-Ar), 7.34-7.14 (m, 8H, H-Ar), 6.23 (d, 1H, J = 2.3, H-9 or
H-12), 4.81 (s, 1H, H-10), 3.98 (d, J = 2.3, 1H, H-9 or H-12),
25 2.36 (s, 3H, CH3 of Ts). 13C NMR (75.4 MHz, CDCl3, ) 194.2
(CO), 144.8, 139.8, 137.9, 137.6, 136.0, 135.1, 129.4, 129.2,
201.0760. Data for 12: IR: 3400-3300, 2954, 1737, 1708, 1643,
1606, 1435, 1270, 1172, 1082, 1010, 963, 872, 697 cm-1. 1H
NMR (300 MHz, CDCl3, ): 7.68 (dd, 1H, J3,2 = 15.2, J3,4= 11.7,
H-3), 6.32 (br t, 1H, J = 11.3, H-4), 5.98 (d, 1H, H-2), 5.72 (m,
128.2, 128.1, 127.8, 127.7, 126.5, 125.8, 125.5, 124.6 (C-Ar), 85 1H, H-5), 5.15 (br d, 1H, J6,5 = 8.6, H-6), 3.79 (s, 3H, COOCH3),
68.9 (C-9 or C-12), 62.2 (C-10), 46.1 (C-9 or C-12), 21.7 (CH3 of
Ts). MS(LSI) m/z: 397 (34%, [M+Na]+). HRMS(LSI) m/z:
30 [M+Na]+ Calcd for C23H18O3SNa 397.0874; Found 397.0882.
(±)-(2RS,5SR)-N-tert-Butoxycarbonyl-2-methoxycarbonyl-
3.76 (s, 3H, COOCH3). 13C NMR (75.4 MHz, CDCl3, ): 173.4
(COOCH3), 167.1 (COOCH3), 138.5 (C-3), 134.4 (C-5), 130.4
(C-4), 124.4 (C-2), 67.8 (C-6), 53.4 (COOCH3), 51.9 (COOCH3).
MS(CI) m/z: 201 (13%, [M+H]+), 183 (22%, [M+H-H2O]+).
5-(methoxycarbonylmethyl)-3-pyrroline
(4a).
In
basic 90 HRMS(CI) m/z: [M+H]+ Calcd for C9H13O5 201.0763; Found
conditions (Method a): To a solution of ketoester 4 (26.8 mg, 0.1
mmol) in anhydrous MeOH (1 mL), a solution of MeONa/MeOH
35 (0.1 equiv.) was added and the mixture was stirred at rt for 1 h.
Then, acidic resin IR-120 H+ was added till pH 7, the resin was
201.0766.
(±)-(1RS,4SR)-Methyl 5-(propan-2-ylidene)-4-(p-toluene-
sulfonylmethyl)cyclopent-2-enecarboxylate (6a). To a solution
of compound 6 (28.7 mg, 0.095 mmol) in anhydrous MeOH (1
filtered and the solution evaporated to give pure 4a (30 mg, 95 mL), a solution of Et3N/MeOH (0.1 equiv.) was added and the
quant.) as a yellowish oil. In acidic conditions (Method b): To a
solution of ketoester 4 (20.8 mg, 0.078 mmol) in MeOH (0.8
40 mL), a solution of AcOH (glacial)/MeOH (0.1 equiv.) was added
and the mixture was stirred for 10 days at rt. Then, the solution
mixture was stirred at rt for 48 h. Then the solution was
evaporated to give pure 6a (31.7 mg, quant.) as a yellowish oil.
IR: 2950, 2921, 1730, 1596, 1434, 1315, 1299, 1287, 1146, 1085,
1
757 cm-1. H NMR (300 MHz, CDCl3, ): 7.83-7.78 (m, 2H, H-
was evaporated to give pure 4a (23 mg, quant.) as a yellowish oil. 100 Ts), 7.38-7.32 (m, 2H, H-Ts), 6.19 (br dt, 1H, J = 6.0, J = 2.2, H-
IR: 2975, 2954, 1736, 1699, 1435, 1390, 1366, 1252, 1197, 1165,
2 or H-3), 5.79 (ddd, 1H, J = 6.0, J = 2.7, J = 1.5, H-2 or H-3),
4.03 (m, 1H, H-1), 3.80 (m, 1H, H-4), 3.63 (s, 3 H, COOCH3),
1
1127, 1108, 988, 769 cm-1. H NMR (300 MHz, DMSO-d6, 363
45 K, ): 6.06 (br dt, 1H, J = 6.2, J = 2.1, H-3 or H-4), 5.86 (br dt,
1H, J = 6.2, J = 2.0, H-3 or H-4), 4.96 (q, 1H, J = 2.1, H-2), 4.74
3.31 (dd, 1H, JH,H = 14.2, JH,4 = 3.0, CH2-Ts), 3.23 (dd, 1H, JH,4
=
10.4, CH2-Ts), 2.44 (s, 3H, CH3 of Ts), 1.61 (s, 6H, 2 Me). 13C
(m, 1H, H-5), 3.69 (s, 3H, COOCH3), 3.64 (s, 3H, COOCH3), 105 NMR (75.4 MHz, CDCl3, ): 173.2 (COOCH3), 144.8, 137.0,
2.84 (br. dd, 1H, JH,H = 15.2, JH,5 = 4.3, CHHCOOMe), 2.41 (dd,
1H, JH,5 = 8.9, CHHCOOMe), 1.41 (s, 9H, C(CH3)3). 13C NMR
50 (75.4 MHz, DMSO-d6, 363 K, ): 170.0 (COOCH3), 169.7
(COOCH3), 151.9 (CO of Boc), 132.1, 124.4 (C-3, C-4), 79.4
136.6, 132.1, 130.1, 130.0, 129.5, 128.1 (C-Ar, C-2, C-3, C-5, C-
2’), 61.5 (CH2Ts), 53.7 (C-1), 52.2 (COOCH3), 42.5 (C-4), 21.8,
21.3, 20.4 (CH3 of Ts, 2 Me). MS(CI) m/z: 335 (6%, [M+H]+).
HRMS(CI) m/z: [M+H]+ Calcd for C18H23O4S 335.1317; Found
(C(CH3)3), 66.0 (C-2), 60.6 (C-5), 51.5 (COOCH3), 50.7 110 335.1307.
(COOCH3), 40.4-38.6 (CH2COOMe, under DMSO), 27.5
(C(CH3)3). MS(CI) m/z: 300 (3%, [M+H]+), 200 (100%, [M+H-
55 isobutene-CO2]+). HRMS(CI) m/z: [M+H]+ Calcd for C14H22NO6
300.1447; Found 300.1443.
(±)-(2RS,5RS)-2-Methoxycarbonyl-5-(methoxycarbonyl-
methyl)-2,5-dihydrofuran (5a) and (2E,4Z)-dimethyl 6-
(±)-(2RS,5SR)-2-Benzylcarbamoyl-5-(p-toluenesulfonyl-
methyl)-2,5-dihydrofuran (2b). To a solution of compound 2
(37 mg, 0.14 mmol) in anhydrous THF (1 mL), benzylamine (16
µL, 0.146 mmol) was added and the mixture was stirred at rt for 1
115 h. The solvent was evaporated to give pure 2b (52 mg, quant.) as
a yellowish oil. IR: 3405, 3342, 2921, 1669, 1596, 1523, 1312,
6
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Page 7 of 9
Organic & Biomolecular Chemistry
1300, 1289, 1139, 1078, 814, 699, 659 cm-1. 1H NMR (300 MHz,
DMSO-d6, ): 7.87 (br t, 1H, JNH,H = 6.2, NH), 7.75-7.69 (m, 2H, 60 stirred at rt for 1 h. Then, saturated NaHCO3(aq) was added, and
monohydrate (20 mg, 0.105 mmol) were added. The mixture was
View Article Online
DOI: 10.1039/C3OB41160E
H-Ts), 7.44-7.39 (m, 2H, H-Ts), 7.36-7.19 (m, 5H, H-Ar), 6.04
(dt, 1H, J = 6.1, J = 1.9, H-3 or H-4), 5.94 (ddd, 1H, J = 6.1, J =
2.4, J = 1.4, H-3 or H-4), 5.20-5.10 (m, 2H, H-5, H-2), 4.27 (d,
2H, CH2Ph), 3.65 (dd, 1H, JH,H = 14.3, JH,5 = 4.5, CHHTs), 3.58
the crude was extracted with DCM, dried over Na2SO4,
concentrated under reduced pressure, and purified by column
chromatography on silica gel (EtOAc/cyclohexane, 1:6) to give
16 (272 mg, 72%) as an amorphous yellow solid. IR: 2973, 2933,
5
(dd, 1H, JH,5 = 7.4, CHHTs), 2.36 (s, 3H, CH3 of Ts). 13C NMR 65 1711, 1595, 1573, 1370, 1321, 1295, 1147, 1115, 1097, 1075,
1
(75.4 MHz, DMSO-d6, ): 169.6 (CO), 144.5, 138.9, 136.7, 129.8
(C-Ar), 129.1 (C-3 or C-4), 128.3 (C-Ar), 128.0 (C-3 or C-4),
10 127.3, 127.1, 126.9 (C-Ar), 85.9, 81.2 (C-2, C-5), 60.3 (CH2Ts),
41.7 (CH2Ph), 21.0 (CH3 of Ts). MS(CI) m/z: 372 (40%,
665 cm-1. H NMR (300 MHz, CDCl3, ): 7.87-7.82 (m, 2H, H-
Ts), 7.38 (d, 2H, J = 8.1, H-Ts), 4.77 (br s, 1H, H-1 or H-4), 4.66
(br s, 1H, H-1 or H-4), 4.56 (d, 1H, J = 5.5, H-5 or H-6), 4.44 (d,
1H, J = 5.5, H-5 or H-6), 2.46 (s, 3H, CH3 of Ts), 1.44 (s, 3H,
[M+H)]+). HRMS(CI) m/z: [M+H]+ Calcd for C20H22NO4S 70 C(CH3)2), 1.31 (s, 3H, C(CH3)2), 1.27 (s, 9H, C(CH3)3). 13C NMR
372.1270; Found 372.1279.
(125 MHz, CDCl3, ): 154.4 (CO of Boc), 145.8 (C-Ar), 144.6
(br, C-2 or C-3), 136.6 (C-Ar), 136.2 (br, C-2 or C-3), 130.3,
128.1 (C-Ar), 117.0 (C(CH3)2), 81.5 (C(CH3)3), 80.4, 78.8 (C-5,
C-6), 72.7, 66.8 (C-1, C-4), 28.0 (C(CH3)3), 26.3, 25.7 (C(CH3)2),
(±)-(4SR)-Methyl 4-(p-toluenesulfonylmethyl)cyclohex-1-
15 enecarboxylate (7a). To a solution of compound 7 (29.7 mg,
0.107 mmol) in anhydrous MeOH/THF (3:1, 1.3 mL), a solution
of NaOMe/MeOH (0.2 equiv.) was added and the mixture was 75 21.8 (CH3 of Ts). MS(LSI) m/z: 524 (36%, [M+Na]+), 522 (33%,
stirred for 48 h at 60 ºC. Then, acidic resin IR-120 H+ was added
till pH 7, the resin was filtered and the solution evaporated to
20 give pure 7a (33 mg, quant.) as a colourless oil. IR: 2923, 1708,
1650, 1596, 1435, 1299, 1287, 1251, 1144, 1084, 815, 664 cm-1.
[M+Na]+), 402 (25%, [M+H-isobutene-CO2]+), 400 (23%, [M+H-
isobutene-CO2]+). HRMS(LSI) m/z: [M+Na]+ Calcd for
C21H26NO6S79BrNa 522.0562; found 522.0565.
(±)-2-Bromo-5,6-exo-isopropylidenedioxy-3-(p-toluene-
1H NMR (300 MHz, CDCl3, ): 7.79-7.75 (m, 2H, H-Ts), 7.37- 80 sulfonyl)-7-oxabicyclo[2.2.1]hept-5-ene (17). This compound
7.32 (m, 2H, H-Ts), 6.86 (m, 1H, H-2), 3.70 (s, 3 H, COOCH3),
was prepared as described for 16, except that pure 14 (115 mg,
0.351 mmol) was used as starting material. Crude 17 was purified
by column chromatography on silica gel (EtOAc/cyclohexane,
1:6) to give 17 (77 mg, 55%) as a colourless oil. IR: 2928, 1583,
3.07 (dd, 1H, JH,H = 14.1, JH,4 = 5.9, CHHTs), 3.00 (dd, 1H, JH,4
=
25 6.9, CHHTs), 2.59-1.85 (m, 6H, CH2, H-4), 2.44 (s, 3H, CH3 of
Ts), 1.42 (m, 1H, CH2). 13C NMR (75.4 MHz, CDCl3, ): 167.5
(COOCH3), 144.9 (C-Ar), 137.4 (C-2), 137.1, 130.1, 127.9 (C- 85 1454, 1374, 1326, 1208, 1152, 1072, 856, 809, 663 cm-1. 1H
Ar, C-1), 61.6 (CH2Ts), 51.7 (COOCH3), 31.7, 28.2, 28.1 23.3 (3
CH2, C-4), 21.7 (CH3 of Ts). MS(CI) m/z: 309 (21%, [M+H]+).
30 HRMS(CI) m/z: [M+H]+ Calcd for C16H21O4S 309.1161; Found
309.1157.
NMR (300 MHz, CDCl3, ): 7.86-7.79 (m, 2H, H-Ts), 7.38 (d,
2H, J = 8.0, H-Ts), 4.86 (d, 1H, J = 1.2, H-1 or H-4), 4.71 (d,
1H, J = 1.2, H-1 or H-4), 4.59 (d, 1H, J = 5.3, H-5 or H-6), 4.52
(d, 1H, J = 5.3, H-5 or H-6), 2.46 (s, 3H, CH3 of Ts), 1.45 (s, 3H,
(±)-(9SR,10SR)-Methyl 10-(p-toluenesulfonylmethyl)-9,10- 90 C(CH3)2), 1.32 (s, 3H, C(CH3)2). 13C NMR (75.4 MHz, CDCl3,
dihydroanthracene-9-carboxylate (8a). To
a
solution of
): 145.9, 144.4, 136.4, 134.7 (C-Ar, C-2, C-3), 130.4, 128.1 (C-
Ar), 117.0 (C(CH3)2), 89.3, 83.9 (C-1, C-4), 80.2, 78.9 (C-5, C-
6), 26.2, 25.9 (C(CH3)2), 21.9 (CH3 of Ts). MS(LSI) m/z: 403
(3%, [M+H]+), 401 (4%, [M+H]+), 387 (10%, [M-Me]+), 385
compound 8 (20 mg, 0.053 mmol) in anhydrous MeOH/CH2Cl2
35 (1:1.5, 1 mL), NaOMe (1.2 mg, 0.022 mmol) was added and the
mixture was stirred at rt for 20 h. Then the solution was
evaporated to give pure 8a (22 mg, quant.) as a yellowish oil. IR: 95 (10%, [M-Me]+). HRMS(LSI) m/z: [M+Na]+ Calcd for
2951, 2924, 1730, 1596, 1485, 1450, 1432, 1402, 1287, 1146,
C16H17O5S79BrNa (M+Na): 422.9878; Found 422.9879.
(±)-2-Bromo-5,6-exo-isopropylidenedioxy-3-(p-toluene-
1
1135, 758, 736, 672 cm-1. H NMR (300 MHz, CDCl3, ): 7.79-
40 7.76 (m, 2H, H-Ar), 7.52-7.49 (m, 2H, H-Ar), 7.37-7-22 (m, 8H,
sulfonyl)bicyclo[2.2.1]hept-2-ene (18). This compound was
prepared as described for 16, except that pure 15 (406 mg, 1.25
100 mmol) was used as starting material. Crude 18 was purified by
column chromatography on silica gel (EtOAc/cyclohexane, 1:5)
to give 18 (351 mg, 70%) as a colourless oil. IR: 2990, 2935,
1595, 1568, 1449, 1375, 1322, 1265, 1207, 1149, 1067, 1051,
H-Ar), 4.99 (s, 1H, H-9), 4.91 (t, 1H, J = 5.6, H-10), 3.64 (d,
2H, CH2Ts), 3.62 (s, 3 H, COOCH3), 2.42 (s, 3H, CH3 of Ts). 13
C
NMR (75.4 MHz, CDCl3, ): 172.9 (COOCH3), 144.6, 137.9,
137.4, 133.3, 129.9, 129.4, 128.9, 128.3, 128.0, 127.4 (C-Ar),
45 65.2 (CH2Ts), 52.8 (COOCH3), 51.8 (C-9), 39.5 (C-10), 21.7
(CH3 of Ts). MS(LSI) m/z: 429 (18%, [M+Na]+). HRMS(LSI)
1
853, 813, 673, 652 cm-1. H NMR (300 MHz, CDCl3, ): 7.85-
m/z: [M+Na]+ Calcd for C24H22O4SNa 429.1137; Found 105 7.79 (m, 2H, H-Ts), 7.38-7.33 (m, 2H, H-Ts), 4.34 (m, 1H, H-5
429.1149.
(±)-7-tert-Butoxycarbonyl-2-bromo-5,6-exo-isopropylidene-
50 dioxy-3-(p-toluenesulfonyl)-7-azabicyclo[2.2.1]hept-2-ene (16).
To a solution of 13 (321 mg, 0.75 mmol) in acetone/H2O (9:1, 21
or H-6), 4.31 (m, 1H, H-5 or H-6), 3.14 (m, 1H, H-1 or H-4), 3.00
(m, 1H, H-1 or H-4), 2.45 (s, 3H, CH3 of Ts), 2.00 (dt, 1H, J7a,7b
= 9.7, J = 1.5, H-7a), 1.91 (dq, 1H, J = 1.6, H-7b), 1.43 (s, 3H,
C(CH3)2), 1.30 (s, 3H, C(CH3)2). 13C NMR (75.4 MHz, CDCl3,
mL) were added NMO (154 mg, 1.31 mmol) and a solution of 110 ): 145.3, 144.7, 137.1, 135.9 (C-Ar, C-2, C-3), 130.2, 128.0 (C-
t
OsO4 in BuOH (2.5 wt %, 0.69 mL). After stirring for 1 h, the
reaction mixture was cooled at 0 ºC and saturated NaHSO3(aq)
55 was slowly added. Then, the crude was extracted with EtOAc,
dried over Na2SO4 and concentrated under reduced pressure. The
Ar), 115.0 (C(CH3)2), 80.4, 79.6 (C-5, C-6), 58.2, 49.4 (C-1, C-
4), 42.4 (C-7), 25.9, 24.6 (C(CH3)2), 21.8 (CH3 of Ts). MS(CI)
m/z: 401 (15%, [M+H]+), 399 (15%, [M+H]+). HRMS(CI) m/z:
[M+H]+ Calcd. for C17H20O4S79Br 399.0266; Found 399.0265.
resulting residue was dissolved in acetone (9 mL) and 2,2- 115 (±)-3-endo
and
3-exo-7-tert-Butoxycarbonyl-5,6-exo-
dimethoxypropane (DMP) (0.63 mL, 5.14 mmol) and PTSA
isopropylidenedioxy-3-(p-toluenesulfonyl)-7-azabicyclo-
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7

Organic & Biomolecular Chemistry
Page 8 of 9
[2.2.1]heptan-2-one (19). This compound was prepared as
5.2, H-5b or H-6b), 4.22 (br d, 1H, J = 5.2, H-5b or H-6b), 3.75
described for 6, except that pure 16 (48.3 mg, 0.097 mmol) as 60 (d, 1H, J = 4.8, H-3a), 3.25 (m 1H, H-4a), 3.21 (m, 1H, H-1b),
View Article Online
starting material and that reaction with Et3N/Et2NH was stirred
for 1 h at rt. Compound 19 was obtained pure enough (39.5 mg,
93%) without chromatographic purification. IR ν 2979, 2934,
1775, 1704, 1596, 1393, 1325, 1304, 1269, 1152-901 cm-1. 13C
3.16 (d, 1H, J = 3.3, H-3b), 2.86 (br s, 1H, DHO-1I:a1)0, .21.08329/(Cb3rOsB, 411H1,60E
H-4b), 2.46-2.39 (m, 7H, CH3 of Ts (a), CH3 of Ts (a), H-7b),
2.29 (m, 1H, H-7a), 2.15 (m, 1H, H-7b), 1.48 (s, 3H, C(CH3)2(a)),
1.47 (s, 3H, C(CH3)2(b)), 1.45 (m, 1H, H-7a), 1.37 (s, 3H,
5
NMR (75.4 MHz, CDCl3, , mixture of rotamers): 195.4, 194.7, 65 C(CH3)2(a)), 1.27 (s, 3H, C(CH3)2(b)). 13C NMR (75.4 MHz,
194.5, 153.3, 152.9, 152.7, 146.0, 146.0, 145.7, 136.1, 135.2,
134.8, 130.2, 130.2, 130.1, 129.4, 129.2, 128.9, 114.1, 114.0,
CDCl3, ): 201.9, 201.7 (CO(a), CO(b)), 145.7, 145.5, 137.0,
136.1, 130.1, 130.0, 129.0, 128.8 (C-Ar), 112.1, 111.3
(C(CH3)2(a), (C(CH3)2(b)), 80.9 (C-5b or C-6b), 77.6-76.7 (C-5a,
C-6a and C-5b or C-6b, under solvent), 71.1 (C-3a), 69.0 (C-3b),
10 113.4, 82.1, 81.7, 81.5, 81.2, 78.4, 78.3, 78.1, 70.0, 69.6, 69.4,
68.2, 67.1, 61.8, 61.6, 61.1, 28.5, 28.4, 28.3, 25.7, 25.6, 25.5,
24.8, 24.6, 24.4, 21.9, 21.8. LSIMS m/z 460 (61%, [M+Na]+), 70 57.0 (C-1a), 55.4 (C-4b), 43.3 (C-4a), 42.9 (C-1b), 29.4 (C-7a),
422 (14%, [M-Me]+), 338 (29%, [M+H-isobutene-CO2]+).
LSIHRMS m/z found 460.1405, calcd. for C21H27NO7SNa
15 (M+Na): 460.1406.
28.8 (C-7b), 25.3, 25.2, 24.4, 24.3 (C(CH3)2(a), C(CH3)2(b)), 21.8
(CH3 of Ts (a), CH3 of Ts (b)). MS(CI) m/z: 337 (50%, [M+H]+),
321 (67%, [M-Me]+), 181 (100%, [M+H-HTs]+). HRMS(CI)
m/z: [M+H]+ Calcd for C17H21O5S 337.1110; Found 337.1109.
(±)-(2RS,3SR,4RS,5SR)-N-tert-Butoxycarbonyl-2-
methoxycarbonyl-3,4-isopropylidene-dioxy-5-(p-toluene-
sulphonylmethyl)pyrrolidine (19a). In basic conditions: This
compound was prepared as described for 4a (Method a), except
that pure 19 (25.9 mg, 0.059 mmol) was used as starting material.
(±)-3-endo and 3-exo-5,6-exo-isopropylidenedioxy-3-(p-
toluenesulfonyl)-7-oxabicyclo[2.2.1]heptan-2-one (20). This
compound was prepared as described for 6, except that pure 17
(66.5 mg, 0.166 mmol) was used as starting material and that the
20 reaction with Et3N/Et2NH was stirred for 3 h at rt. Compound 20
was obtained pure enough (52.9 mg, 94%) as a mixture of
75
isomers (exo/endo = 1.6) without chromatographic purification. 80 In this case, acidic resin was not added. Compound 19a (27.6 mg,
IR: 2949, 1771, 1596, 1375, 1315, 1264, 1213, 1141, 1126, 1082,
856, 809, 663 cm-1. 1H NMR (300 MHz, CDCl3, , mixture of
25 isomers a/b: 1/1.6): 7.87-7.82 (m, 2H, H-Ts(a)), 7.77-7.73 (m,
2H, H-Ts(b)), 7.42-7.37 (m, 2H, H-Ts(a)), 7.37-7.32 (m, 2H, H-
quant.) was obtained as a yellowish solid. In acidic conditions:
To a solution of ketosulfone 19 (25.8 mg, 0.059 mmol) in MeOH
(1.0 mL), a solution of AcOH (glacial)/MeOH (0.1 equiv.) was
added and the mixture was stirred for 2 h at 55 ºC. Then, the
Ts(b)), 5.46 (d, 1H, J = 5.5, H-5a or H-6a), 5.20 (br. d, 1H, J = 85 solution was evaporated to give pure 19a (27.5 mg, quant.). IR:
1.5, H-1b or H-4b), 5.11 (dd, 1H, J4,3 = 6.1, J4,1 = 1.4, H-4a), 4.68
(d, 1H, J = 5.5, H-5a or H-6a), 4.52 (d, 1H, J = 5.5, H-5b or H-
30 6b), 4.44 (d, 1H, J = 5.5, H-5b or H-6b), 4.40 (m, 1H, H-1a), 4.21
(br d, 1H, H-1b or H-4b), 4.09 (dd, 1H, J = 1.0, H-3a), 3.45 (s,
2980, 2934, 1748, 1699, 1381, 1368, 1206, 1153, 1124, 1052,
1
772 cm-1. H NMR (300 MHz, DMSO-d6, 363 K, ): 7.84-7.79
(m, 2H, H-Ts), 7.53-7.47 (m, 2H, H-Ts), 4.93 (dd, 1H, J3,4 = 5.8,
J3,2 = 1.7, H-3), 4.78 (d, 1H, H-4), 4.30 (br s, 1H, H-2), 4.24 (m,
1H, H-3b), 2.46 (s, 3H, CH3 of Ts (a)), 2.45 (s, 3H, CH3 of Ts 90 1H, H-5), 3.70 (s, 3H, COOCH3), 3.57-3.54 (m, 2H, CH2Ts), 2.45
(b)), 1.50 (s, 3H, C(CH3)2(a)), 1.47 (s, 3H, C(CH3)2(b)), 1.37 (s,
3H, C(CH3)2(a)), 1.28 (s, 3H, C(CH3)2(b)). 13C NMR (75.4 MHz,
35 CDCl3, ): 197.7, 197.3 (CO(a), CO(b)), 146.1, 146.0, 136.2,
135.3, 130.2, 130.1, 129.3, 128.9 (C-Ar), 114.7, 113.9
(s, 3H, CH3 of Ts), 1.39 (s, 3H, C(CH3)2), 1.31 (s, 9H, C(CH3)3),
1.27 (s, 3H, C(CH3)2). 13C NMR (75.4 MHz, DMSO-d6, 363 K,
): 169.9 (COOCH3), 152.0 (CO of Boc), 144.3, 136.2, 129.6,
127.2 (C-Ar), 111.4 (C(CH3)2), 82.5 (C-4), 81.3 (C-3), 80.2
(C(CH3)2(a), (C(CH3)2(b)), 85.9 (C-1a), 83.9 (C-1b or C-4b), 81.9 95 (C(CH3)3), 65.9 (C-2), 58.6 (C-5), 55.3 (br, CH2Ts), 51.8
(C-1b or C-4b), 81.7 (C-5b or C-6b), 81.1 (C-4a), 79.4 (C-5a or
C-6a), 78.54, 78.48 (C-5a or C-6a, C-5b or C-6b), 69.4 (C-3a),
40 68.9 (C-3b), 25.8, 25.31, 25.30 (C(CH3)2(a), C(CH3)2(b)), 21.9
(CH3 of Ts (a), CH3 of Ts (b)). MS(CI) m/z: 339 (37%, [M+H]+),
(COOCH3), 27.3 (C(CH3)3), 26.3, 24.5 (C(CH3)2), 20.5 (CH3 of
Ts). MS(LSI) m/z: 492 (30%, [M+Na]+), 454 (15%, [M-Me]+),
370 (100%, [M+H-isobutene-CO2]+). HRMS(LSI) m/z: [M+Na]+
Calcd for C22H31NO8SNa 492.1668; Found 492.1682.
183 (77%, [M+H-HTs]+). HRMS(CI) m/z: [M+H]+ Calcd for 100 (±)-(2RS,3RS,4SR,5SR)-2-Methoxycarbonyl-3,4-
C16H19O6S 339.0902; Found 339.0897.
isopropylidenedioxy-5-(p-toluenesulphonylmethyl)-
(±)-3-endo and 3-exo-5,6-exo-isopropylidenedioxy-3-(p-
tetrahydrofuran (20a). In basic conditions: This compound was
prepared as described for 4a (Method a), except that pure 20
(22.2 mg, 0.066 mmol) in MeOH:DCM (2:1, 1.1 mL) was used as
45 toluenesulfonyl)bicyclo[2.2.1]heptan-2-one
(21).
This
compound was prepared as described for 6, except that pure 18
(125 mg, 0.313 mmol) was used as starting material and that the 105 starting material. In this case, acidic resin was not added.
reaction with Et3N/Et2NH was stirred at 50 ºC. After 24 h further
Et3N/Et2NH were added and the reaction was stirred for another
50 24 h at 50 ºC. Crude 21 was purified by chromatography column
on silica gel (EtOAc/Cyclohexane, 1/4) to give pure 21 (80 mg,
Compound 20a (25 mg, quant.) was obtained as an amorphous
white solid. In acidic conditions: To a solution of ketosulfone 20
(54 mg, 0.16 mmol) in MeOH:DCM (2:1, 2.7 mL), a solution of
AcOH (glacial)/MeOH (0.1 equiv.) was added and the mixture
76%) as a mixture of isomers (exo/endo = 3.9) and as an 110 was stirred for 9 h at rt. Then, the solution was evaporated and
amorphous white solid. IR: 2978, 2936, 1755, 1596, 1376, 1318,
1309, 1294, 1262, 1210, 1185, 1147, 1137, 1065, 823, 716 cm-1.
55 1H NMR (300 MHz, CDCl3, , mixture of isomers a/b: 1/3.9):
7.87-7.81 (m, 2H, H-Ts(a)), 7.79-7.73 (m, 2H, H-Ts(b)), 7.38-
the resulting crude purified by column chromatography on silica
gel (DCM/acetone, 40:1) to give 20a (41 mg, 70%) as an
amorphous white solid. IR: 2988, 2937, 1749, 1596, 1381, 1315,
1300, 1209, 1140, 1082, 864, 732 cm-1. 1H NMR (300 MHz,
7.35 (m, 4H, H-Ts(a), H-Ts(b)), 5.35 (br d, 1H, J = 5.2, H-5a or 115 CDCl3, ): 7.84-7.79 (m, 2H, H-Ts), 7.35 (d, 2H, J = 8.0, H-Ts),
H-6a), 4.52 (br d, 1H, J = 5.2, H-5a or H-6a), 4.25 (br d, 1H, J =
4.86 (dd, 1H, J3,4 = 6.2, J = 2.3, H-3 or H-4), 4.80 (dd, 1H, J =
8
|
Journal Name, [year], [vol], 00–00
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Organic & Biomolecular Chemistry
60 5 (a) G. Pandey, S. Rajender, Chem. Eur. J. 2011, 17, 6304. (b) A.
Kamimura, T. Nakano, J. Org. Chem. 2010, 75, 3133. (c) G. Pandey,
K. N. Tiwari, V. G. Puranik, Org. Lett., 2008, 10, 3611.
2.2, H-4 or H-3), 4.54 (ddd, 1H, J = 8.1, J = 5.4, J = 2.3, H-5),
4.50 (d, 1H, J = 2.3, H-2), 3.71 (s, 3H, COOCH3), 3.58 (dd, 1H,
H,H = 14.5, CHHTs), 3.34 (dd, 1H, CHHTs), 2.44 (s, 3H, CH3 of
Ts), 1.51 (s, 3H, C(CH3)2), 1.33 (s, 3H, C(CH3)2). 13C NMR (75.4
View Article Online
J
DOI: 10.1039/C3OB41160E
For the preparation of cyclopentene/cyclopentane systems, see ref. 7-
6
10.
5
MHz, CDCl3,  ppm)  171.0 (COOCH3), 145.1, 136.5, 130.0, 65 7 S. Pellegrino, F. Clerici, M. L. Gelmi, Tetrahedron, 2008, 64, 5657.
8
C. Cabrele,F. Clerici, R. Gandolfi, M. L. Gelmi, F. F. Molinari, S.
Pellegrino, Tetrahedron, 2006, 62, 3502.
128.5 (C-Ar), 114.4 (C(CH3)2), 84.6 (C-4), 83.8 (C-3, C-2), 81.3
(C-5), 58.9 (CH2Ts), 52.6 (COOCH3), 27.0, 25.3 (C(CH3)2), 21.8
(CH3 of Ts). MS(LSI) m/z: 393 (100%, [M+Na]+), 371 (13%,
[M+H]+). HRMS(LSI) m/z: [M+Na]+ Calcd for C17H22O7SNa
9
F. Clerici, M. L. Gelmi, S. Pellegrino, T. Pilati, J. Org. Chem., 2003,
68, 5286.
70 10 M. L. Gelmi, F. Clerici, R. Gandolfi, S. Pellegrino,
Tetrahedron:Asymmetry, 2008, 19, 584.
10 393.0984; Found 393.0984.
11 For the preparation of dihydrofurans: (a) J. D. Rainier, Q. Xu, Org.
Lett. 1999, 1, 27.
12 For the preparation of pyrrolidine derivatives: (a) A. Avenoza, J. I.
(±)-(1RS,2SR,3RS,4SR)-Methyl 2,3-isopropylidenedioxy 4-
(p-toluenesulphonylmethyl)-cyclopentanecarboxylate (21a).
To a solution of compound 21 (23.5 mg, 0.07 mmol) in
anhydrous MeOH/CH2Cl2 (4:1, 1 mL), a solution of Py/MeOH
15 (0.1 equiv.) was added and the mixture was stirred at rt for 3 h.
Then the solution was evaporated to give pure 21a (26 mg,
quant.) as a yellowish oil. IR: 2990, 2918, 1718, 1596, 1442,
1380, 1283, 1245, 1195, 1173, 1136, 1068, 870, 806, 780, 632
75
80
Barriobero, J. H. Busto, J. M. Peregrina, J. Org. Chem., 2003, 68,
2889.
13 For the preparation of pyrroline derivatives: G. M. Weeresakare, Q.
Xua, J. D. Rainier, Tetrahedron Lett., 2002, 43, 8913.
14 E. Moreno-Clavijo, A. J. Moreno-Vargas, R. Kieffer, T. Sigstam, A.
T. Carmona, I. Robina, Org. Lett., 2011, 13, 6244.
15 Exo- and endo-isomers were not assigned on the mixture.
16 C. Zhang, M. L. Trudell, J. Org. Chem., 1996, 61, 7189.
17 C. Zhang, C. J. Ballay II, M. L. Trudell, J. Chem. Soc., Perkin Trans.
1, 1999, 675.
1
cm-1. H NMR (300 MHz, CDCl3, ): 7.81-7.76 (m, 2H, H-Ts),
20 7.35 (d, 2H, J = 8.0, H-Ts), 4.79 (dd, 1H, J2,3 = 6.5, J2,1 = 4.0, H-
2), 4.33 (dd, 1H, J3,4 = 4.0, H-3), 3.69 (s, 3H, COOCH3), 3.26
(dd, 1H, JH,H = 14.2, JH,4 = 5.6, CHHTs), 3.05 (dd, 1H, JH,4 = 8.0,
CHHTs), 2.91 (m, 1H, H-1), 2.57-2.44 (m, 2H, H-5a, H-4), 2.44
(s, 3H, CH3 of Ts), 1.79 (m, 1H, H-5b), 1.43 (s, 3H, C(CH3)2),
25 1.25 (s, 3H, C(CH3)2). 13C NMR (75.4 MHz, CDCl3, ): 174.1
(COOCH3), 144.9, 136.6, 130.1, 128.2 (C-Ar), 112.9 (C(CH3)2),
85.1 (C-3), 82.5 (C-2), 58.9 (CH2Ts), 52.3 (COOCH3), 49.8 (C-
1), 40.4 (C-4), 33.9 (C-5), 27.3, 25.0 (C(CH3)2), 21.7 (CH3 of Ts).
MS(CI) m/z: 369 (13%, [M+H]+), 353 (100%, [M-Me]+).
30 HRMS(CI) m/z: [M+H]+ Calcd for C18H25O6S 369.1372; Found
369.1375.
85 18 For compounds 1 and 4, see ref. 16 and 17, respectively. For -
Ketoester 5, see: J. Leroy, Tetrahedron Lett., 1992, 33, 2969, where
this compound is firstly synthesized by a different synthetic pathway.
For compounds 2 and 3, see ref. 14.
19 (a) T. G. Back, D. Wehrli, Synlett, 1995, 1123. (b) T. G. Back, R. J.
90
Bethell, M. Parvez, J. A. Taylor, D. Wehrli, J. Org. Chem., 1999, 64,
7426. The synthesis of compound 7 was described by another
procedure in these references but it was not isolated therein.
20 Since the exo- and endo-isomers of compound 8 are not diasteromers
but enantiomers, they can not be distinguished by NMR (“simple”)
spectroscopy.
95
21 p-Tolyl 2-bromoethynyl sulfone can be easily obtained by
bromination
of
commercially
available
p-tolyl
2-
(trimethylsilyl)ethynyl sulfone, see ref. 17.
Acknowledgements
22 The synthesis of compound 10 was previously described in ref. 17,
however characterization data are given herein for the first time.
23 J. Leroy, Synth. Commun., 1992, 22, 567.
100
We thank Ministerio de Economia y Competitividad of Spain
(CTQ2012-31247),
the
European
Commission
(FP7,
35 PANACREAS, HEALTH-F2-2011-256986), and Junta de
Andalucía (FQM 345) for financial support.
Notes and references
a Department of Organic Chemistry, Faculty of Chemistry, University of
Seville. C/ Prof. García-González, 1, E-41012, Seville, Spain. Fax:
40 +34954624960; Tel: +34954559997; E-mail: ajmoreno@us.es,
robina@us.es.
† Electronic Supplementary Information (ESI) available: 1H- and 13C-
NMR spectra for all new compounds. See DOI: 10.1039/b000000x/
‡ Dedicated to Prof. Pierre Vogel on the occasion of his 70th anniversary.
45
1
(a) M. North, In Advances in Strained and Interesting Organic
Molecules; Halton B., Ed.; JAI Press: Stamford, CN, 2000, Vol. 8, pp
145-185. (b) NIST Chemistry WebBook.
2
For a recent review: B. Heasley, Eur. J. Org. Chem. 2009, 1477.
50 3 For reviews, see: (a) P. Vogel, J. Cossy, J. Plumet, O. Arjona,
Tetrahedron, 1999, 55, 13521. (b) P. Vogel, Curr. Org. Chem., 2000,
4, 455. (c) I. Robina, P. Vogel, Synthesis, 2005, 675. (d) P. Vogel, In
Organic Chemistry of Sugars; Levy, D. E., Fügedi, P., Eds.; CRC
LLC: Boca Raton, FL, 2006; p 629.
55 4 (a) A. J. Moreno-Vargas, P. Vogel, Tetrahedron Lett., 2003, 44,
5069. (b) A. J. Moreno-Vargas, I. Robina, E. Petricci, P. Vogel, J.
Org. Chem. 2004, 69, 4487. (c) A. A. Ruggiu, R. R. Lysek, E.
Moreno-Clavijo, A. J. Moreno-Vargas, I. Robina, P. Vogel,
Tetrahedron, 2010, 66, 7309.
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