C-O and C-C bond formation in the cyclisation of gem-(dialkoxymethyl)-1,6- dienes catalysed by tin(IV) triflimidate at room temperature

Article abstract of DOI:10.1016/j.tetlet.2012.07.036

We described herein a Sn(NTf₂)₄-catalysed cyclisation of gem-(dialkoxymethyl)-1,6-dienes and derivatives where cyclohexane or tetrahydrofuran rings are formed following either a 6-enexo-endo-trig process or a 5-exo-trig process, resp

Full text of DOI:10.1016/j.tetlet.2012.07.036

Tetrahedron Letters 53 (2012) 5102–5105
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
C–O and C–C bond formation in the cyclisation
of gem-(dialkoxymethyl)-1,6-dienes catalysed by tin(IV) triflimidate
at room temperature
⇑
⇑
Vito Vece, Khadija Ben Hadj Hassen, Sylvain Antoniotti , Elisabet Duñach
Institut de Chimie de Nice, UMR 7272 CNRS - Université de Nice Sophia Antipolis, Parc Valrose, 06108 Nice, France
a r t i c l e i n f o
a b s t r a c t
Article history:
We described herein a Sn(NTf2)4-catalysed cyclisation of gem-(dialkoxymethyl)-1,6-dienes and deriva-
tives where cyclohexane or tetrahydrofuran rings are formed following either a 6-enexo-endo-trig process
or a 5-exo-trig process, respectively, depending on substitution patterns. The latter process features an
unusual dealkylative ether cyclisation, triggered by the strong Lewis acid character of the tin(IV) triflim-
idate catalyst.
Received 15 June 2012
Revised 3 July 2012
Accepted 9 July 2012
Available online 20 July 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Lewis superacids
Diene cycloisomerisation
Carbocycles
Tetrahydrofurans
Lewis superacids such as metal triflates and triflimidates have
been widely used in the recent years in catalytic transformations
where electrophilic activation is required1 with salts derived from
Sn(NTf2)4
(5 mol%)
MeOOC
MeOOC
MeOOC
MeOOC
2
indium, rare earth metals,3 or bismuth, 4,5 for example. We have
CH3NO2, RT
90%
been interested in the preparation of metal triflates and triflimi-
dates6,7 and their use in homogeneous catalysis, in various inter-
and intramolecular C–O, C–S and C–C bonds formation processes.8
In particular, we have described a cycloisomerisation reaction of
1,6-dienes catalysed by Sn(NTf2)4 (Scheme 1),9 showing an unusual
preference for 6-enexo-endo-trig cyclisation, while transition met-
als typically exhibit 5-endo-trig and 5-exo-trig cyclisation
modes.10–12
Of concern in the 1,6-diene transformation was the role of side
groups on the tether, the best results being obtained with a gem-
diester moiety at the homoallylic position. Should these groups
influence the course of the reaction by a Thorpe–Ingold effect or
by a stabilisation of intermediate species by coordination? In this
Letter we report our results on the cyclisation of a series of gem-
(dialkoxymethyl)-1,6-dienes catalysed by Sn(NTf2)4 where we
show that in the absence of the carbonyl function, replaced by a
methylene, the cycloisomerisation to 6-membered carbocycles is
in competition with an unusual dealkylative cyclisation to cyclic
Scheme 1. Sn(NTf2)4-catalysed cycloisomerisation of gem-diester-containing 1,6-
dienes.
cycloisomerisation of gem-diester-1,6-dienes was the formation
of two isomers, 1b and 1c, differing by the final position of the dou-
ble bond.
Nitromethane as the solvent allowed the best results as com-
pared to dichloroethane or toluene, which gave almost no conver-
sion at room temperature. The results of the catalyst screening are
summarised in Table 1. We identified that Sn(NTf2)4 could be used
at 5 mol % in CH3NO2 at 25 °C to obtain the cyclisation of 1a into
1b + 1c in 86% yield, in a 1:1.7 ratio, respectively.
We further examined the effect of structural changes on the
cyclisation reaction (Table 2). Exchange of the methoxy groups into
ethoxy (2a) or acetoxy (3a) did not alter the reaction outcome and
the C–C cyclised products 2b/2c and 3b/3c were obtained in 74%
and 82% yields, respectively (entries 2, 3). However, the selectivity
between isopropenyl cyclohexane 3b and isopropyl cyclohexene 3c
was modified. The presence of two acetoxy groups strongly
favoured the formation of 3b, in a 10:1 ratio with 3c.
ethers. We initially performed
a screening of catalysts and
conditions on model substrate 1a. A striking difference with the
⇑
Corresponding authors.
E-mail addresses: sylvain.antoniotti@unice.fr (S. Antoniotti), dunach@unice.fr
We examined the reactivity of 4a, the monoester analogue of
1a, which could be a probe to evaluate the importance of a
(E. Duñach).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.07.036

V. Vece et al. / Tetrahedron Letters 53 (2012) 5102–5105
5103
Table 1
Screening of catalyst and conditions in the cyclisation of 1a
Catalyst
(x mol%)
MeO
MeO
MeO
+
OMe
1b
OMe
1c
CH3NO2, T°C
OMe
1a
Entrya
Catalyst, x mol %b
T (°C), time
Conversion
(1b + 1c) yieldc
1b:1c
1
2
3
4
5
6
7
8
Zn(NTf2)2, 10
Bi(NTf2)3, 10
In(NTf2)3, 10
Sn(NTf2)4, 10
Sn(NTf2)4, 5
Sn(NTf2)4, 3
Sn(NTf2)4, 1
Sn(NTf2)4, 5
25, 24 h
25, 24 h
25, 24 h
25, 20 h
25, 24 h
25, 24 h
25, 24 h
40, 18 h
<5%
10%
20%
100%
100%
90%
76%
100%
—
5%
—
N.D.
1:1.2
1:2.3
1:1.7
1:1.6
1:1.3
1:2.4
10%
71%
86%
77%
68%
73%
a
b
c
Conditions: 1a (0.5 mmol), in anhydrous CH3NO2 (0.5 M).
7
Catalysts solvated with DMSO molecules, see Ref.
.
GC–FID yields determined by internal standard method.
Table 2
C–C and C–O bonds formation in the cyclisation of gem-(dialkoxymethyl)-1,6-dienes 1a–10a
Entrya
Substrate
Time
Products
Yieldb (ratio b/c)
86% (1:1.7)
MeO
MeO
MeO
MeO
+
MeO
MeO
1 (from Table 1)
24 h
1b
1c
2c
3c
1a
EtO
EtO
EtO
EtO
+
EtO
EtO
2
3
24 h
72 h
74% (1:2.1)
82% (10:1)
2b
3b
2a
AcO
AcO
AcO
AcO
+
AcO
AcO
3a
MeO
1 dia.
MeO
+
4
5
6 h
80% (5:3)
4b
4c
MeO
4a
MeO
MeO
48 h
Mixture of isomerised products
50%c
5a
MeO
MeO
MeO
6
7
72 h
72 h
39%c
6d
O
6a
MeO
MeO
MeO
53%d
7d
O
7a
(continued on next page)

5104
V. Vece et al. / Tetrahedron Letters 53 (2012) 5102–5105
Table 2 (continued)
Entrya
Substrate
Time
6 h
Products
Yieldb (ratio b/c)
O
O
TMSO
TMSO
8
9
96%
8e
8e
8a
O
O
O
23 h
66%
O
9a
O
OMe
HO
MeO
10a
10
3 h
100%
10d
a
Conditions: Substrate (0.5 mmol) and 5 mol % Sn(NTf2)4 in anhydrous CH3NO2 (0.5 M) at 25 °C.
b
GC–FID yields determined by internal standard method. Products were isolated and characterised by 1H and 13C NMR, MS and compared with literature data or authentic
samples.
c
Along with elimination products.
Conversion 100% (66% after 48 h).
d
Thorpe–Ingold effect in this cyclisation. The C–C cycloisomerisa-
tion was not affected and 4b/4c was obtained in 80% yield, as a
5:3 mixture (entry 4).
ether formation was favoured, showing that when 5-membered
rings could be formed, the ether formation is favoured to the det-
riment of the cyclopentane, which suffers from destabilising
eclipsing interactions (Scheme 2).
The access to fused bicyclic compounds was envisaged through
the cyclisation of 5a, but a complex mixture of isomerised products
was obtained (entry 5). By changing the prenyl side chain(s) for
one or two methallyl side chain(s), a significant shift of reactivity
was observed towards C–O cyclisation. In particular, methallyl–
prenyl substrate 6a afforded the monocyclic ether 6d in 39% yield
(entry 6). Ether 6d was presumably formed by dealkylative alkoxy-
lation of the methallyl moiety, triggered by Sn(NTf2)4. A similar
reaction was reported to occur with stoichiometric TfOH in the
dealkylative lactonisation of related gem-diester substrates.13
Bismethallyl substrate 7a afforded the cyclic ether 7d in 53% yield
after 72 h (entry 7). TMS-protected derivative 8a was cleanly and
rapidly converted into the spirocyclic diether 8e in 96% yield, after
a Sn(NTf2)4-catalysed desilylation/C–O cycloisomerisation (entry
8). The same product was obtained in 66% yield when cyclic ketal
9a was used as the substrate (entry 9). The preference for C–O ver-
sus C–C cyclisation was confirmed when using 10a as the starting
material. The substrate bearing a free hydroxyl group and two pre-
nyl moieties afforded the cyclic ether 10d in 100% yield after 3 h at
room temperature in the presence of Sn(NTf2)4 (entry 10).14
The dealkylation reaction observed is rather surprising since
such reaction usually takes place in the presence of stoichiometric
Lewis acids, including metal chlorides or boron-derivatives.15 Un-
der our conditions, dealkylation could become the main reaction
(Table 2, entries 6, 7). This divergence between (C–C) and (C–O)
bond-forming cyclisations, comparing the fate of 1a, 5a and 6a
for example, appeared to us as a consequence of the combined
electronic effects of substituents on the double bonds and size of
the ring to be formed. In the case of 1a, one double bond acts as
an electrophile and undergoes the nucleophilic attack of either
an oxygen atom of the functional groups in a (C–O)-6-endo-trig
process, or a carbon atom of the other double bond in a (C–C)-6-
enexo-endo-trig process. As a consequence of the trisubstitution,
the double bond is nucleophilic enough and the (C–C)-6-
enexo-endo-trig process is favoured, ring size being identical in
both processes. For 6a, the competition is between a (C–C)-5-
enexo-exo-trig, a (C–C)-7-enendo-endo-trig, a (C–O)-6-endo-trig
and a (C–O)-5-exo-trig, and we observed that the 5-membered ring
In the case of 7a, the disubstituted double bond is not nucleo-
philic enough to enter into a (C–C)-6-enendo-exo-trig process, in
competition with a (C–O)-5-exo-trig process, which is favoured.
Comparing these reactions with the previously reported cycloiso-
merisation of 1,6-dienes bearing a gem-diester moiety9 instead of
the gem-(dialkoxymethyl), it seems that the overall efficiency of
the process is improved with gem-(dialkoxymethyl) substrates,
efficiently converted at room temperature while gem-diester sub-
strates sometimes required heating. The selectivity is however at-
tained with diester substrates, as depicted in Scheme 1, affording
one single product. In contrast with the C–O type cyclisation pre-
sented here, with gem-diester substrates the C–C process is highly
favoured. It is frequent to invoke that the ester groups could be
involved in Thorpe–Ingold effects or in the stabilisation of cationic
intermediates, but these two features are also possible with gem-
(dialkoxymethyl) substrates. The attack of olefin could also be
anchimerically-assisted by one ester group, thereby favouring the
C–C bond forming process.
The variation of the b/c ratio from 7:1 to 1:2.4 depending on the
substrate and the reaction conditions suggested an additional
O
O
[Sn]
MeO
MeO
[Sn]
O
vs
O
(C-C)-6-enexo-endo-trig
(C-O)-6-endo-trig
Favoured
Disfavoured
O
O
O
[Sn]
vs
MeO
MeO
[Sn]
O
(C-O)-5-exo-trig
(C-C)-5-enexo-exo-trig
Scheme 2. Proposed rationale for the cyclisation of 1a and 6a.

V. Vece et al. / Tetrahedron Letters 53 (2012) 5102–5105
5105
NaH
(2.4 equiv.)
MeI
cyclisation, probably triggered by the strong Lewis acid character
of the tin(IV) triflimide salt.
LiAlH4
(2 equiv.)
MeOOC
MeOOC
HO
MeO
(2.5 equiv.)
Acknowledgments
OH
OMe
THF, RT
78%
THF, RT
87%
This project was supported by the ANR (French research agency,
Grant number ANR-07-CP2D-CASAL-04-01), the CNRS and the Uni-
versity of Nice–Sophia Antipolis.
1b
Scheme 3. Access to 1b via reduction and methylation of the gem-diester
containing cyclised product.
References and notes
isomerisation reaction. This was tested with a sample of pure 1b,
prepared from the cyclisation of the gem-diester analogue of 1a
affording selectively the desired cyclised compounds further re-
duced by LiAlH4 and methylated (Scheme 1+Scheme 3, 61%, three
steps).
1. Antoniotti, S.; Dalla, V.; Duñach, E. Angew. Chem., Int. Ed. 2010, 49, 7860–7888.
2. Ghosh, R.; Maiti, S. J. Mol. Catal. A 2007, 264, 1–8.
3. Kobayashi, S.; Sugiura, M.; Kitagawa, H.; Lam, W. W. L. Chem. Rev. 2002, 102,
2227–2302.
4. Antoniotti, S. Synlett 2003, 1566–1567.
5. Gaspard-Iloughmane, H.; Le Roux, C. Eur. J. Org. Chem. 2004, 2517–2532.
6. Favier, I.; Duñach, E. Tetrahedron Lett. 2003, 44, 2031–2032.
7. Antoniotti, S.; Duñach, E. Chem. Commun. 2008, 993–995.
8. Antoniotti, S.; Poulain-Martini, S.; Duñach, E. Synlett 2010, 2973–2988.
9. Grau, F.; Heumann, A.; Duñach, E. Angew. Chem., Int. Ed. 2006, 45, 7285–7289.
10. Lloyd-Jones, G. C. Org. Biomol. Chem. 2003, 1, 215–236.
11. Bray, K. L.; Lloyd-Jones, G. C.; Muñoz, M. P.; Slatford, P. A.; Tan, E. H. P.; Tyler-
Mahon, A. R.; Worthington, P. A. Chem. Eur. J. 2006, 12, 8650–8663.
12. Bray, K. L.; Charmant, J. P. H.; Fairlamb, I. J. S.; Lloyd-Jones, G. C. Chem. Eur. J.
2001, 7, 4205–4215.
13. Munoz, M. P.; Lloyd-Jones, G. C. Eur. J. Org. Chem. 2009, 516–524.
14. Coulombel, L.; Favier, I.; Duñach, E. Chem. Commun. 2005, 2286–2288.
15. Sudo, Y.; Arai, S.; Nishida, A. Eur. J. Org. Chem. 2006, 2006, 752–758.
16. Wabnitz, T. C.; Yu, J.-Q.; Spencer, J. B. Chem. Eur. J. 2004, 10, 484–493.
17. Williams, D. B. G.; Lawton, M. J. Mol. Catal. A 2010, 317, 68–71.
18. Williams, D. B. G.; Lawton, M. J. Org. Chem. 2010, 75, 8351–8354.
19. Ishihara, K.; Ishibashi, H.; Yamamoto, H. J. Am. Chem. Soc. 2002, 124, 3647–
3655.
When 1b was submitted to the reaction conditions of Table 2,
1c was slowly formed and the ratio 1b/1c was of 7:3 after 6 h;
1:1 after 24 h and 3:7 after 48 h. The phenomenon could not be ob-
served beyond 120 h because degradation occurred (6% after 24 h
and 10% after 48 h). This set of data clearly indicates that 1b could
be converted into 1c, which is the thermodynamic product.
As the question frequently appears in Lewis acid-catalysed pro-
cesses,16,17 we investigated the hypothesis of protons as the active
catalytic species. Various Bronsted acids (AcOH, H3PO4, TfOH, Tf2NH
at a loading of 5 mol %) were used under our conditions (0.5 M in
CH3NO2 at rt). After 24 h, the weak acids AcOH and H3PO4 showed
no conversion of 1a. After 18 h, TfOH and Tf2NH both led to 100%
conversion, however the cumulated yields of (1b + 1c) were of
62% and 58%, respectively, significantly lower than the 86% obtained
with Sn(NTf2)4. The controversy in metallic triflate catalysis is based
on the hypothesis of a slow hydrolysis of the triflate salt by trace
amounts of water. In our case, a triflimidate salt is used, and the con-
jugate acid, the triflimide Tf2NH, is not considered a Bronsted super-
acid. The catalyst was prepared as a solvate with DMSO molecules,
thereby limiting the quantity of water in the reaction medium, after
drying of the solvent used by conventional procedures.18 Under our
conditions, it is however possible to have a discrete number of water
molecules coordinated to the metal centre therefore affording a hy-
brid Lewis assisted Bronsted acid (LBA)19 catalyst rather than
hydrolysing the catalyst to triflimide HNTf2. Regardless of the exact
nature of the active species, the best experimental results were ob-
tained using Sn(NTf2)4.20
20. Typical experiment: Cyclisation of 1a. Sn(NTf2)4Á6DMSO (0.015 mmol, 26 mg)
was introduced under a nitrogen atmosphere in a Schlenk tube closed with a
septum. Nitromethane (0.5 mL), previously dried over CaCl2, was added with a
syringe and the mixture stirred at room temperature until dissolution of the
catalyst. Diene 1a (0.3 mmol, 72 mg) in nitromethane (0.1 mL) was added to
the solution with a syringe. The reaction progress was monitored by GC–FID
analysis. After completion, the reaction mixture was filtrated over a pad of
silica gel and eluted with diethylether (10 mL). After solvent removal, the
crude mixture was submitted to column chromatography over silica gel with a
gradient Et2O/pentane 1:9 to 1:1 as eluent to afford the mixture 1b + 1c as a
colourless oil. Spectral data for 1b: 1H NMR (CDCl3, 200 MHz, 20 °C): 4.76 (s,
1H); 4.55 (s, 1H); 3.27 (s, 2H); 3.26 (s, 6H); 3.08 (s, 2H); 1.90 (m, 1H); 1.65 (s,
3H); 1.55–1.00 (m, 6H); 0.82 & 0.78 (s, 3H & s, 3H). 13C NMR (CDCl3, 50 MHz,
20 °C): 146.3; 111.6; 79.1; 71.7; 58.4; 47.4; 36.7; 32.7; 38.1; 30.6; 24.4; 30.2;
22.9; 19.2. MS (EI, 70 eV): 240(0) [M+.], 208(74), 193(5), 176(5), 163(100),
133(16), 121(30), 107(96), 93(76), 79(58), 71(65). Spectral data for 1c: 1H NMR
(CDCl3, 200 MHz, 20 °C): 5.20 (s, 1H); 3.27 (s, 6H); 3.25–3.00 (m, 4H); 2.24
(hept, J = 6.8 Hz, 1H); 1.75–1.05 (m, 4H); 0.93 (d, J = 6.8 Hz, 6H); 0,93 (s, 6H).
13C NMR (CDCl3, 50 MHz, 20 °C): 153.5; 119.9; 75.4; 58.4; 39.6; 34.4; 22.8;
34.3; 26.9; 26.8; 24.2. MS (EI, 70 eV): 240(1) [M+.], 208(1), 195(100), 163(24),
133(20), 121(92), 111(23), 107(87), 93(87), 79(32), 69(22). HRMS calcd for
In summary, we described here a Sn(NTf2)4-catalysed cyclisa-
tion reaction of gem-(dialkoxymethyl)-1,6-dienes where cyclohex-
ane derivatives could be formed following a 6-enexo-endo-trig
C
C
15H28O2 [M]ꢀ+ 240.2089, found: 240.2091,
D
D
= 0.83 ppm. HRMS calcd for
= 0.84 ppm.
process or tetrahydrofuran derivatives following
a 5-exo-trig
15H27O2 [MÀH]ꢀ 239.2011, found: 239.2009,
process, depending on the substitution pattern of the double
bonds. The latter process featured an unusual dealkylative ether