Copper-catalysed intramolecular O-H addition to unactivated alkenes

Article abstract of DOI:10.1016/j.tet.2009.10.055

Intramolecular cyclisation of ω-alkenoic acids and alkenols can be achieved using a catalytic amount of Cu(OTf)₂ to afford lactones and cyclic ethers, offering a practical alternative to existing catalysts.

Full text of DOI:10.1016/j.tet.2009.10.055

Tetrahedron 65 (2009) 10334–10338
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Copper-catalysed intramolecular O–H addition to unactivated alkenes
*
Luis A. Adrio, Louisa Shuyi Quek, Jason G. Taylor, King Kuok (Mimi) Hii
Department of Chemistry, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 June 2009
Received in revised form 3 October 2009
Accepted 15 October 2009
Available online 20 October 2009
Intramolecular cyclisation of
Cu(OTf)2 to afford lactones and cyclic ethers, offering a practical alternative to existing catalysts.
u-alkenoic acids and alkenols can be achieved using a catalytic amount of
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
reaction was established with a number of u-alkenoic acid pre-
cursors, at 2 mol % catalyst loading (Table 1). At the end of each
reaction, the paramagnetic catalyst was removed by passing the
reaction mixture through a short column of silica gel, prior to 1H
NMR spectroscopic analysis. In all cases, clean ‘spot-to-spot’ con-
versions were observed, i.e., no side product was detected.
Oxygen heterocycles such as lactones, furans and pyrans are
prevalent in nature and exhibit a wide range of important biological
activities. Consequently, their synthesis constitutes an important
area of organic chemistry. One of the ways of constructing an
O-heterocycle is by the intramolecular addition of an OH or CO2H
functionality to a C]C bond. Known as hydroalkoxylation or
hydroacyalkoxylation, respectively, these atom-economical pro-
cesses can be effected using strong Brønsted acids.1 Conversely,
O
Cu(OTf)2 (5 mol%)
O
Ligand, DCE, 83 °C
O
2
OH
2c
several metal catalysts, such as Pt(II)/PR3,2a Sn(OTf)4,2b Al(OTf)3
1a
and gold2d have also been reported for (either or both of) these
reactions. It is interesting to note that AgOTf was known as an
active catalyst,3a but did not preclude its use as a ‘co-catalyst’ with
FeCl3.3b,3c
Scheme 1. Cyclisation of 4-pentenoic acid to a g-lactone.
Compared to the cyclisation of 1a, the formation of the six-
membered heterocycle (from 1b) was noticeably slower (Table 1,
entries 1 and 2). The introduction of a methyl group in the terminal
2. Results and discussion
position (1c) led to a mixture of g- and d-lactones 4 and 5, in favour
of the smaller ring (entry 3). This is notable, as it is in contrast to the
regioselectivity observed previously using AgOTf, which was
reported to favour the larger lactone ring by 10:1.3a On the other
hand, the presence of the methyl substituent at the internal posi-
In our earlier work, we have reported the use of Cu(OTf)2 as
a catalyst in a number of intermolecular C–O and C–N bond for-
mations, including additions of acids, phenols and alcohols to
norbornene, sulfonamides to conjugate dienes and vinylarenes, and
the annulation of phenols with 1,3-dienes.4 Herein, we will report
the first application of this catalyst for the intramolecular O–H
additions to unactivated alkenes, leading to the formation of lac-
tone and tetrahydrofuran rings.
tion (1d) yielded only the smaller g-lactone 6 (entry 4). The pres-
ence of a 3-phenyl substituent led to significant reduction in the
rate of reaction of 1e, giving lactone 7 as a mixture of syn:anti
isomers (entry 5); this is attributed to unfavourable 1,2-allylic
strain during the cyclisation process.
Synthesis of bicyclic rings was also attempted; this can be ach-
ieved by using the cyclopentene precursor 1f, to give the cis-fused
rings 8 exclusively (entry 6). Alternatively, spiro-lactones 9 and 10
can be obtained in high yields from diacids 1g and 1h, respectively
(entries 7 and 8). Again, the introduction of a methyl substituent at
the terminal alkene compromised the regioselectivity slightly
(entry 9).
Initially, reactions were conducted in air by heating at reflux
a solution of 4-pentenoic acid 1a in 1,2-dichloroethane in the
presence of 5 mol % of Cu(OTf)2. Cyclisation of the substrate pro-
ceeded smoothly to afford the g-lactone 2 exclusively (Scheme 1).
Subsequent investigations precluded the need for ligands, as they
did not exert any beneficial effect.5 Consequently, the scope of the
Many of the
u-alkenoic acid precursors were reduced to cor-
* Corresponding author. Tel.: þ44 20 7594 1142; fax: þ44 20 7594 5804.
E-mail address: mimi.hii@imperial.ac.uk (K. Kuok (Mimi) Hii).
responding alkenols, and these were also subjected to copper
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.055

L.A. Adrio et al. / Tetrahedron 65 (2009) 10334–10338
10335
Table 1
Intramolecular cyclisation of
g
- and d
-alkenoic acidsa
Entry
1
Substrate
Product
t/h
Conv.b/%
O
24
100 (88)
O
O
2
OH
1a
O
2
3
36
24
83 (80)
OH
OH
O
3
O
2
1b
O
+
100 (95)
Et
O
O
O
O
4 : 5 (3 : 1)
1c
O
O
4
5
18
48
100 (92)
82 (72)c
O
6
OH
1d
Ph
O
O
O
7
Ph
OH
1e
(syn:anti = 3:2)
H
O
6
24
100 (91)c
O
H
8
O
HO
1f
8 (cis- only)
O
O
OH
O
O
7
HO
22
100 (91)
O
O
9
1g
18
100 (88)
72
8
24d
O
O
10
O
OH
1h
+
9
22
82 (73)
Et
O
O
O
O
O
OH
1i
11 : 12 (6 : 1)
a
Typical reaction: Cu(OTf)2 (2 mol %) and 0.5 M of substrate at reflux in DCE.
b
c
Conversions determined by 1H NMR integration of crude reaction mixtures. Yields of isolated products indicated in parentheses.
5 mol % Cu(OTf)2.
0.2 mol % Cu(OTf)2.
d

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L.A. Adrio et al. / Tetrahedron 65 (2009) 10334–10338
Table 2
Intramolecular cyclisation of
g
and
d
-alkenolsa
Entry
1
Substrate
Product
t/h
Conv.b/%
100 (96)c
OH
OH
21
O
13
1j
Ph
26
46
75
59 (37)
88 (81)
96 (91)
2
3
O
Ph
14
1k
(syn:anti = 1:2.6)
OH
20
22
100 (92)
O
15
1l
4
5
80 (77)
O
OH
16
1m
18
24
100 (96)
71d
O
O H
1n
17
OH
O
6
22
100 (89)
O
HO
18
1o
OTIPS
OTIPS
100 (98)
HO
7
18
100 (96)e
O
1p
19
a
Typical reaction: Cu(OTf)2 (2 mol %) and 0.5 M of substrate at reflux in DCE.
b
c
Conversions and diastereomeric ratios determined by 1H NMR integration of crude reaction mixtures. Yields of isolated products indicated in parentheses.
65 ꢀC.
0.2 mol % Cu(OTf)2.
10% TfOH.
d
e
catalysis (Table 2).6 Intramolecular hydroalkoxylation reactions
promptly ensued and, in many cases, quantitative conversions
could be attained, furnishing cyclic ethers in high isolated yields.
Compared to their corresponding CO2H additions, OH additions are
not only more facile, e.g., Table 2, entry 2 (2 mol % catalyst) vs Table
1, entry 5 (5 mol % catalyst), but are also much more regioselective
(Table 2, entries 3 and 5 vs Table 1, entries 3 and 9). In one particular
case, the reaction can be conducted at 65 ꢀC without affecting
turnover or yield (Table 2, entry 1), showing that milder conditions
may be feasible. Catalyst loading can be further reduced in these
systemsdpreliminary tests conducted with substrates 1h and 1n
using 0.2 mol % of catalyst showed acceptable conversions within
24 h (Table 1, entry 8 and Table 2, entry 5, final turnover numbers
unoptimised), demonstrating its efficiency favourably against other
catalytic systems, which typically employ 5 mol % catalytic loading,
sometimes even 10 mol %.
Triflic acid has been implicated as the true catalytic species in
metal triflate-catalysed processes.7 This was investigated in the
present study by performing control reactions with numerous
substrates (1g–h, 1j, 1l–o). In contrast to our previous studies,4 the
use of 10% TfOH was found to be equally effective, giving the de-
sired products with similar yields to copper-catalysed reactions.
This includes the cyclisation of the mono-TIPS protected substrate
1p,8 which proceeded to completion cleanly with either catalyst, to
furnish tetrahydrofuran 19 in comparable yields and product dis-
tribution (Table 2, entry 7); contrary to expectations, none of the
spiro structure 18 or its deprotected precursor (1o) can be detected
in the crude reaction mixture (1H NMR).

L.A. Adrio et al. / Tetrahedron 65 (2009) 10334–10338
10337
Thus, the catalytic activity of Cu(OTf)2 is very similar to triflic
acid in these intramolecular O–H addition reactions. While it is
impossible to rule out the involvement of Brønsted acid-catalysis in
this case, the copper catalyst may be a preferred option, due to three
distinct advantages: firstly, Cu(OTf)2 is a non-corrosive and non-
hygroscopic solid, making it more attractive than triflic acid in terms
of practicality, safety and long-term storage.9 Secondly, over the
course of our investigations, we have demonstrated its utility and
superiority over the Brønsted acid in a number of inter- and intra-
molecular C]C heterofunctionalisation reactions,4 i.e., it has wider
applicability.10 Last but not least, copper(II) triflate is considerably
cheaper, less toxic and offers similar, if not better, turnovers at
a much lower catalytic loading than other metal catalysts.2,3
(1H, m), 1.97–1.78 (3H, m), 1.58–1.45 (1H, m), 1.37 (3H, d, J¼6.3). dC
(101 MHz, CDCl3) 171.8, 76.9, 29.6, 29.2, 21.7, 18.5.
4.2.3. 5-Ethyl-3,3-dimethyldihydrofuran-2(3H)-one, 43a. Colourless
oil. dH (400 MHz, CDCl3) 4.39–4.29 (1H, m), 2.13 (1H, dd, J¼12.6,
5.8), 1.82–1.67 (2H, m), 1.67–1.54 (1H, m), 1.26 (3H, s), 1.24 (3H, s),
0.98 (3H, t, J¼7.5). dC (101 MHz, CDCl3) 182.1, 78.3, 43.1, 40.5, 28.6,
25.1, 24.5, 9.5.
4.2.4. 3,3,6-Trimethyltetrahydro-2H-pyran-2-one,
53a. Colourless
oil. dH (400 MHz, CDCl3) 4.52–4.38 (1H, m), 1.88–1.78 (1H, m), 1.78–
1.66 (3H, m), 1.37 (3H, d, J¼6.3), 1.29 (3H, s), 1.28 (3H, s). dC
(101 MHz, CDCl3) 177.6, 78.0, 37.8, 34.5, 27.9, 27.8, 22.1.
3. Conclusions
4.2.5. 5,5-Dimethyldihydrofuran-2(3H)-one, 61b. Colourless oil. dH
(400 MHz, CDCl3) 2.62 (2H, t, J¼8.2), 2.05 (2H, t, J¼8.2), 1.41 (6H, s).
dC (101 MHz, CDCl3) 176.7, 84.6, 34.6, 29.3, 27.7.
In summary, the result from the present study showed that
Cu(OTf)2 can be used in the synthesis of O-heterocycles by facili-
tating the intramolecular O–H addition to unactivated C]C bonds.
Compared to the other catalysts, the copper system is cheaper,
more practical and effective at lower catalytic loadings. Thus
broadening the scope of Cu(OTf)2 as a catalyst in C]C hetero-
functionalisation reactions.
4.2.6. Dihydro-5-methyl-4-phenyl-2(3H)-furanone, 73a. Colourless
oil. syn-isomer: dH (400 MHz, CDCl3) 7.41–7.27 (3H, m), 7.14 (2H, dt,
J¼8.3, 2.5), 4.93 (1H, dq, J¼6.4, 6.5), 3.76 (1H, dt, J¼8.4, 6.4), 2.95
(1H, dd, J¼17.4, 8.4), 2.82 (1H, dd, J¼17.4, 6.0), 1.03 (3H, d, J¼6.5). dC
(101 MHz, CDCl3) 176.7, 137.6, 128.8, 127.8, 127.6, 80.0, 44.8, 34.8,
16.7. anti-isomer: dH (400 MHz, CDCl3) 7.42–7.18 (5H, m), 4.56 (1H,
dq, J¼8.6, 6.2), 3.25 (1H, dt, J¼11.0, 8.6), 2.95 (1H, dd, J¼17.6, 8.6),
2.83–2.76 (1H, dd, J¼17.6, 11.0), 1.43 (3H, d, J¼6.2). dC (101 MHz,
CDCl3) 175.5, 138.3, 129.2, 127.9, 127.2, 83.2, 49.7, 37.5, 19.2.
4. Experimental section
4.1. General
Copper(II) trifluoromethanesulfonate was procured from
Sigma–Aldrich and used as-received. Acyclic precursors were pur-
chased from commercial sources and used without further purifi-
cation, except 1c–e, 1g–i and 11a–g, which were prepared by
literature procedures (see Supplementary data).
4.2.7. cis-Hexahydrocyclopenta[b]furan-2-one, 811. Colourless oil. dH
(400 MHz, CDCl3) 4.96 (1H, dd, J¼8.3, 3.4), 2.74–2.89 (2H, m), 2.24
(1H, dd, J¼8.3, 3.4), 2.06–1.94 (1H, m), 1.90–1.73 (1H, m), 1.61–1.75
(3H, m), 1.56–1.43 (1H, m). dC (101 MHz, CDCl3) 177.8, 86.4, 37.9,
36.1, 33.6, 33.5, 23.4.
Catalytic reactions were performed in parallel in a Radley’s
12-placed reaction carousel in air. Column chromatography was
performed on silica gel (Merck Kieselgel 60 F254 230–400 mesh).
Thin layer chromatography (TLC) was performed on aluminium-
backed plates pre-coated with silica (0.2 mm) and developed in
suitable solvents.
4.2.8. 3, 8-Dimethyl-2,7-dioxaspiro[4.4]nonane-1,6-dione, 912. White
solid. Obtained as an inseperable mixture of diastereomers. Mp 105–
107 ꢀC (lit.13 105–106 ꢀC). Isomer 1: dH (400 MHz, CDCl3) 5.09–4.93
(2H, m), 2.86–2.77 (2H, m),1.90 (2H, ddd, J¼13.2, 9.6, 3.8), 1.49 (3H, d,
J¼6.3), 1.48 (3H, d, J¼6.3). Isomer 2: dH (400 MHz, CDCl3) 4.80–4.60
(2H, m), 2.66–2.25 (4H, m), 1.53 (6H, d, J¼6.2). dC (101 MHz, CDCl3)
173.8, 173.5, 76.0, 75.9, 75.5, 75.0, 53.9, 41.6, 40.7, 40.4, 39.6, 21.1,
20.9, 20.6.
1H and 13C NMR spectra were recorded using 400 MHz Bruker
AVANCE spectrometers. The chemical shifts are expressed as parts
per million (ppm) and coupling constants (J) are given in Hertz
(Hz). Multiplicity is abbreviated to s (singlet), d (doublet), t (triplet),
q (quartet) and m (multiplet). Melting points were determined
using an Electrothermal Gallenhamp apparatus fitted with a cali-
brated thermometer with an error of ꢁ2 ꢀC.
4.2.9. 3-Methyl-2-oxaspiro[4.5]decan-1-one, 1014. Colourless oil. dH
(400 MHz, CDCl3) 4.54 (1H, tq, J¼9.5, 6.2), 2.40 (1H, dd, J¼12.9, 6.2),
1.90–1.17 (14H, m). dC (101 MHz, CDCl3) 181.68, 73.70, 45.43, 41.22,
34.38, 31.53, 25.33, 22.21, 22.15, 21.45.
4.2. General procedure for copper-catalysed reactions
4.2.10. 3-Ethyl-2-oxaspiro[4.5]decan-1-one, 1115. Colourless oil. dH
(400 MHz, CDCl3) 4.32 (1H, ddd, J¼12.9, 9.7, 6.2), 2.38 (1H, dd,
J¼12.9, 6.2), 1.90–1.16 (13H, m), 0.99 (3H, t, J 7.4). dC (101 MHz,
CDCl3) 181.7, 78.7, 45.0, 39.0, 34.3, 31.6, 28.9, 25.3, 22.2, 22.1, 9.6.
A Radley’s reaction tube was charged with a magnetic stir bar,
the requisite alkenoic acid or alcohol (1 mmol), copper(II) tri-
fluoromethanesulfonate (0.02 mmol 2 mol %) and 1,2-di-
chloroethane (2 mL). The reaction tube was then placed in the
carousel and heated at reflux for the required length of time. After
cooling to room temperature, the solvent was removed under re-
duced pressure to furnish a residue, which was purified by column
chromatography, to afford the corresponding lactones or cyclic
ethers.
4.2.11. 3-Methyl-2-oxaspiro[5.5]undecan-1-one, 12. Colourless oil.
dH (400 MHz, CDCl3) 4.47–4.36 (1H, m), 2.10–1.94 (2H, m),1.90–1.67
(2H, m), 1.71–1.54 (7H, m), 1.35 (3H, d, J¼6.3), 1.35–1.48 (3H, m). dC
(101 MHz, CDCl3) 183.9, 76.9, 41.4, 35.7, 33.6, 28.8, 27.6, 25.5, 22.1,
20.9, 20.8.
4.2.1. 5-Methyldihydrofuran-2(3H)-one, 23a. Colourless oil. dH
(400 MHz, CDCl3) 4.69–4.59 (1H, m), 2.59–2.51 (2H, m), 2.41–2.30
(1H, m), 1.89–1.77 (1H, m), 1.41 (3H, d, J¼6.3). dC (101 MHz, CDCl3)
177.5, 77.4, 29.6, 29.1, 21.0.
4.2.12. 2,2-Dimethyltetrahydrofuran, 132b. Colourless oil. dH
(400 MHz, CDCl3) 3.87–3.80 (2H, m), 1.99–1.88 (2H, m), 1.73–1.65
(2H, m), 1.23 (6H, s). dC (101 MHz, CDCl3) 80.2, 66.1, 38.2, 27.8, 26.1.
4.2.13. 2-Methyl-3-phenyltetrahydrofuran, 143a. Colourless oil. As
a mixture of 1:2.6 of syn/anti isomers. dH (400 MHz, CDCl3) major
isomer: 7.44–7.05 (5H, m), 4.09–3.98 (2H, m), 3.94–3.80 (1H, m),
4.2.2. 6-Methyltetrahydro-2H-pyran-2-one, 33a. Colourless oil. dH
(400 MHz, CDCl3) 4.51–4.37 (1H, m), 2.64–2.53 (1H, m), 2.51–2.37

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L.A. Adrio et al. / Tetrahedron 65 (2009) 10334–10338
´
2.81 (1H, q, J¼8.8), 2.36–2.44 (1H, m), 2.25–2.06 (1H, m), 1.23 (3H,
d, J¼6.0). minor isomer: 7.44–7.05 (5H, m), 4.24–4.11 (2H, m), 3.94–
3.80 (1H, m), 3.40–3.27 (1H, m), 2.36–2.44 (1H, m), 2.25–2.06 (1H,
m), 0.85 (3H, d, J¼6.4). dC (101 MHz, CDCl3): syn: 141.8, 128.4, 128.2,
126.3, 78.2, 67.0, 48.4, 32.9, 16.9; anti: 141.5,128.6, 127.6,126.7, 82.2,
67.4, 53.0, 35.4, 19.0.
postdoctoral support (LAA), Ministerio de Educacion y Ciencia
(project number CTQ2006-15621-C02-01/BQU), for a collaborative
grant, and EPSRC/GSK for studentship support (JGT).
Supplementary data
Preparation of non-commercially available acyclic precursors
and copies of 1H and 13C NMR spectra are provided as Supple-
mentary Material. Supplementary data associated with this article
can be found in online version, at doi:10.1016/j.tet.2009.10.055.
4.2.14. 2-Ethyl-4,4-dimethyltetrahydrofuran, 1516. Colourless oil. dH
(400 MHz, CDCl3) 3.95–3.86 (1H, m), 3.50 (1H, d, J¼8.1), 3.43 (1H, d,
J¼8.1), 1.76 (1H, dd, J¼12.2, 6.5), 1.69–1.56 (1H, m), 1.53–1.41 (1H,
m), 1.31 (1H, dd, J¼12.2, 9.0), 1.10 (6H, s), 0.92 (3H, t, J¼7.5). dC
(101 MHz, CDCl3): 80.9, 79.9, 46.5, 39.5, 29.1, 27.0, 26.6, 10.4.
References and notes
4.2.15. 3-Methyl-2-oxaspiro[4.5]decane, 1617. Colourless oil. dH
(400 MHz, CDCl3) 4.09–3.97 (1H, m), 3.63 (1H, d, J¼8.5), 3.48 (1H, d,
J¼8.4), 1.86 (1H, dd, J¼12.3, 6.3), 1.33–1.52 (11H, m), 1.24 (3H, d,
J¼6.0). dC (101 MHz, CDCl3): 78.6, 74.8, 37.4, 35.9, 26.0, 24.0, 23.6,
21.4.
1. (a) Coulombel, L.; Dun˜ach, E. Green Chem. 2004, 499–501; (b) Coulombel, L.;
Dun˜ach, E. Synth. Commun. 2005, 35, 153–160; (c) Zhou, Y.; Woo, L. K.; Angelici,
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4.2.16. 3-Ethyl-2-oxaspiro[4.5]decane,
17. Colourless
oil.
dH
(400 MHz, CDCl3) 3.87–3.76 (1H, m), 3.60 (1H, d, J¼8.4), 3.49 (1H, d,
J¼8.4), 1.83 (1H, dd, J¼12.3, 6.4), 1.69–1.32 (12H, m), 1.23 (1H, dd,
J¼12.3, 9.1), 0.92 (3H, t, J¼7.5). dC (101 MHz, CDCl3): 80.3, 78.4, 37.2,
4. (a) Taylor, J. G.; Whittall, N.; Hii, K. K. Chem. Commun. 2005, 5103–5105; (b)
Taylor, J. G.; Whittall, N.; Hii, K. K. Org. Lett. 2006, 8, 3561–3564; (c) Adrio, L. A.;
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35.7, 29.0, 26.0, 24.0, 23.6, 10.5. MS-CIþ (m/z) calcd for C11H20
[MþNH4
O
]
þ þ 186.186, found 186.
5. Monophosphines (PPh3 and P(o-tolyl)3) and 2,20-bipy inhibited the reaction
completely, while diphosphines (dppe, dppp, dppb, Xantphos and BINAP) did
not lead to any acceleration in turnover.
4.2.17. 3,8-Dimethyl-2,7-dioxaspiro[4.4]nonane, 18. Colourless oil.
Obtained as an inseparable mixture of isomers (ratio 1:1:1, by in-
tegration of methyl signals). dH (400 MHz, CDCl3) 4.15–3.94 (1H, m),
3.84–3.54 (2H, m), 2.19–1.96 (1H, m), 1.60–1.46 (1H, m), 1.32–1.20
(3H, m). dC (101 MHz, CDCl3) 77.6, 76.5, 75.3, 75.3, 75.2, 51.9, 45.2,
6. 4-Pentenol and 5-hexenol were not included, due to the volatility of their
cyclised products.
7. For example, see: (a) Wabnitz, T. C.; Yu, J. Q.; Spencer, J. B. Chem.dEur. J. 2004,
10, 484–493; (b) Rosenfeld, D. C.; Shekhar, S.; Takemiya, A.; Utsunomiya, M.;
Hartwig, J. F. Org. Lett. 2006, 8, 4179–4182.
45.0, 44.2, 21.2. MS-CIþ (m/z) calcd for C9H16O2 [MþNH4
]
þ þ 174.149,
8. A TIPS-protected substrate was reported to be unstable in the presence of 5%
TfOH (giving <10% product yield): Ref. 3a.
found 174.
9. The following handling, storage and precautions were recommended by the
‘Encyclopedia of Reagents for Organic Synthesis’ (Ed. L. A. Paquette, Wiley &
Sons, 2006): ‘(trifluoromethanesulfonic acid) is a stable, hygroscopic liquid,
which fumes copiously on exposure to moist air. Transfer under dry nitrogen is
recommended. Contact with cork, rubber and plasticised materials will cause
rapid discolouration of the acid and deterioration of the materials. Samples are
best stored in sealed glass ampules or glass bottles with Kel-FTM or PTFE
plastic screw cap linings. Use in a fume hood.’
10. In most cases, particularly for intermolecular reactions, excess amounts of triflic
acid can lead to competitive poly/oligomerisation of the alkene precursor, lead-
ing to lower yields of the desired product (see Ref. 7b, also 4a and 4b).
11. Shimizu, H.; Onitsuka, S.; Egami, H.; Katsuki, T. J. Am. Chem. Soc. 2005, 127,
5396–5413.
4.2.18. ((3-Allyl-5-methyltetrahydrofuran-3-yl)methoxy)-
triisopropylsilane, 19. Colourless oil. Exists as an inseparable
mixture of diastereomers dH (400 MHz, CDCl3) 5.88–5.71 (1H, m),
5.14–5.02 (2H, m), 4.07–3.93 (1H, m), 3.84–3.38 (4H, d, J¼8.9),
2.36–2.18 (2H, m), 1.99–1.79 (1H, m), 1.31–1.17 (7H, m), 1.13–0.98
(18H, m). dC (101 MHz, CDCl3) 135.1,117.6, 75.4, 74.5, 67.8, 66.9, 49.4,
49.3, 41.7, 41.3, 40.3, 38.9, 21.1, 18.1, 12.0. TOF MS ESþ (m/z) calcd for
C18H36O2Si (MþH)þ 313.2563, found 313.2553.
12. Mun˜oz, M. P.; Lloyd-Jones, G. C. Eur. J. Org. Chem. 2009, 516–524.
13. Fittig, H. Liebigs Ann. Chem. 1883, 216, 63–69.
Acknowledgements
´
ˇ ´
14. Maslak, V.; Matovic, R.; Saicic, R. N. Tetrahedron 2004, 60, 8957–8966.
15. Larchevegue, M.; Debal, A. Synth. Commun. 1980, 10, 49–58.
´
The authors are grateful to Fundacion Caixa Galicia (Becas
16. Mazet, M.; Desmaison-Brut, M. Bull. Soc. Chim. Fr. 1971, 2656–2662.
17. Picard, P.; Moulines, J.; Lecoustre, M. Bull. Soc. Chim. Fr. 1984, 65–70.
´
Postgrado 2008) and Xunta Galicia (Angeles Alvarin˜o) for