Z-selective, anti-Markovnikov addition of alkoxides to terminal alkynes: An electron transfer pathway?

Article abstract of DOI:10.1016/j.tet.2015.04.038

Potassium alkoxides undergo anti-Markovnikov addition to aryl-substituted alkynes with Z selectivity in DMF as the solvent. The yields and efficiency of the reaction was also found to be enhanced by the addition of a secondary amine ligand such as N,N′-di

Full text of DOI:10.1016/j.tet.2015.04.038

Tetrahedron 71 (2015) 4385e4392
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Z-selective, anti-Markovnikov addition of alkoxides to terminal
alkynes: an electron transfer pathway?
*
James Cuthbertson, Jonathan D. Wilden
Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Potassium alkoxides undergo anti-Markovnikov addition to aryl-substituted alkynes with Z selectivity in
DMF as the solvent. The yields and efficiency of the reaction was also found to be enhanced by the
addition of a secondary amine ligand such as N,N0-dimethylethylenediamine. Mechanistic investigations
suggest that the products, reaction rates and selectivity can be explained via a single electron transfer
from the alkoxide to the alkyne. This leads to a radical anion intermediate, which then rapidly combines
with the alkoxide to yield a vinyl anion whose lifetime governs the E:Z selectivity observed in the
products.
Received 2 February 2015
Received in revised form 23 March 2015
Accepted 13 April 2015
Available online 22 April 2015
Keywords:
Radicals
Alkynes
Enol ethers
Electron transfer
Alkoxides
Ó 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction
Remarkably perhaps, relatively few reports of anti-Markovnikov
addition of alkoxides to alkynes exist in the literature. Exceptions
The reaction of alkynes with nucleophiles is a class of reaction
that has been extensively investigated by chemists over many de-
cades, since the products obtained are usually highly functionalised
and adaptable building blocks for organic synthesis. In particular,
hydration and similar reactions yield carbonyl compounds and
their derivatives, and so leads to further facile manipulation of
these synthetic intermediates. Despite this fact, these types of re-
action have not been widely applied in target synthesis, mainly
because harsh reaction conditions are required (e.g., strong acids),
or toxic reagents are employed (e.g., 40% of a mercury(II) salt).1 In
recent years a number of transition metals have been employed to
facilitate the addition of nucleophiles to alkynes. These have in-
cluded gold,2 rhodium,3 ruthenium4 and palladium5 as well as
many others.6 In general, these reagents are expensive and often
toxic although both Markovnikov and anti-Markovnikov addition
products can be formed depending on the catalyst selected
(Scheme 1).
include a few examples catalysed by transition metals, and one
report where hydrated caesium hydroxide is employed as catalyst
to promote the addition of alcohols and amines to phenylacetylene
alone to yield enol ethers and enamines.7 No satisfactory mecha-
nistic pathway has been proposed to explain the observed product
distribution. In this work we demonstrate that the efficiency of the
addition of alkoxides to various substituted phenylacetylenes can
be significantly improved by employing potassium alkoxide in
combination with a diamine additive. We also present a range of
other observations and studies, which raise the possibility of
a mechanism based on electron transfer rather than simple nu-
cleophilic addition.
2. Results and discussion
We made the observation that potassium methoxide adds to
phenylacetylene in 49% over 15 h producing an excess of the cis
isomer of the corresponding enol ether (Scheme 2). Knowing that
Scheme 1. Markovnikov and anti-Markovnikov addition to alkynes.
* Corresponding author. Tel.: þ44 20 7679 3395; e-mail address: j.wilden@ucl.ac.
Scheme 2. Anti-Markovnikov addition of KOMe to phenylacetylene.
uk (J.D. Wilden).
http://dx.doi.org/10.1016/j.tet.2015.04.038
0040-4020/Ó 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

4386
J. Cuthbertson, J.D. Wilden / Tetrahedron 71 (2015) 4385e4392
such anti-Markovnikov reactions were rare in the literature, we
were keen to investigate both the scope and mechanism of the
transformation.
processes, resulted in a significantly enhanced yield with a similar
Z:E ratio. With this observation in hand, we then decided to explore
this reaction with different substrates to establish the scope and
efficiency. We had noted that the rate of reactions seemed to de-
pend upon the electronic characteristics of the arene; where those
bearing electron withdrawing groups proceed at a faster rate (or
alternatively require lower temperatures) than their electron do-
nating analogues. We therefore chose 55 ꢀC as a median operating
temperature, which would allow us to directly compare the dif-
ferent substrates employed in the reaction. The results are outlined
in Table 1.
Given the parallels with our previous work8 and the work of
others9 who have noted that potassium alkoxides (particularly
potassium tert-butoxide) can behave as single electron transfer
agents, we postulated that this reaction might be radical in nature.
Often the alkoxide is coupled with a ligand10 to render it more
effective, and we were curious to know whether ligands such as
simple secondary diamines might improve the reaction outlined in
Scheme 2.9
Addition of the secondary diamine N,N0-dimethylethylenedi-
amine (DMEDA), commonly employed in alkoxide mediated radical
The most striking first observations from Table 1 is that a re-
action considered to be the preserve of transition metal mediation
Table 1
Substrate scope for alkyne reactions with methoxidea
Entry
1
1aei
M
K
Temp ꢀC
55
Time (h)
4
Additive
Yield (2þ3) %
Z:E (2:3) ratiob
Other productsc
d
40
65:35
d
2
3
4
K
K
K
55
55
55
4
15
15
DMEDA
d
56
49
70
66:34
66:34
68:32
d
d
d
DMEDA
5
6
7
K
K
K
55
55
55
15
15
15
d
51
66
13
80:20
80:20
90:10
d
DMEDA
d
d
36% 1
8
9
10
11
12
13
K
K
K
K
Na
Li
55
75
75
75
75
75
15
15
15
30
15
15
DMEDA
d
34
50
69
30
15
0
91:9
88:12
84:16
96:4
90:10
d
56% 1
7% 5
7% 5
55% 1
44% 1
100% 1
DMEDA
DMEDAþ5% MeOH
DMEDA
DMEDA
14
K
55
15
d
57
61:39
d
15
16
K
K
55
75
15
15
DMEDA
DMEDAþ5% MeOH
72
65
60:40
81:19
d
28% 4
17
K
55
15
d
<5
95:5
ca. 95% 1
18
19
20
K
K
K
55
100
100
15
15
15
DMEDA
d
<5
23
47
95:5
80:20
80:20
ca. 95% 1
16% 1, 5% 5
7% 1, 7% 5
DMEDA
21
22
23
24
K
K
K
K
55
55
55
55
15
15
15
15
d
42
51
37
53
54:46
52:48
41:59
41:59
22% 4
21% 4
14% 4
14% 4
DMEDA
d
DMEDA

J. Cuthbertson, J.D. Wilden / Tetrahedron 71 (2015) 4385e4392
4387
Table 1 (continued )
Entry
1aei
M
K
Temp ꢀC
55
Time (h)
15
Additive
Yield (2þ3) %
Z:E (2:3) ratiob
Other productsc
25
d
31
30:70
15% 4
26
27
K
K
55
55
15
15
DMEDA
DMEDAþ5% MeOH
31
30
30:70
74:26
14% 4
32% 4
28
K
55
15
d
0
d
100% 1
29
30
K
K
55
55
15
15
DMEDA
Phen
0
0
d
d
100% 1
100% 1
a
Reaction Conditions: Alkyne (0.24 mmol, 1.0 equiv), DMF (1.5 mL), additive (0.48 mmol, 2.0 equiv).
Z:E ratio calculated from reaction 1H NMR.
Remainder comprised polymeric and decomposed material.
b
c
can be achieved with both anti-Markovnikov and Z-selectivity un-
employed as the base (though a ‘base free’ background reaction was
inhibited). Interestingly, the authors also note a similar preference
for the lower alkali metals with sodium and lithium carbonates
significantly inferior to their potassium and caesium counterparts.
Accordingly, we also employed TEMPO in the methoxide addi-
tion to 4-methylphenylacetylene under conditions identical to
those employed in entry 6 of Table 1. In common with Oshima and
Yorimitsu, we also found no effect on the yield or the rate of the
reaction. Although this might lead us to conclude that neither of
these reactions is proceeding via single electron transfer and/or
radical intermediates, we wondered if TEMPO was simply not
capturing the radical species involved. Consequently we added the
electron acceptor m-dinitrobenzene to the reaction in order to in-
tercept any electron transfer processes. This resulted in a fall in
yield from 66% to less than 10% under otherwise identical condi-
tions to those outlined in entry 6, Table 1.
der certain carefully controlled conditions. The potassium coun-
terion (entries 11e13) appears critical since employing lithium
methoxide yielded no addition products (entry 13), and sodium
methoxide yields only small amounts of the desired products with
the bulk of the material being returned as the starting alkyne 1.
In all cases, the addition of DMEDA gives an improvement in
yield in the order of 20% and occasionally higher. Our previous
work11 has also demonstrated the benefit of employing a combi-
nation of a potassium alkoxide (although usually potassium tert-
butoxide) with secondary amine additives for various synthetic
purposes. At first we assumed that the amine was behaving as
a ligand for the metal ion and improving the solubility of the alk-
oxide to allow the reaction to proceed at a sufficient rate. We
therefore attempted to improve the yield and efficiency of the re-
action by the addition of a crown ether to the reaction medium. To
our surprise, when 18-crown-6 is added to the reaction the yield
remains roughly the same, however the Z:E ratio falls significantly.
When DMEDA and the crown ether are present the yield improves
slightly but the ratio of Z:E isomers remains the same as when the
crown ether was present alone. These results suggest that the role
of DMEDA is more complex than merely a solubilizing ligand. We
have speculated elsewhere as to the role of the amine however
work continues to disambiguate the precise role of this additive12
Scheme 3.
The proposed mechanistic pathway is outlined in Scheme 4. Our
hypothesis firstly involves a single electron transfer from the alk-
oxide to the alkyne resulting in a radical anion reminiscent of the
radical anion intermediate invoked in dissolving metal reductions
of alkynes, which invariably lead to Z geometries of the resulting
products.
Scheme 4. Proposed mechanistic pathway.
Rapid coupling of the alkoxy radical and the radical anion then
leads to a discrete vinyl anion intermediate, which on protonation
from trace quantities of moisture or methanol in the reaction me-
dium leads to the observed enol ethers with Z-selectivity. Given
that TEMPO is generally employed to trap discrete carbon centred
radicals its ineffectiveness in attenuating this reaction may well be
explained.
One striking observation from the results in Table 1 is the de-
pendence of the Z:E ratio on the nature of the aryl substituent, R. As
the aryl group becomes more electron deficient the amount of the
more sterically favoured E isomer increases. The ratio correlates
very well with the Hammett parameters for each substituent as can
be seen in Fig. 1.
Scheme 3. Effect of additives on anti-Markovnikov addition of KOMe to 4-
methylphenylacetylene.
The observed Z-selectivity of these reactions coupled with the
observation that potassium seems to be essential for the reaction to
occur led us to postulate a reaction mechanism based on a single
electron transfer pathway. In 2005 Oshima and Yorimitsu disclosed
a similar reaction where the addition of a thiol to alkynes resulted
in the thio-enol ether in good yields with high Z-selectivity.13
A
radical mechanism appears to have been ruled out since the addi-
tion of TEMPO did not attenuate the reaction when Cs2CO3 was

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J. Cuthbertson, J.D. Wilden / Tetrahedron 71 (2015) 4385e4392
of small amounts of protic solvents will result in rapid protonation
of this intermediate and hence allow isolation of greater quantities
of the Z isomer. Despite this, the addition of protic solvents is not
a good strategy to improve the efficiency of the reaction overall.
Even modest amounts of methanol (5%) result in lengthy reaction
times. Presumably protic solvents significantly decelerate the initial
electron transfer step.
An interesting observation from the results in Table 1 is the
small amount of ketone 5 isolated where the alkyne bears a par-
ticularly electron rich substituent. Although at first sight this might
seem like a routine alkyne hydrolysis reaction, under these condi-
tions this would seem unlikely. A more likely explanation is found
in consideration of the stability of the radical anion. In general,
radical anions derived from aryl alkynes retain anion character on
the internal carbon atom (where it is delocalised over the aromatic
ring) with the remaining spin density residing on the external
carbon atom.15 In cases where the aryl group is particularly electron
rich the mesomerically donating group will destabilise the anion.
Consequently the alternative resonance structure contributes suf-
ficiently to allow occasional reaction with an alkoxy radical. This
yields the corresponding enol ether, which is hydrolysed rapidly on
aqueous work-up (Scheme 5).
Fig. 1. Relationship between Z-selectivity and Hammett constants.
At first this led us to suggest that the pure Z isomers initially
generated in the reaction were undergoing an inversion under the
highly basic reaction conditions. However, isolation of a pure Z
isomer (2b) and resubmitting this compound to the reaction con-
ditions led to no isomerisation and so an alternative explanation
was sought.
We therefore hypothesise that the discrete vinyl anion formed
from coupling with an alkoxy radical can invert at a rate that is
dependent on the electron withdrawing capacity of the substituent
on the aryl ring. Although the inversion of vinyl anions is usually
slow, the fact that the anions in Fig. 2 can be delocalised over the
aromatic ring, coupled with the observation that electron-
withdrawing groups increase the amount of the E isomer leads us
to conclude that inversion is feasible in this case. In addition, the
work of Houk14 has also demonstrated that the barrier to inversion
is dramatically lowered when alkenes are substituted with electron
withdrawing substituents. This model may also account for the
drop in selectivity when a crown ether is added. Complete disso-
ciation of the potassium cation from the vinyl anion 6a might be
expected to lead to more rapid inversion.
Scheme 5. Mechanism for the hydrolysis of electron rich arylacetylenes.
The acetal products 4 obtained from substrates bearing electron
deficient aryl rings are easily explained by a simple addition process
not mediated by single electron transfer. This conclusion was
reached since the inclusion of methanol in the reaction mixture
severely attenuates the first step of the process but does not at-
tenuate the rate of formation of the acetal products.
We also wished to demonstrate that other alkoxides as well as
methoxide could be employed. Pleasingly, the isopropyl and benzyl
enol ethers were also obtained in acceptable yields under similar
conditions (Fig. 3). Similarly, we observed that internal alkenes
such as 1-phenyl-1-propyne were also applicable under the same
conditions (although with poorer Z:E selectivity, Fig. 3, compounds
7e9).
Fig. 3. Reaction with alternative alkoxides and an internal alkyne.
With the addition to internal alkynes proceeding with similar
efficiency and under the same conditions as other examples we
decided to explore the possibility of trapping the putative radical
anion in order to confirm our hypothesis that the reaction proceeds
via initial electron transfer from the nucleophile to the alkyne (in
a similar way to that proposed by Ashby16 for many SN2 displace-
ments). As such, we prepared the known diyne 10, commonly
employed in transition metal mediated cyclisation reactions. Sim-
ple nucleophilic addition of methoxide to this substrate might only
be expected to yield acyclic addition products or six-membered
ring products such as 11, resulting from intramolecular cyclisation
(Fig. 4). Conversly, initial electron transfer yielding the acetylinic
Fig. 2. Mechanistic rationale for vinyl anion inversion.
This mechanistic pathway also explains why the proportion of
the Z isomer isolated is dramatically increased when the reaction
solvent is doped with a small amount of methanol. The proportion
of the sterically less favoured Z-isomer will depend not only on the
substituent attached to the aryl ring, but also on the lifetime of the
anion. In anhydrous media a long-lived vinyl anion will have suf-
ficient time to invert to the more favoured E isomer. The inclusion

J. Cuthbertson, J.D. Wilden / Tetrahedron 71 (2015) 4385e4392
4389
radical anion (with spin density residing on the
might be expected to yield five-membered ring products such as 12
(Fig. 4).
b
-carbon atom
4. Experimental section
4.1. General information
1H and 13C NMR spectra were recorded on a Bruker AMX500 or
AMX600 using CDCl3 as the deuterated solvent. Coupling constants
are reported in Hertz (Hz). 13C NMR spectra were recorded at
125 MHz or 150 MHz on either a Bruker AMX500 or AMX600 MHz
spectrometer, and are reported in parts per million. Mass spectra
were measured on a Thermo Finnigan MAT900 XP operating in EI
and CI mode. Melting points were measured using Gallenkamp
apparatus and are uncorrected. Analysis by thin layer chromatog-
raphy (TLC) was conducted using aluminium-backed plates pre-
coated (250
mm) with silica (Merck, TLC silica gel 60 F254). TLC
plates were visualised using ultraviolet light (254 nm), and then
using KMnO4 solution and heating. Flash chromatography was
performed using silica gel (Merck Kieselgel 60) 0.04/0.063 mm
(230e400 mesh) silica gel. Infra-red spectra were measured on
a FTIR Perkin Elmer Spectrum 100 operating in ATR mode as thin
films.
Fig. 4. Possible fates of diyne 10.
In fact, when we exposed diene 10 to KOMe we were surprised
to isolate only the tetracyclic compound 14 in 20% yield (the re-
mainder of the material being recovered starting material). The
formation of this compound under relatively mild conditions and
short reaction time suggests strongly that a radical mechanism is in
operation and that this product is derived from the radical anion
intermediate. Electron transfer to the acetylene followed by 5-exo
cyclisation yields the intermediate 13, which has the appropriate
stereochemistry (Z, E) to undergo radical addition to the pendant
aryl group. Subsequent rearomatisation then yields the observed
product ( Scheme 6). This result is noteworthy since naphthalene 14
has been prepared previously from 1017 and related allenes,18
however these preparations have all required transition metal ca-
4.2. General procedure for the preparation of vinyl ethers
2aeh and 3aeh
Potassium methoxide (67.0 mg, 0.96 mmol, 4.0 equiv), N,N0-
dimethylethylenediamine (50 mL, 0.48 mmol, 2.0 equiv) and ter-
minal acetylene 1aeh (0.24 mmol, 1.0 equiv) were added to
a flame-dried, sealed tube under an atmosphere of argon. DMF
(1.5 mL) was added via syringe, and the mixture was stirred at 55 ꢀC
(unless otherwise stated) for 15 h. Upon completion, the mixture
was allowed to cool to rt and was quenched by the addition of
water (2 mL). The crude mixture was diluted with CH2Cl2 (100 mL)
and washed with LiCl solution (3ꢁ20 mL). The organic portion was
dried over MgSO4, filtered and concentrated in vacuo, then purified
via column chromatography (0e5 % EtOAc/PE) to yield alkenyl
ethers 2aeh and 3aeh.
talysis (usually p-acids such as Au(I)). Other preparations of 14 and
related compounds have employed pericyclic processes,19,17a
however high temperatures (180e225 ꢀC) and extended reaction
times (18e24 h) are required.
4.3. (2-Methoxyvinyl)benzene 2/3a20
70% Combined yield; 2a; colourless oil; nmax (film/cmꢂ1) 2926,
2862, 1649, 1491, 1454, 1442, 1399, 1299, 1269, 1202; 1H NMR
(600 MHz, CDCl3) dH 7.57 (d, J¼7.2 Hz, 2H, ArH), 7.29 (t, J¼7.6 Hz, 2H,
ArH), 7.15 (t, J¼7.3 Hz, 1H, ArH), 6.15 (d, J¼7.0 Hz, 1H, CH3OCH), 5.23
(d, J¼7.0 Hz,1H, CH3OCHCH), 3.19 (s, 3H, CH3O); 13C NMR (150 MHz,
CDCl3) dC 148.1 (CH), 136.0 (Cq), 128.31, 125.9 (CH), 105.8 (CH), 60.8
(CH3); LRMS (CI) 135 (100), 91 (8), 85 (3).
3a; Colourless oil; nmax (film/cmꢂ1) 3023, 2933, 2832, 1638,
1599, 1575, 1492, 1450, 1329, 1235, 1190, 1148, 1122; 1H NMR
(600 MHz, CDCl3) dH 7.28e7.23 (m, 4H, ArH), 7.14 (t, J¼7.1 Hz, 1H,
ArH), 7.06 (d, J¼13.0 Hz, 1H, CH3OCH), 5.82 (d, J¼13.0 Hz, 1H,
CH3OCHCH), 3.69 (s, 3H, CH3O); 13C NMR (150 MHz, CDCl3) dC 149.0
(CH), 136.4 (Cq), 128.7 (CH), 125.8 (CH), 125.2 (CH), 105.1 (CH), 56.6
(CH3); LRMS (EI) 135 (6), 122 (33), 105 (100), 91 (16).
Scheme 6. Mechanistic rationale for the formation of 11.
3. Conclusions
4.4. 1-(2-Methoxyvinyl)-4-methylbenzene 2/3b20
In conclusion we have described the transformation of aryl al-
kynes into enol ethers mediated by secondary diamines in the
absence of transition metal catalysis. We have presented experi-
ments and observations that lead us to believe that the reaction
might proceed via an initial electron transfer step yielding a radical
anion akin to those intermediates involved in dissolving metal re-
ductions. Also presented is a mechanistic pathway that accounts for
the observed regio- and stereochemistry of the products and by-
products. A sound understanding of the reaction mechanism cou-
pled with an understanding of the behaviour of group 1 alkoxides
will be key principles in the future development and improvement
of these reactions to become truly useful synthetic methods.
66% Combined yield; 2b; colourless oil; nmax (film/cmꢂ1) 2840,
1730, 1684, 1600, 1579, 1509, 1443, 1426, 1398, 1354, 1303, 1256,
1243; 1H NMR (600 MHz, CDCl3) dH 7.46 (d, J¼8.0 Hz, 2H, ArH),
7.10 (d, J¼8.0 Hz, 2H, ArH), 6.09 (d, J¼7.0 Hz, 1H, CH3OCH), 5.20
(d, J¼7.0 Hz, 1H, CH3OCHCH), 3.77 (s, 3H, CH3O), 2.32 (s, 3H,
CH3(C)); 13C NMR (150 MHz, CDCl3) dC 147.4 (CH), 135.5 (Cq),
133.1 (Cq), 129.0 (CH), 128.2 (CH), 105.7 (CH), 60.7 (CH3), 21.3
(CH3); LRMS (EI) 148 (54), 133 (11), 119 (11), 105 (41), 86 (64), 84
(100). 3b; Colourless oil (contaminated with 9% Z-isomer); nmax
(film/cmꢂ1) 2922, 2852, 1637, 1512, 1461, 1336, 1317, 1297, 1236,

4390
J. Cuthbertson, J.D. Wilden / Tetrahedron 71 (2015) 4385e4392
1189, 1149; 1H NMR (600 MHz, CDCl3) dH 7.13 (d, J¼8.0 Hz, 2H,
ArH), 7.08 (d, J¼8.0 Hz, 2H, ArH), 7.01 (d, J¼13.0 Hz, 1H, CH3OCH),
5.80 (d, J¼13.0 Hz, 1H, CH3OCHCH), 3.68 (s, 3H, CH3OCH), 2.31 (s,
3H, CH3(C)); 13C NMR (150 MHz, CDCl3) dC 148.3 (CH), 135.4 (Cq),
133.2 (Cq), 129.4 (CH), 125.1 (CH), 105.0 (CH), 56.6 (CH3), 21.2
(CH3).
4.8. 2-Methoxy-6-(2-methoxyvinyl)naphthalene 2/3f
51% Combined yield; 2f; colourless oil; nmax (film/cmꢂ1) 2933,
1648, 1602, 1482, 1387, 1265, 1216, 1149, 1087, 1029; 1H NMR
(600 MHz, CDCl3) dH 7.94 (s, 1H, ArH), 7.69 (t, J¼8.5 Hz, 2H, ArH),
6.43 (d, J¼8.7 Hz, 1H, ArH), 7.10e7.08 (m, 2H, ArH), 6.19 (d, J¼7.0 Hz,
1H, CH3OCH), 5.34 (d, J¼7.0 Hz, 1H, CH3OCHCH), 3.91 (s, 3H,
CH3O(C)), 3.83 (s, 3H, CH3OCH); 13C NMR (150 MHz, CDCl3) dC 157.4
(Cq), 147.8 (CH), 133.0 (Cq), 131.5 (Cq), 129.5 (CH), 129.2 (Cq), 127.7
(CH), 126.5 (CH), 126.5 (CH), 118.7 (CH), 105.9 (CH), 105.7 (CH), 60.9
(CH3), 55.4 (CH3); LRMS (CI) 215 (100), 200 (10), 183 (7), 171 (8), 128
(3); HRMS (CI) calcd for C14H15O2 (MþH) requires 215.1072, found
215.1070. 3f; Pale cream solid (contaminated with 10% Z-isomer);
nmax (solid/cmꢂ1) 2930, 2839, 1633, 1599, 1504, 1482, 1448, 1437,
1387, 1266, 1247, 1207, 1166; 1H NMR (600 MHz, CDCl3) dH
7.65e7.63 (m, 2H, ArH), 7.53 (s, 1H, ArH), 7.40 (dd, J¼8.6, 1.8 Hz, 1H,
ArH), 7.14 (d, J¼12.9 Hz, 1H, CH3OCH), 7.11e7.08 (m, 2H, ArH), 5.95
(d, J¼12.9 Hz, 1H, CH3OCHCH), 3.91 (s, 3H, CH3O(C)), 3.72 (s, 3H,
CH3OCH); 13C NMR (150 MHz, CDCl3) dC 157.2 (Cq), 148.7 (CH), 133.1
(Cq), 131.7 (Cq), 129.4 (Cq), 129.0 (CH), 127.2 (CH), 124.0 (CH), 123.8
(CH), 119.0 (CH), 105.9 (CH), 105.4 (CH), 56.7 (CH3), 55.4 (CH3).
4.5. 1-Methoxy-4-(2-methoxyvinyl)benzene 2/3c20
69% combined yield; 2c: Colourless oil, nmax (film/cmꢂ1) 2930,
2831, 1649, 1603, 1571, 1507, 1453, 1397, 1239, 1175, 1089, 1029; 1H
NMR (500 MHz, CDCl3) dH 7.51 (d, J¼8.8 Hz, 2H, ArH), 6.83 (d,
J¼8.8 Hz, 2H, ArH), 6.05 (d, J¼7.0 Hz,1H, CH3OCH), 5.18 (d, J¼7.0 Hz,
1H, CH3OCHCH), 3.80 (s, 3H, CH3O(C)), 3.76 (s, 3H, CH3OCH); 13C
NMR (150 MHz, CDCl3) dC 157.7 (Cq), 146.5 (CH), 129.5 (CH), 128.8
(Cq), 113.7 (CH), 105.3 (CH), 60.6 (CH3), 55.3 (CH3); LRMS (CI) 165
(100), 150 (12), 135 (4), 121 (6). 3c:White solid; MP¼45e46 ꢀC;
nmax (film/cmꢂ1) 2954, 2937, 2835, 1658, 1637, 1604, 1574, 1508,
1460,1337, 1286, 1236, 1178; 1H NMR (600 MHz, CDCl3) dH 7.16 (d,
J¼8.7 Hz, 2H, ArH), 6.93 (d, J¼13.0 Hz, 1H, ArH), 6.82 (d, J¼8.7 Hz,
2H, CH3OCH), 5.78 (d, J¼13.0 Hz, 1H, CH3OCHCH), 3.79 (s, 3H,
CH3O(C)), 3.66 (s, 3H, CH3OCH); 13C NMR (150 MHz, CD2Cl2) dC
157.9 (Cq), 147.5 (CH), 128.9 (Cq), 126.0 (CH), 114.0 (CH), 104.3 (CH),
56.4 (CH3), 55.2 (CH3); LRMS (EI) 164 (81), 149 (45), 121 (100), 91
(16).
4.9. 1-Bromo-4-(2-methoxyvinyl)benzene 2/3g
53% Combined yield; 2g; colourless oil; nmax (film/cmꢂ1) 2933,
1649, 1624, 1485, 1453, 1407, 1311, 1289, 1266, 1200, 1088; 1H NMR
(600 MHz, CDCl3) dH 7.43 (d, J¼8.6 Hz, 2H, ArH), 7.38 (d, J¼8.6 Hz,
2H, ArH), 6.16 (d, J¼7.0 Hz, 1H, CH3OCH), 5.16 (d, J¼7.0 Hz, 1H,
CH3OCHCH), 3.79 (s, 3H, CH3O); 13C NMR (150 MHz, CDCl3) dC 148.7
(CH), 134.9 (Cq), 131.3 (CH), 129.8 (CH), 119.2 (Cq), 104.7 (CH), 60.9
(CH3); LRMS (EI) 214 (30), 212 (29), 171 (16), 169 (19), 118 (92), 90
(51), 89 (65), 86 (68), 84 (100); HRMS (EI) calcd for C9H9BrO (Mþ)
requires 211.9837, found 211.9832. 3g; Colourless oil (contaminated
with 14% Z-isomer); nmax (film/cmꢂ1) 2934, 2833, 1700, 1640, 1487,
1462, 1400, 1312, 1291, 1241, 1190; 1H NMR (600 MHz, CDCl3) dH
7.36 (d, J¼8.5 Hz, 2H, ArH), 7.09 (2H, d, J¼8.5 Hz, 2H, ArH), 7.03 (d,
J¼13.0 Hz, 1H, CH3OCH), 5.73 (d, J¼13.0 Hz, 1H, CH3OCHCH), 3.68 (s,
3H, CH3O); 13C NMR (150 MHz, CDCl3) dC 149.4 (CH), 135.5 (Cq),
131.7 (CH), 126.7 (CH), 119.1 (Cq), 104.1 (CH), 56.7 (CH3); LRMS (EI)
214 (15), 212 (15), 185 (42), 183 (38), 171 (33), 169 (35), 157 (19), 155
(20), 118 (59), 90 (57), 89 (100).
4.6. 1-Methoxy-3-(2-methoxyvinyl)benzene 2/3d
72% Combined yield; 2d; colourless oil; nmax (film/cmꢂ1) 2936,
2831, 1649, 1597, 1573, 1484, 1455, 1428, 1399, 1256, 1238, 1165,
1094; 1H NMR (600 MHz, CDCl3) dH 7.21e7.19 (m, 2H, ArH),
7.12e7.11 (m, 1H, ArH), 6.71 (ddd, J¼8.2, 2.7, 0.8 Hz, 1H, ArH), 6.14
(d, J¼6.9 Hz, 1H, CH3OCH), 5.20 (d, J¼6.9 Hz, 1H, CH3OCHCH), 3.80
(s, 3H, CH3O(C)), 3.78 (s, 3H, CH3OCH); 13C NMR (150 MHz, CDCl3)
dC 159.5 (Cq), 148.3 (CH), 137.3 (Cq), 129.2 (CH), 121.0 (CH), 113.7
(CH), 111.6 (CH), 105.6 (CH), 60.9 (CH3), 55.3 (CH3); LRMS (CI) 164
(85), 149 (3), 121 (40), 91 (17), 86 (64), 84 (100); HRMS (EI) calcd
for C10H12O2 (Mþ) requires 164.0837, found 164.0835. 3d; Col-
ourless oil (contaminated with 18% Z-isomer); nmax (film/cmꢂ1
)
2935, 2833, 1640, 1598, 1576, 1487, 1453, 1427, 1252, 1217, 1145,
1121, 1096; 1H NMR (600 MHz, CDCl3) dH 7.18 (t, J¼7.8 Hz, 1H, ArH),
7.05 (d, J¼13.0 Hz, 1H, CH3OCH), 6.84e6.83 (m, 1H, ArH),
6.77e6.76 (m, 1H, ArH), 6.69 (dd, J¼8.2, 2.0 Hz, 1H, ArH), 5.78 (d.
J¼13.0 Hz, 1H, CH3OCHCH), 3.80 (s, 3H, CH3O(C)), 3.68 (s, 3H,
CH3OCH); 13C NMR (150 MHz, CDCl3) dC 159.9 (Cq), 149.2 (CH),
137.9 (Cq), 129.7 (CH), 117.8 (CH), 111.2 (CH), 110.8 (CH), 105.0 (CH),
56.6 (CH3), 55.3 (CH3); LRMS (EI) 165 (100), 164 (35), 87 (7), 85
(16).
4.10. 1-(2-Methoxyvinyl)-4-(trifluoromethyl)benzene 2/3h20
31% Combined yield; 2h; pale yellow oil; nmax (film/cmꢂ1) 2924,
2853, 1643, 1614, 1323, 1273, 124, 1186, 1161, 1121, 1095; 1H NMR
(600 MHz, CDCl3) dH 7.64 (d, J¼8.1 Hz, 2H, ArH), 7.51 (d, J¼8.1 Hz,
2H, ArH), 6.24 (d, J¼6.9 Hz, 1H, CH3OCH), 5.25 (d, J¼6.9 Hz, 1H,
CH3OCHCH), 3.82 (s, 3H, CH3O); 13C NMR (150 MHz, CDCl3) dC 150.0
(CH), 139.5 (Cq), 128.2 (CH), 127.4 (q, J¼32.1 Hz) (Cq), 125.2 (q,
J¼3.8 Hz) (CH), 124.5 (q, J¼271.8 Hz) (Cq), 104.5 (CH), 61.1 (CH3);
LRMS (EI) 202 (21), 183 (24), 159 (100), 151 (15), 133 (5), 109 (73).
3h; Pale yellow oil (contaminated with 8% Z-isomer); nmax (film/
cmꢂ1) 2926, 2854, 1728, 1657, 1642, 1615, 1413, 1324, 1163, 1123; 1H
NMR (600 MHz, CDCl3) dH 7.50 (d, J¼8.2 Hz, 2H, ArH), 7.30 (d,
J¼8.2 Hz, 2H, ArH), 7.14 (d, J¼13.0 Hz, 1H, CH3OCH), 5.81 (d,
J¼13.0 Hz, 1H, CH3OCHCH), 3.72 (s, 3H, CH3O); 13C NMR (150 MHz,
CDCl3) dC 150.7 (CH), 140.3 (Cq), 127.5 (q, J¼33.0 Hz) (Cq), 125.7 (q,
J¼3.8 Hz) (CH), 125.1 (CH), 124.6 (q, J¼271.3 Hz) (Cq), 104 (CH), 56.8
(CH3); LRMS (EI) 202 (100), 183 (10), 173 (34), 159 (72), 151 (5), 145
(12), 109 (14).
4.7. 4-(2-Methoxyvinyl)-N,N-dimethylaniline 2/3e
Could not separate E and Z isomers. Pale yellow oil, 47%; nmax
(film/cmꢂ1) 2927, 1648, 1605, 1517, 1443, 1396, 1347, 1264, 1188,
1088; 1H NMR (600 MHz, CDCl3) dH (Z-isomer) 7.47 (d, J¼8.9 Hz, 2H,
ArH), 6.70 (d, J¼8.9 Hz, 2H, ArH), 6.00 (d, J¼7.0 Hz, 1H, CH3OCH),
5.15 (d, J¼7.0 Hz, 1H CH3OCHCH), 3.74 (s, 3H, OCH3), 2.93 (s, 6H,
2ꢁNCH3); 1H NMR (600 MHz, CDCl3) dH (E-isomer) 7.13 (d, J¼8.8 Hz,
2H, ArH), 6.90 (d, J¼13.0 Hz, 1H, ArH), 6.70e6.69 (m, 2H, CH3OCH),
5.77 (d, J¼13.0 Hz, 1H, CH3OCHCH), 3.65 (s, 3H, OCH3), 2.92 (s, 6H,
2ꢁNCH3); 13C NMR (150 MHz, CDCl3) dC (Z-isomer)148.8 (Cq), 145.4
(CH), 129.2 (CH), 124.9 (Cq), 112.7 (CH), 105.8 (CH), 60.5 (CH3), 40.9
(CH3); 13C NMR (150 MHz, CDCl3) dC (E-isomer) 149.2 (Cq), 146.6
(CH), 126.1 (CH), 124.9 (Cq), 113.3 (CH), 105.1 (CH), 56.6 (CH3), 41.0
(CH3); HRMS (ESI) calcd for C11H15NO (MþH) requires 178.1232,
found 178.1231.
4.11. 1-(2,2-Dimethoxyethyl)-3-methoxybenzene 4d
Colourless oil, 28%; nmax (film/cmꢂ1) 2934, 2829, 1600, 1583,
1488, 1452, 1435, 1361, 1309, 1292, 1257, 1229, 1116, 1041; 1H NMR

J. Cuthbertson, J.D. Wilden / Tetrahedron 71 (2015) 4385e4392
4391
(500 MHz, CDCl3) dH 7.21 (t, J¼7.8 Hz, 1H), 6.84e6.76 (m, 3H), 4.55
give a bubbling white paste. The mixture was stirred at rt for
10 min, then gently heated to 50 ꢀC for 20 min, before being cooled
to rt. The remaining THF was removed in vacuo and the resulting
paste diluted with DMF (1.5 mL). To the solution was added DMEDA
(0.48 mmol, 2.0 equiv) then p-tolylacetylene (0.24 mmol, 1.0 equiv)
as a single burst. The mixture was stirred at 55 ꢀC until complete
consumption of p-tolylacetylene was observed by TLC (3 h). The
crude mixture was quenched by addition of iPrOH (1 mL) and di-
luted with CH2Cl2 (100 mL), which was washed with 2.0 M LiCl
(3ꢁ20 mL). The organic portion was dried over MgSO4, filtered and
concentrated in vacuo, then purified via column chromatography
(0e5% EtOAc/P.E.) to yield the alkenyl ethers.
(t, J¼5.6 Hz, 1H), 3.80 (s, 3H), 3.34 (s, 6H), 2.89 (d, J¼5.6 Hz, 2H); 13
C
NMR (150 MHz, CDCl3) dC 159.6 (Cq), 138.7 (Cq), 129.4 (CH), 121.9
(CH), 115.3 (CH), 111.8 (CH), 105.3 (CH), 55.3 (CH3), 53.5 (CH3), 39.8
(CH2); LRMS (EI) 196 (4), 165(18), 135 (3), 121 (9), 75 (100); HRMS
(EI) calcd for C11H16O3 (Mþ) requires 196.1099, found 196.1099.
4.12. 2-(2,2-Dimethoxyethyl)-6-methoxynaphthalene 4f
White solid, 21%; MP¼57e58 ꢀC; nmax (film/cmꢂ1) 2957, 2937,
2903, 2834, 1632, 1601, 1483, 1460, 1390, 1260, 1232, 1183, 1117,
1047; 1H NMR (600 MHz, CDCl3) dH 7.69 (t, J¼8.0 Hz, 2H), 7.62 (s,
1H), 7.35 (dd, J¼8.4, 1.6 Hz, 1H), 7.14e7.12 (m, 2H), 4.62 (t, J¼5.7 Hz,
1H), 3.92 (s, 3H), 3.37 (s, 6H), 3.05 (d, J¼5.7 Hz, 2H); 13C NMR 157.4
(Cq), 133.4 (Cq), 132.3 (Cq), 129.2 (CH), 129.1 (Cq), 128.5 (CH), 127.8
(CH), 126.8 (CH), 118.9 (CH), 105.7 (CH), 105.6 (CH), 55.4 (CH3), 53.6
(CH3), 39.8 (CH2); HRMS (ESI) calcd for C15H18ONa (MþNa) requires
269.1154, found 269.1153.
4.18. 1-(2-Isopropoxyvinyl)-4-methylbenzene 7
43% (Z and E combined yield). Z-isomer: Pale yellow oil; nmax
(film/cmꢂ1) 2974, 1648, 1511, 1453, 1422, 1383, 1372, 1338, 1259,
1117, 1074; 1H NMR (600 MHz, CD2Cl2) dH 7.45 (d, J¼8.0 Hz, 2H,
ArH), 7.07 (d, J¼8.0 Hz, 2H, ArH), 6.22 (d, J¼7.0 Hz, 1H, OCHCH), 5.16
(d, J¼7.0 Hz, 1H, OCHCH), 4.05 (quintet, J¼6.3 Hz, 1H, OCH(CH3)2),
2.29 (s, 3H, CH3(C)), 1.31 (d, J¼6.3 Hz, 6H, CH(CH3)2); 13C NMR
(150 MHz, CD2Cl2) dC 144.9 (CH), 135.0 (Cq), 133.5 (Cq), 128.7 (CH),
127.9 (CH), 104.9 (CH), 75.8 (CH), 22.3 (CH3), 20.1 (CH3); LRMS (EI)
176 (43), 134 (100), 119 (48), 105 (76), 91 (20); HRMS (EI) calcd for
4.13. 1-Bromo-4-(2,2-dimethoxyethyl)benzene 4g21
Colourless oil, 14%; nmax (film/cmꢂ1) 2932, 2830, 1488, 1362,
1189, 1118, 1071, 1043, 1011; 1H NMR (600 MHz, CDCl3) dH 7.41 (d,
J¼8.3 Hz, 2H, ArH), 7.11 (d, J¼8.3 Hz, 2H, ArH), 4.49 (t, J¼5.6 Hz, 1H,
CH3OCH), 3.33 (s, 6H, 2ꢁCH3O), 2.86 (d, J¼5.6 Hz, 2H, CH3OCHCH2);
13C NMR (150 MHz, CDCl3) dC 136.1 (Cq),131.5 (CH),131.3 (CH),120.7
(Cq), 105.1 (CH), 53.6 (CH3), 39.2 (CH2); LRMS (EI) 245 (1), 243 (1),
171 (44), 169 (46), 134 (100), 118 (19); HRMS (EI) calcd for
C
12H16O (Mþ) requires 176.1201, found 176.1206. E-isomer: Col-
ourless oil; nmax (film/cmꢂ1) 2974,1654,1635,1513,1384,1372,1317,
1218, 1177, 1151, 1111; 1H NMR (600 MHz, CD2Cl2) dH 7.10 (d,
J¼8.0 Hz, 2H, ArH), 7.05 (d, J¼8.0 Hz, 2H, ArH), 6.84 (d, J¼12.7 Hz,
1H, OCHCH), 5.83 (d, J¼12.7 Hz,1H, OCHCH), 4.11 (quintet, J¼6.2 Hz,
1H, OCH(CH3)2), 2.28 (s, 3H, CH3(C)), 1.26 (d, J¼6.2 Hz, 6H,
CH(CH3)2); 13C NMR (150 MHz, CD2Cl2) dC 146.2 (CH), 135.1 (Cq),
133.7 (Cq), 129.1 (CH), 124.7 (CH), 107.0 (CH), 73.6 (CH), 22.1 (CH3),
20.7 (CH3); LRMS (EI) 176 (9), 134 (25), 105 (16), 85 (63), 83 (100);
C
10H13BrO2 (Mþ) requires 244.0098, found 244.0092.
4.14. 1-(2,2-Dimethoxyethyl)-4-(trifluoromethyl)benzene 4h
Colourless oil, 32%; nmax (film/cmꢂ1) 2935, 2831, 1618, 1438,
1417, 1363, 1321, 1228, 1161, 1107, 1063; 1H NMR (600 MHz, CDCl3)
dH 7.55 (d, J¼8.0 Hz, 2H, ArH), 7.35 (d, J¼8.0 Hz, 2H, ArH), 4.54 (t,
J¼5.6 Hz, 1H, CH(OCH3)2), 3.35 (s, 6H, 2ꢁOCH3), 2.96 (d, J¼5.6 Hz,
2H, CHCH2Ar); 13C NMR (150 MHz, CDCl3) dC 141.2 (Cq), 129.9 (CH),
128.8 (q, J¼32.3 Hz) (Cq), 125.3 (q, J¼3.8 Hz) (CH), 123.5 (q,
J¼273.8 Hz) (Cq), 104.9 (CH), 53.6 (CH3), 39.6 (CH2); LRMS (CI) Mass
ion not observed, 220 (8), 205 (30), 188 (100), 75 (31). Not observed
by HRMS.
HRMS (EI) calcd for
176.1204.
C12H16O
(Mþ) requires 176.1201, found
4.19. 1-(2-(Benzyloxy)vinyl)-4-methylbenzene 823
61% (Z and E combined yield). Z-isomer: Pale yellow oil; nmax
(film/cmꢂ1) 3029, 2921, 2859, 1649, 1512, 1453, 1419, 1367, 1299,
1261, 1198, 1086, 1074; 1H NMR (600 MHz, CDCl3) dH 7.53 (d,
J¼7.9 Hz, 2H, ArH), 7.40e7.36 (m, 4H, ArH), 7.33e7.31 (m, 1H, ArH),
7.11 (d, J¼7.9 Hz, 2H, ArH), 6.23 (d, J¼7.0 Hz, 1H, OCHCH), 5.25 (d,
4.15. 1-(4-Methoxyphenyl)ethanone 5c21
J¼7.0 Hz, 1H, OCHCH), 4.99 (s, 2H, OCH2Ph), 2.32 (s, 3H, CH3(C)); 13
C
Colourless oil, 7%; 1H NMR (600 MHz, CDCl3) dH 7.95 (d,
J¼8.8 Hz, 2H, ArH), 6.94 (d, J¼8.8 Hz, 2H, ArH), 3.88 (s, 3H, CH3O),
2.57 (s, 3H, CH3(C)); 13C NMR (150 MHz, CDCl3) dC 197.0 (Cq), 163.6
(Cq), 130.7 (CH), 130.4 (Cq), 113.8 (CH), 55.6 (CH3), 26.5 (CH3); LRMS
(EI) 150 (34), 135 (100), 121 (5), 107 (11), 92 (23).
NMR (150 MHz, CDCl3) dC 145.7 (CH), 137.5 (Cq), 135.5 (Cq), 133.1
(Cq), 129.0 (CH), 128.7 (CH), 128.3 (CH), 128.1 (CH), 127.3 (CH), 106.3
(CH), 74.9 (CH2), 21.3 (CH3); LRMS (CI) 225 (29), 224 (32), 207 (32),
195 (10), 147 (6), 133 (8), 119 (8), 105 (46), 91 (100); HRMS (CI) calcd
for C16H17O (MþHþ) requires 225.1279, found 225.1274. E-isomer
(contaminated with 15% Z-isomer); Pale yellow oil; nmax (film/
cmꢂ1) 3033, 3017, 2913, 2870, 1636, 1512, 1453, 1377, 1319, 1224,
1213, 1150, 1104, 1080; 1H NMR (600 MHz, CDCl3) dH 7.40e7.37 (m,
4H, ArH), 7.34e7.32 (m, 1H, ArH), 7.13 (d, J¼8.0 Hz, 2H, ArH), 7.07 (d,
J¼8.0 Hz, 2H, ArH), 7.04 (d, J¼13.0 Hz, 1H, OCHCH), 5.95 (d,
J¼13.0 Hz, 1H, OCHCH), 4.89 (s, 2H, OCH2Ph), 2.31 (s, 3H, CH3(C));
13C NMR (150 MHz, CDCl3) dC 147.2 (CH), 136.9 (Cq), 135.5 (Cq), 133.4
(Cq), 129.4 (CH), 128.7 (CH), 128.2 (CH), 127.7 (CH), 125.2 (CH), 106.9
(CH), 71.9 (CH2), 21.2 (CH3); LRMS (CI) 225 (14), 224 (15), 207 (21),
173 (5), 125 (5), 111 (33), 105 (40), 97 (31), 91 (100).
4.16. 1-(4-(Dimethylamino)phenyl)ethanone 5e22
White film, 7%; 1H NMR (600 MHz, CDCl3) dH 7.88 (d, J¼9.0 Hz,
2H, ArH), 6.66 (d, J¼9.0 Hz, 2H, ArH), 3.07 (s, 6H, (CH3)2N), 2.52 (s,
3H, CH3(C)); 13C NMR (150 MHz, CDCl3) dC 196.6 (Cq), 153.5 (Cq),
130.7 (CH), 125.4 (Cq), 110.7 (CH), 40.2 (CH3), 26.2 (CH3). HRMS (ESI)
calcd for C10H14NO (MþH) requires 164.1075, found 164.1076.
4.17. General procedure for the synthesis of isopropyl and
benzyl alkenyl ethers
4.20. (2-Methoxyprop-1-en-1-yl)benzene 924
To a flame-dried flask under an atmosphere of argon was added
benzyl alcohol or isopropanol (0.96 mmol, 4.0 equiv) and anhy-
drous THF (1.0 mL). To the solution was added potassium hydride
(0.96 mmol, 4.0 equiv washed with petroleum ether and dried
using filter paper immediately prior to use) as a single portion to
Colourless oil, 51% combined yield; 1H NMR (600 MHz, CD2Cl2)
dH (E-isomer) 7.28 (t, J¼7.7 Hz, 2H, ArH), 7.19 (d, 2H, J¼7.5 Hz, ArH),
7.12 (t, J¼7.4 Hz, 1H, ArH), 5.60 (s, 1H, ArCH), 3.64 (s, 3H, CH3O), 1.98
(s, 3H, CH3(C)); 13C NMR (150 MHz, CD2Cl2) dC (E-isomer) 156.4 (Cq),

4392
J. Cuthbertson, J.D. Wilden / Tetrahedron 71 (2015) 4385e4392
137.9 (Cq), 128.6 (CH), 128.1 (CH), 124.9 (CH), 99.3 (CH), 54.5 (CH3),
17.7 (CH3); 1H NMR (600 MHz, CD2Cl2) dH (Z-isomer) 7.50 (d,
J¼7.4 Hz, 2H, ArH), 7.23 (t, J¼7.6 Hz, 2H, ArH), 7.07 (t, J¼7.4 Hz, 1H,
References and notes
1. (a) Kutscheroff, M. Chem. Ber. 1881, 14, 1540e1542; (b) Kutscheroff, M. Chem.
Ber. 1884, 17, 13e29; (c) Thomas, R. J.; Campbell, K. N.; Hennion, G. F. J. Am.
Chem. Soc. 1938, 60, 718e720.
ArH), 5.29 (s, 1H, ArCH), 3.72 (s, 3H, CH3O), 2.05 (s, 3H, CH3(C)); 13
C
NMR (150 MHz, CD2Cl2) dC (Z-isomer) 153.8 (Cq), 136.9 (Cq), 127.9
(CH), 127.7, 124.9 (CH), 105.8 (CH), 54.9 (CH3), 18.3 (CH3); LRMS (CI)
149 (100), 117 (24), 105 (4). Data in agreement with literature
values.24
2. (a) Imi, K.; Imai, K.; Utimoto, K. Tetrahedron Lett. 1987, 28, 3217e3220; (b)
Norman, R. O.; Parr, W. J. E.; Thomas, C. B. J. Chem. Soc., Perkin Trans. 1 1976,
1983e1987; (c) Fukuda, Y.; Utimoto, K. J. J. Org. Chem. 1991, 56, 3729e3731.
3. James, B. R.; Rempel, G. L. J. Am. Chem. Soc. 1969, 91, 863e865.
4. (a) Tokunaga, M.; Wakatsuki, Y. Angew. Chem., Int. Ed. 1998, 37, 2867e2869; (b)
Hansen, H. D.; Nelson, J. H. Organometallics 2000, 19, 4740e4755; (c) Ghe-
breyessus, K. Y.; Nelson, J. H. Inorg. Chim. Acta 2003, 350, 12e24; (d) Cadierno,
V.; Crochet, P.; Garcia-Garrido, S. E.; Gimeno, J. Dalton Trans. 2004, 3635e3641.
5. Utimoto, K. Pure Appl. Chem. 1983, 55, 1845e1852.
4.21. 4-Phenyl-2,3-dihydro-1H-cyclopenta[b]naphthalene
1418
6. Hintermann, L.; Labonne, A. Synthesis 2007, 1121e1150.
7. (a) Tzalis, D.; Koradin, C.; Knochel, P. Tetrahedron Lett. 1999, 40, 6193e6195; (b)
Bellucci, G.; Chiappe, C.; Lo Moro, G. Synlett 1996, 880e882.
20%; Colourless oil, nmax (film/cmꢂ1) 3056, 2948, 1600, 1493,
1027, 850; 1H NMR (600 MHz, CDCl3) dH 7.82 (d, J¼8.2 Hz, 1H, ArH),
7.70 (s, 1H, CH2(C)CH), 7.58 (d, J¼8.5 Hz, 1H, ArH), 7.50 (t, J¼7.3 Hz,
2H, ArH), 7.43e7.36 (m, 4H, ArH), 7.30 (t, J¼7.6 Hz,1H, ArH), 3.13 (td,
J¼7.5, 1.0 Hz, 2H, CH2(C)CH), 2.83 (t, J¼7.3 Hz, 2H, CH2(C) (C)), 2.09
(quint, J¼7.4 Hz, 2H, CH2CH2CH2); 13C NMR (150 MHz, CDCl3) dC
143.0 (Cq), 141.8 (Cq), 139.6 (Cq), 134.7 (Cq), 133.3 (Cq), 131.6 (Cq),
130.1 (CH), 128.4 (CH), 127.7 (CH), 127.1 (CH), 125.9 (CH), 125.0 (CH),
124.9 (CH), 121.9 (CH), 33.2 (CH2), 32.6 (CH2), 26.1 (CH2); HRMS (EI)
calcd for C19H16 (Mþ) requires 244.1247, found 244.1251. Data in
agreement with literature values.
8. Gray, V. J.; Slater, B.; Wilden, J. D. Chem.dEur. J. 2012, 18, 15582e15585.
9. Roman, D. S.; Takahashi, Y.; Charette, A. B. Org. Lett. 2011, 13, 3242e3245.
10. (a) Shirakawa, E.; Zhang, X. J.; Hayashi, T. Angew. Chem., Int. Ed. 2011, 50,
4671e4674; (b) Liu, W.; Cao, H.; Zhang, H.; Chung, K. H.; He, C.; Wang, H.;
Kwong, F. Y.; Lei, A. J. Am. Chem. Soc. 2010, 132, 16737e16740.
11. Gray, V. J.; Cuthbertson, J.; Wilden, J. D. J. Org. Chem. 2014, 79, 5869e5874.
12. Cuthbertson, J.; Gray, V. J.; Wilden, J. D. Chem. Commun. 2014, 2575e2578.
13. Kondoh, A.; Takami, K.; Yorimitsu, H.; Koichiro, O. J. Org. Chem. 2005, 70,
6468e6473.
14. Caramella, P.; Houk, K. N. Tetrahedron Lett. 1981, 22, 819e822.
15. Akiyama, S.; Tajima, K.; Nakatsuji, S.; Nakashima, K.; Abiru, K.; Watanabe, M.
Bull. Chem. Soc. Jpn. 1995, 68, 2043e2051.
16. Ashby, E. C.; Pham, T. N. Tetrahedron Lett. 1987, 28, 3183e3186.
17. (a) Shibata, T.; Fujiwara, R.; Takano, D. Synlett 2005, 2062e2066; (b) Lian, J.-J.;
Chen, P.-C.; Lin, Y.-P.; Ting, H.-C.; Liu, R.-S. J. Am. Chem. Soc. 2006, 128,
11372e11373.
Acknowledgements
18. Lin, G.-Y.; Yang, C.-Y.; Liu, R.-S. J. Org. Chem. 2007, 72, 6753e6757.
19. Kocsis, L. S.; Benedetti, E.; Brummond, K. M. Org. Lett. 2012, 14, 4430e4433.
The authors would like to thank UCL for support via the doctoral
training programme in Organic Chemistry: Drug Discovery.
20. Kondo, M.; Kochi, T.; Kakiuchi, F. J. Am. Chem. Soc. 2011, 133, 32e34.
ꢀ
~
ꢀ
ꢀ
21. Fananas, F. J.; Alvarez-Perez, M.; Rodriguez, F. Chem.dEur. J. 2005, 11,
5938e5944.
22. Bassetti, M.; Ciceri, S.; Lancia, F.; Pasquini, C. Tetrahedron Lett. 2014, 55,
1608e1612.
Supplementary data
ꢀ
23. (a) Alcaide, B.; Perez-Castells, J.; Polanco, C.; Sierra, M. A. J. Org. Chem. 1995, 60,
ꢀ
6012e6016; (b) Barluenga, J.; Escribano, M.; Moriel, P.; Aznar, F.; Valdes, C.
Supplementary data (1H and 13C NMR spectra of the compounds
presented are available.) related to this article can be found at
http://dx.doi.org/10.1016/j.tet.2015.04.038.
Chem.dEur. J. 2009, 15, 13291e13294.
24. Gronheid, R.; Lodder, G.; Ochiai, M.; Sueda, T.; Okuyama, T. J. Am. Chem. Soc.
2001, 123, 8760e8765.