Fragmentations observed in the reactions of α-methoxy-γ- alkoxyalkyl iodide substrates with super-electron-donors derived from 4-DMAP and N-methylbenzimidazole

Article abstract of DOI:10.1039/c0ob01282c

Reactions of super-electron-donors (SEDs) derived from 4- dimethylaminopyridine and from N-methylbenzimidazole with α-methoxy- γ-alkoxyalkyl iodides lead to liberation of the γ-alkoxy groups as their alcohols. This is consistent with generation of alkyl radicals from the alkyl halide precursors, and trapping of these radicals by the radical-cation of the SED, followed by a heterolytic fragmentation.

Full text of DOI:10.1039/c0ob01282c

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PAPER
Fragmentations observed in the reactions of a-methoxy-c-alkoxyalkyl iodide
substrates with super-electron-donors derived from 4-DMAP and
N-methylbenzimidazole†‡§
Ryan Sword, Luke A. Baldwin and John A. Murphy*
Received 31st December 2010, Accepted 22nd February 2011
DOI: 10.1039/c0ob01282c
Reactions of super-electron-donors (SEDs) derived from 4-dimethylaminopyridine and from
N-methylbenzimidazole with a-methoxy-g-alkoxyalkyl iodides lead to liberation of the g-alkoxy groups
as their alcohols. This is consistent with generation of alkyl radicals from the alkyl halide precursors,
and trapping of these radicals by the radical-cation of the SED, followed by a heterolytic fragmentation.
The driving force for oxidation of the donor is stronger for 4
and 5 than for 3, likely due to differences in aromatic stabilisation
Introduction
energy in their oxidised forms.4i Another factor that impacts on
their ease of oxidation is the repulsion that can arise between
the two positive charges in their oxidised disalts e.g. 2. It has
been shown that for the dication 2 derived from the commercially
available donor TDAE 1, substantial twisting occurs about the
central C–C bond to minimise the repulsion between the two
positive ends of the molecule.6 This is also seen in the oxidation of
3, where the twisted nature of the oxidised dication resulted in the
protons within both of the NCH2 groups being diastereotopic.4a
The computed angle between the planes of the two fused planar
heterocycles increases from 16◦ in 3 to 26.3◦ in the corresponding
radical-cation and to 41.3◦ in the dication.4b Likewise, in oxidation
of donor 4, the angle between the two six-membered rings opens
to 36◦ in the radical-cation, while the X-ray structure of the
oxidised diaction shows the angle at 53◦. However, the donor
5 is constrained by its two trimethylene straps. A computed initial
angle of 10.2◦ between the two planar 5-membered rings in the
parent molecule 5 changes only slightly to 12◦ in the radical-cation
6, but decreases to 1.5◦ in the dication 7.4b These small angles
might leave the oxidised forms 6 and 7 unusually open to attack
by radicals or anions formed in the electron transfer reactions.
In support of this, we recently demonstrated4g that the radical-
cation 6 can trap alkyl radicals; this was illustrated both by
homologation of Cn alkyl halides to the Cn+1 aldehydes, where
the added carbon was derived from the electron donor 5, and also
by fragmentation of a series of a,g-dialkoxyalkyl halides 14, from
which alcohols ROH 16 and methanol 17 were liberated, as shown
in Scheme 2.
Neutral, ground-state organic electron donors are currently widely
studied.1–5 Whereas the tetrathiafulvalenes1 have received much
attention in materials science and occasionally in synthesis, the
tetraazaalkenes,2–4 including compounds 1 and 3–5, are consider-
ably more powerful donors and include the most powerful neutral
organic ground-state donors known.5 The commerically available
parent compound, tetrakisdimethylaminoethene (TDAE) 1, has
been widely used2 as a two-electron donor to strongly electron-
deficient organic systems such as CF3I, thereby affording the
trifluoromethyl anion and the oxidised dication 2. The stronger
donor, benzimidazole-derived 3,3a–c,4a reacted with iodoarenes, e.g.
8 and iodoalkanes e.g. 10 at high temperature to afford aryl and
alkyl radicals respectively after transfer of a single electron; after
cyclisation, reductive termination by hydrogen atom abstraction
afforded products 9 and 11 respectively in good yield.4a This was
the first time that a neutral organic ground-state electron donor
had achieved the conversion of iodoarenes to aryl radicals, and the
term ‘super-electron-donor’ was applied to such reagents. More
powerful organic donors 44d–f,h,j and 5,3a,d subsequently converted
aryl halides to aryl anions4b,c,g by donation of two electrons. The
presence of the aryl anions derived from iodoarene 12 was shown
by cyclisation of the aryl anion derived from substrate 12 onto the
ester group to afford ketone 13 (Scheme 1). Whereas aryl anions
could be generated in this way, the less stabilised alkyl anions could
not.
WestCHEM, Department of Pure and Applied Chemistry, University of
Strathclyde, 295 Cathedral Street, Glasgow, United Kingdom G1 1XL.
E-mail: john.murphy@strath.ac.uk; Tel: +44 (0)141 548 2389
The purpose of the investigation leading to this paper was to
probe whether this trapping chemistry of the oxidised forms of
donor 5 is really an anomaly arising from the almost planar nature
of its oxidised forms, 6 and 7, or whether such trapping occurs
routinely in more flexible super-electron-donors; the result would
be important for understanding the fundamental chemistry of
reactive tetraazaalkenes. The investigation would be carried out
† This paper is dedicated to the late Professor Athel Beckwith.
‡ We thank EPSRC for funding and the Carroll University Thronson
International Research Initiative for support (to L.A.B.), and the EPSRC
mass spectrometry Service Centre, Swansea for mass spectra.
§ Electronic supplementary information (ESI) available: Experimental
procedures and 1H and 13C NMR spectra of key products. See DOI:
10.1039/c0ob01282c
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Table 1 Alcohols 16 liberated from ethers 14 on reaction with 4
Entry
ROH formed
isolated (%)
1
2
3
4
5
6
7
8
16a, R = Ph(CH2)3
62
67
69
92
87
63
30
43
16b, R = Ph(CH2)4
16c, R = PhO(CH2)3
16d, R = p-MeOC6H4O(CH2)3
16e, R = p-MeC6H4O(CH2)3
16f, R = p-MeC6H4O(CH2)4
16g, R = b-C10H7O(CH2)3
16h, R = b-C10H7O(CH2)4
precursor salt is treated with NaH in DMF to form the donor)
and reacted with the iodoalkanes 14. The results of reaction with
the DMAP-derived donor 4 are as shown in Table 1. It is clear that
alcohols 16a–h are liberated from these reactions, and generally in
good yields. To account for this, we propose the mechanism shown
in Scheme 2.
A number of features are worth noting. Firstly, as expected from
previous reactions with this strong donor, there is no indication of
conversion of the alkyl iodide substrates 14 to alkyl anions. This
would be expected to result in detection of alkenes 29 (shown in
Scheme 3), but none was seen, and this fact reinforces the difficulty
in accessing unstabilised naked alkyl anions by electron transfer.
The second point is that no product resulting from hydrogen atom
abstraction by intermediate radicals 18 is seen. Instead, the sole
products seen in the crude organic fractions following work up
are the alcohols 16. Trapping of the initial radical 18 by the
radical cation 19 derived from the donor would afford salt 21.
Fragmentation of this salt 21, would afford the pyridinium salt-
carbene 22. The fragmentation to form a pyridinylidene, as shown
here, is not precedented, although corresponding fragmentations
to form imidazolylidene carbenes are well precedented.7 Since
this pyridinylidene carbene is expected to be more reactive than
an imidazolylidene,8 it is rewarding to see that it forms quite
efficiently. The basic carbene in 22 could then deprotonate the
a-position to the pyridinium ring to form enamine 23, which can
then expel methoxide. Deprotonation of 24, perhaps by methoxide,
affords dienamine 25 which, in turn, expels the alkoxide, affording
alcohol 16 on work up.
This shows that alkyl radicals can be trapped by radical-cation
19, which, as already stated, has been computed to have a 36◦ twist
between its two 6-membered rings. Hence, the trapping of alkyl
radicals is not confined to the unusual and rigid doubly-strapped
radical-cation 6. Previous reactions [e.g. the conversion of 12 to
13] show that when aryl anions are formed from reaction of aryl
halides with donor 4, they can undergo efficient reaction without
significant diversion along this trapping pathway.
To explain the products seen, a range of possibilities was
considered. Firstly, given that intermediate 21 is the precursor
of alcohol 16, we considered whether such a product (21) might
have arisen simply by SN2 reaction of enamine 4 with substrates
14 (Scheme 4). The same point had been considered in our study
of donor 5.4g What was needed was to see if the same outcome,
the liberation of the alcohol 16, could arise from a substrate where
SN2 reaction was not possible. The iodoarene 33 was prepared and
subjected to the reaction (Scheme 4). Initial electron transfer to
33 would afford an aryl radical 34 plus an iodide anion. Kinetic
competition would then arise between (a) further reduction of this
radical to an aryl anion 37 and (b) cyclisation of the aryl radical
Scheme 1
by exploring the reactions of substrates 14 with donors 3 and 4,
and looking for the liberation of alcohol 16. Scheme 2 shows a
prospective pathway for formation of alcohol 16 from reaction of
substrate 14 with donor 4 that is analogous to the mechanism that
we proposed earlier with donor 5.4g
Results and Discussion
A series of the desired substrates 14a–h was prepared.4g 3-
Methylbut-3-enol 27 was reacted with a range of alkyl bromides
RBr, 28a–h. The alkenyl ethers 29a–h, produced in this way,
were functionalised by reaction with N-iodosuccinimide and
methanol to afford the a-methoxy-g-alkoxyalkyl iodides 14a–h
(Scheme 3). The fragmentation reactions proposed to occur on
reaction of substrates 14 with super-electron-donors (Scheme 2)
would liberate methanol as well as a non-volatile alcohol, ROH
16. Our plan was to detect isolate and quantify alcohol 16, if it
was produced.
The precursors to the donors 3 and 4, namely disalts 31 and 32,
were prepared by our previous methods.4a,4d The corresponding
donors, 3 and 4, were prepared by the in situ method (where the
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Scheme 2
onto the pendant alkene to form radical 35. We had previously
shown with donor 5 that very little cyclisation occurs in substrates
like 33, because of the speed of transfer of the second electron
and, since donor 4 has a greater driving force for transfer of its
second electron, we expected the same here. Nevertheless any aryl
radicals that cyclised rather than receiving a second electron would
afford radical 35 that should be in a position to be intercepted by
radical-cation 19 (or by the corresponding dication) and thereby
lead to liberation of alcohol 16a. Alternatively, if trapping is slow,
then hydrogen atom abstraction would afford product 36. When
the experiment was conducted, two products were formed: the
alcohol 16a (3%) and the reduced but uncyclised product 38 (14%).
The formation of the alcohol shows that under these conditions,
an intermediate of the type 21 can be formed, supportive of the
trapping of the alkyl radicals by such radical-cation intermediates.
A second possibility for formation of the alcohols 16 was also
addressed. In principle, such compounds might be formed by
base-induced E2 elimination from a preceding ether, rather than
by electron transfer to a halide, if either the donor or the NaH
were to act as a base. If such an elimination were to occur in
our experiments, it should happen most favourably in unsaturated
ethers where an alkene might acidify the proton that needs to be
removed to trigger the elimination. Accordingly, the unsaturated
ether 29h was selected as a test substrate, and added to a blank
reaction in the presence of 4, instead of a normal iodoalkyl
substrate. When the organic layer was examined following workup,
no elimination was seen; instead, only the starting ether 29h was
detected. It was subsequently isolated (82%) but no alcohol 16h
was detected, thereby ruling out this E2 reaction as a possible route
to the observed product 16 in the reactions of substrates 14a–h.
Having examined the behaviour of donor 4, we were now keen to
use these special substrates 14 to see if similar chemistry would be
detected using less reactive donor 3. As shown in the reactions of 8
and 10, this donor efficiently converts substrates to alkyl radicals,
and the principal products isolated, in high yield, are the products
of reductive termination of these radicals. It would seem therefore
that trapping of alkyl radicals (or indeed of their precursor aryl
radicals) should not be a problem with this donor. However, even
in the optimised conditions for substrates like 10 (Scheme 1), only
83% of the product is formed, and so we determined to check for
evidence of alkyl radical trapping featuring formation of alcohols
16 from substrates 14.
When the reactions were conducted, the results were as shown
in Table 2. Small amounts of alcohols 16 were indeed formed (8–
15%), but these were accompanied by the products of reductive
termination, 30, of the intermediate alkyl radicals. Thus, it appears
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Scheme 3
Table 2 Alcohols 16 liberated from ethers 14 on reaction with 3
Products isolated (%)
Entry
(Substrate)
R
16
30
1
2
3
4
(14e)
(14f)
(14g)
(14h)
p-MeC6H4O(CH2)3
p-MeC6H4O(CH2)4
C10H7O(CH2)3
13
8
15
12
29
24
29
34
C10H7O(CH2)4
that some trapping of intermediate alkyl radicals occurs even with
this donor, leading to the formation of alcohols 16. The question
also arises about why products 30 form with 3 but not with 4. This
suggests that trapping by the radical-cation 20, derived from 3,
is not so rapid. Although canonical forms 6, 19 and 20 represent
radical-cations as having one heterocyclic aromatic ring and a
separate ring containing a radical, the structures are expected to
show symmetrical distribution of spin-density across both rings,
so that in reality neither heterocyclic ring is markedly aromatic.
When these radical-cations trap a radical, e.g. in the formation of
21, the resulting structures can fully express their aromaticity. With
4 (and with 5), the gain in aromatic stabilisation energy is greater
than with 3, and so we expect that the trapping of a radical by the
radical cation carries more driving force, and perhaps therefore
more rapid, with 4 than with 3.
Test reactions were also performed on donor 3 with substrates
33 and 29h (Scheme 4). With 33, a small amount of alcohol 16
(8%) was indeed formed together with an inseparable mixture of
the two expected products of reductive termination, 36 and 38.
With the blank ether substrate 29h, once again no alcohol was
liberated and the starting compound 29h was isolated as the sole
product (76%).
Scheme 4
Conclusions
These substrates show that alkyl radicals can be trapped during
SED reactions of non-rigid donors, and most likely by the radical-
cation of the donors. Although we did not look to optimise the
reaction outcomes for these substrates, the important point was
that alcohols 16 were indeed formed, and so we now know that
it does not require an anomalously planar system to afford these
products, but that they can be expected from a broad range of
super-electron donors.
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was stirred at -78 ◦C for 1 h. The reaction was stirred at
room temperature under argon overnight. The reaction mixture
was quenched with sodium thiosulfate (30 mL), causing the
solution to change from dark purple to colourless. The reaction
mixture was extracted with DCM (3 ¥ 60 mL), and the combined
organics were washed with brine (3 ¥ 60 mL), dried over Na2SO4
and concentrated under reduced pressure. The crude product
was purified by silica gel chromatography, eluting with 0–5%
diethyl ether in petroleum ether, to afford 1-(3-(4-iodo-3-methoxy-
3-methylbutoxy)propoxy)-4-methylbenzene 14e as a colourless
oil (0.80 g, 87%). (Found: [M+NH4]+ 410.1183. C16H25IO3 (M)
requires [M+NH4]+ 410.1187); nmax(neat)/cm-1 2933, 2870, 1615,
1511, 1243, 1113; dH (CDCl3) 1.33 (3H, s, CH3), 1.90–2.00 (2H,
m, CH2), 2.01–2.06 (2H, m, CH2), 2.31 (3H, s, CH3), 3.21 (3H, s,
OCH3), 3.29 (1H, d, J 10.8, CHHI), 3.34 (1H, d, J 10.8, CHHI),
3.52 (2H, t, J 7.0, CH2O), 3.60 (2H, t, J 6.2, CH2O), 4.05 (2H, t,
J 6.4, OCH3), 6.81 (2H, d, J 8.6, ArH), 7.10 (2H, d, J 8.2, ArH);
dC (CDCl3) 15.6 (CH2), 20.0 (CH3), 22.2 (CH3), 29.3 (CH2), 36.0
(CH2), 49.0 (CH3), 64.4 (CH2), 66.3 (CH2), 67.1 (CH2), 73.35 (C),
113.9 (CH), 129.3 (CH), 129.4 (C), 156.4 (C).
Experimental Section
A. Preparation of substrates
For preparation of substrates 14a–d, see ref. 4g.
1-(3-Bromopropoxy)-4-methylbenzene 28e. Sodium carbonate
(11.72 g, 110.56 mmol, 2 eq.) was added to a solution of p-cresol
(6.0 g, 55.6 mmol, 1 eq.) and 1,3-dibromopropane (28.2 mL,
277 mmol, 5 eq.) in acetonitrile (150 mL). The reaction mixture
was stirred under reflux (80 ◦C) for 72 h under argon. The
reaction mixture was washed with diethyl ether (3 ¥ 100 mL).
The combined organics were then further washed with water (4 ¥
100 mL), brine (100 mL), dried over Na2SO4 and concentrated
under reduced pressure. The crude product was purified by
silica gel chromatography, eluting with 0–5% diethyl ether in
petroleum ether, to afford 1-(3-bromopropoxy)-4-methylbenzene
28e as a colourless oil (3.54 g, 28%).9 (Found: [M+H]+ 229.0215.
C10H13BrO requires [M+H]+ 229.0223); nmax(neat)/cm-1 2952,
2879, 1451, 1249, 785; dH (CDCl3) 2.30–2.36 (2H, m, CH2), 2.31
(3H, s, CH3), 3.62 (2H, t, J 6.4, CH2Br), 4.10 (2H, t, J 5.8, OCH2),
6.82 (2H, d, J 8.6, ArH), 7.10 (2H, d, J 8.2, ArH); dC (CDCl3)
20.0 (CH3), 29.6 (CH2), 32.0 (CH2), 64.95 (CH2), 114.0 (CH), 129.4
(CH), 129.7 (C), 156.1 (C).
1-(4-Bromobutoxy)-4-methylbenzene 28f. Sodium carbonate
(11.72 g, 105.5 mmol, 2 eq.) was added to a solution of p-
cresol (6.0 g, 55.5 mmol, 1 eq.) and 1,4-dibromobutane (33.3 mL,
277 mmol, 5 eq.) in acetonitrile (150 mL). The reaction mixture
was stirred under reflux (80 ◦C) for 72 h under argon. The
reaction mixture was washed with diethyl ether (3 ¥ 100 mL).
The combined organics were then further washed with water (4 ¥
100 mL), brine (100 mL), dried over Na2SO4, and concentrated
under reduced pressure. The crude product was purified by
silica gel chromatography, eluting with 0–5% diethyl ether in
petroleum ether, to afford 1-(4-bromobutoxy)-4-methylbenzene
28f as a colourless oil (5.30 g, 39%).10 (Found: [M+H]+ 243.0374.
C11H1579BrO (M) requires [M+H]+ 243.0379); nmax(neat)/cm-1
3044, 2998, 2951, 2833, 1616, 1592, 1508, 1451; dH (CDCl3) 1.91–
1.96 (2H, m, CH2), 2.05–2.10 (2H, m, CH2), 2.31 (3H, s, CH3),
3.50 (2H, t, J 6.6, CH2Br), 3.99 (2H, t, J 6.4, OCH2), 6.89 (2H,
d, J 8.6, ArH), 7.10 (2H, d, J 8.2, ArH); dC (CDCl3) 20.0 (CH3),
27.5 (CH2), 29.0 (CH2), 33.0 (CH2), 66.4 (CH2), 113.9 (CH), 129.4
(CH), 129.5 (C), 156.2 (C).
1-Methyl-4-(3-((3-methylbut-3-en-1-yl)oxy)propoxy)benzene
29e. Sodium hydride (60% in mineral oil, 0.63 g, 15.79 mmol,
1.2 eq.) was washed three times with anhydrous hexane. The
hexane was removed via cannula and trace residual amounts of
hexane were removed using a flow of argon. Anhydrous N,N-
dimethylformamide (25 mL) was then added. 3-Methylbut-3-en-1-
ol (1.32 mL, 13.16 mmol, 1 eq.) was added and the resulting orange
suspension stirred under argon at room temperature for 1 h. The
reaction mixture was cooled to 0 ◦C and 1-(3-bromopropoxy)-4-
methylbenzene 28e (3.0 g, 13.16 mmol, 1 eq.) was slowly added.
The reaction mixture was stirred at room temperature under
argon overnight. Water (15 mL) was slowly added to quench the
reaction mixture. The reaction mixture was washed with diethyl
ether (2 ¥ 50 mL). The combined organics were then further
washed with water (2 ¥ 50 mL), brine (50 mL), dried over Na2SO4
and concentrated under reduced pressure. The crude product was
purified by silica gel chromatography, eluting with 0–5% diethyl
ether in petroleum ether, to afford 1-methyl-4-(3-((3-methylbut-
3-en-1-yl)oxy)propoxy)benzene 29e as a colourless oil (811 mg,
26%). (Found: [M+H]+ 235.1690. C15H22O2 (M) requires [M+H]+
235.1693); nmax(neat)/cm-1 2941, 2862, 1451, 1440, 1250, 773; dH
(CDCl3) 1.76 (3H, s, CH3), 2.02–2.09 (2H, m, CH2), 2.30–2.34
(2H, m, CH2), 2.31 (3H, s, CH3) 3.57 (2H, t, J 7.0, CH2O), 3.63
(2H, t, J 6.2, CH2O), 4.05 (2H, t, J 6.3, CH2O), 4.74 (1H, m,
HCH C), 4.78 (1H, m, HCH C), 6.81 (2H, d, J 8.6, ArH),
7.10 (2H, d, J 8.2, ArH); dC (CDCl3) 20.0 (CH3), 22.2 (CH3),
29.3 (CH2), 37.3 (CH2), 64.5 (CH2), 66.9 (CH2), 69.0 (CH2), 110.9
(CH2), 114.0 (CH), 129.2 (CH), 129.3 (C), 142.4 (C), 156.4 (C).
1-Methyl-4-(4-((3-methylbut-3-en-1-yl)oxy)butoxy)benzene 29f.
Sodium hydride (60% in mineral oil, 1.03 g, 25.66 mmol, 1.2
eq.) was washed three times with anhydrous hexane. The hex-
ane was removed via cannula and trace residual amounts of
hexane were removed using a flow of argon. Anhydrous N,N-
dimethylformamide (25 mL) was then added. 3-Methylbut-3-en-1-
ol (2.16 mL, 21.39 mmol, 1 eq.) was added and the resulting orange
suspension stirred under argon at room temperature for 1 h. The
reaction mixture was cooled to 0 ◦C and 1-(4-bromobutoxy)-4-
methylbenzene 28f (5.20 g, 21.39 mmol, 1 eq.) was slowly added.
The reaction mixture was stirred at room temperature under
argon overnight. Water (15 mL) was slowly added to quench the
reaction mixture. The reaction mixture was washed with diethyl
ether (2 ¥ 50 mL). The combined organics were then further
washed with water (2 ¥ 50 mL), brine (50 mL), dried over Na2SO4,
and concentrated under reduced pressure. The crude product was
purified by silica gel chromatography, eluting with 0–5% diethyl
ether in petroleum ether, to afford 1-methyl-4-(4-((3-methylbut-3-
en-1-yl)oxy)butoxy)benzene 29f as a colourless oil (1.22 g, 23%).
1-(3-(4-Iodo-3-methoxy-3-methylbutoxy)propoxy)-4-methylben-
zene 14e. 1-Methyl-4-(3-((3-methylbut-3-en-1-yl)oxy)propoxy)-
benzene (0.56 g, 2.34 mmol, 1 eq.) was dissolved in a solution
of dry DCM (15 mL) and anhydrous methanol (0.19 mL,
4.68 mmol, 2 eq.). The reaction mixture was cooled to -78 ◦C.
N-Iodosuccinimide (0.56 g, 2.51 mmol, 1.5 eq.) was added to
the reaction mixture in one portion, and the resultant suspension
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(Found: [M+H]+ 249.1851. C16H25O2 requires [M+H]+ 249.1849);
max(neat)/cm-1 2934, 2872, 1512, 1240; dH (CDCl3) 1.78 (3H, s,
2-(3-((3-Methylbut-3-en-1-yl)oxy)propoxy)naphthalene
29g.
n
Sodium hydride (60% in mineral oil, 0.54 g, 13.58 mmol,
1.2 eq.) was washed three times with anhydrous hexane. The
hexane was removed via cannula and trace residual amounts
of hexane were removed using a flow of argon. Anhydrous
N,N-dimethylformamide (25 mL) was then added. 3-Methylbut-
3-en-1-ol (1.14 mL, 11.32 mmol, 1 eq.) was added and the
resulting orange suspension stirred under argon at room
temperature for 1 h. The reaction mixture was cooled to 0 ◦C and
2-(3-bromopropoxy)naphthalene 28g (3.0 g, 11.32 mmol, 1 eq.) in
DMF (5 mL) was slowly added. The reaction mixture was stirred
at room temperature under argon overnight. Water (15 mL) was
slowly added to quench the reaction mixture. The reaction mixture
was washed with diethyl ether (2 ¥ 50 mL). The combined organics
were then further washed with water (2 ¥ 50 mL), brine (50 mL),
dried over Na2SO4, and concentrated under reduced pressure.
The crude product was purified by silica gel chromatography,
eluting with 0–5% diethyl ether in petroleum ether, to afford
2-(3-((3-methylbut-3-en-1-yl)oxy)propoxy)naphthalene 29g as a
colourless oil (1.06 g, 34%). Found: [M+H]+ 271.1694. C18H22O2
requires [M+H]+ 271.1693); nmax(neat)/cm-1 3059, 2935, 2867,
1630, 1259, 1119, 837; dH (CDCl3) 1.76 (3H, s, CH3), 2.11–2.17
(2H, m, CH2), 2.32–2.35 (2H, m, CH2), 3.60 (2H, t, J 7.0, CH2O),
3.68 (2H, t, J 6.4, CH2O), 4.21 (2H, t, J 6.4, OCH3), 4.75 (1H,
m, HCH C), 4.79 (1H, m, HCH C), 7.15–7.19 (2H, m, ArH),
7.44 (1H, t, J 6.0, ArH), 7.48 (1H, t, J 6.9, ArH), 7.74–7.80 (3H,
m, ArH); dC (CDCl3) 22.2 (CH3), 29.3 (CH2), 37.3 (CH2), 64.5
(CH2), 66.8 (CH2), 69.0 (CH2), 110.6 (CH), 111.0 (CH), 118.5
(CH), 123.0 (CH), 125.8 (CH), 126.2 (CH), 127.1 (CH), 128.4
(C), 128.8 (CH), 134.1 (C), 142.4 (C), 156.5 (C).
CH3), 1.74–1.81 (2H, m, CH2), 1.83–1.91 (2H, m, CH2), 2.29–
2.35 (2H, m, CH2), 2.31 (3H, s, CH3), 3.51 (2H, t, J 6.3, CH2O),
3.55 (2H, t, J 7.0, CH2O), 3.98 (2H, t, J 6.3, CH2O), 4.74 (1H,
m, HCH C), 4.78 (1H, m, HCH C), 6.81 (2H, d, J 8.6, ArH),
7.10 (2H, d, J 8.2, ArH); dC (CDCl3) 20.5 (CH3), 22.8 (CH3), 26.2
(CH2), 26.4 (CH2), 37.9 (CH2), 67.8 (CH2), 69.3 (CH2), 70.5 (CH2),
111.4 (CH2), 114.4 (CH), 129.7 (C), 129.9 (CH), 143.0 (C), 157.0
(C).
1-(4-(4-Iodo-3-methoxy-3-methylbutoxy)butoxy)-4-methylben-
zene 14f. 1-Methyl-4-(4-((3-methylbut-3-en-1-yl)oxy)butoxy)-
benzene 29f (1.0 g, 4.03 mmol, 1 eq.) was dissolved in a solution
of dry DCM (15 mL) and anhydrous methanol (0.33 mL,
8.06 mmol, 2 eq.). The reaction mixture was cooled to -78 ◦C.
N-Iodosuccinimide (1.36 g, 6.05 mmol, 1.5 eq.) was added to the
reaction mixture in one portion, and the resultant suspension
was stirred at -78 ◦C for 1 h. The reaction was stirred at room
temperature under argon overnight. The reaction mixture was
quenched with sodium thiosulfate (15 mL), causing the solution
to change from dark purple to colourless. The reaction mixture
was extracted with DCM (3 ¥ 30 mL), and the combined organics
were washed with brine (3 ¥ 30 mL), dried over Na2SO4 and
concentrated under reduced pressure. The crude product was
purified by silica gel chromatography, eluting with 0–5% diethyl
ether in petroleum ether, to afford 1-(4-(4-iodo-3-methoxy-3-
methylbutoxy)butoxy)-4-methylbenzene 14f as a colourless oil
(1.04 g, 63%). (Found: [M+NH4]+ 424.1335. C17H27IO3 (M)
requires [M+NH4]+ 424.1343); nmax(neat)/cm-1 2934, 2863, 1512,
1240, 812; dH (CDCl3) 1.33 (3H, s, CH3), 1.71–1.79 (2H, m, CH2),
1.81–1.89 (2H, m, CH2), 1.91–2.02 (2H, m, CH2), 2.29 (3H, s,
CH3), 3.21 (3H, s, OCH3), 3.29 (1H, d, J 10.8, CHHI), 3.34 (1H,
d, J 10.8, CHHI), 3.46–3.53 (4H, m, 2 ¥ CH2O), 3.96 (2H, t, J
6.4, OCH3), 6.81 (2H, d, J 8.6, ArH), 7.10 (2H, d, J 8.2, ArH);
dC (CDCl3) 15.6 (CH2), 20.0 (CH3), 22.2 (CH3), 25.7 (CH2), 25.9
(CH2), 36.0 (CH2), 49.0 (CH3), 66.2 (CH2), 67.2 (CH2), 70.2
(CH2), 73.4 (C), 113.9 (CH), 129.3 (CH), 129.4 (C), 156.4 (C).
2-(3-(4-Iodo-3-methoxy-3-methylbutoxy)propoxy)naphthalene
14g. 2-(3-((3-Methylbut-3-en-1-yl)oxy)propoxy)naphthalene
29g (0.95 g 3.51 mmol, 1 eq.) was dissolved in a solution
of dry DCM (15 mL) and anhydrous methanol (0.28 mL,
7.02 mmol, 2 eq.). The reaction mixture was cooled to -78 ◦C.
N-Iodosuccinimide (1.19 g, 5.27 mmol, 1.5 eq.) was added to
the reaction mixture in one portion, and the resultant suspension
was stirred at -78 ◦C for 1 h. The reaction was stirred at room
temperature under argon overnight. The reaction mixture was
quenched with sodium thiosulfate (15 mL), causing the solution
to change colour from dark purple to colourless. The reaction
mixture was extracted with DCM (3 ¥ 30 mL), and the combined
organics were washed with brine (3 ¥ 30 mL), dried over Na2SO4,
and concentrated under reduced pressure. The crude product was
purified by silica gel chromatography, eluting with 0–5% diethyl
ether in petroleum ether, to afford 2-(3-(4-iodo-3-methoxy-3-
methylbutoxy)propoxy)naphthalene 14g as a colourless oil (0.94 g,
63%) (Found: [M+NH4]+ 446.1188 C19H25IO3 requires [M+NH4]+
446.1187); nmax(neat)/cm-1 2940, 2871, 1629, 1600, 1465, 1258,
1217, 1119, 747; dH (CDCl3) 1.34 (3H, s, CH3), 1.91–2.05 (2H,
m, CH2), 2.10–2.17 (2H, m, CH2), 3.21 (3H, s, OCH3), 3.31 (1H,
d, J 10.8, CHHI), 3.35 (1H, d, J 10.8, CHHI), 3.56 (2H, t, J
6.8, CH2O), 3.64 (2H, t, J 6.2, CH2O), 4.21 (2H, t, J 6.4, CH2O)
7.15–7.19 (2H, m, ArH), 7.44 (1H, t, J 6.0, ArH), 7.48 (1H, t, J
6.9, ArH), 7.74–7.80 (3H, m, ArH); dC (CDCl3) 15.6 (CH2), 22.2
(CH3), 29.2 (CH2), 36.1 (CH2), 49.0 (CH3), 64.4 (CH2), 66.4 (CH2),
67.0 (CH2), 73.4 (C), 106.2 (CH), 118.4 (CH), 123.0 (CH), 125.8
2-(3-Bromopropoxy)naphthalene 28g. Sodium carbonate
(6.76 g, 63.76 mmol, 3 eq.) was added to a solution of 2-naphthol
(3.0 g, 20.81 mmol, 1 eq.) and 1,3-dibromopropane (16.17 mL,
149 mmol, 7.2 eq.) in acetonitrile (100 mL). The reaction mixture
was stirred under reflux (80 ◦C) for 3 days under argon. The
reaction mixture was washed with diethyl ether (3 ¥ 50 mL). The
combined organic layers were then further washed with water
(4 ¥ 50 mL), brine (50 mL), dried over Na2SO4 and concentrated
under reduced pressure. The crude product was purified by
silica gel chromatography, eluting with 0–5% diethyl ether in
petroleum ether, to afford 2-(3-bromopropoxy)naphthalene
28g as a colourless oil (1.76 g, 32%).11 (Found: [M]+ 264.0145.
C13H13BrO requires [M]+ 264.0144); nmax(neat)/cm-1 2945, 2874,
1567, 1448, 1435, 1248, 786; dH (CDCl3) 2.39–2.45 (2H, quintet, J
6.0, CH2), 3.68 (2H, t, J 6.4, CH2Br), 4.26 (2H, t, J 6.0, CH2O),
7.15–7.19 (2H, m, ArH), 7.44 (1H, t, J 6.0, ArH), 7.48 (1H, t, J
6.9, ArH), 7.74–7.80 (3H, m, ArH); dC (CDCl3) 29.5 (CH2), 31.9
(CH2), 64.9 (CH2), 106.3 (CH), 118.3 (CH), 123.2 (CH), 125.9
(CH), 126.3 (CH), 127.1 (CH), 128.6 (CH), 129.0 (C), 134.0 (C),
156.1 (C).
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◦
(CH), 126.2 (CH), 127.1 (CH), 128.4 (C), 128.8 (CH), 134.1 (C),
156.4 (C).
The reaction mixture was cooled to -78 C. N-Iodosuccinimide
(1.66 g, 7.38 mmol, 1.5 eq.) was added to the reaction mixture
in one portion, and the resultant suspension was stirred at
-78 ◦C for 1 h. The reaction was stirred at room temperature
under argon overnight. The reaction mixture was quenched
with sodium thiosulfate (15 mL), causing the solution to change
colour from dark purple to colourless. The reaction mixture was
extracted with DCM (3 ¥ 30 mL), and the combined organics
were washed with brine (3 ¥ 30 mL), dried over Na2SO4 and
concentrated under reduced pressure. The crude product was
purified by silica gel chromatography, eluting with 0–5% diethyl
ether in petroleum ether, to afford 2-(4-(4-iodo-3-methoxy-3-
methylbutoxy)butoxy)naphthalene 14h as a colourless oil (1.61 g,
74%). (Found: [M+NH4]+ 460.1332. C20H27IO3 (M) requires
[M+NH4]+ 460.1343); nmax(neat)/cm-1 2940, 2868, 1629, 1465,
1259, 749; dH (CDCl3) 1.35 (3H, s, CH3), 1.78–1.86 (2H, m, CH2),
1.90–2.00 (4H, m, 2 ¥ CH2), 3.21 (3H, s, CH3O) 3.31 (1H, d,
J 10.8, CHHI), 3.34 (1H, d, J 10.8, CHHI), 3.54 (4H, m, 2 ¥
CH2O), 4.13 (2H, t, J 6.4, CH2O) 7.15–7.19 (2H, m, ArH), 7.44
(1H, t, J 6.0, ArH), 7.48 (1H, t, J 6.9, ArH), 7.74–7.80 (3H, m,
ArH); dC (CDCl3) 16.2 (CH2), 22.8 (CH3), 26.2 (CH2), 26.4 (CH2),
36.5 (CH2), 49.5 (CH3), 66.7 (CH2), 67.7 (CH2), 70.7 (CH2), 73.8
(C), 106.6 (CH), 119.0 (CH), 123.5 (CH), 126.3 (CH), 126.7 (CH),
127.6 (CH), 128.9 (C), 129.3 (CH), 134.6 (C), 157.0 (C).
2-(4-Bromobutoxy)naphthalene
28h. Sodium
carbonate
(6.76 g, 63.76 mmol, 3 eq.) was added to a solution of 2-naphthol
(3.0 g, 20.81 mmol, 1 eq.) and 1,4-dibromobutane (19.04 mL,
159 mmol, 5 eq.) in acetonitrile (100 mL). The reaction mixture
was stirred under reflux (80 ◦C) for 72 h under argon. The
reaction mixture was washed with diethyl ether (3 ¥ 50 mL). The
combined organics were then further washed with water (4 ¥
50 mL), brine (50 mL), dried over Na2SO4, and concentrated
under reduced pressure. The crude product was purified by silica
gel chromatography, eluting with 0–5% diethyl ether in petroleum
ether, to afford 2-(4-bromobutoxy)naphthalene 28h as a colourless
oil (1.80 g, 31%).12 (Found: [M]+ 278.0301. C14H15BrO requires
[M]+ 278.0301); nmax(neat)/cm-1 2952, 2880, 1565, 1451, 1439,
1249, 772; dH (CDCl3) 2.02–2.08 (2H, m, CH2), 2.12–2.17 (2H,
m, CH2), 3.54 (2H, t, J 6.4, CH2Br), 4.15 (2H, t, J 6.0, CH2O),
7.15–7.19 (2H, m, ArH), 7.44 (1H, t, J 6.0, ArH), 7.48 (1H, t, J
6.9, ArH), 7.73–7.80 (3H, m, ArH); dC (CDCl3) 27.4 (CH2), 29.0
(CH2), 32.9 (CH2), 66.4 (CH2), 106.1 (CH), 118.4 (CH), 123.1
(CH), 125.9 (CH), 126.2 (CH), 127.1 (CH), 128.5 (C), 128.9 (CH),
134.1 (C), 156.3 (C).
2-(4-((3-Methylbut-3-en-1-yl)oxy)butoxy)naphthalene
29h.
Sodium hydride (60% in mineral oil, 1.28 g, 31.81 mmol,
1.2 eq.) was washed three times with anhydrous hexane. The
hexane was removed via cannula and trace residual amounts
of hexane were removed using a flow of argon. Anhydrous
N,N-dimethylformamide (40 mL) was then added. 3-Methylbut-
3-en-1-ol (2.67 mL, 26.51 mmol, 1 eq.) was added and the
resulting orange suspension stirred under argon at room
temperature for 1 h. The reaction mixture was cooled to 0 ◦C and
2-(4-bromobutoxy)naphthalene 28h (7.40 g, 26.51 mmol, 1 eq.) in
DMF (5 mL) was slowly added. The reaction mixture was stirred
at room temperature under argon overnight. Water (15 mL) was
slowly added to quench the reaction mixture. The reaction mixture
was washed with diethyl ether (2 ¥ 50 mL). The combined organics
were then further washed with water (2 ¥ 50 mL), brine (50 mL),
dried over Na2SO4 and concentrated under reduced pressure.
The crude product was purified by silica gel chromatography,
eluting with 0–5% diethyl ether in petroleum ether, to afford
2-(4-((3-methylbut-3-en-1-yl)oxy)butoxy)naphthalene 29h as a
colourless oil (2.2 g, 29%). (Found: [M+H]+ 285.1849. C19H24O2
(M) requires [M+H]+ 285.1849; nmax(neat)/cm-1 3055, 2934, 2857,
1624, 1462, 1254, 1180, 1114, 834; dH (CDCl3) 1.82 (3H, s, CH3),
1.83–1.86 (2H, m, CH2), 1.94–1.99 (2H, m, CH2), 2.34 (2H,
t, J 6.8, CH2O), 3.54–3.60 (4H, m, 2 ¥ CH2O), 4.14 (2H, t, J
6.4, OCH2), 4.77 (1H, m, HCH C), 4.81 (1H, m, HCH C),
7.15–7.19 (2H, m, ArH), 7.44 (1H, t, J 6.0, ArH), 7.48 (1H, t,
J 6.9, ArH), 7.74–7.80 (3H, m, ArH); dC (CDCl3) 22.9 (CH3),
26.3 (CH2), 26.7 (CH2), 38.0 (CH2), 67.7 (CH2), 69.5 (CH2), 70.5
(CH2), 106.7 (CH), 111.5 (CH2), 119.0 (CH), 123.6 (CH), 126.3
(CH), 126.8 (CH), 127.7 (CH), 128.9 (C), 129.4 (CH), 134.7 (C),
143.0 (C), 157.1 (C).
B. Reactions of substrates with Donor 4
Reaction of substrate 14a with Donor 4. 1,3-Bis (N,N-
dimethyl-4-aminopyridinium)propane diiodide 32 (640 mg,
1.19 mmol, 1.8 eq.) was dried under vacuum at 100 ◦C for 1 h, then
cooled. Sodium hydride (60% in mineral oil, 473 mg, 11.90 mmol,
18 eq.) was added, and the mixture was washed with dry hexane
three times (3 ¥ 20 mL). The hexane was removed via cannula
and residual trace amounts of hexane were removed using a flow
of argon. Anhydrous N,N-dimethylformamide (15 mL) was then
added, causing a purple suspension to form, which was left to
stir at room temperature under argon for 4 h. The purple donor
suspension was centrifuged at 2000 rpm for 10 min to afford the
solution, which was added, via cannula, to (3-(4-iodo-3-methoxy-
3-methylbutoxy)propyl)benzene 14a (239 mg, 0.66 mmol, 1 eq.)
The reaction mixture was left to stir at room temperature under
argon overnight. Water (50 mL) was slowly added to quench the
reaction mixture. The reaction mixture was washed with diethyl
ether (3 ¥ 50 mL). The combined organics were then further
washed with water (4 ¥ 50 mL), brine (50 mL), dried over Na2SO4
and concentrated under reduced pressure. The crude product was
purified by silica gel chromatography, eluting with 0–10% diethyl
ether in petroleum ether, to afford 3-phenylpropan-1-ol 16a as a
colourless oil (56 mg, 62%).13 (Found: [M]+ 136.0883. C9H12O (M)
requires [M]+ 136.0883); nmax(neat)/cm-1 3349, 3341, 3027, 2927,
2863, 1667, 1603, 1496, 1454; dH (CDCl3) 1.89–1.95 (2H, m CH2),
2.73 (2H, t, J 7.8, CH2Ar), 3.69 (2H, t, J 6.4, CH2OH), 7.18–7.22
(3H, m, ArH), 7.28– 7.31 (2H, m, ArH); dC (CDCl3) 32.1 (CH2),
34.2 (CH2), 62.3 (CH2), 126.0 (CH), 128.4 (CH), 128.5 (CH),
141.8 (C).
2-(4-(4-Iodo-3-methoxy-3-methylbutoxy)butoxy)naphthalene
14h. 2-(4-((3-Methylbut-3-en-1-yl)oxy)butoxy)naphthalene 29h
(1.40 g, 4.92 mmol, 1 eq.) was dissolved in a solution of dry DCM
(15 mL) and anhydrous methanol (0.40 mL, 9.84 mmol, 2 eq.).
Reaction of substrate 14b with Donor 4. Similarly: (4-
(4-iodo-3-methoxy-3-methylbutoxy)butyl)benzene 14b (250 mg,
0.66 mmol, 1 eq.) was reacted with 1,3-bis(N,N-dimethyl-4-
aminopyridinium)propane diiodide 32 (640 mg, 1.19 mmol,
3566 | Org. Biomol. Chem., 2011, 9, 3560–3570
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1.8 eq.) to afford 4-phenylbutan-1-ol 16b as a colourless oil
(60 mg, 67%).14 (Found: [M+NH4]+ 168.1383. C10H14O (M)
requires [M+NH4]+ 168.1383); nmax(neat)/cm-1 3338, 3027, 2937,
2861, 1666, 1496, 1454; dH (CDCl3) 1.60–1.76 (4H, m 2 ¥ CH2),
2.66 (2H, t, J 7.6, CH2Ar), 3.68 (2H, t, J 5.6, CH2OH), 7.18–7.21
(3H, m, ArH), 7.29–7.31 (2H, m, ArH); dC (CDCl3) 27.5 (CH2),
32.3 (CH2), 35.7 (CH2), 62.9 (CH2), 125.8 (CH), 128.3 (CH), 128.4
(CH), 142.3 (C).
Reaction of substrate 14g with Donor 4. Similarly: 2-(3-(4-iodo-
3-methoxy-3-methylbutoxy)propoxy)-naphthalene 14g (141 mg,
0.33 mmol, 1 eq.) was reacted with 1,3-bis-(N,N-dimethyl-4-
aminopyridinium)propane diiodide 32 (268 mg, 0.5 mmol, 1.5 eq.)
to afford 3-(naphthalen-2-yloxy)propan-1-ol 16g as a white solid
(60 mg, 30%).17 M.Pt. 99–100 ◦C. nmax(neat)/cm-1 3338, 3026,
2936, 2861, 1496, 1453, 1061, 699; dH (CDCl3) 2.11–2.20 (2H,
quintet, J 6.0, CH2), 3.94 (2H, t, J 6.0, CH2O), 4.27 (2H, t, J
6.0, CH2OH), 7.15–7.19 (2H, m, ArH), 7.44 (1H, t, J 6.0, ArH),
7.48 (1H, t, J 6.9, ArH), 7.74–7.80 (3H, m, ArH); dC (CDCl3)
31.7 (CH2) 60.1 (CH2), 65.3 (CH2), 106.3 (CH), 118.3 (CH), 123.2
(CH), 125.9 (CH), 126.3 (CH), 127.1 (CH), 128.5 (C), 128.9 (CH),
134.0 (C), 156.4 (C).
Reaction of substrate 14c with Donor 4. Similarly: (3-(4-
iodo-3-methoxy-3-methylbutoxy)propoxy)benz-ene 14c (250 mg,
0.66 mmol, 1 eq.) was reacted with 1,3-bis-(N,N-dimethyl-4-
aminopyridinium)propane diiodide (642 mg, 1.19 mmol, 1.8 eq.)
to afford 3-phenoxypropan-1-ol 16c as a colourless oil (69 mg,
69%).15 (Found: [M+NH4]+ 170.1904. C9H12O2 (M) requires
[M+NH4]+ 170.1904) nmax(neat)/cm-1 3349, 3040, 2950, 1665,
1599, 1496; dH (CDCl3) 2.07 (2H, quintet, J 5.9, CH2), 3.88 (2H,
t, J 5.9, CH2OH), 4.14 (2H, t, J 5.9, CH2OAr), 6.91–6.98 (3H,
m, ArH), 7.28–7.31 (2H, m, ArH). dC (CDCl3) 32.1 (CH2), 60.8
(CH2), 65.9 (CH2), 114.7 (CH), 121.0 (CH), 129.6 (CH), 158.7 (C).
Reaction of substrate 14h with Donor 4. Similarly: 2-(3-(4-iodo-
3-methoxy-3-methylbutoxy)propoxy)-naphthalene 14h (147 mg,
0.33 mmol, 1 eq.) was reacted with 1,3-bis(N,N-dimethyl-4-
aminopyridinium)propane diiodide 32 (268 mg, 0.5 mmol, 1.5
eq.) to afford 4-(naphthalen-2-yloxy)butan-1-ol 16h as a white
solid (31 mg, 43%). M.Pt. 118–120 ◦C. (Found: [M+H]+ 217.1224.
C14H16O2 (M) requires [M+H]+ 217.1223); nmax(neat)/cm-1 3238,
2956, 2931, 2878, 1629, 1600, 1389, 1261, 1040, 838, 749; dH
(CDCl3) 1.82–1.87 (2H, m, CH2), 1.95–2.07 (2H, m, CH2), 3.78
(2H, t, J 6.2, CH2O), 4.16 (2H, t, J 6.2, CH2OH), 7.15–7.19 (2H,
m, ArH), 7.44 (1H, t, J 6.0, ArH), 7.48 (1H, t, J 6.9, ArH),
7.74–7.80 (3H, m, ArH); dC (CDCl3) 25.8 (CH2), 29.5 (CH2), 62.7
(CH2), 67.8 (CH2), 106.7 (CH), 118.9 (CH), 123.7 (CH), 126.4
(CH), 126.8 (CH), 127.6 (CH), 129.0 (C), 129.4 (CH), 134.6 (C),
156.9 (C).
Reaction of substrate 14d with Donor 4. Similarly: 1-(3-(4-iodo-
3-methoxy-3-methylbutoxy)propoxy)-4-methoxybenzene
14d
(98 mg, 0.25 mmol, 1 eq.) was reacted with 1,3-bis-(N,N-dimethyl-
4-aminopyridinium)propane diiodide (268 mg, 0.5 mmol, 2.0 eq.)
to afford 3-(4-methoxyphenoxy)propan-1-ol 16d as a colourless
oil (40 mg, 92%). The compound data were consistent with
the reported analytical data;4g (Found: [M+NH4]+ 200.2164.
C10H14O3 (M) requires [M+NH4]+ 200.2164) nmax(neat)/cm-1
3273, 2953, 2872, 1513, 1471, 827; dH (CDCl3) 2.00–2.07 (2H,
quintet, J 5.9, CH2), 3.88 (2H, t, J 5.9, CH2OH), 4.14 (2H, t, J
5.9, CH2OAr), 6.82–6.88 (4H, m, ArH). dC (CDCl3) 32.1 (CH2),
55.8 (CH3), 60.8 (CH2), 66.7 (CH2), 114.7 (CH), 115.5 (CH),
152.8 (C), 153.9 (C).
C. Reactions of substrates with Donor 3
Reaction of substrate 14e with Donor 3. 3,3¢-(Propane-1,3-
diyl)bis(1-methyl-1H-benzo[d]imidazol-3-ium) iodide 31(336 mg,
0.6 mmol, 2.1 eq.) was dried under vacuum at 100 ◦C for 1 h, then
cooled. Sodium hydride (60% in mineral oil, 0.24 g, 6.0 mmol, 20
eq.) was added, and the mixture was washed with dry hexane (3 ¥
20 mL). The hexane was removed via cannula and residual trace
amounts of hexane were removed using a flow of argon. Anhydrous
N,N-dimethylformamide (15 mL) was then added, causing a yel-
low suspension to form, which was left to stir at room temperature
under argon for 4 h. The yellow donor suspension was centrifuged
at 2000 rpm for 10 min to afford the solution, which was added, via
cannula, to 1-(3-(4-iodo-3-methoxy-3-methylbutoxy)propoxy)-4-
methylbenzene 14e (0.143 g, 0.29 mmol, 1.0 eq.) The reaction
mixture was heated to 110 ◦C and left stirring under argon for 18 h.
Water (50 mL) was slowly added to quench the reaction mixture.
The reaction mixture was washed with diethyl ether (3 ¥ 50 mL).
The combined organics were then further washed with water (4 ¥
50 mL) and brine (50 mL). The organic extract was dried over
anhydrous sodium sulfate, filtered and concentrated under reduced
pressure. The crude product was purified by silica gel chromatogra-
phy, eluting with 0–10% diethyl ether in petroleum ether, to afford
1-(3-(3-methoxy-3-methylbutoxy)propoxy)-4-methylbenzene 30e,
(21 mg, 29%) as a colourless oil and (p-tolyloxy)propan-1-ol 16e,
(7 mg, 13%) as a colourless oil.
Reaction of substrate 14e with Donor 4. Similarly: 1-(3-(4-
iodo-3-methoxy-3-methylbutoxy)propoxy)-4-methylbenzene 14e
(131 mg, 0.33 mmol,
1 eq.) was reacted with 1,3-bis-
(N,N-dimethyl-4-aminopyridinium)propane diiodide (268 mg,
0.5 mmol, 1.5 eq.) to afford 3-(p-tolyloxy)propan-1-ol 16e as a
colourless oil (48 mg, 87%). The compound data were consistent
with the reported analytical data;16
n
max(neat)/cm-1 3272, 2936,
2876, 1610, 1512, 1243, 1061; dH (CDCl3) 2.00–2.07 (2H, quintet,
J 5.9, CH2), 2.31 (3H, s, ArCH3), 3.89 (2H, t, J 5.9, CH2OH),
4.13 (2H, t, J 5.9, CH2O), 6.83 (2H, d, J 8.4, ArH), 7.10 (2H, d,
J 8.4, ArH). dC (CDCl3) 20.0 (CH3), 29.3 (CH2), 37.3 (CH2), 66.9
(CH2), 114.0 (CH), 129.4 (CH), 129.6 (C),156.4 (C).
Reaction of substrate 14f with Donor 4. Similarly: 1-(3-(4-
iodo-3-methoxy-3-methylbutoxy)propoxy)-4-methylbenzene 14f
(135 mg, 0.33 mmol,
1 eq.) was reacted with 1,3-bis-
(N,N-dimethyl-4-aminopyridinium)propane diiodide 32 (268 mg,
0.5 mmol, 1.5 eq.) to afford 4-(p-tolyloxy)butan-1-ol 16f as a
colourless oil (38 mg, 63%). nmax(neat)/cm-1 3292, 2935, 2876,
1613, 1512, 1472, 1243, 1062, 813; dH (CDCl3) 1.76–1.80 (2H, m,
CH2), 1.88–1.90 (2H, m, CH2), 2.30 (3H, s, CH3), 3.74 (2H, t, J
5.9, CH2OH), 4.00 (2H, t, J 5.9, CH2O), 6.83 (2H, d, J 8.4, ArH),
7.10 (2H, d, J 8.4, ArH). dC (CDCl3) 19.9 (CH2), 25.4 (CH2), 29.1
(CH3), 62.1 (CH2), 67.4 (CH2), 113.9 (CH), 129.3 (C), 129.4 (CH).
30e (Found: [M+H]+ 267.3758. C16H26O3 (M) requires [M+H]+
267.3758). nmax(neat)/cm-1 2941, 2867, 1613, 1512, 1243, 1111,
1084, 818; dH (CDCl3) 1.17 (6H, s, 2 ¥ CH3), 2.31 (3H, s, CH3),
3.21 (3H, s, OCH3), 3.52 (2H, t, J 7.2, CH2O), 3.59 (2H, t, J 7.2,
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CH2), 4.00 (2H, t, J 6.3, OCH3), 6.81 (2H, d, J 8.4, ArH), 7.10 (2H,
d, J 8.4, ArH). dC (CDCl3) 20.4 (CH3), 25.4 (CH3), 29.7 (CH2),
39.2 (CH2), 49.2 (CH3), 65.0 (CH2), 67.2 (CH2), 67.5 (CH2), 73.8
(C), 114.3 (CH), 129.8 (CH), 130.0 (C), 156.9 (C).
16e (Found: [M+NH4]+ 184.2170. C10H14O2 (M) requires
[M+NH4]+ 184.2170) nmax(neat)/cm-1 3273, 2953, 2872, 1513,
1471, 827; dH (CDCl3) 2.00–2.07 (2H, quintet, J 5.9, CH2), 3.89
(2H, t, J 5.9, CH2OH), 4.13 (2H, t, J 5.9, CH2O), 6.83 (2H, d, J
8.4, ArH), 7.10 (2H, d, J 8.4, ArH). dC (CDCl3) 20.0 (CH3), 29.3
(CH2), 37.3 (CH2), 66.9 (CH2), 114.0 (CH), 129.3 (CH), 142.4 (C),
156.4 (C).
Reaction of Substrate 14h with Donor 3. Similarly: 2-
(3-(4-iodo-3-methoxy-3-methylbutoxy)propoxy)-naphthalene 14h
(147 mg, 0.33 mmol,
1
eq.) was reacted with 3,3¢-
(propane-1,3-diyl)bis(1-methyl-1H-benzo[d]imidazol-3-ium) io-
dide 31 (336 mg, 0.6 mmol, 1.8 eq.) to afford 2-(4-(3-methoxy-3-
methylbutoxy)butoxy)naphthalene 30h (36 mg, 38%) as a colour-
less oil and 4-(naphthalen-2-yloxy)butan-1-ol 16h (9 mg, 12%) as
a white solid.
30h (Found: [M+H]+ 317.2114. C20H28O3 (M) requires [M+H]+
317.2111). nmax(neat)/cm-1 2926, 2856, 1629, 1601, 1465, 1217,
1118, 1084, 836; dH (CDCl3) 1.20 (6H, s, 2 ¥ CH3), 1.82–1.98 (6H,
m, 3 ¥ CH2), 3.21 (3H, s, OCH3), 3.51–3.55 (4H, m, 2 ¥ CH2O),
4.16 (2H, t, J 6.2, CH2OH) 7.15–7.19 (2H, m, ArH), 7.44 (1H, t,
J 6.0, ArH), 7.48 (1H, t, J 6.9, ArH), 7.74–7.80 (3H, m, ArH);
dC (CDCl3) 24.9 (CH3), 25.7 (CH2), 26.0 (CH2), 38.7 (CH2), 48.7
(CH2), 66.6 (CH2), 67.3 (CH2), 70.2 (CH2), 73.2 (C), 106.0 (CH),
118.4 (CH), 123.0 (CH), 125.7 (CH), 126.1 (CH), 127.2 (CH),
128.4 (C), 128.8 (CH), 134.1 (C).
Reaction of Substrate 14f with Donor 3. Similarly: 1-(3-(4-
iodo-3-methoxy-3-methylbutoxy)propoxy)-4-methylbenzene 14f
(135 mg, 0.33 mmol, 1.0 eq.) was reacted with the 3,3¢-
(propane-1,3-diyl)bis(1-methyl-1H-benzo[d]imidazol-3-ium) io-
dide 31 (336 mg, 0.6 mmol, 1.8 eq.) to afford 1-(4-(3-methoxy-
3-methylbutoxy)butoxy)-4-methylbenzene 30f as a colourless oil
(22 mg, 24%) and 4-(p-tolyloxy)butan-1-ol 16f as a colourless oil
(7 mg, 8%).
30f: nmax(neat)/cm-1 2929, 2868, 1613, 1509, 1240, 1108, 812,
765; dH (CDCl3) 1.21 (6H, s, 2 ¥ CH3), 1.77–1.88 (6H, m, 3 ¥
CH2), 2.30 (3H, s, CH3), 3.21 (3H, s, OCH3), 3.48–3.54 (4H, m,
2 ¥ CH2O), 3.99 (2H, t, J 6.4, OCH2), 6.81 (2H, d, J 8.4, ArH),
7.10 (2H, d, J 8.4, ArH); dC (CDCl3) 19.9 (CH3), 24.9 (CH3), 25.7
(CH2), 25.9 (CH2), 38.7 (CH2), 48.7 (CH3), 66.6 (CH2), 67.2 (CH2),
70.1 (CH2), 73.3 (C) 113.9 (CH), 129.3 (CH), 129.4 (C), 156.4 (C).
16f: (Found: [M+NH4]+ 198.2435. C11H16O2 (M) requires
[M+NH4]+ 198.2435); nmax(neat)/cm-1 3273, 2953, 2872, 1513,
1471, 827; dH (CDCl3) 2.00–2.07 (2H, quintet, J 5.9, CH2), 3.89
(2H, t, J 5.9, CH2OH), 4.13 (2H, t, J 5.9, CH2O), 6.83 (2H, d, J
8.4, ArH), 7.10 (2H, d, J 8.4, ArH). dC (CDCl3) 19.9 (CH2), 25.4
(CH2), 29.1 (CH3), 62.1 (CH2), 67.4 (CH2), 113.9 (CH), 129.3 (C),
129.4 (CH).
◦
16h M.Pt. 118–120 C. (Found: [M+H]+ 217.1224. C14H16O2
(M) requires [M+H]+ 217.1223);nmax(neat)/cm-1 3238, 2956, 2931,
2878, 1629, 1600, 1389, 1261, 1040, 838, 749; dH (CDCl3) 1.82–
1.87 (2H, m, CH2), 1.95–2.07 (2H, m, CH2), 3.78 (2H, t, J 6.2,
CH2O), 4.16 (2H, t, J 6.2, CH2OH), 7.15–7.19 (2H, m, ArH),
7.44 (1H, t, J 6.0, ArH), 7.48 (1H, t, J 6.9, ArH), 7.74–7.80 (3H,
m, ArH); dC (CDCl3) 25.8 (CH2), 29.5 (CH2), 62.7 (CH2), 67.8
(CH2), 106.7 (CH), 118.9 (CH), 123.7 (CH), 126.4 (CH), 126.8
(CH), 127.6 (CH), 129.0 (C), 129.4 (CH), 134.6 (C), 156.9 (C).
D. Preparation and Reactions of Substrate 33
(Z)-4-(3-phenylpropoxy)-but-2-en-1-ol. (Z)-But-2-ene-1,4-
diol (16.5 mL, 200 mmol, 1.1 eq) was added dropwise to a stirred
suspension of sodium hydride (60% in mineral oil, 0.88 g, 22 mmol,
10 eq) in dry DMF (10 mL) at 0 ◦C and under argon. After
20 min, 1-bromo-3-phenylpropane (3.04 mL, 20 mmol, 1 eq) was
added dropwise and the reaction was left to stir at 0 ◦C for
1 h and heated to 90 ◦C for 24 h. The reaction mixture was
poured into water (30 mL) and extracted with diethyl ether (3 ¥
100 mL). The combined organic layers were washed with water
(2 ¥ 100 mL), brine (100 mL), dried over NaSO4 and concentrated
under reduced pressure. The crude product was purified using
silica gel chromatography, eluting with diethyl ether/PE (1 : 1),
to afford (Z)-4-(3-phenylpropoxy)-but-2-en-1-ol as a yellow oil
(2.84 g, 68%);1 nmax(neat)/cm-1 3393, 2931, 2861, 1454, 1102, 699;
dH (CDCl3) 1.93 (2H, m, CH2), 2.70 (2H, t, J 7.9, CH2Ar), 3.46
(2H, t, J 6.8, CH3O), 4.05 (2H, t, J 6.6, CH2O), 4.22 (2H, t,
J 7.0, CH2O), 5.71–5.75 (1H, m, CH = CH), 5.80–5.84 (1H, m,
CH = CH), 7.24–7.27 (3H, m, ArH), 7.33–7.37 (2H, m, ArH);
dC (CDCl3) 31.3 (CH2), 32.3 (CH2), 58.8 (CH2), 66.5 (CH2), 69.9
(CH2), 125.8 (CH), 128.3 (CH), 128.4 (CH), 128.5 (CH), 132.1
(CH), 141.8 (C). m/z (CI+) 224 [(M+ NH4)+, 100%] 207 (95), 189
(50), 118 (30).
Reaction of Substrate 14g with Donor 3. Similarly: 2-
(3-(4-iodo-3-methoxy-3-methylbutoxy)propoxy)-naphthalene 14g
(143 mg, 0.33 mmol, 1.0 eq.) was reacted with 3,3¢-
(propane-1,3-diyl)bis(1-methyl-1H-benzo[d]imidazol-3-ium) io-
dide 31 (336 mg, 0.6 mmol, 1.8 eq.) to afford 2-(3-(3-methoxy-3-
methylbutoxy)propoxy)naphthalene 30g as a colourless oil (32 mg,
29%) and 3-(naphthalen-2-yloxy)propan-1-ol 16g as a white solid
(8 mg, 15%).
30g (Found: [M+H]+ 303.4079. C19H26O3 (M) requires [M+H]+
303.4079); nmax(neat)/cm-1 2923, 2868, 1509, 1246, 1114, 815. dH
(CDCl3) 1.17 (6H, s, 2 ¥ CH3), 1.83 (2H, t, J 7.3, CH2), 2.09–
2.13 (2H, quintet, J 7.3, CH2), 3.19 (3H, s, CH3), 3.55 (2H, t, J
6.0, CH2O), 3.64 (2H, t, J 6.0, CH2O), 4.19 (2H, t, J 6.3, CH2),
7.14–7.16 (2H, m, ArH), 7.34 (1H, t, J 6.0, ArH), 7.42 (1H, t, J
6.9, ArH), 7.71–7.78 (3H, m, ArH); dC (CDCl3) 25.4 (CH3), 29.8
(CH2), 39.2 (CH2), 49.2 (CH3), 65.0 (CH2), 67.2 (CH2), 67.4 (CH2),
73.8 (C), 106.7 (CH), 119.0 (CH), 123.5 (CH), 126.3 (CH), 126.7
(CH), 127.6 (CH), 128.9 (C), 129.3 (CH), 134.7 (C), 157.0 (C).
16g;17 M.Pt. 99–100 ◦C. nmax(neat)/cm-1 3273, 2953, 2872, 1513,
1471, 827; dH (CDCl3) 2.11–2.20 (2H, m, CH2), 3.94 (2H, t, J 6.0
CH2O), 4.27 (2H, t, J 6.0, CH2OH), 7.15–7.19 (2H, m, ArH),
7.44 (1H, t, J 6.0, ArH), 7.48 (1H, t, J 6.9, ArH), 7.74–7.80 (3H,
m, ArH); dC (CDCl3) 31.5 (CH2), 60.1 (CH2), 65.3 (CH2), 106.2
(CH), 118.3 (CH), 123.2 (CH), 125.9 (CH), 126.3 (CH), 127.1
(CH), 128.5 (C), 128.9 (CH), 134.0 (C), 156.4 (C).
1-(3-((Z)-4-(2-iodophenoxy)but-2-enyloxy)propyl)benzene 33.
To a stirred solution of (Z)-4-(3-phenylpropoxy)but-2-en-1-ol
(1.50 g, 7.27 mmol, 1 eq), 2-iodophenol (1.92 g, 8.73 mmol,
1.2 eq) and triphenylphosphine (2.86 g, 10.91 mmol, 1.5 eq) in
THF (20 mL) at 0 ◦C was added diisopropyl azodicarboxylate
(2.16 mL, 10.91 mmol, 1.5eq) and the mixture was allowed to
warm to rt overnight. After evaporation of the solvent under
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reduced pressure, the remaining solid was dissolved in DCM
(100 mL). The solution was sequentially washed with 2 N NaOH
(3 ¥ 75 mL), 2 N hydrochloric acid (75 mL), sat. aqueous NaHCO3
(75 mL) and brine (75 mL), dried over NaSO4 and concentrated
under reduced pressure. The crude product was purified using
silica gel chromatography, eluting with a solvent system of 12%
diethyl ether/PE to afford 1-(3-((Z)-4-(2-iodophenoxy)but-2-
enyloxy)propyl)benzene 33 as a colourless oil (2.26 g, 76%).
(Found: [M+NH4]+ 426.0920. C19H21IO2 (M) requires [M+ NH4]+
409.0924); nmax(neat)/cm-1 3060, 3025, 2938, 2859, 1581, 1471,
1017, 747; dH (CDCl3) 1.93 (2H, m, CH2), 2.70 (2H, t, J 7.9,
CH2Ar), 3.47 (2H, t, J 6.8, CH2O), 4.10 (2H, d, J 6.6, CH2O),
4.70 (2H, t, J 6.9, CH2O), 5.81–5.88 (1H, m, CH = CH), 5.89–5.91
(1H, m, CH = CH), 6.72 (1H, dt, J 1.3, 7.6, ArH) 6.82 (1H, dd, J
6.6, 1.0, ArH), 7.21–7.26 (3H, m, ArH), 7.33–7.37 (3H, m, ArH),
7.8 (1H, dd, J 6.2, 1.3, ArH); dC (CDCl3) 31.3 (CH2), 32.4 (CH2),
65.4 (CH2), 67.0 (CH2), 69.9 (CH2), 112.6 (CH), 122.8 (CH),
125.8 (CH), 127.3 (CH), 128.3 (CH), 128.5 (CH), 129.4 (CH),
130.3 (CH), 139.7 (CH), 141.9 (C), 157.2 (C).
cannula. The reaction mixture was left stirring at rt overnight,
under argon. After cooling, the reaction mixture was poured into
water (100 mL). The reaction mixture was extracted with diethyl
ether (3 ¥ 75 mL), and the organic layers were combined and
washed with water (3 ¥ 75 mL), brine (75 mL), dried over Na2SO4
and concentrated in vacuo. The crude product was purified using
column chromatography, eluting with 50 : 50 diethyl ether/PE to
afford (Z)-(3-((4-phenoxybut-2-en-1-yl)oxy)propyl)benzene 38 as
a colourless oil (25 mg, 14%), and 3-phenylpropan-1-ol 16a as a
colourless oil (6 mg, 3%);
((Z)-(3-((4-phenoxybut-2-en-1-yl)oxy)propyl)benzene
38.
Found: [M + H+] 283.1688. C19H22O2 (M) requires [M + H+]
283.1693); nmax(neat)/cm-1 3027, 2937, 2858, 1598, 1495, 1241,
1104, 752; dH (CDCl3) 1.93 (2H, m, CH2), 2.75 (2H, t, J 7.9,
CH2Ar), 3.40 (2H, t, J 6.8, CH2O), 4.15 (1H, d, J 5.3, CH = CH),
4.60 (1H, d, J 6.4, CH = CH), 6.94–7.01 (3H, m, ArH), 7.22–7.24
(3H, m, ArH), 7.3–7.32 (4H, m, ArH); dC (CDCl3) 30.8 (CH2),
31.9 (CH2), 63.5 (CH2), 66.3 (CH2), 69.3 (CH2), 114.2 (CH), 120.4
(CH), 125.3 (CH), 127.4 (CH), 127.8 (CH), 128.0 (CH), 129.0
(CH), 129.6 (CH), 141.4 (C), 158 (C).
Reaction of Substrate 33 with donor 3. 3,3¢-(Propane-1,3-
diyl)bis(1-methyl-1H-benzo[d]imidazol-3-ium) iodide (554 mg,
1.00 mmol, 1.6 eq.) was heated to 110 ◦C for 1 h under vacuum.
Once cooled, sodium hydride (0.475 g, 11.88 mmol, 18 eq.) was
added and the reaction mixture washed three times with dry hex-
ane, and then DMF (15 mL) was added. The reaction mixture was
left stirring at room temperature under argon for 4 h. The yellow
donor suspension was centrifuged at 2000 rpm for 10 min. The
yellow solution was added to 1-(3-((Z)-4-(2-iodophenoxy)but-2-
enyloxy)propyl)benzene 33 (269 mg, 0.66 mmol, 1 eq.) via cannula.
The reaction mixture was heated to 110 ◦C overnight. After
cooling, the reaction mixture was poured into water (100 mL).
The reaction mixture was extracted with diethyl ether (3 ¥ 75 mL),
and the organic layers were combined and washed with water (3 ¥
75 mL), brine (75 mL), dried over Na2SO4 and concentrated in
vacuo. The crude product was purified using column chromatog-
raphy, eluting with a solvent system of 50 : 50 diethyl ether/PE
to afford 3-(2-(3-phenylpropoxy)ethyl)-2,3-dihydrobenzofuran 36
and (Z)-(3-((4-phenoxybut-2-en-1-yl)oxy)propyl)benzene 38 as an
inseparable mixture as a colourless oil (88 mg; the ratio of 5 : 2 is
seen in the 1H-NMR spectrum; since the products have the same
MW, this would equate to 34% of 36 and 13% of 38), and 3-
phenylpropan-1-ol 16a as a colourless oil (7 mg, 8%); (Found:
[M + H]+ 137.0883. C9H12O (M) requires [M + H]+ 137.0883);
Phenylpropan-1-ol 16a. Found: [M + H]+ 137.0883. C9H12O
(M) requires [M + H]+ 137.0883); nmax(neat)/cm-1 3349, 3341,
3027, 2927, 2863, 1667, 1603, 1496, 1454; dH (CDCl3) 1.89–1.95
(2H, m CH2), 2.73 (2H, t, J 7.8, CH2Ar), 3.69 (2H, t, J 6.4,
CH2OH), 7.18–7.22 (3H, m, ArH), 7.28–7.31 (2H, m, ArH); dC
(CDCl3) 32.1 (CH2), 34.2 (CH2), 62.3 (CH2), 126.0 (CH), 128.4
(CH), 128.5 (CH), 141.8 (C).
Test for E2 elimination with alkene 29h using Donor 4. 1,3-
Bis-N,N-dimethyl-4-aminopyridinium)propane diiodide (641 g,
1.19 mmol, 1.8 eq.) was dried under vacuum at 100 ◦C for
1 h, then cooled. Sodium hydride (60% in mineral oil, 475 mg,
11.90 mmol, 18 eq.) was added, and the mixture was washed
with dry hexane three times. The hexane was removed via cannula
and residual trace amounts of hexane were removed using a flow
of argon. Anhydrous N,N-dimethylformamide (15 mL) was then
added, causing a purple suspension to form, which was left to
stir at room temperature under argon for 4 h. The purple donor
suspension was centrifuged at 2000 rpm for 10 min to afford the
solution, which was added, via cannula, to 2-(4-((3-methylbut-3-
en-1-yl)oxy)butoxy)naphthalene 29h (187 mg, 0.66 mmol, 1 eq.)
The reaction mixture was left to stir at room temperature under
argon overnight. Water (50 mL) was slowly added to quench
the reaction mixture. The reaction mixture was washed with
diethyl ether (3 ¥ 50 mL). The combined organic layers were
then further washed with water (4 ¥ 50 mL), brine (50 mL),
dried over Na2SO4 and concentrated under reduced pressure.
n
max(neat)/cm-1 3349, 3341, 3027, 2927, 2863, 1667, 1603, 1496,
1454; dH (CDCl3) 1.89–1.95 (2H, m CH2), 2.73 (2H, t, J 7.8,
CH2Ar), 3.69 (2H, t, J 6.4, CH2OH), 7.18–7.22 (3H, m, ArH),
7.28–7.31 (2H, m, ArH); dC (CDCl3) 32.1 (CH2), 34.2 (CH2), 62.3
(CH2), 126.0 (CH), 128.4 (CH), 128.5 (CH), 141.8 (C).
1
The H NMR taken of the crude NMR indicated only starting
material was present. The crude product was purified by silica
gel chromatography, eluting with 0–5% diethyl ether in petroleum
ether, to afford the starting material, 2-(4-((3-methylbut-3-en-1-
yl)oxy)butoxy)naphthalene 29h as a colourless oil (154 mg, 82%
recovery). (Found: [M+NH4]+ 302.1775. C19H24O2 (M) requires
[M+NH4]+ 302.1776); nmax(neat)/cm-1 2934, 2872, 1600, 1497,
1471, 754; dH (CDCl3) 1.82 (3H, s, CH3), 1.83–1.86 (2H, m, CH2),
1.94–1.99 (2H, m, CH2), 2.34 (2H, t, J 6.8, CH2O), 3.54–3.60 (4H,
m, 2 ¥ CH2O), 4.14 (2H, t, J 6.4, OCH2), 4.77 (1H, m, HCH C),
4.81 (1H, m, HCH C), 7.15–7.19 (2H, m, ArH), 7.44 (1H, t,
J 6.0, ArH), 7.48 (1H, t, J 6.9, ArH), 7.74–7.80 (3H, m, ArH);
Reaction of Substrate 33 with donor 4. 1,3-Bis-(N,N-dimethyl-
4-aminopyridinium)propane diiodide 32 (641 mg, 1.19 mmol, 1.8
eq.) was heated to 110 ◦C for 1 h under vacuum. Once cooled,
sodium hydride (0.475 g, 11.88 mmol, 18 eq.) was added and
the reaction mixture washed three times with dry hexane, then
dried and DMF (15 mL) was added. The reaction mixture was
left stirring at room temperature under argon for 4 h. The yellow
donor suspension was centrifuged at 2000 rpm for 10 min. The
yellow solution was added to 1-(3-((Z)-4-(2-iodo-phenoxy)but-
2-enyloxy)propyl)benzene 33 (269 mg, 0.66 mmol, 1 eq.) via
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dC (CDCl3) 22.2 (CH3), 25.7 (CH2), 25.9 (CH2), 37.3 (CH2), 67.2
(CH2), 68.9 (CH2), 70.0 (CH2), 106.1 (CH), 110.9 (CH2), 118.5
(CH), 123.0 (CH), 125.8 (CH), 126.2 (CH), 127.1 (CH), 128.4 (C),
128.8 (CH), 134.1 (C), 142.5 (C), 156.5 (C).
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Test for E2 elimination with alkene 29h using Donor 3. 3,3¢-
(Propane-1,3-diyl)bis(1-methyl-1H-benzo[d]imidazol-3-ium) io-
dide (547 mg, 0.6 mmol, 1.8 eq.) was dried under vacuum at
100 ◦C for 1 h, then cooled. Sodium hydride (60% in mineral
oil, 475 mg, 11.90 mmol, 18 eq.) was added, and the mixture was
washed with dry hexane three times. The hexane was removed via
cannula and residual trace amounts of hexane were removed using
a flow of argon. Anhydrous N,N-dimethylformamide (15 mL)
was then added, causing a purple suspension to form, which
was left to stir at room temperature under argon for 4 h. The
purple donor suspension was centrifuged at 2000 rpm for 10 min
to afford the solution, which was added, via cannula, to 2-
(4-((3-methylbut-3-en-1-yl)oxy)butoxy)naphthalene 29h (187 mg,
0.66 mmol, 1 eq.) The reaction mixture was heated to 110 ◦C,
under argon, for 18 h. Water (50 mL) was slowly added to
quench the reaction mixture. The reaction mixture was washed
with diethyl ether (3 ¥ 50 mL). The combined organic layers were
then further washed with water (4 ¥ 50 mL), brine (50 mL),
dried over Na2SO4 and concentrated under reduced pressure.
1
The H NMR taken of the crude NMR indicated only starting
material was present. The crude product was purified by silica
gel chromatography, eluting with 0–5% diethyl ether in petroleum
ether, to afford the starting material, 2-(4-((3-methylbut-3-en-1-
yl)oxy)butoxy)naphthalene 29h as a colourless oil (142 mg, 76%
recovery). (Found: [M+NH4]+ 302.1775. C19H24O2 (M) requires
[M+NH4]+ 302.1776); nmax(neat)/cm-1 2934, 2872, 1600, 1497,
1471, 754; dH (CDCl3) 1.82 (3H, s, CH3), 1.83–1.86 (2H, m, CH2),
1.94–1.99 (2H, m, CH2), 2.34 (2H, t, J 6.8, CH2O), 3.54–3.60 (4H,
m, 2 ¥ CH2O), 4.14 (2H, t, J 6.4, OCH2), 4.77 (1H, m, HCH C),
4.81 (1H, m, HCH C), 7.15–7.19 (2H, m, ArH), 7.44 (1H, t,
J 6.0, ArH), 7.48 (1H, t, J 6.9, ArH), 7.74–7.80 (3H, m, ArH);
dC (CDCl3) 22.2 (CH3), 25.7 (CH2), 25.9 (CH2), 37.3 (CH2), 67.2
(CH2), 68.9 (CH2), 70.0 (CH2), 106.1 (CH), 110.9 (CH2), 118.5
(CH), 123.0 (CH), 125.8 (CH), 126.2 (CH), 127.1 (CH), 128.4 (C),
128.8 (CH), 134.1 (C), 142.5 (C), 156.5 (C).
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3570 | Org. Biomol. Chem., 2011, 9, 3560–3570
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