Gold(I)-catalysed iodoalkoxylation of allenes

Article abstract of DOI:10.1016/j.tet.2011.01.021

Gold(I)-catalysed intermolecular iodoalkoxylation of allenes occurs in a regioselective and stereoselective manner to produce versatile iodo-tert-allyllic ether products. The products can be further elaborated through cross-couplings to yield highly substituted tert-allylic ethers.

Full text of DOI:10.1016/j.tet.2011.01.021

Tetrahedron 67 (2011) 1609e1616
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Gold(I)-catalysed iodoalkoxylation of allenes
*
Amelie Heuer-Jungemann, Ross G. McLaren, Maximillian S. Hadfield, Ai-Lan Lee
School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, United Kingdom
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 October 2010
Received in revised form 13 December 2010
Accepted 6 January 2011
Available online 13 January 2011
Gold(I)-catalysed intermolecular iodoalkoxylation of allenes occurs in a regioselective and stereo-
selective manner to produce versatile iodo-tert-allyllic ether products. The products can be further
elaborated through cross-couplings to yield highly substituted tert-allylic ethers.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Gold catalysis
Allenes
Ethers
Iodoalkoxylation
1. Introduction
tertiary alkoxides or tertiary halides are used.4 A mild and general
method for the synthesis of alkyl tert-allylic ethers thus still re-
Allenes are a class of versatile compounds that have proven to
be useful building blocks in organic synthesis.1 For example, Ma
and co-workers have carried out pioneering work into electrophilic
additions to allenes.2e Extensive investigations into the stereo-
selective iodohydroxylation of functionalised allenes to furnish
synthetically useful alcohol products2 and intramolecular iodoal-
koxylations of allenes have been successfully achieved.3
The intermolecular iodoalkoxylation of allenes, however, ap-
pears to be a very challenging transformation (1/2, Scheme 1).
Nevertheless, if catalytic and regioselective intermolecular iodoal-
koxylation of allenes could be achieved, this would constitute an
efficient entry into iodo-tert-allylic ethers 2, which could be further
elaborated via cross-couplings to form functionalised tert-allylic
ethers 3 (Scheme 1). Although ethers are ubiquitous in organic
chemistry, the most widely used method for formation of ethers,
the Williamson ether synthesis, is seldom useful for preparing
tertiary ethers as elimination reactions tend to be favoured when
mains a challenge for synthetic chemists.5,6
As part of our effort to address this issue, we recently disclosed
a regioselective gold(I)-catalysed hydroalkoxylation of allenes to
form tert-allylic ethers.7e9 As proof-of-principle, we also reported
one preliminary result where the putative vinylgold species 5 can
be trapped with N-iodosuccinimide (NIS) in situ to carry out an
overall iodoalkoxylation of the allene 4 under mild conditions
(Scheme 2).7a,10,11 To the best of our knowledge, the only previous
successful report on intermolecular iodoalkoxylation of allenes
requires stoichiometric amounts of mercury(II) salts, and produces
iodo-allylic ethers with tertiary/primary regioselectivities from
w5:1 to 20:1.12 Without mercury(II), iodohydroxylation pre-
dominates, even when reactions of allenes and I2 are carried out in
the presence of excess alcohol, showing how challenging it is to
form the tertiary ether moiety.2d
Ph
Ph
Ph
(IPr)AuCl/AgOTf
(10 mol %)
R1
R2
DMF, 0 oC, 24 h
R1
R2
OR5
R4
R1
R2
OR5
R4
I
(IPr)Au
cross-
OR
6 73%
OR
I
R6
catalyst, "I+"
R5OH
coupling
ROH (10 equiv)
NIS (1.05 equiv)
R3
R4
4
5
R = (CH2)4Ph
R3
R3
(IPr = bis-2,6-diisopropylphenyl imidazolylidene)
1
2
3
Scheme 1. Iodoalkoxylation ofallenes and furtherelaboration ofversatile intermediates2.
Scheme 2. Gold(I)-catalysed iodoalkoxylation of allene 4.
The iodoalkoxylation ofallenes isofparticularinterest because the
resulting tertiary ethers can now be functionalised at the R6 position
by further cross-coupling reactions, potentially allowing for the
* Corresponding author. Tel.: þ44 131 4518030; e-mail address: a.lee@hw.ac.uk
(A.-L. Lee).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.01.021

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A. Heuer-Jungemann et al. / Tetrahedron 67 (2011) 1609e1616
synthesis of highly substituted tertiarty allylic ethers 3. In this full
paper, we explore the scope and generality of this regioselective
iodoalkoxylation reaction as well as further elaboration of the iodo-
tert-allylic ether products2, to furnish substituted tert-allylic ethers 3.
Reaction of trisubstituted allenes 14 and 16 yielded pleasing
results. Both react regioselectively and stereoselectively with phe-
nethyl alcohol to provide the Z-alkene ethers in good yields (entries
5 and 6). The ester and silyl ether groups are also unaffected by the
reaction conditions. Exocyclic allene 18 reacts less well under these
conditions, providing product 19 in modest yield (42%, entry 7) and
with an 85:5 ratio of 19/hydroalkoxylation product 20. Finally, even
tetrasubstituted allene 21 reacts smoothly to provide the tetra-
substituted iodo-allylic ether 22 in 76% yield (entry 8).
2. Results and discussion
A series of monosubstituted, disubstituted, trisubstituted and
tetrasubstituted allenes were either purchased or synthesised
according to literature reported procedures14 and subjected to gold
(I)-catalysed iodoalkoxylation (Table 1). 1,1-Dialkylsubstituted
allenes 7 and 9 react smoothly to give 8 and 10 in 73% and 60%
yields, respectively (entries 1 and 2). As with the parent hydro-
alkoxylation reaction,7a the iodoalkoxylation reaction is also sen-
sitive to sterics; for example, while allene 4 reacts smoothly to
provide 6 in 73% yield (entry 3), allene 11 suffers from poorer yields
of the desired iodoalkoxylation product 12 (27% yield, entry 4). The
major side-product is the iodohydroxylation product 13. It appears
that where there is steric hindrance, attack of adventitious water
becomes competitive.15
The gold(I)-catalysed iodoalkoxylation is not confined to 1,1-di-
substituted allenes as substrates to form iodo-tert-allylic ethers.
Iodo-sec-allylic ethers are also accessible from the corresponding
monosubstituted (23) or 1,3-disubstituted (26) allenes. However,
the conditions have to be altered for these allene substrates: stan-
dard conditions (Scheme 2) resulted in lowconversions with allenes
23 and 26. Interestingly, when allene 23 is subjected to (IPr)AuCl16
(10 mol %), AgOTf (10 mol %), ROH (10 equiv), NIS (1.05 equiv) at rt
in DCM, a 1:1 ratio of 24/25 is produced in w63% combined yield.
17
Changing the catalyst to PPh3AuNTf2 in DCM at rt produces the
desired iodo-sec-allyl ether 24 in 60% isolated yield and with a better
Table 1
The regioselective gold(I)-catalysed iodoalkoxylation of allenesa
Entry
Allene
ROH
Product
Yieldb (%)
73%
I
I
Ph
Ph
1
O
HO
HO
Ph
Ph
7
8
8
8
2
3
60%
73%
O
10
9
Ph
Ph
I
HO
HO
HO
O
6
3
4 Ph
4
Ph
Ph
Ph
27% 12
32% 13
+
I
I
Ph
Ph
4
5
OH
O
Ph
Ph
11
12
13
I
O
TBDPSO
68%
73%
Ph
14
TBDPSO
EtO2C
15
I
Ph
O
6
HO
EtO2C
Ph
16
17
I
O
O
O
7
8
42%c
76%
MeOH
O
MeO
I
18
19
Ph
Ph
O
HO
HO
Ph
21
22
Cy
I
H
Cy
O
(a) Using (IPr)AuCl/AgOTf:d
63% 24/25 1:1;
Cy
I
9
(b) using PPh3AuNTf2:e 24/
25 5:1; 60% yield of 24
Ph
Ph
O
24
25
23

A. Heuer-Jungemann et al. / Tetrahedron 67 (2011) 1609e1616
1611
Table 1 (continued )
Entry
Allene
ROH
Product
Yieldb (%)
H
4
4
I
10
60%f
Ph
O
HO
EtO2C
Ph
EtO2C
26
27
I
O
TBDPSO
11
49%
OH OH
28
OH
14
29
TBDPSO
a
All reactions were carried out with (IPr)AuCl (10 mol %), AgOTf (10 mol %), ROH (10 equiv), NIS (1.05 equiv) at 0 ꢀC in DMF for 20e24 h unless otherwise stated. The
primary isomers of the products shown were generally not detected by crude 1H NMR analysis (<5%), unless otherwise stated. Crude 1H NMR analysis usually indicates <5% of
iodohydroxylation by-product (unless otherwise stated).
b
Isolated yield, unless otherwise stated.
The hydroalkoxylation product 22 (H replacing I in 19) is also observed in a 85:5 ratio of 19/20.
c
d
Reactioncarriedoutwith(IPr)AuCl(10 mol %), AgOTf(10 mol %), ROH(10 equiv), NIS(1.05 equiv)inDCMatrtfor4 h. Leavingthereactionfor24 hgivesthesame1:1ratioof24/25.
e
Reaction carried out with PPh3AuNTf2 (3ꢁ5 mol %), ROH (10 equiv), NIS (1.05 equiv) in DCM at rt for 14 h.13 1H NMR analysis of crude mixture shows approx. 5:1 of 24/25.
f
Reaction carried out with PPh3AuNTf2 (10 mol %), ROH (10 equiv), NIS (1.05 equiv) in DCM at rt for 18 h.
selectivity of approx. 5:1 of 24/25 (entry 9).18 Disubstituted allene 26
undergoes the reaction regioselectively at the alkyl substituted end
to yield sec-iodo-allylic ether 27 in 60% yield (entry 10).
formed in a 2:3 ratio (entry 4). Increasing the steric hindrance
further by using a tertiary alcohol results in the iodohydroxylation
product 31 being observed as the main product (entry 5). Phenol is
also not a viable nucleophile in this reaction, the main product
formed with phenol is 4-iodophenol (entry 6). However, since
tertiary alcohols are not reactive under these conditions, the diol
28 can be used unprotected and iodoalkoxylation occurs chemo-
selectively at the primary alcohol position to produce 29 (Table 1,
entry 11).
In order to investigate whether the reaction is truly gold(I)-
catalysed, several control reactions were carried out in the absence
of the gold catalyst (Scheme 3). In the absence of both (IPr)AuCl and
AgOTf, the iodohydroxylation product 32 is observed as the major
product, though in only w30% conversion (Scheme 3, cf. entry 3,
Table 1). The desired iodoalkoxylation product 6 is observed in only
trace amounts. It is thus clear that NIS alone cannot produce the
desired product 6.
Having investigated the allene scope, we set out to investigate
the scope of the alcohol nucleophiles. The equivalent gold(I)-
catalysed regioselective hydroalkoxylation reaction7a proceeds in
good yields for a variety of primary alcohols, but performs poorly
for more sterically hindered alcohols (secondary and tertiary al-
cohols). It is thus unsurprising that the gold(I)-catalysed iodoal-
koxylation also appears to work smoothly for primary alcohols
(Table 2, entries 1e3) but not secondary alcohols, tertiary alcohols
or phenols (Table 2, entries 4e6). The extra steric hindrance from
the secondary alcohol nucleophile results in poor selectivity of
iodoalkoxylation versus iodohydroxylation; products 30/31 are
Table 2
A screen of alcoholsdonly primary alcohols are good nucleophiles
(IPr)AuCl/AgOTf
(10 mol %)
DMF, 0 oC, 24 h
ROH (10 equiv)
NIS (1.05 equiv.)
Ph
Ph
Ph
I
I
OR
OH
No catalyst
or
NIS (1.05 equiv.)
I
I
OH
32
O(CH2)4Ph
7
30
31
DMF, 0 oC, 24 h
Ph(CH2)4OH (10 equiv.)
6
traces <5%
4
main product
Conversion ~30%
Entry
Alcohol
Result
Scheme 3. Control reaction with the absence of (IPr)AuCl and AgOTf.
Ph
1
2
73% Yield of 30a
50% Yield of 30a,b
HO
Next, a control reaction was carried out with NIS and AgOTf as
the reagents (Scheme 4). In the absence of (IPr)AuCl (but with
AgOTf present), the conversion is w90%, but the iodohydroxylation
compound 33 is formed as the major product (33/10 5:1 ratio). It is
clear from these control reactions that the gold(I) catalyst is nec-
essary for iodoalkoxylation to occur efficiently.
MeOH
3
4
60% Yield of 30a
HO
30/31, 2:3 ratio,c w50% conv.d
HO
No gold catalyst
Main product 31, <5% 30
observed, w50% conv.d
5
AgOTf (10 mol%)
8
8
OH
8
I
I
HO
NIS (1.05 equiv.)
O
+
DMF, 0 oC, 24 h
Ph
<5% 30 or 31, Main product
Ph(CH2)2OH (10 equiv.)
6
9
33
10
major
minor
, ~90% conv.
is 4-iodophenolc
OH
33 10
:
5:1 ratio of
Scheme 4. Control reaction with the absence of (IPr)AuCl.
a
Isolated yield, <5% of 31 observed by 1H NMR.
b
c
Moderate yield due to volatility of the product.
The trapping of putative intermediate 5 was also attempted with
N-bromosuccinimide (NBS) and Selectfluor in order to form bromo-
tert-allylic ethers and fluoro-tert-allylic ethers, respectively.
Determined by analysis of 1H NMR of the crude mixture.
d
Determined by analysis of 1H NMR of the crude mixture with dibenzyl ether as
internal standard.

1612
A. Heuer-Jungemann et al. / Tetrahedron 67 (2011) 1609e1616
Unfortunately, under our standard gold(I)-catalysed reaction condi-
tions (replacing NIS with NBS or Selectfluor, respectively), a complex
mixture of products was observed with the NBS reaction, while the
hydroalkoxylation product was observed exclusively with Select-
fluor. With respect to the latter, protodeauration is clearly much
faster than any trapping with Selectfluor.
In the related gold(I)-catalysed hydroalkoxylation of allenes,
either primary allylic ethers 3519 or tertiary allylic ethers 36 can be
formed regioselectively depending on the reaction conditions
(Scheme 5). In the regioselective formation of primary allylic
ethers, it is thought that gold(I)-catalysed isomerisation of the ki-
netic tertiary allylic ether product 36 to the thermodynamic pri-
mary allylic ether product 35 occurs.7a,b,20 The change of reaction
conditions (conditions B, Scheme 5) prevents the isomerisation of
36 to 35, thus switching the regioselectivity of the reaction.
Although iodo-tert-allylic ethers such as 8 do not seem to isomerise
(thus the excellent selectivity for iodo-tert-allylic ethers vs the
primary counterpart in entries 1e7, Table 1), the selectivity for
forming iodo-sec-allylic ether 24 (entry 9, Table 1) appears to be
dependent on the catalyst employed. The NHC catalyst (IPr)AuCl/
AgOTf produces a 1:1 mixture of 24 and 25, whereas PPh3AuNTf2
produces the iodo-sec-allylic ether 24 in better selectivity (w5:1,
entry 9, Table 1). However, when iodo-sec-allylic ether 24 is sub-
jected to each catalyst, neither (IPr)AuCl/AgOTf nor PPh3AuNTf2
catalyses the isomerisation (Scheme 8). This observation suggests
that for monosubstituted allenes such as 23, any erosion in selec-
tivity results from the initial gold(I)-catalysed iodoalkoxylation
step, rather than from further isomerisation of the products.
(IPr)AuCl/AgOTf
H
H
Cy
O
(5 mol %)
I
I
No reaction
No reaction
(IPr)AuCl (5 mol%)
AgOTf (5 mol%)
DCM, RT, 24 h
Ph
R1
R2
24
ROH (1 equiv.)
Toluene, 23 o
C
PPh3AuNTf2
(5 mol %)
Cy
O
R1
R2
OR
35
Conditions A, ref. 19a
DCM, RT, 24 h
Ph
24
Conditions B, ref. 7a
R1
R2
OR
34
Scheme 8. Isomerisation studies on iodo-sec-allylic ether 24.
(IPr)AuCl (10 mol%)
AgOTf (10 mol%)
ROH (10 equiv.)
DMF, 0 oC
36
The iodoalkene is a good handle for further elaboration of the
iodo-tert-allylic ether products (Scheme 1). For example, Sonoga-
shira coupling22 with phenylacetylene successfully produces 38 in
95% yield (Scheme 9). Even the tetrasubstituted iodoalkene 22 can
be successfully cross-coupled to yield the fully substituted 39 in 60%
yield, albeit higher catalyst loadings and temperatures are required
due to the steric crowding in the iodo-tert-allylic ether substrates.
Mizoroki-Heck coupling23 can also be carried out in order to further
functionalise the iodo-tert-allyl ether products. The MizorokieHeck
coupling proceeds smoothly at 80 ꢀC to furnish 40 in 50% yield
(Scheme 9). The gold(I)-catalysed iodoalkoxylation of allenes fol-
lowed by cross-coupling is thus a good way of producing tert-allylic
ethers with various substitution patterns across the alkene moeity.
Scheme 5. Regioselectivity of the gold(I)-catalysed hydroalkoxylation of allenes is
dependent on reaction conditions.
We were thus keen to ascertain whether the regioselectivity of
the gold(I)-catalysed iodoalkoxylation could be similarly switched,
thus enabling the synthesis of either primary or tertiary iodo-allylic
ethers depending on the reaction conditions. To this end, a reaction
using conditions A was carried out (Scheme 5) but with added NIS
(1.05 equiv), to investigate whether primary-iodo-allylic ether 37
will be formed selectively (Scheme 6). However, analysis by crude
1H NMR showed that the tertiary ether product 8 is still formed as
the major product, rather than the primary ether 37 (8:1 ratio of 8/
37).21 It appears that iodo-tert-allylic ethers such as 8 do not un-
dergo gold(I)-catalysed isomerisation to primary-iodo-allylic
ethers 37 as readily as their tertiary allylic ether counterparts 36.
Indeed, when 8 is subjected to either (IPr)AuOTf or PPh3AuNTf2, no
isomerisation to 37 is observed (Scheme 7).
Ph
Ph
PdCl2(PPh3)2
(8 mol%)
Ph
I
O(CH2)4Ph
O(CH2)4Ph
38, 95%
Ph
CuI, Na2CO3
6
50 o
C
(IPr)AuCl (5 mol%)
AgOTf (5 mol%)
PdCl2(PPh3)2
(10 mol%)
Ph
Toluene, 23 o
C
I
O(CH2)2Ph
O(CH2)2Ph
O(CH2)2Ph
39, 60%
Ph
(Conditions A)
I
O
O
CuI, Na2CO3
I
Ph
8, major product
Ratio of 8:37 = 8:1
80 o
O
C
Ph
22
HO
Ph
37
7
(1.1 equiv.)
NIS (1.05 equiv.)
O
I
OEt
O(CH2)2Ph
Scheme 6. Gold(I)-catalysed iodoalkoxylation using conditions A, with added NIS, still
provides tertiary ether 8 as major product, rather than 37.
EtO
Pd(OAc)2 (5 mol%)
Na2CO3, DMF, 80 o
C
40, 50%
8
(IPr)AuCl/AgOTf
Scheme 9. Sonogashira and Heck couplings of iodoalkene products.
(5 mol %)
I
No reaction
No reaction
O
Ph
Toluene, RT, 4 h
8
3. Conclusions
PPh3AuNTf2
(5 mol %)
Gold(I)-catalysed intermolecular iodoalkoxylation of allenes
occurs in a regioselective and stereoselective manner to produce
versatile iodo-tert-allyllic ether products, which can be further
elaborated through cross-couplings such as the Sonogashira and
Heck reactions to yield highly substituted alkyl tert-allylic ethers.
I
O
Ph
Toluene, RT, 24 h
8
Scheme 7. Iodo-tert-allylic ether 8 does not isomerise under gold(I)-catalysis, unlike
tert-allylic ethers 36.

A. Heuer-Jungemann et al. / Tetrahedron 67 (2011) 1609e1616
1613
The iodoalkoxylation reaction is sensitive to steric hindrance, thus
4.3. (2-(2-Iodo-3-methyldodec-1-en-3-yloxy)ethyl)benzene (10)
the alcohol nucleophile is restricted to primary alcohols. However,
a range of mono, di, tri and tetrasubstituted allene substrates
readily undergo the reaction. Unlike tert-allylic ethers, the iodo-
tert-allylic ethers do not undergo gold(I)-catalysed isomerisation to
primary ethers and thus form the tertiary- rather than primary-
iodo-allylic ethers regioselectively.
To a stirred solution of allene 9 (51.0 mg, 0.283 mmol), DMF
(0.3 mL) and 2-phenyl ethanol (0.350 mL, 2.94 mmol) at 0 ꢀC were
added (IPr)AuCl (17.5 mg, 0.028 mmol), AgOTf (8.8 mg,
0.034 mmol) and NIS (70.0 mg, 0.311 mmol). The reaction mixture
was stirred for 22 h at 0 ꢀC, after which the mixture was diluted
with Et2O, filtered through a silica plug, washed with water and
brine and dried (MgSO4). The product was isolated using flash
column chromatography (99:1 hexane/diethyl ether) as a clear oil
(73.0 mg, 0.171 mmol, 60%). Rf¼0.39 (97:3 hexane/diethyl ether).
nmax/cmꢂ11606 w, 1496 m, 1454 m (Ar C]C), 1070 s (CeO); 1H NMR
4. Experimental
4.1. General experimental section
(200 MHz, CDCl3)
d 7.48e7.32 (5H, m, AreH), 6.30 (1H, d, J 2.2, ]
All reactions were performed under an N2 atmosphere. 1H NMR
spectra were recorded on Bruker AC200, AV 300, DPX 400 and AV
400 spectrometers at 200, 300 and 400 MHz, respectively, and ref-
erenced to residual solvent. 13C NMR spectra were recorded using
the same spectrometers at 50, 75 and 100 MHz, respectively.
CH), 6.14 (1H, d, J 2.2, ]CH), 3.54 (2H, t, J 7.8, OCH2), 3.04 (2H, t, J 7.8,
PhCH2), 1.81e1.64 (2H, m, CH2), 1.47e1.28 (17H, m, 7CH2þCH3), 1.01
(3H, t, J 6.6, CH3). 13C NMR (50 MHz, CDCl3)
d 139.2 (C), 129.3 (CH),
128.5 (CH), 127.8 (CH2), 126.4 (CH), 123.1 (C), 80.8 (C), 64.2 (CH2),
39.9 (CH2), 37.2 (CH2), 32.1 (CH2), 30.1 (CH2), 29.7 (CH2), 29.7 (CH2),
29.5 (CH2), 24.0 (CH2), 22.9 (CH2), 20.9 (CH3), 14.4 (CH3).
[MþNH4]þ¼446.1913 (calcd for C21H33IOþNHþ4 ¼446.1914).
Chemical shifts (d in parts per million) were referenced to tetra-
methylsilane (TMS) or to residual solvent peaks (CDCl3 at dH 7.26).
J values are given in hertz and s, d, dd, t, q and m abbreviations
correspond to singlet, doublet, doublet of doublet, triplet, quartet
and multiplet. Mass spectra were obtained at the EPSRC National
Mass Spectrometry Service Centre in Swansea. Infrared spectrawere
obtained on PerkineElmer Spectrum 100 FT-IR Universal ATR
Sampling Accessory, deposited neat or as a chloroform solution to
a diamond/ZnSe plate. All reagents used were purchased from
commercial suppliers and were used without any further purifica-
tion unless otherwise stated. NIS used in the reactions was recrys-
tallised using dioxane and CCl4 and stored in a dessicator. DMF and
4.4. (4-Iodo-3-methyl-3-(4-phenylbutoxy)pent-4-enyl)
benzene (6)7a
To a stirred solution of allene 4 (44.2 mg, 0.279 mmol) and
4-phenyl-1-butanol (0.43 mL, 2.8 mmol) in anhydrous DMF
(0.28 mL) at 0 ꢀC were added (IPr)AuCl (17.4 mg, 0.028 mmol),
AgOTf (7.2 mg, 0.028 mmol) and NIS (66.2 mg, 0.294 mmol). The
reaction mixture was stirred for 20 h at 0 ꢀC, after which the mix-
ture was diluted with Et2O, filtered through a silica plug, washed
with water and brine and dried (MgSO4). The product was isolated
by flash column chromatography (eluent 98:2 n-pentane/diethyl
ether) to yield 6 as a pale yellow oil (88.7 mg, 0.204 mmol, 73%).
Rf¼0.27 (98:2 n-pentane/diethyl ether); 1H NMR (CDCl3, 200 MHz)
ꢀ
DCM (CH2Cl2) were distilled over CaH2 and stored over 4 A molec-
ular sieves. All alcohol reagents and allene substrates were dried
ꢀ
over 4 A molecular sieves prior to use. Tetrahydrofuran was dried by
distillation from sodium/benzophenone under nitrogen. Petrol
ether refers to petroleum ether (40e60%). Unless otherwise stated,
all iodoalkoxylation reactions were performed at 0 ꢀC using a jack-
eted reaction vessel attached to a Julabo FP40 Bohdan mini block
temperature controlled recirculator with a Julabo temperature
regulator. All glassware were oven dried. Flash column chromatog-
raphy was carried out using Matrix silica gel 60 from Fisher Chem-
icals and TLC was performed using Merck silica gel 60 F254 precoated
sheets and visualised by UV (254 nm) or stained by the use of
aqueous acidic KMnO4 or aqueous acidic ammonium molybdate as
appropriate. 3-Methyl-buta-1,2-diene 7, cyclohexyl allene 23 and
tetramethylallene 21 were purchased from SigmaeAldrich. All other
allenes (4,14a 9,7a 11,14b 14,7a 16,14c 18,7a 26,14c) were prepared
according to literature procedures.14
d
7.35e7.10 (m, 10H, AreH), 6.31 (d, J 1.8, 1H, ]CH), 6.07 (d, J 1.8, 1H,
]CH), 3.29 (t, J 6.3, 2H, OCH2), 2.60 (m, 4H, AreCH2), 1.94 (m, 2H,
CH2), 1.68 (m, 4H, CH2), 1.45 (s, 3H, CH3). 13C NMR (CDCl3, 50 MHz)
d
142.8 (C), 142.3 (C), 128.7 (CH), 128.6 (CH), 128.6 (CH), 128.5 (CH),
128.0 (CH), 126.0 (CH), 125.9 (CH), 122.6 (C), 80.1 (C), 62.6 (CH2),
41.5 (CH2), 36.0 (CH2), 30.5 (CH2), 30.1 (CH2), 28.4 (CH2), 21.5 (CH3).
[MþNH4]þ¼452.1438 (calcd for C22H27IOþNHþ4 ¼452.1445).
4.5. (3-Iodo-2-phenethoxybut-3-en-2-yl)benzene (12) and 3-
iodo-2-phenylbut-3-en-2-ol (13)
To a stirred solution of 11 (41.0 mg, 0.315 mmol), DMF (0.3 mL)
and 2-phenyl ethanol (0.35 mL, 2.94 mmol) at 0 ꢀC were added (IPr)
AuCl (19.6 mg, 31.5 mmol), AgOTf (8.1 mg, 31.5 mmol) and NIS
4.2. (2-(3-Iodo-2-methylbut-3-en-2-yloxy)ethyl)benzene (8)
(74.5 mg, 0.331 mmol). The reaction mixture was stirred for 20 h at
0 ꢀC, after which the mixture was diluted with Et2O, filtered
through a silica plug, washed with water and brine and dried
(MgSO4). The product 12 was isolated using flash column chro-
matography (100% hexane) as a clear oil (32.6 mg, 0.086 mmol,
27%). Rf¼0.06 (99:1 hexane/diethyl ether). nmax/cmꢂ1 1603 w, 1493
m, 1447 m (Ar C]C), 1082 s (CeO); 1H NMR (200 MHz, CDCl3)
To a stirred solution of allene 7 (22.0 mg, 0.323 mmol), DMF
(0.3 mL) and 2-phenyl ethanol (0.350 mL, 2.94 mmol) at 0 ꢀC were
added (IPr)AuCl (19.0 mg, 0.031 mmol), AgOTf (8.4 mg,
0.031 mmol) and NIS (76.3 mg, 0.339 mmol). The reaction mixture
was stirred for 20 h at 0 ꢀC, after which the mixture was diluted
with Et2O, filtered through a silica plug, washed with water and
brine and dried (MgSO4). The product was isolated using flash
column chromatography (eluent: 99:1 hexane/diethyl ether) as
a clear oil (74.8 mg, 0.237 mmol, 73%). Rf¼0.21 (99:1 hexane/diethyl
ether). nmax/cmꢂ1 1607 w, 1496 m, 1453 m (Ar C]C), 1066 s (CeO);
d
7.36e7.15 (10H, m, AreH), 6.39 (1H, d, J 2.1, ]CH), 6.04 (1H, d, J 2.1,
]CH), 3.59e3.39 (2H, m, OCH2), 2.94 (2H, t, J 7.4, PhCH2), 1.59 (3H,
s, CH3). 13C NMR (50 MHz, CDCl3)
144.1 (C), 139.1 (C), 129.2 (CH),
d
128.3 (CH), 128.0 (CH), 127.5 (CH2), 127.2 (CH), 126.2 (CH), 125.9
(CH), 121.4 (C), 82.6 (C), 64.1 (CH2), 36.9 (CH2), 23.6 (CH3).
[MþNH4]þ¼396.0819 (calcd for C18H19IOþNHþ4 ¼396.0819).
3-Iodo-2-phenylbut-3-en-2-ol 13 (27.8 mg, 0.101 mmol, 32%)
was also isolated as the major side-product. Rf¼0.30 (4:1 n-pen-
tane/diethyl ether). nmax/cmꢂ1 3409 br (OH), 1613 w, 1599 w, 1492
1H NMR (200 MHz, CDCl3)
d 7.35e7.12 (5H, m, AreH), 6.20 (1H, d, J
2.2, ]CH), 5.96 (1H, d, J 2.2, ]CH), 3.41 (2H, t, J 7.8, OeCH2), 2.92
(2H, t, J 7.8, PheCH2), 1.39 (6H, s, 2ꢁCH3). 13C NMR (50 MHz, CDCl3)
d
139.1 (C), 129.3 (CH), 128.5 (CH), 127.0 (CH2), 126.4 (CH), 123.4 (C),
78.5 (C), 64.6 (CH2), 37.2 (CH2), 26.2 (CH3). [MþNH4]þ¼334.0666
w, 1446 w (AreC]C); 1H NMR (200 MHz, CDCl3)
m, Ar-H), 6.42 (1H, d, J 2.4, ]CH), 6.00 (1H, d, J 2.4, ]CH), 1.79 (3H,
d 7.47e7.26 (5H,
(calcd for C13H17IOþNHþ4 ¼334.0662).

1614
A. Heuer-Jungemann et al. / Tetrahedron 67 (2011) 1609e1616
s, CH3). 13C NMR (50 MHz, CDCl3)
d
144.7 (C), 128.4 (CH), 127.7 (CH),
76.7 (C), 64.1 (CH2), 63.8 (CH2), 49.6 (CH3), 30.5 (CH2), 29.9 (CH2).
125.9 (CH2), 125.4 (CH), 123.5 (C), 78.8 (C), 27.9 (CH3).
HREI [M]þ¼324.0216 (calcd for C11H17IO3¼324.0217).
[M]þ¼273.9852 (calcd for C10H11IO¼273.9849).
4.9. (2-(3-Iodo-2,4-dimethylpent-3-en-2-yloxy)ethyl)benzene
(22)
4.6. tert-Butyl-(4-iodo-5-methyl-5-phenethyloxyhex-3-
enyloxy)-diphenyl-silane (15)
To
a stirred solution of tetramethylallene 21 (27.0 mg,
0.281 mmol) and 2-phenyl ethanol (0.43 mL, 2.8 mmol) in anhy-
To a stirred solution of 14 (108 mg, 0.308 mmol), DMF (0.3 mL)
drous DMF (0.28 mL) at 0 ꢀC were added (IPr)AuCl (17.4 mg,
and 2-phenyl ethanol (0.35 mL, 2.9 mmol) at 0 ꢀC were added (IPr)
28.0 mmol), AgOTf (7.2 mg, 28.0 mmol) and NIS (66.2 mg,
AuCl (19.1 mg, 30.8 mmol), AgOTf (9.5 mg, 0.037 mmol) and NIS
0.290 mmol). The reaction mixture was stirred for 20 h at 0 ꢀC, after
which the mixture was diluted with Et2O, filtered through a silica
plug, washed with water and brine and dried (MgSO4). The product
22 was obtained by flash column chromatography (eluent 50:1
petrol ether/diethyl ether) as a pale yellow oil (73.5 mg, 0.214 mmol,
76%). Rf¼0.38 (97:3 petrol ether/diethyl ether). nmax/cmꢂ1 1604 w,
1495 m, 1453 m (Ar C]C), 1064 s (CeO); 1H NMR (CDCl3, 400 MHz)
(73.3 mg, 0.326 mmol). The reaction mixture was stirred for 20 h at
0 ꢀC, after which the mixture was diluted with Et2O, filtered
through a silica plug, washed with water and brine and dried
(MgSO4). The product 15 was isolated using flash column chro-
matography (eluent: 98:2 hexane/diethyl ether) as a clear oil
(126 mg, 0.210 mmol, 68%). Rf¼0.10 (98:2 hexane/diethyl ether).
Stereochemistry of alkene was confirmed through NOE. nmax/cmꢂ1
1589 w, 1496 m, 1472 m (Ar C]C), 1106 s (SieO), 1087 s (CeO); 1H
d
7.30e7.16 (m, 5H, AreH), 3.51 (t, J 7.6, 2H, OeCH2), 2.84 (t, J 7.6, 2H,
PhCH2), 2.06 (s, 3H, CH3), 2.03 (s, 3H, CH3),1.53 (s, 6H, CH3). 13C NMR
(CDCl3, 100 MHz) 140.7 (C), 139.1 (C), 129.0 (CH), 128.3 (CH), 126.1
NMR (200 MHz, CDCl3) d 7.70e7.21 (15H, m, AreH), 5.88 (1H, t, J 6.3,
]CH), 3.78 (2H, t, J 6.3, TBDPSOCH2), 3.41 (2H, t, J 7.5, OCH2CH2Ph),
2.95 (2H, t, J 7.5, PhCH2), 2.52 (2H, dt, J 6.3, 6.3, CH2CH), 1.45 (6H, s,
d
(CH),108.2 (C), 80.0 (C), 63.9 (CH2), 37.0 (CH2), 35.7 (CH3), 30.9 (CH3),
21.61 (CH3). HREI [M]þ¼344.0636 (calcd for C15H21IO¼344.0632).
2ꢁCH3), 1.08 (9H, s, t-Bu). 13C NMR (50 MHz, CDCl3)
d 138.9 (C),
135.5(CH), 133.6 (C), 133.1 (CH), 129.6 (CH), 129.1 (CH), 128.2 (CH),
127.6 (CH),126.1 (CH), 121.8 (C), 78.3 (C), 64.1 (CH2), 62.2 (CH2), 40.4
(CH2), 37.0 (CH2), 26.9 (CH3), 26.7 (CH3), 19.1 (C). [MþNH4]þ m/
z¼616.2095 (calcd for C31H39IO2SiþNHþ4 ¼616.2102).
4.10. (2-(1-Cyclohexyl-2-iodoallyloxy)ethyl)benzene (24)
To a stirred solution of cyclohexyl allene 23 (35.0 mg, 0.287 mmol)
and 2-phenyl ethanol (0.34 mL, 2.9 mmol) in DCM (0.29 mL), were
added PPh3AuNTf2 (2:1 toluene adduct,11.0 mg, 0.014 mmol) and NIS
(68.3 mg, 0.304 mmol). The reaction mixture was stirred at rt. A fur-
ther two portions of catalyst (11.0 mgꢁ2, 0.014 mmolꢁ2) was added
after2 handafter4 h.Thereactionmixturewasthenallowedtostirfor
14 h at rt. The reaction mixture was then flushed through a plug of
silica (diethyl ether). The product, 24, was obtained by flash column
chromatography (eluent 99:1 hexane/diethyl ether) as a colourless oil
4.7. (Z)-Ethyl 4-iodo-5-methyl-5-phenethoxyhex-3-enoate (17)
To a stirred solution of allene 16 (40.0 mg, 0.259 mmol), DMF
(0.3 mL) and 2-phenyl ethanol (0.35 mL, 2.94 mmol) at 0 ꢀC were
added (IPr)AuCl (18.0 mg, 30.0 mmol), AgOTf (8.0 mg, 0.031 mmol)
and NIS (72.0 mg, 0.320 mmol). The reaction mixture was stirred
for 22 h at 0 ꢀC, after which the mixture was diluted with Et2O,
filtered through a plug of silica, washed with water and brine and
dried (MgSO4). The product was isolated using flash column chro-
matography (eluent: 9:1 hexane/diethyl ether) as a clear oil
(75.9 mg, 0.189 mmol, 73%). Rf¼0.15 (9:1 hexane/diethyl ether).
Stereochemistry of alkene was confirmed through NOE. nmax/cmꢂ1
1734 s (C]O), 1635 w (C]C), 1604 w, 1496 m, 1453 m (Ar C]C),
(64.0 mg, 0.173 mmol, 60%). Rf¼0.23 (99:1 hexane/diethyl ether). nmax
cmꢂ11652 w (C]C), 1612 m, 1573 m, 1512 m (Ar C]C), 1126 s (CeO);
1H NMR (300 MHz, CDCl3)
7.24e7.10 (5H, m, AreH), 6.17 (1H, dd, J1.3,
/
d
0.8, ]CH), 5.90 (1H, d, J 1.3, ]CH), 3.62 (1H, ddd, J 9.3, 7.6, 6.7, OCHH),
3.26 (1H, ddd, J 9.3, 7.9, 6.9, OCHH), 2.88e2.79 (m, 2H, PhCH2), 2.64
(1H, dd, J 8.1, 0.8, OCHCy),1.96 (1H, m, OCHCH (CH2)5),1.73e0.60 (10H,
m, 5ꢁCH2). 13C NMR (75 MHz, CDCl3)
d 138.9 (C), 129.0 (CH), 128.2
1159 s (CeO), 1066 s (CeO); 1H NMR (200 MHz)
d 7.40e7.09 (5H, m,
AreH), 6.05 (1H, t, J 6.1, ]CH), 4.16 (2H, q, J 7.1, OCH2CH3), 3.38 (2H,
t, J 7.8, OCH2CH2Ph), 3.24 (2H, d, J 6.1, COCH2CH), 2.90 (2H, t, J 7.8,
CH2Ph), 1.44 (6H, s, CH3), 1.26 (3H, t, J 7.1, OCH2CH3). 13C NMR
(CH),127.6 (CH2),126.1 (CH),116.51 (C), 90.1 (CH), 69.7 (CH2), 40.8 (CH),
36.2 (CH2), 29.1 (CH2), 28.56 (CH2), 26.5 (CH2), 25.9 (CH2), 25.8 (CH2).
[MþNH4]þ¼388.1140 (calcd for C17H23IOþNHþ4 ¼388.1132).
Using (IPr)AuCl/AgOTf conditions: To a stirred solution of cyclo-
hexyl allene 23 (34.7 mg, 0.284 mmol) and 4-phenyl-1-butanol
(0.33 mL, 2.8 mmol) in DCM (0.28 mL) were added (IPr)AuCl
(17.3 mg, 0.0279 mmol), AgOTf (7.2 mg, 0.028 mmol) and NIS
(65.3 mg, 0.290 mmol). The reaction mixture was stirred under N2
atmosphere for 4 h at rt. The reaction mixture was then flushed
through a plug of silica (diethyl ether). Crude 1H NMR analysis
shows w1:1 mixture of 24/25. The products were obtained by flash
column chromatography (eluent 99:1 hexane/diethyl ether) as
(50 MHz, CDCl3)
d 170.9 (C), 138.9 (C), 129.2 (CH), 128.7 (CH), 128.3
(CH), 126.2 (CH), 123.7 (C), 78.5 (C), 64.3 (CH2), 61.0 (CH2), 42.7
(CH2), 37.0 (CH2), 26.9 (CH3), 14.2 (CH3). [MþNH4]þ¼420.1032
(calcd for C17H23IO3þNHþ4 ¼420.1030).
4.8. 8-(1-Iodo-vinyl)-8-methoxy-1,4-dioxa-spiro[4.5]decane (19)
To a stirred solution of allene 18 (50.0 mg, 0.300 mmol), DMF
(0.3 mL) and methanol (0.12 mL, 2.94 mmol) at 0 ꢀC were added
a pale yellow oil: 24 (32.0 mg, 86.5
contaminated with w11% 24, 33.6 mg, 90.7
for 25: 1H NMR (300 MHz, CDCl3)
7.25e7.10 (5H, m, AreH), 5.54
mmol, 31%) and 25 (not pure,
(IPr)AuCl (18.0 mg, 30.0
mmol), AgOTf (8.5 mg, 0.033 mmol) and NIS
mmol, 32%). NMR data
(72.6 mg, 0.323 mmol). The reaction mixture was stirred for 22 h at
0 ꢀC, after which the mixture was diluted with Et2O, filtered
through a silica plug, washed with water and brine and dried
(MgSO4). The product was isolated using flash column chroma-
tography (4:1/1:2 hexane/diethyl ether) as a clear oil (39.8 mg,
0.128 mmol, 42%). The product was contaminated with approx. 15%
hydroalkoxylation7a product 20. Rf¼0.43 (1:1 hexane/diethyl
ether). nmax/cmꢂ1 1639 w (C]C), 1096 s (CeO), 1071 s (CeO); 1H
d
(1H, dt, J 8.7, 1.2, ]CH), 4.04 (2H, d, J 1.2, OCH2), 3.55 (2H, t, J 7.2,
OCH2CH2), 2.84 (2H, t, J 7.2, PhCH2), 2.20 (1H, m, CH(CH2)5),
1.65e0.95 (10H, m, 5ꢁCH2). 13C NMR (75 MHz, CDCl3)
d 142.3 (CH),
138.8 (C), 129.0 (CH), 128.4 (CH), 126.3 (CH), 101.9 (C), 78.9 (CH2),
70.6 (CH2), 44.7 (CH), 36.3 (CH2), 31.5 (CH2), 25.9 (CH2), 25.6 (CH2).
4.11. (Z)-Ethyl 4-iodo-5-phenethoxydec-3-enoate (27)
NMR (200 MHz, CDCl3)
]CH), 3.94 (4H, m, OCH2), 3.09 (3H, s, OCH3), 2.06e1.56 (8H, m,
CH2). 13C NMR (50 MHz, CDCl3)
127.4 (CH2), 122.1 (C), 108.2 (C),
d 6.28 (1H, d, J 2.4, ]CH), 6.07 (1H, d, J 2.4,
To a stirred solution of allene 26 (22.0 mg, 0.112 mmol) and
2-phenyl ethanol (0.13 mL, 1.1 mmol) in DCM (0.15 mL) were added
d

A. Heuer-Jungemann et al. / Tetrahedron 67 (2011) 1609e1616
1615
PPh3AuNTf2 (2:1 toluene adduct, 8.8 mg, 0.011 mmol) and NIS
(26.4 mg, 0.118 mmol). The reaction mixture was stirred for 18 h at
rt. The reaction mixture was then flushed through a plug of silica
(diethyl ether). The product, 27, was obtained by flash column
chromatography (eluent 9:1 hexane/diethyl ether) as a pale yellow
0 ꢀC after which the mixture was diluted with Et2O, filtered through
a plug of silica, washed with water and brine and dried (MgSO4).
The product was isolated using flash column chromatography (el-
uent: 98:2 n-pentane/diethyl ether) as a pale yellow oil (93.0 mg,
0.347 mmol, 60%). Rf¼0.53 (98:2 n-pentane/diethyl ether). nmax
/
oil (30.0 mg, 67.5
m
mol, 60%). Stereochemistry of alkene was con-
cmꢂ11608 w (C]C), 1072 s (CeO); 1H NMR (300 MHz, CDCl3)
d
6.23
firmed through NOE. Rf¼0.28 (9:1 petrol/diethyl ether). nmax/cmꢂ1
(1H, d, J 2.1, ]CH), 5.96 (1H, d, J 2.1, ]CH), 3.21 (2H, t, J 6.8, OCH2),
1.69e1.30 (4H, m, CH2CH2), 1.38 (6H, s, 2ꢁCH3), 0.91 (3H, t, J 6.8,
1736 s (C]O), 1653 vw (C]C), 1598, 1522, 1487 (Ar C]C), 1241 s
(CeO); 1H NMR (CDCl3, 300 MHz)
d
7.33e7.19 (5H, m, AreH), 6.19
CH3). 13C NMR (75 MHz, CDCl3)
d 126.4 (CH2), 123.6 (C), 77.8 (C),
(1H, t, J 6.3, ]CH), 4.17 (2H, q, J¼4.5, OCH2CH3), 3.68 (1H, ddd,
J¼9.3, 7.8, 6.5, OCHHCH2Ph), 3.39 (1H, ddd, J¼9.3, 8.0, 6.8,
OCHHCH2Ph), 3.29 (1H, t, J¼6.6, OCH), 3.27 (2H, d, J¼6.3,
OCH2CH]), 2.95e2.89 (2H, m, CH2Ph), 1.65e1.51 (2H, m, CH2),
1.32e1.24 (9H, m, CH2ꢁ3þOCH2CH3), 0.89 (3H, t, J 6.9, CH3). 13C
62.7 (CH2), 32.4 (CH2), 26.0 (CH3), 19.5 (CH2), 14.0 (CH3).
[MþNH4]þ¼286.0671 (calcd for C9H17IOþNHþ4 ¼286.0662).
1H NMR for side-product 3-iodo-2-methylbut-3-en-2-ol (31):12
d 6.32 (1H, d, J 2.3, ]CH), 5.81 (1H, d, J
2.3, ]CH), 1.48 (6H, s, 2ꢁCH3).
1H NMR (300 MHz, CDCl3)
NMR (CDCl3, 75 MHz)
d 170.5 (C), 138.9 (C), 129.7 (CH), 129.0 (CH),
128.3 (CH), 126.2 (CH), 117.9 (C), 85.6 (CH), 69.4 (CH2), 61.0 (CH2),
41.2 (CH2), 36.3 (CH2), 35.4 (CH2), 31.6 (CH2), 24.7 (CH2), 22.5 (CH2),
14.2 (CH3), 14.0 (CH3). [MþNH4]þ¼462.1488 (calcd for
C20H29IO3þNHþ4 ¼462.1500).
4.15. (4-Methyl-3-methylene-4-(4-phenylbutoxy)hex-1-yne-
1,6-diyl)dibenzene (38)7a
(4-Iodo-3-methyl-3-(4-phenylbutoxy)pent-4-enyl)benzene, 6,
(18.0 mg, 41.4
stirred at rt. PdCl2(PPh3)2 (2.4 mg, 3.4
potassium carbonate (14.5 mg, 0.11 mmol) and phenylacetylene
mmol) was dissolved in anhydrous MeCN (1 mL) and
4.12. (Z)-4-(6-(tert-Butyldiphenylsilyloxy)-3-iodo-2-methyl
hex-3-en-2-yloxy)-2-methylbutan-2-ol (29)
m
mol), CuI (1.3 mg, 6.7 mol),
m
(12 mL, 0.11 mmol) wereadded and the resulting mixturewas heated
To a stirred solution of allene 14 (101 mg, 0.288 mmol), DMF
(0.3 mL) and 3-methyl-1,3-butanediol 28 (0.16 mL, 1.47 mmol) at
0 ꢀC were added (IPr)AuCl (18.0 mg, 0.030 mmol), AgOTf (8.0 mg,
0.031 mmol) and NIS (71.0 mg, 0.316 mmol). The reaction mixture
was stirred for 22 h at 0 ꢀC, after which the mixture was diluted
with Et2O, filtered through a plug of silica, washed with water and
brine and dried (MgSO4). The product was isolated using flash
column chromatography (2:1 hexane/diethyl ether) as a colourless
oil (82.3 mg, 0.142 mmol, 49%). Stereochemistry of alkene was
to 50 ꢀC for 20 h under N2 atmosphere. The reaction mixture was
then washed (diethyl ether) through a plug of silica and the product,
38, was obtained by flash column chromatography (eluent 98:2 n-
pentane/diethyl ether) as a yellow viscous oil (16.2 mg, 39.7 mmol,
95%). Rf¼0.20 (99:1 n-pentane/diethyl ether); 1H NMR (CDCl3,
200 MHz) d 7.42e7.07 (15H, m, AreH), 5.67 (1H, d, J 1.8, ]CH), 5.60
(1H, d, J 1.8, ]CH), 3.39 (2H, t, J 6.3, OCH2), 2.62 (4H, m, AreCH2), 2.03
(2H, m, CH2), 1.68 (4H, m, CH2), 1.45 (3H, s, CH3). 13C NMR (CDCl3,
50 MHz) d 142.9 (C),142.8 (C),136.2 (C),131.8 (CH),128.7 (CH),128.6
confirmed through NOE. Rf¼0.38 (1:2 hexane/diethyl ether). nmax
cmꢂ1 3454 br (OH), 1631 w (C]C), 1590 w, 1472 m, 1427 m (Ar C]
C), 1111 s (SieO), 1088 s (CeO); 1H NMR (200 MHz, CDCl3)
7.49
/
(CH),128.5 (CH),128.5 (CH),128.5 (CH),128.4 (CH),125.8 (CH),125.8
(CH),123.5 (C),122.1 (CH2), 90.4 (C), 88.8 (C), 78.7 (C), 62.2 (CH2), 41.0
(CH2), 36.1 (CH2), 30.4 (CH2), 30.2 (CH2), 28.5 (CH2), 23.0 (CH3).
[MþNH4]þ¼426.2793 (calcd for C30H32OþNH4¼426.2791).
d
(10H, m, AreH), 5.89 (1H, t, J 6.4, ]CH), 3.76 (2H, t, J 6.3, SiOCH2),
3.44 (2H, t, J 5.9, OCH2), 2.49 (2H, td, J 6.3, 6.4, CH2CH]C), 1.75 (2H,
t, J 5.9, OCH2CH2CMe2OH), 1.44 (6H, s, CH3), 1.25 (6H, s, CH3), 1.05
4.16. (2-(2,4-Dimethyl-3-(phenylethynyl)pent-3-en-2-yloxy)
ethyl)benzene (39)
(9H, s, CH3). 13C NMR (50 MHz, CDCl3)
d 135.5 (CH), 133.7 (C),
133.6 (CH), 129.7 (CH), 127.7 (CH), 120.7 (C), 78.6 (C), 70.6 (C),
62.2 (CH2), 59.9 (CH2), 41.6 (CH2), 40.5 (CH2), 29.4 (CH3), 26.9
(CH3), 26.8 (CH3), 19.2 (C). [MþNH4]þ¼598.2202 (calcd for
C28H41IO3SiþNHþ4 ¼598.2208).
(2-(3-Iodo-2,4-dimethylpent-3-en-2-yloxy)ethyl)benzene 22
(19.0 mg, 55.2
stirred at rt. PdCl2(PPh3)2 (4.1 mg, 5.8
potassium carbonate (20.0 mg, 0.145 mmol) and phenylacetylene
mmol) was dissolved in anhydrous MeCN (1 mL) and
m
mol), CuI (2.3 mg,10.2 mol),
m
4.13. 2-Iodo-3-methoxy-3-methylbut-1-ene (30, R[Me)12
(16 mL, 0.145 mmol) were added and the reaction mixture heated to
80 ꢀC for 20 h under N2 atmosphere. The reaction mixture was then
washed (diethyl ether) through a plug of silica and the product, 39,
was obtained by flash column chromatography (eluent 98:2 hexane/
To a stirred solution of allene 7 (30.0 mg, 0.441 mmol), DMF
(0.4 mL) and dry methanol (0.18 mL, 4.4 mmol) at 0 ꢀC were added
(IPr)AuCl (27.3 mg, 44.0
m
mol), AgOTf (11.3 mg, 44.0
m
mol) and NIS
diethyl ether) as a pale yellow oil (10.5 mg, 33.0
m
mol, 60%). Rf¼0.11
(104 mg, 0.462 mmol). The reaction mixture was stirred for 17 h at
0 ꢀC after which the mixture was diluted with Et2O, filtered through
a plug of silica, washed with water and brine and dried (MgSO4).
The product was isolated using flash column chromatography (el-
uent: 98:2 n-pentane/diethyl ether) as a pale yellow oil (49.4 mg,
0.219 mmol, 50%). The product is slightly volatile. Rf¼0.19 (98:2 n-
pentane/diethyl ether). nmax/cmꢂ1 1645 w (C]C), 1091 s (CeO); 1H
(98:2 hexane/diethyl ether). nmax/cmꢂ1 2194 w (C^C), 1595 w, 1489
m, 1442 m (Ar C]C), 1069 s (CeO); 1H NMR (CDCl3, 300 MHz)
d
7.50e7.20 (10H, m, AreH), 3.51 (2H, t, J 7.5, OCH2), 2.87 (2H, t, J 7.5,
PhCH2), 2.09 (3H, s, CH3), 2.03 (3H, s, CH3),1.52 (6H, s, CH3). 13C NMR
(CDCl3, 75 MHz) 145.3 (C), 139.3 (C), 130.9 (CH), 129.0 (CH), 128.4
d
(CH), 128.2 (CH), 127.5 (CH), 126.1 (CH), 124.3 (C), 120.9 (C), 93.8 (C),
90.3 (C), 77.2 (C), 63.9 (CH2), 37.1 (CH2), 28.3 (CH3), 25.8 (CH3), 21.0
(CH3). [MþH]þ¼319.2060 (calcd for C23H27O¼319.2056).
NMR (300 MHz, CDCl3)
d 6.26 (1H, d, J 2.2, ]CH), 6.00 (1H, d, J
2.2, ]CH), 3.14 (3H, s, OCH3), 1.39 (6H, s, 2ꢁCH3). 13C NMR (75 MHz,
CDCl3)
d
127.1 (CH2), 122.7 (C), 78.3 (C), 50.7 (CH3), 25.5 (CH3).
4.17. (E)-ethyl 5-methyl-4-methylene-5-phenethoxyhex-2-
enoate (40)
4.14. 3-Butoxy-2-iodo-3-methylbut-1-ene (30, R[n-Bu)
Toa solution of 2-(2-iodo-1,1-dimethyl-allyloxy)-ethyl]-benzene8
To a stirred solution of allene 7 (39.6 mg, 0.581 mmol), DMF
(0.6 mL) and dry n-BuOH (0.53 mL, 5.8 mmol) at 0 ꢀC were added
(18.0 mg, 56.9
added Pd(OAc)2 (0.6 mg, 2.8
m
mol) and ethyl acrylate (0.024 mL, 0.23 mmol) were
m
mol), nBu4NCl (15.6 mg, 56.1 mol) and
m
(IPr)AuCl (36.0 mg, 58.0
(139 mg, 0.618 mmol). The reaction mixture was stirred for 20 h at
m
mol), AgOTf (14.9 mg, 58.0
m
mol) and NIS
sodium carbonate (14.8 mg, 0.140 mmol). The resulting mixture was
heated under a N2 atmosphere at 80 ꢀC for 18 h. The mixture was

1616
A. Heuer-Jungemann et al. / Tetrahedron 67 (2011) 1609e1616
18057; (b) Shintou, T.; Mukaiyama, T. J. Am. Chem. Soc. 2004, 126, 7359; (c)
Corma, A.; Renz, M. Angew. Chem., Int. Ed. 2007, 46, 298 and references cited
therein.
7. (a) Hadfield, M. S.; Lee, A.-L. Org. Lett. 2010, 12, 484; See also: (b) Bauer, J. T.;
Hadfield, M. S.; Glen, P. E.; Lee, A.-L. Org. Biomol. Chem. 2010, 8, 4090; (c) Bauer,
J. T.; Hadfield, M. S.; Lee, A.-L. Chem. Commun. 2008, 6405; (d) Kilpin, K. J.; Paul,
U. S. D.; Lee, A.-L.; Crowley, J. D. Chem. Commun. 2011, 328.
cooled to rt, diluted with ether and washed with water. The aqueous
layer was extracted with ether (ꢁ3), washed with brine and dried
(MgSO4). The product 40 was isolated using flash column chroma-
tography as a pale yellow oil (8.0 mg, 0.028 mmol, 50%). Rf¼0.26 (9:1
hexane/diethyl ether). nmax/cmꢂ1 1713 s (C]O), 1630 m (C]C), 1590
w, 1496 m, 1454 m (Ar C]C), 1275, 1179, 1067 s (CeO); 1H NMR
8. For a review on gold-catalysed reaction of alcohols, see: Muzart, J. Tetrahedron
2008, 64, 5815.
(300 MHz, CDCl3) d 7.34 (1H, d, J 16.0, COCH]CH), 7.30e7.16 (5H, m,
9. For selected recent reviews on gold-catalysis, see: (a) Li, Z.; Brouwer, C.; He, C.
Chem. Rev. 2008,108, 3239; (b) Bongers, N.; Krause, N. Angew. Chem., Int. Ed. 2008,
AreH), 6.35 (1H, d, J 16.0, COCH]CH), 5.50(1H, s, ]CH), 5.26(1H, s, ]
CH), 4.23 (2H, q, J 7.1, OCH2CH3), 3.38 (2H, J 7.6, OCH2CH2Ph), 2.81 (2H,
t, J 7.6, PhCH2),1.37 (6H, s, 2ꢁCH3),1.32 (3H, t, J 7.1, OCH2CH3).13C NMR
€
47, 2178; (c) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395; (d) Furstner, A.; Davies,
ꢁ
ꢁ
P. W. Angew. Chem., Int. Ed. 2007, 46, 3410; (e) Jimenez-Nunez, E.; Echavarren,
A. M. Chem. Commun. 2007, 333; (f) Hashmi, A. S. K. Chem. Rev. 2007,107, 3180; (g)
Shen, H. C. Tetrahedron 2008, 64, 3885; (h) Shen, H. C. Tetrahedron 2008, 64, 7847;
(i) Marion, N.; Nolan, S. P. Chem. Soc. Rev. 2008, 37, 1776.
(75 MHz, CDCl3) d 167.1 (C),149.1 (C),143.6 (CH),139.0 (C),129.0 (CH),
128.3(CH),126.1 (CH),120.6(CH),118.9 (CH2), 77.2(C), 64.1 (CH2), 60.4
(CH2), 37.0 (CH2), 26.4 (CH3), 14.3 (CH3). [MþNH4]þ¼306.2072 (calcd
for C18H24O3þNHþ4 ¼306.2064).
10. For examples of capture of vinylgold intermediates with iodine, see: (a) Schuler,
M.; Silva, F.; Bobbio, C.; Tessier, A.; Gouverneur, V. Angew. Chem., Int. Ed. 2008,
ꢁ
47, 7927; (b) Kirsch, S. F.; Binder, J. T.; Crone, B.; Duschek, A.; Haug, T. T.; Liebert,
C.; Menz, H. Angew. Chem., Int. Ed. 2007, 46, 2310; (c) Buzas, A.; Gagosz, F.
Synlett 2006, 2727; (d) Buzas, A.; Gagosz, F. Org. Lett. 2006, 8, 515; (e) Yu, M.;
Zhang, L. Org. Lett. 2007, 9, 2147; (f) Alcaide, B.; Almendros, P.; del Campo, T. M.
Angew. Chem., Int. Ed. 2007, 46, 6684; (g) Liu, L.-P.; Hammond, J. B. Chem. Asian J.
2009, 4, 1230.
Acknowledgements
We would like to thank the Nuffield Foundation for a Nuffield
Undergraduate Research Bursary (A.H.-J), ScotChem (M.S.H), EPSRC
and The Royal Society for funding and the EPSRC Mass Spectrom-
etry services at Swansea for analytical support. We thank Ursula
S.D. Paul for the synthesis of allene 26.
11. For an example of gold-catalysed intramolecular iodoalkoxylation of allenes,
see: Gockel, B.; Krause, N. Eur. J. Org. Chem. 2010, 311.
12. Georgoulis, C.; Smada, W.; Valery, J. M. Synthesis 1981, 572.
13. When the reaction was carried out with either 5 mol % or 15 mol % catalyst
added in one portion at the beginning, conversions were w70%. A reaction time
of 4 h versus 24 h seems to make no difference to the conversion. Therefore, the
catalyst was added in three portions as described in order to force the reaction
to completion.
Supplementary data
14. For example, see: (a) Takaya, J.; Iwasawa, N. J. Am. Chem. Soc. 2008, 130, 15254;
(b) Ngai, M. Y.; Skucas, E.; Krische, M. Org. Lett. 2008, 10, 2705; (c) Xu, D.; Lu, Z.;
Li, Z.; Ma, S. Tetrahedron 2004, 60, 11879 Commercially available allenes were
purchased from SigmaeAldrich.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.01.021.
ꢀ
15. Reaction with added 3 A MS to remove any adventitious water during the re-
action results in poor conversions.
References and notes
16. Commercially available from SigmaeAldrich. For a review on applications of
NHCeAu complexes, see: Marion, N.; Nolan, S. P. Chem. Soc. Rev. 2008, 37, 1776.
17. Commercially available from SigmaeAldrich. For development of PPh3AuNTf2
1. For some recent reviews, see: (a) Ma, S. Chem. Rev. 2005, 105, 2829; (b) Ma, S.
Aldrichimica Acta 2007, 40, 91; (c) Hoffman-Roder, A.; Krause, N. Angew. Chem.,
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Wiley-VCH: Weinheim, Germany, 2004.
ꢁ
see: Mezailles, N.; Richard, L.; Gagosz, F. Org. Lett. 2005, 7, 4133.
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1103; (e) Cui, D.-M.; Zheng, Z.-L.; Zhang, C. J. Org. Chem. 2009, 74, 1426.
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21. cf. Under our standard conditions (Table 1), the primary isomers of the products
shown were not detected by crude 1H NMR analysis (<5%), unless otherwise
stated. In addition, small amounts of the corresponding hydroalkoxylation
products (primary and tertiary allylic ethers, w12%) were also observed as by-
products using conditions shown in Scheme 6.
2. For representative examples, see: (a) Ma, S.; Xie, H. Tetrahedron 2005, 61, 251;
(b) Guo, H.; Qian, R.; Guo, Y.; Ma, S. J. Org. Chem. 2008, 73, 7934; (c) Gu, Z.;
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S. Acc. Chem. Res. 2009, 42, 1679.
€
3. For example, see: Lu, B.; Jiang, X.; Fu, C.; Ma, S. J. Org. Chem. 2009, 74, 438.
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(b) Trost, B. M.; McEachern, E. J.; Toste, F. D. J. Am. Chem. Soc. 1998, 120, 12702;
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allylic ethers), see: (a) Mitchell, T. A.; Bode, J. W. J. Am. Chem. Soc. 2009, 131,