Expedient syntheses of β-iodofurans by 5-endo-dig cyclisations

Article abstract of DOI:10.1002/ejoc.200700681

5-endo-dig cyclisations of 3-alkyne-1,2-diols using iodine as the electrophile proceed smoothly to deliver excellent yields of the corresponding β-iodofurans. The necessary precursors are available from a number of different approaches, notably regioselec

Full text of DOI:10.1002/ejoc.200700681

FULL PAPER
DOI: 10.1002/ejoc.200700681
Expedient Syntheses of β-Iodofurans by 5-endo-dig Cyclisations
Sean P. Bew,[a] Gamila M. M. El-Taeb,[a] Simon Jones,[a] David W. Knight,*[a] and
Wen-Fei Tan[a]
Keywords: Cyclisation / Iodocyclisation / Furans
5-endo-dig cyclisations of 3-alkyne-1,2-diols using iodine as
the electrophile proceed smoothly to deliver excellent yields
of the corresponding β-iodofurans. The necessary precursors
are available from a number of different approaches, notably
regioselective bis-hydroxylation of conjugated enynes and
the addition of acetylides to α-hydroxy carbonyl groups. The
initial iodofurans can be homologated using a number of
strategies, ranging from various transition metal-catalysed
couplings to halogen–metal exchange and subsequent coup-
ling with an electrophile. Hence, this method overall repre-
sents a flexible, relatively brief and very efficient approach
to a variety of highly substituted furans.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
sis of saturated heterocycles, that of overall 5-endo-trig cy-
clisations.[4] Although highly successful in many cases, the
latter type of cyclisation is disfavoured according to
Baldwin’s rules;[5] by contrast, 5-endo-dig processes are fav-
oured.
Despite this, and perhaps because at first sight, such cy-
clisations do not look viable because of the distance be-
tween the necessary reacting centres (Figure 1), there was
little activity in this area until very recently, notwithstand-
ing the existence of some earlier reports hinting at their via-
bility and potential.[6]
Introduction
Despite enormous advances in drug development and in
other endeavours involving applications of previously un-
known structures, such as in the design of new materials
and effect chemicals in general, heteroaromatic residues still
occupy a central position in all of these areas. Perhaps even
more surprising is that, even after over one hundred years
of development, there is still room and indeed a need for
the definition of more efficient or operationally simpler
routes to these important heterocycles. The current and fu-
ture demands of a more environmentally demanding pop-
ulation on the chemical industry in general only serve to
emphasise this. In broad terms, heteroaromatic targets are
obtained either by late formation of the heteroaromatic ring
from a complex acyclic precursor or by (multiple) function-
alisation of a simple or even parent heteroaromatic pre-
dominantly by using some of the myriad of electrophilic
substitution methods or by metallation strategies.[1] In this
respect, halogen substituents have always occupied a special
position by, for example, facilitating regioselective metalla-
tion using halogen–metal exchange.[2] However, this status
has been enhanced enormously by the development of a
whole host of predominantly palladium-catalysed coupling
methods which, collectively, represent a paradigm shift in
synthetic design over the past twenty years or so.[3] A most
attractive tactic in heteroaromatic synthesis therefore would
be to create the heterocycle at the same time as incorporat-
ing a halogen atom. We reasoned that this might be achiev-
able using 5-endo-dig halocyclisations of homopropargylic
systems, based on an extrapolation of what was emerging
as a useful synthetic strategy for the stereoselective synthe-
Figure 1. Electrophile-driven 5-endo-dig cyclisation.
Results and Discussion
We were also inspired to investigate the general area of
5-endo-dig cyclisations by what seemed to us to be a re-
markable key step in a synthesis of the antifungal pyrrol-
idine (+)-preussin (5), which involved a mercury(II)-induced
conversion of the ynone 3 into the pyrrolone 4, subsequent
reductions of which led to the target 5 (Scheme 1).[7] The
very fact that this central 5-endo-dig cyclisation works with
an electron-deficient alkyne and also that the single stereo-
genic centre in the precursor 3 remained unmolested as
far as the target 5 attested to a cyclisation procedure which
was both mild and favoured, a conclusion further sup-
ported by the survival of the N-Boc group. The latter func-
tion is, of course, well positioned to compete with nitrogen
[a] School of Chemistry, Cardiff University, Main College,
Park Place, Cardiff, CF10 3AT, UK
E-mail: knightdw@cf.ac.uk
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in a 6-exo reaction mode when presented with the nearby obvious limitations, an attraction of this approach is the
electron-deficient centre; the fact that it does not participate availability of the enynes 9 from Sonogashira coupling[10]
boded well for further developments of such 5-endo cyclisa- between a 1-alkyne 11 and a 1-halo-1-alkene 10, which can
tions.
often be derived most expediently from a second 1-alkyne
12, as well as using many other methods (Scheme 3).
Scheme 3.
This is illustrated by the efficient conversion of the di-
phenyl butenyne 13 into the syn-diol 14a in 78% isolated
yield (Scheme 4), which also provided some useful stereo-
chemical insights into the cyclisation (see below).
Scheme 1. i) Hg(OAc)2, ii) NaCl.
A few isolated examples of similar, mercury(II)-induced
furan syntheses from related 3-alkyne-1,2-diols have also
previously been reported in the Russian literature.[6] For a
viable furan synthesis, we needed to look beyond using mer-
cury(II) salts as the source of the necessary electrophilic
trigger for reasons of toxicity and practicality and obviously
we needed an alcohol group to act as a nucleophile in place
of the NHBoc function used in Scheme 1. Incorporation of
an additional hydroxy group, which we hoped would be lost
as water during an aromatisation step subsequent to cycli-
sation, then led to this idea of obtaining the iodofurans 8
from the 3-alkyne-1,2-diols 6, presumably via the dihy-
drofuran species 7, as shown in Scheme 2.
Scheme 4. i) K2OsO4·2H2O (cat.), K3Fe(CN)6 (xs), K2CO3 (xs),
MeSO2NH2, quinuclidine (cat.), tBuOH/H2O (1:1), 20 °C, 96 h
(78%).
All the diols shown in Scheme 5 were prepared in the
same manner from the corresponding (E)-enynes, specifi-
cally using the non-enantiomeric recipe for bis-hydroxyla-
tion developed by the Warren group.[11] The enynes were
obtained in turn from Sonogashira couplings of a 1-alkyne
and a 1-bromoalkene, all of which are commercially avail-
able.
Scheme 2.
We chose to use iodine, partly because it had been so
successful in triggering our 5-endo-trig cyclisations leading
to β-iodotetrahydrofurans[4] and partly because, if the pro-
posed cyclisations proved successful, then the iodofuran
products 8 would be highly amenable to subsequent homol-
ogation using a wide range of metallation reactions, as ar-
gued above. Herein, we report in full the successful outcome
of the chemistry shown in Scheme 2, a few of its limitations
and its application to the formation of highly substituted
furans.[8]
Scheme 5. i) I2 (3.3 equiv.), NaHCO3 (3.3 equiv.), MeCN, 0–20 °C,
1 h.
Success in the key cyclisation step (Scheme 5) turned out
to be readily achieved using conditions employed previously
Although there are many possibilities for the synthesis of in our 5-endo-trig cyclisations.[4] The diols 14 were stirred
the necessary starting diols 6, initially we chose to employ with slightly over three equivalents of iodine in acetonitrile
a single approach, that of the highly regioselective bis-hy- containing three equivalents of sodium hydrogen carbonate,
droxylation of a disubstituted conjugated enyne 9, a very initially with ice-water cooling but subsequently without
useful method highlighted by the Sharpless group.[9] Within cooling. Under these conditions, the cyclisations were com-
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β-Iodofurans by 5-endo-dig Cyclisations
plete in around one hour and delivered good to excellent as both substrates 17a and 17b underwent equally smooth
isolated yields of the β-iodofurans 15. In subsequent experi- iodocyclisation to give the iodofurans 18a and 18b in excel-
ments, we found that dichloromethane or tetrahydrofuran lent yields; again, losses due to product volatility were a
could equally well be used as the solvent. Workup consisted factor. However, the fact that these two products both con-
of reduction of the excess iodine using aqueous sodium sul- tained an α-free position meant that they were more prone
fite (or, less conveniently due to its substantially lower solu- to subsequent electrophilic substitution by the residual mo-
bility in water, thiosulfate), followed by an aqueous wash lecular iodine. For example, when a cyclisation reaction of
and straightforward chromatography. Isolated yields were the hexynyl-derived diol 17a was stirred for three hours
generally in excess of 80%, with the major losses largely rather than the usual one hour, significant quantities (ca.
due to product volatility.
20% of the total product) of the diiodofuran 19 were de-
1
The requirement for at least three equivalents of iodine tected by both GC-MS and H NMR analysis. This was
is essential; using less results in incomplete conversion. This almost completely avoided by reaction workup as soon as
is a common phenomenon throughout these and related the cyclisation was completed.
iodolactonisations and iodoetherifications in general when
using molecular iodine and has, to the best of our knowl-
edge, not been explained.[12] We assume that such an excess
is necessary to generate a particularly reactive and/or suit-
able electrophilic species, perhaps iodonium pentaiodide,
I·I5, based on the need for three equivalents. Of course, this
requirement does rather detract from the overall efficiency
of the scheme, especially seriously if it were to be applied
on a large scale. However, this brief sequence does other-
wise arrive at useful substituted furans, which would usually
dition of 2.1 equivalents of lithiated 1-hexyne directly to
be tricky to prepare in comparable yields and in so few
steps using alternative methods.
While these examples all worked well, we were however
hydrogen carbonate to give an excellent yield of the fully
concerned that each contained a secondary alcohol group
that underwent (eventual) elimination to give the heteroaro-
We were also successful in extending the methodology to
include fully substituted examples. Thus, the adduct 21a,
formed as essentially a single diastereoisomer by the ad-
benzoin 20, underwent similarly smooth cyclisation upon
exposure to three equivalents each of iodine and sodium
substituted iodofuran 22a (Scheme 7).
matic system (Scheme 5). This was evidently an extremely
facile step under the condition used as, despite many
attempts using 1H NMR monitoring, we were never able to
obtain any unambiguous evidence for the existence of the
dihydrofurans 7 (Scheme 2). In view of this, we were some-
what concerned that a tertiary alcohol might be too sensi-
tive to allow smooth cyclisation as shown in Scheme 2. To
test this, we used an alternative general approach for pre-
cursor synthesis, that of the addition of an acetylide to an
O-protected α-hydroxy ketone or aldehyde, which of course
also served the purpose of adding flexibility to this overall
Scheme 7. i) [21a, 21b] 2.1 equiv. RCCLi, THF, –78 °C to 0 °C
approach to iodofurans (Scheme 6).
[68%; 77%]; ii) [21c] TBAF, THF, 0 °C, 20 min. [80%]; iii) 2-iodo-
thiophene, Pd(PPh3)4, Et2NH, 20 °C, 16 h [81%]; iv) as Scheme 5
[22a: 93%; 22b: 71%].
A similarly stereoselective addition of lithiated trimethyl-
silylacetylene to benzoin (20) also gave a decent yield of the
expected adduct 21b, which was desilylated by brief expo-
sure to tetrabutylammonium fluoride (TBAF) in tetra-
hydrofuran. The resulting diol 21c then underwent a
smooth Sonogashira coupling with 2-iodothiophene to give
the anticipated homologue 21d, which then also underwent
Scheme 6. i) [17a] RCCLi, THF, 0 °C, 2 h then TBAF, THF [89%];
smooth conversion into the corresponding β-iodofuran 22b
ii) [17b] as i) then pTSA, MeOH, 20 °C, 2 h [71%]; iii) as Scheme 5
under the same conditions.
[18a: 82%; 18b: 61%].
Two caveats follow: firstly, it was both more time- and
In the first examples aimed at extending the range to atom-efficient to employ one equivalent of acetylide to de-
substrates having tertiary alcohol functions, lithiated al- protonate the benzoin prior to addition of the second
kynes were added to the protected hydroxyacetone deriva- equivalent to the ketone than to protect the benzoin hy-
tives 16; subsequent standard deprotection then gave the droxy as, for example, a tert-butyldimethylsilyl ether. This
alkynediols 17 in good yields. Our fears proved groundless, is generally true in cases where the acetylene is reasonably
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FULL PAPER
volatile and completely removed upon evaporation of the
final reaction workup; presumably, on a large scale, this ex-
cess could even be recovered and recycled. A second caveat
concerns the diol stereochemistry: we were surprised to
note that the diol 21a was isolated as essentially a single
diastereoisomer (ca. 99:1). We have not yet determined the
stereochemistry of the major isomer, as this was not espe-
cially irrelevant to the central iodocyclisation (but see be-
low). We are currently following up this observation in a
separate study, which will be reported shortly. The presence
of the thiophene residue evidently had no deleterious effect
upon the iodocyclisation, as far as we could tell. However,
we did uncover one limitation of the present iodocyclisation
methodology: it appears that terminal alkyne groups do not
participate. Thus, attempts to cyclise the terminal alkyne
21c failed to provide the iodofuran 23 (Scheme 8).
Scheme 9. i) TMSCCLi, THF, –78 °C to 0 °C [78%]; ii) TBAF,
THF, 20 min. [68%]; iii) 2-iodofuran, CuI (cat.), Pd(PPh3)4 (cat.),
Et2NH, 20 °C, 16 h [74%]; iv) 3I2, 3NaHCO3, dry EtOAc, 20 °C,
1 h [25%].
the intermediates and final product just too sensitive. Fu-
ture efforts in this direction will therefore begin with the
furoins derived from precursors such as 5-phenyl- or 5-
alkyl-2-furancarboxaldehydes.
A final idea was to attempt to obtain iodofurans 32 from
the 2-silyloxy or 2-hydroxy esters 30, as shown in
Scheme 10. Clearly, the intermediate diols 31 will contain
two identical alkyne substituents and hence the products 32
will be “pseudosymmetrical”. At the outset, it was far from
clear if the second alkyne unit would survive or would inter-
fere with the cyclisation in some way.
Scheme 8.
It occurred to us that a continuation of this theme of
incorporating heterocycles onto the furan could be taken to
an interesting extreme by a synthesis of tetra(2-furyl)furan
(24), a novel chromophore, which might display some useful
properties; it would also be interesting to determine its
lower energy conformations, both in the solid state and in
solution. Obviously, the conformation shown (24) is drawn
simply for style and may well not represent the real orienta-
tion of the furan rings.
In the event, condensation of furoin (25) with lithiated
trimethylsilylacetylene followed by desilylation gave a re-
spectable return of the alkyne diol 26 (Scheme 9).
This proved to be a rather delicate molecule which never-
theless underwent smooth Sonogashira coupling with 2-
iodofuran, fortunately at ambient temperature, to give the
trifuryl derivative 27. The key 5-endo-dig iodocyclisation
was successful after a fashion and gave the expected iodofu-
ran 28 but as a very unstable oil in poor yield, almost cer-
tainly due to product decomposition during both the cycli-
sation and purification steps. Unfortunately, a number of
attempts at a final Suzuki coupling step using 2-furyl-
boronic acid gave variable yields of the deiodinated trifuryl-
furan 29 as the only isolable product. In retrospect, perhaps
a more successful strategy to obtain the target chromophore
24 would have been to use 5-substituted furans throughout
Scheme 10. i) 2 (R = TBS) or 3 (R = H) equiv. R2CCLi, THF,
the sequence, as the unsubstituted furan α-positions render –78 °C, 1 h; ii) 3 I2, 3 NaHCO3, MeCN, 20 °C, 1 h.
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β-Iodofurans by 5-endo-dig Cyclisations
In the event, both the acetylide condensations with the
2-substituted esters 30 and the key iodocyclisations worked
very smoothly in most examples carried out; the results are
summarised in Scheme 10. Once again, the seemingly
wasteful tactic of reacting some 2-hydroxy esters directly
with, now, just over three equivalents of an acetylide,
proved viable and arguably more atom efficient that em-
ploying a protecting group strategy. However, when an O-
silyl group such as tert-butyldimethylsilyl was used, the
finding that its presence hardly affected the rate of the iodo-
cyclisation step obviated the requirement for a separate de-
protection step, thereby offering an alternative method for
abbreviating the overall sequence.
This in situ deprotection tactic will very likely be success-
ful in the case of a number of alternative hydroxy protecting
groups, such as other silyl functions, O-benzyl, OPMB and
possibly O-allyl, amongst others. Overall, however, the
yields of iodofurans recovered from cyclisations of dialk-
ynyl diols (Entries 5–8, Scheme 10) were up to 10% higher
that the corresponding reactions of the O-silyl derivatives,
possibly due to some removal of the necessary excess of
iodine by reaction(s) with the silicon residues. This not un-
reasonable observation came to an extreme in the case of
the adduct formed between O-silylmandelate and 1-hexyne
(Entry 2), when the O-silyl derivative refused to cyclise; in
Scheme 11.
Scheme 12. i) PhSeCl, K2CO3, THF, –78 0C, 5 h [29%].
contract, the corresponding diol underwent highly efficient bonate, the β-selanylfuran 37 was isolated in 29% yield. We
cyclisation (Entry 6). No products resulting from the ad- suggest that optimisation will prove feasible.
dition of iodine or from any other reactions with the re-
maining alkyne group were observed in any of the examples has been considerable activity in the general area of 5-endo-
quoted.
dig cyclisations[4] triggered by halogens in particular. Re-
Since our initial report of this type of cyclisation,[8] there
Some comments on the stereochemistry of these cyclisa- lated iodocyclisations using different precursors leading to
tions are perhaps appropriate. Our first reactions were car- furans and ring-fused derivatives have been developed.[13]
ried out using single syn-diastereoisomers of the alkynediols Unassisted by a subsequent dehydration step, 5-endo-dig cy-
derived from stereochemically pure (E)-enynes. However, clisations have also proven especially effective in the direct
subsequently some examples, such as diols 14d and 14e synthesis of β-iodo-benzothiophenes,[14] -benzofurans[15]
were prepared as diastereoisomeric mixtures when we and -indoles.[16] Similarly, β-iododihydropyrroles and iodo-
started with a commercial E/Z mixture of 1-bromopropene pyrroles can be obtained from homopropargylic sulfon-
[ca. 2:1 in favour of the (Z)-isomer]. We were therefore able amides by iodocyclisation followed by various elimination
to correlate and confirm which isomer was which in the steps.[17] Two further and very significant development have
diol mixture. We noted that the syn-isomers 33 underwent been the use of aryl rings as the nucleophilic components
significantly faster cyclisation in a mixed sample, by stop- of such cyclisations and the general usage of metallic spe-
ping the reaction before completion. This is consistent with cies to trigger 5-endo-dig cyclisations in general. These now
the intermediacy of conformation 34, wherein hydrogen form a considerable body of methodology, very recently ex-
bonding may also assist in the cyclisation process emplified and summarised by the Larock group.[18] Hence,
(Scheme 11). The resulting unobserved dihydrofurans 35 this general type of cyclisation can now be regarded as a
are then especially well set up for the final E2 elimination generally useful synthetic method. The present approach to
of water, which may also contribute to faster formation of β-iodofurans exemplifies this and has potential as a general
the final iodofuran from these syn-isomers. Similarly, we furan synthesis. The necessary precursors can be readily ob-
would therefore anticipate that the related geometry 36 tained by at least two distinct and direct routes: the regio-
might be involved in cyclisations of the bis-alkynes 31, specific bis-hydroxylation of enynes or the addition of ace-
which might therefore proceed via the dihydrofurans 37.
tylides to α-alkoxycarbonyls. Of course, alternatives exist
There may, of course, be other electrophiles which could for the synthesis of such 3-alkyne-1,2-diols, the viability of
be equally successful in inducing such 5-endo cyclisations. which will often depend on the desired substitution pattern.
A single example, albeit not an especially efficient one, indi- The β-iodofurans themselves are best viewed as intermedi-
cates that selenocyclisations could be developed into useful ates towards many types of highly substituted derivatives,
transformations in this area (Scheme 12). When the alkynyl accessible by replacing the iodine using a Pd0- or Ni0-cata-
diol 14a was treated with phenylselanyl chloride at –78 °C lysed coupling reaction,[3] by halogen–metal exchange or by
for five hours in tetrahydrofuran-containing potassium car- radical generation.
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S. P. Bew, G. M. M. El-Taeb, S. Jones, D. W. Knight, W.-F. Tan
122.5 (C), 127.6 (2 CH), 128.7 (4 CH), 132.0 (2 CH), 139.5 (C)
FULL PAPER
Experimental Section
ppm. IR (CHCl ): ν = 3440, 2940, 1650, 1444, 1380, 1080 cm–1.
˜
3
HRMS: (APCI): calcd. for C16H15O2 239.1072 (M+ + H); found
239.1076. C16H14O2 (238.29): calcd. C 80.65, H 5.9; found C 80.65,
H 6.1.
General Remarks: NMR spectra were recorded with a Bruker WM
or DPX spectrometers, operating at 250 MHz or 400 MHz respec-
tively for 1H spectra and at 67.5 MHz or 100.6 MHz for 13C spectra
respectively. Unless stated otherwise, NMR spectra were measured
using dilute solutions in deuteriochloroform. All NMR measure-
ments were carried out at 30 °C and chemical shifts are reported
as ppm on the delta scale downfield from tetramethylsilane (TMS:
Iodocyclisation: General Procedure for Scales Less Than ca. 2 g of
Alkynediol: Sodium hydrogen carbonate (3.3 equiv.) was added to
dry acetonitrile (3 mL/mmol–1 of alkynediol), stirred under dry ni-
trogen and cooled in an ice-water bath, followed by the alkynediol
(1 equiv.). After stirring for 5 min, solid iodine (3.3 equiv.) was
added in one portion and, after a further 5 min, the cooling bath
was removed and stirring continued until tlc analysis indicated
complete reaction (ca. 1 h). Aqueous 10% sodium sulfite was then
added dropwise until the excess iodine colour was completely dis-
charged (ca. 3 mL/mmol of iodine), followed by ether (5 mL/mmol
of alkynediol). The two layers were separated and the aqueous layer
extracted with diethyl ether (2ϫ5 mL/mmol of alkynediol). The
combined organic solutions were washed with water (2ϫ equal vol-
ume) and brine (1ϫ equal volume) then dried (MgSO4), filtered
and carefully evaporated. The essentially pure product could then
be further purified by filtration through silica gel using 5% ether
in pentane, distillation or crystallisation, as appropriate.
δ = 0.00 ppm) or relative to the resonances of CHCl3 (δH
=
7.27 ppm in proton spectra and δC = 77.0 ppm for the central line
of the triplet in carbon spectra respectively). Coupling constants
(J) are reported in Hz. Infrared spectra were recorded as thin films
for liquids and as nujol mulls for solids, using a Perkin–Elmer 1600
series FTIR spectrophotometer and sodium chloride plates. Low
resolution mass spectra were obtained using a VG Platform II Qua-
drupole spectrometer operating in the electron impact (EI; 70 eV)
or atmospheric pressure chemical ionisation (ApcI) modes, as
stated. High resolution mass spectrometric data was obtained from
the EPSRC Mass Spectrometry Service, University College, Swan-
sea, using the ionisation modes specified. Melting points were de-
termined with a Kofler hot-stage apparatus and are uncorrected.
Elemental analyses were obtained using a Perkin–Elmer 240C Ele-
mental Microanalyser.
On scales larger than around two grams, the production of heat
caused by the sudden single addition of solid iodine should be con-
trolled either by portionwise addition of the solid with temperature
monitoring or by adding the halogen dropwise after dissolution in
a minimum of acetonitrile.
All reactions were conducted in oven-dried apparatus under dry
nitrogen unless otherwise stated. All organic solutions from aque-
ous workups were dried by brief exposure to dried magnesium sul-
fate, followed by gravity filtration. The resulting dried solutions
were evaporated using a Büchi rotary evaporator under water aspi-
rator pressure and at ambient temperature unless otherwise stated.
Column chromatography was carried out using Merck Silica Gel
60 (230–400 mesh). TLC analyses were carried out using Merck
silica gel 60 F254 pre-coated, aluminium-backed plates, which were
visualized using ultraviolet light or potassium permanganate or
ammonium molybdenate sprays.
All of the following preparations of iodofurans 15 were carried out
on 3–5 mmol scales a number of times in each case. Yields quoted
are an average of those obtained using the specified conditions;
variations were typically around 5–8%.
3-Iodo-2,5-diphenylfuran (15a): By the foregoing general procedure,
the alkynediol 14a was converted into the iodofuran 15a (60%), a
1
yellow crystalline solid (from ether/hexane), m.p. 84 °C. H NMR:
“Ether” refers to diethyl ether and petroleum ether to the fraction
with boiling range 60–80 °C, unless stated otherwise.
δ = 6.88 (s, 1 H, 4-H), 7.30–7.62 (m, 6 H), 7.77 (dd, J = 7.0, 1.8 Hz,
2 H), 8.15 (dd, J = 7.0, 1.8 Hz, 2 H) ppm. 13C NMR: δ = 62.8 (3-
CI), 115.8 (4-CH), 123.9 (2 CH), 126.1 (2 CH), 128.1 (CH), 128.2
(CH), 128.4 (2 CH), 128.8 (2 CH), 129.6 (C), 130.2 (C), 151.1 (C),
The enynes 13 were prepared by Sonogashira coupling,[10,19] fol-
lowed by regiospecific bis-hydroxylation, using the method devel-
oped by Sharpless,[9] to obtain the 3-alkyne-1,2-diols 14. As an al-
ternative in the latter step, the “racemic” method reported by the
Warren group[11] was also used in some cases. A typical example
of the latter method is as described below.
154.0 (C) ppm. IR (film): ν = 3081, 3065, 1606, 1585, 1489, 1440,
˜
1117, 946, 762, 688 cm–1. MS (EI): m/z (%) = 346 (65) [M+], 202
(23), 191 (38), 113 (20), 105 (73), 77 (100), 57 (61). C16H11IO
(346.17): calcd. C 55.5, H 3.2; found C 55.7, H 3.2.
2-Butyl-3-iodo-5-phenylfuran (15b): By the general procedure, iodo-
cyclisation of the alkynediol 14b gave the expected product [71%]
as a yellow oil, which could be distilled with some loss to give the
iodofuran 15b as a pale yellow oil, b.p. 70–85 °C (oven temp.) at
(1RS,2RS)-1,4-Diphenylbut-3-yne-1,2-diol (14a): Potassium ferri-
cyanide (9.72 g, 29.62 mmol), potassium osmate(IV) dihydrate
(0.08 g), potassium carbonate (4.08 g, 29.56 mmol), methanesul-
fonamide (0.946 g, 9.94 mmol) and quinuclidine (0.07 g)[11] were
added to a stirred mixture of tert-butyl alcohol (50 mL) and water
(50 mL), followed by the (E)-1,4-diphenylbut-1-en-3-yne (13)
(2.01 g, 9.85 mmol). The resulting mixture was stirred at ambient
temperature for 96 h, then sodium sulfite (15.05 g, 5.96 mmol) was
added and stirring continued for 1 h. The bulk of tert-butyl alcohol
was then evaporated and the residual slurry extracted with dichlo-
romethane (3ϫ100 mL). The combined extracts were washed with
2  aqueous potassium hydroxide (20 mL), water (20 mL) and
brine (20 mL) then dried and evaporated to leave a solid yellow
residue which was purified by short column chromatography (5%
MeOH in chloroform) and crystallisation from CHCl3/petroleum
ether to give the diol 14a (1.83 g, 78%) as a pale yellow solid, m.p.
125–6 °C. 1H NMR: δ = 4.38 (d, J = 8.0 Hz, 1 H), 4.61 (d, J =
8.0 Hz, 1 H), 7.00–7.21 (m, 8 H), 7.30 (d, J = 6.5 Hz, 2 H) ppm.
1
1 Torr. H NMR: δ = 0.90 (t, J = 7.3 Hz, 3 H, 4Ј-Me), 1.32 (hex,
J = 7.3 Hz, 2 H, 3Ј-CH2), 1.63 (pent, J = 7.3 Hz, 2 H, 2Ј-CH2),
2.69 (t, J = 7.3 Hz, 2 H, 1Ј-CH2), 6.56 (s, 1 H, 4-H), 7.18–7.23 (m,
1 H), 7.29–7.35 (m, 2 H), 7.51 (dd, J = 7.0, 1.2 Hz, 2 H, 2 o-H)
ppm. 13C NMR: δ = 13.9 (Me), 22.2, 27.2, 30.3, 64.0 (3-CI), 112.4
(4-CH), 123.5 (2 CH), 127.5 (CH), 128.7 (2 CH), 130.2 (C), 153.4
(C), 156.6 (C) ppm. IR (film): ν = 1555, 1483, 1441, 1009, 747 cm–1.
˜
MS (EI): m/z (%) = 326 (1) [M+], 286 (5), 285 (18), 131 (12), 105
(92), 84 (20), 77 (100), 57 (48). C14H15IO (326.18): calcd. C 51.55,
H 4.6; found C 51.6, H 4.6.
5-Butyl-3-iodo-2-phenylfuran (15c): By the general procedure, iodo-
cyclisation of the isomeric alkynediol 15c gave the iodofuran 15c
[77%] as a yellow oil which showed 1H NMR: δ = 0.99 (t, J =
7.4 Hz, 3 H, 4Ј-Me), 1.43 (hex, J = 7.4 Hz, 2 H, 3Ј-CH2), 1.71
13C NMR: δ = 68.4 (CHOH), 77.9 (CHOH), 86.9 (C), 87.5 (C), (pent, J = 7.4 Hz, 2 H, 2Ј-CH2), 2.76 (t, J = 7.4 Hz, 2 H, 1Ј-CH2),
5764
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5759–5770

β-Iodofurans by 5-endo-dig Cyclisations
6.64 (s, 1 H, 4-H), 7.27 (app. t, J = 7.4 Hz, 1 H, p-CH), 7.39 (app. = 156 (18) [M+], 84 (40), 77 (70), 76 (100), 68 (42). HRMS: calcd.
t, J = 7.9 Hz, 2 H, 2 m-H), 7.61 (dd, J = 7.1, 1.3 Hz, 2 H, 2 o-H)
ppm. 13C NMR: δ = 13.7 (4Ј-Me), 22.1, 27.2, 30.3, 64.0 (3-CI),
112.4 (4-CH), 123.4 (2 CH), 127.4 (2 CH), 128.6 (CH), 130.1 (C),
for C9H16O2 156.1150; found 156.1150.
2-Butyl-3-iodo-4-methylfuran (18a): Iodocyclisation of the forego-
ing diol 17a (0.78 g, 5.0 mmol) using the general procedure gave
the iodofuran 18a (1.09 g, 82%) as a volatile, yellow oil. H NMR:
δ = 0.82 (t, J = 7.0 Hz, 3 H, 4Ј-Me), 1.12–1.28 (m, 2 H), 1.50–1.58
(m, 2 H), 1.85 (d, J = 1.0 Hz, 4-Me), 2.59 (distorted t, J = 7.0 Hz,
1Ј-CH2), 7.11 (q, J = 1.0 Hz, 5-H) ppm. 13C NMR: δ = 11.7 (Me),
14.3 (Me), 22.5 (CH2), 27.9 (CH2), 30.5 (CH2), 70.0 (3-CI), 123.7
153.4 (C), 156.5 (C) ppm. IR (film): ν = 1560, 1490, 1450, 1020,
˜
1
750 cm–1. m/z 326 (M+, 7%), 285 (31), 131 (21), 105 (100), 77 (94),
57 (56).
3-Iodo-5-methyl-2-phenylfuran (15d): By the general procedure,
iodocyclisation of the alkynediol 14d[20] gave the iodofuran 15d as
a yellow oil [88%]. 1H NMR: δ = 2.36 (s, 3 H, 5-Me), 6.25 (s, 1 H,
4-H), 7.28–7.34 (m, 1 H, p-CH), 7.38–7.48 (m, 2 H, 2 m-H), 7.94–
8.02 (m, 2 H, 2 o-H) ppm. 13C NMR: δ = 13.4 (5-Me), 61.2 (3-CI),
116.4 (4-CH), 125.8 (2 CH), 127.7 (CH), 128.3 (2 CH), 130.4 (C),
(4-C), 137.6 (5-CH), 157.0 (2-C) ppm. IR (film): ν = 2954, 1602,
˜
1551, 1458, 1380, 1272, 1122, 1022, 957, 907, 735 cm–1. MS (EI):
m/z (%) = 264 (50) [M+], 221 (100), 137 (55), 95 (30), 77 (10), 66
(34), 65 (63). HRMS: calcd. for C9H13IO 264.0011; found
264.0009.
150.3 (C), 152.8 (C) ppm. IR (film): ν = 3081, 3052, 1593, 1544,
˜
1483, 1448, 1221, 1083, 1071 cm–1. MS (EI): m/z (%) = 285 (18)
[M+ + H], 284 (100), 157 (10), 129 (35), 128 (17), 114 (15). MS
(CH4-CI): m/z (%) = 285 (100) [M+ + H], 159 (85), 58 (83). HRMS:
calcd. for C11H10IO 284.9776; found 284.9772.
After a longer reaction time, beyond 2 h, significant quantities of
the iodination product, 2-butyl-3,5-diiodo-4-methylfuran (19) be-
gan to be formed, according to GC-MS analysis: MS (EI): m/z (%)
= 390 (58) [M+], 347 (100) [M+ – Pr], 319 (43) [M+ – Pr – CO],
263 (5) [M+ – I], 235 (19) [M+ – ICO], 192 (16) [M+ – Pr – ICO],
136 (82) [M+ – 2I], 93 (22) [M+ – 2I – Pr], 77 (30), 65 (96). Its
2-Butyl-3-iodo-5-methylfuran (15e): By the general procedure, iodo-
cyclisation of the alkynediol 14e gave the iodofuran 15e [65%] as
1
presence could also be detected by H NMR analysis of the crude
1
a pale yellow oil. H NMR: δ = 0.88 (t, J = 7.3 Hz, 3 H, 4Ј-Me),
product and was best quantified by the reduced integration of the
5-H resonance, relative to that of the combined integration of its
4-Me resonance and that of 18a.
1.28 (hex, J = 7.3 Hz, 2 H, 3Ј-CH2), 1.50 (pent, J = 7.3 Hz, 2 H,
2Ј-CH2), 2.19 (s, 3 H, 5-Me), 2.54 (t, J = 7.3 Hz, 2 H, 1Ј-CH2),
5.86 (s, 1 H, 4-H) ppm. 13C NMR: δ = 13.5 (Me), 13.8 (Me), 22.1,
27.0, 30.4, 62.1 (3-CI), 112.8 (4-CH), 151.6 (C), 155.1 (C) ppm. IR
2-Methyl-4-phenylbut-3-yne-1,2-diol (17b): Butyllithium (34.4 mL
of a 1.6  solution in hexanes, 55 mmol) was added dropwise to a
stirred solution of phenylacetylene (5.10 g, 50 mmol) in tetra-
hydrofuran (80 mL) maintained at 0 °C. After 0.5 h, 1-(tetra-
hydropyran-2-yloxy)-2-propanone (16b) (9.48 g, 60 mmol) was
added and the resulting mixture stirred at 0 °C for 2 h then
quenched by the careful addition of water (20 mL). The resulting
mixture was extracted with diethyl ether (3ϫ50 mL) and the com-
bined extracts washed with water (40 mL) then dried, filtered and
the solvents evaporated. The residue was dissolved in methanol
(20 mL) containing p-toluenesulfonic acid monohydrate (1.0 g) and
the resulting solution stirred at ambient temperature for 2 h, then
diluted with diethyl ether (20 mL), washed with brine (40 mL),
dried, filtered through a small plug of silica gel and the solvents
evaporated. Crystallisation of the residue from hexane/ether gave
the alkynediol 17b (7.50 g, 71%) as a pale yellow, crystalline solid,
(film): ν = 1600, 1542, 1455, 1380, 1265, 1130, 1020, 960, 910,
˜
735 cm–1. MS (EI): m/z (%) = 264 (77) [M+], 221 (100), 137 (70),
95 (20), 77 (10), 66 (40), 65 (73). HRMS: calcd. for C9H13IO
264.0011; found 264.0012.
Methyl 4-Iodo-5-phenylfuran-2-carboxylate (15f): By the general
procedure, iodocyclisation of alkynediol 14f gave the iodofuran 15f
1
[47%] as a yellow oil. H NMR: δ = 3.91 (s, 3 H, OMe), 7.35 (s, 1
H, 3-H), 7.40–7.49 (m, 3 H), 8.04–8.08 (m, 2 H) ppm. 13C NMR:
δ = 52.1 (OMe), 61.7 (4-CI), 127.1 (2 CH), 127.8 (CH), 128.5 (2
CH), 129.0 (C) ppm. 129.5 (CH), 144.2 (C), 155.3 (C), 158.3 (C)
ppm. IR (film): ν = 1695 cm–1. MS (EI): m/z (%) = 328 (53) [M+],
˜
241 (14), 173 (13), 145 (54), 114 (100), 113 (43). HRMS: calcd. for
C12H9IO3 327.9596; found 327.9599.
2-Methyl-3-octyne-1,2-diol (17a): Butyllithium (11.3 mL of a 1.6 
solution in hexanes, 18.1 mmol) was added dropwise to a stirred
solution of 1-hexyne (1.48 g, 18.1 mmol) in tetrahydrofuran
(80 mL) cooled in an ice-water bath. After 0.5 h, 1-(tert-butyldi-
phenylsilyloxy)-2-propanone (16a, 4.57 g, 18.1 mmol)[21] diluted
with tetrahydrofuran (3 mL) was slowly added and the resulting
solution stirred for a further 2 h, then quenched by the addition of
water (20 mL). The resulting mixture was extracted with diethyl
ether (3ϫ50 mL) and the combined extracts washed with water
(40 mL) and brine (40 mL) then dried, filtered and the solvents
evaporated. The residue, a dark yellow liquid (5.6 g), was immedi-
ately dissolved in a 1  solution of tetrabutylammonium fluoride
(20 mL) and the resulting solution stirred at ambient temperature
for 48 h then evaporated. The residue was separated using silica gel
column chromatography, eluting with 5% methanol in chloroform
m.p. 105–106 °C [ref.[22] m.p. 109.5 °C]. H NMR: δ = 1.55 (s, 3 H,
1
2-Me), 3.62 (d, J = 11.0 Hz, 1 H, 1-Ha), 3.80 (d, J = 11.0 Hz, 1 H,
1-Hb), 7.25–7.35 (m, 3 H), 7.42 (d, J = 6.4 Hz, 2 H) ppm. 13C
NMR: δ = 19.6 (Me), 68.1 (C), 71.0 (1-CH2), 84.7 (C), 90.9 (C),
122.0 (C), 127.4 (2 CH), 127.7 (CH), 131.2 (2 CH) ppm. IR (film):
ν = 3556, 1339, 1460, 1401, 1287, 1050, 972, 778 cm–1. MS (EI):
˜
m/z (%) = 176 (8) [M+], 158 (28), 145 (100), 129 (35), 115 (45), 102
(35), 84 (45), 71 (42). C11H12O2 (176.21): calcd. C 75.0, H 6.9;
found C 75.0, H 7.1.
3-Iodo-4-methyl-2-phenylfuran (18b): Iodocyclisation of the alkyne-
diol 17b (0.85 g, 4.82 mmol) following the general procedure, but
with tetrahydrofuran (10 mL) as solvent in place of acetonitrile and
the usual workup provided the iodofuran 18b (0.83 g, 61%) as a
colourless crystalline solid, m.p. 83–4 °C (ether/hexane). 1H NMR:
δ = 2.05 (d, J = 1.0 Hz, 1 H, 4-Me), 7.34–7.41 (m, 2 H, p-H, 5-H),
1
to give the diol 17a (2.50 g, 89%)[22] as a colourless oil. H NMR:
δ = 0.85 (t, J = 7.0 Hz, 3 H, 8-Me), 1.33–1.40 (m, 2 H, 7-CH2), 7.45–7.51 (m, 2 H, 2 m-H), 8.05 (d, J = 7.0 Hz, 2 o-H) ppm. 13C
1.43–1.51 (m, 2 H, 6-CH2), 1.80 (s, 3 H, 2-Me), 2.25 (t, J = 7.0 Hz, NMR: δ = 12.3 (4-Me), 69.4 (3-CI), 126.2 (C), 126.6 (2 CH), 128.5
2 H, 5-CH2), 3.38 (d, J = 11.0 Hz, 1 H, 1-Ha), 3.52 (d, J = 11.0 Hz,
1 H, 1-Hb) ppm. 13C NMR: δ = 13.9 (8-Me), 18.6 (7-CH2), 22.3
(6-CH2), 25.9 (2-Me), 31.0 (5-CH2), 69.0 (1-CH2), 69.9 (C), 81.9
(CH), 128.9 (2 CH), 131.0 (C), 138.6 (5-CH), 152.1 (C) ppm. IR
(film): ν = 3062, 1587, 1537, 1473, 1380, 1272, 1129, 1022, 914,
˜
764 cm–1. MS (EI): m/z (%) = 284 (88) [M+], 157 (15), 129 (85),
128 (95), 127 (100), 102 (45), 76 (62), 73 (42). C11H9IO (284.10):
calcd. C 46.5, H 3.2; found C 46.9, H 3.2.
(C), 85.7 (C) ppm. IR (film): ν = 3400, 2962, 2933, 2246, 1652,
˜
1458, 1373, 1158, 1115, 1050, 950, 914, 728 cm–1. MS (EI): m/z (%)
Eur. J. Org. Chem. 2007, 5759–5770
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5765

S. P. Bew, G. M. M. El-Taeb, S. Jones, D. W. Knight, W.-F. Tan
FULL PAPER
1,2-Diphenyloct-3-yne-1,2-diol (21a): 1-Hexyne (2.3 mL, 20 mmol)
2918, 1456, 1377, 1216, 1193, 1137, 1082, 1060, 954, 833, 757 cm–1.
MS (APCI): m/z = 221 [M+ + H – H2O]. HRMS: (NH4CI): calcd.
for C16H18NO2 256.1338 (M+ + NH4); found 256.1337. C16H14O2
(238.29): calcd. C 80.65, H 5.9; found C 80.2, H 5.7.
and butyllithium (13.8 mL of
a 1.6  solution in hexanes,
22.0 mmol) were added sequentially to tetrahydrofuran (30 mL)
maintained at –78 °C. After stirring at the temperature for 2 h, a
solution of benzoin 20 (2.12 g, 10 mmol) in tetrahydrofuran (2 mL)
was added dropwise and the resulting solution stirred for 16 h with-
out further cooling. Saturated aqueous ammonium chloride
(20 mL) was then carefully added followed by dichloromethane
(20 mL). The two layers were separated and the aqueous layer ex-
tracted with dichloromethane (2ϫ20 mL). The combined organic
solutions were dried, filtered and the solvents evaporated. Column
chromatography of the waxy residue (5% MeOH/CHCl3) separated
the diol 21a (2.0 g, 68%) m.p. 96 °C (from CHCl3/hexanes). 1H
NMR: δ = 0.82 (t, J = 7.2 Hz, 3 H, 8-Me), 1.30–1.60 (m, 4 H),
2.25 (t, J = 7.2 Hz, 2 H, 5-CH2), 2.68 (br. s, 2 H, 2 OH), 4.78 (s, 1
H, 1-H), 7.00–7.45 (m, 10 H) ppm. 13C NMR: δ = 14.2 (8-Me),
18.1 (CH2), 28.3 (CH2), 31.2 (CH2), 76.0 (2-C), 76.5 (1-CH), 78.5
(C), 86.1 (C), 127.7 (2 CH), 128.1 (2 CH), 128.4 (CH), 128.6 (CH),
129.0 (CH), 129.5 (2 CH), 130.0 (C), 133.2 (C), 134.3 (CH) ppm.
1,2-Diphenyl-4-(thien-2-yl)but-3-yne-1,2-diol (21d): Copper(I) io-
dide (26 mg, 0.14 mmol) was added to a stirred solution of 2-iodo-
thiophene (Aldrich; 0.31 mL, 2.81 mmol), 1,2-diphenylbut-3-yne-
1,2-diol 21c (0.67 g, 2.81 mmol) and tetrakis(triphenylphosphane)-
palladium(0) (0.16 g, 0.14 mmol) in dry, degassed diethylamine
(10 mL) and the resulting mixture stirred under argon at ambient
temperature overnight. The bulk of the diethylamine was then
evaporated and the residue separated by column chromatography
(20% EtOAc/petroleum ether) to give the thienyl alkynediol 21d
(0.69 g, 81%) as a yellow crystalline solid, m.p. 119–120 °C (from
1
hexane/ether). H NMR: δ = 2.61 (br. d, J = 3.2 Hz, 1 H, 1-OH),
2.83 (br. s, 1 H, 2-OH), 4.88 (d, J = 3.2 Hz, 1 H, 1-H), 6.92 (dd, J
= 5.2, 3.8 Hz, 1 H, 3Ј-H), 7.16–7.25 (m, 10 H), 7.41–7.45 (m, 2 H)
ppm. 13C NMR: δ = 77.3 (C), 81.4 (1-CH), 81.6 (C), 93.7 (C), 122.5
(C), 127.1, 127.4, 127.8, 127.9, 128.1, 128.3, 128.4, 128.6, 133.0 (all
IR (CHCl ): ν = 3445, 2923, 1679, 1458, 1377, 1059 cm–1. MS (EI):
˜
3
ArCH), 137.9 (C), 140.1 (C) ppm. IR (CHCl ): ν = 3416, 2170,
˜
3
m/z (%) = 294 (3) [M+], 277 (28), 195 (35), 187 (40), 146 (28), 108
(52), 107 (88), 105 (98), 79 (93), 76 (100). C20H22O2 (294.39): calcd.
C 81.6, H 7.5; found C 81.9, H 7.6.
1461, 1376, 1171, 1041, 926, 851, 832, 759, 698 cm–1. MS (APCI):
m/z (%) = 321 (11) [M+ + H], 303 (100) [M+ + H – H2O]. HRMS:
calcd. for C20H17O2S 321.0949; found 321.0948.
1,2-Diphenyl-4-(trimethylsilyl)but-3-yne-1,2-diol (21b): Butyllithium
(9.0 mL of a 2.3  solution in hexanes, 20.7 mmol) was added drop-
wise to a stirred solution of (trimethylsilyl)acetylene (2.66 mL,
18.8 mmol) in dry tetrahydrofuran (50 mL) stirred and maintained
at –78 °C. After 1 h, benzoin 20 (2.00 g, 9.4 mmol) was added in
one portion and stirring continued without further cooling for 1 h.
Saturated aqueous ammonium chloride (80 mL) was then added
and the resulting two layers separated. The aqueous layer was ex-
tracted with diethyl ether (3ϫ50 mL) and the combined organic
solutions washed with brine (2ϫ100 mL), then dried and the sol-
vents evaporated. Column chromatography of the residue (20%
EtOAc/petroleum ether) separated the alkynediol 21b (2.26 g,
77%), which separated from petroleum ether as a colourless solid,
2-Butyl-4,5-diphenyl-3-iodofuran (22a): By the general iodocycli-
sation procedure, the alkynediol 21a was converted into the iodofu-
ran 22a (93%), as a pale yellow crystalline solid, m.p. 60–61 °C
(from hexane). 1H NMR: δ = 0.91 (t, J = 7.4 Hz, 3 H, 4Ј-Me), 1.38
(hex, J = 7.4 Hz, 2 H, 3Ј-CH2), 1.66 (pent, J = 7.4 Hz, 2 H, 2Ј-
CH2), 2.74 (t, J = 7.4 Hz, 2 H, 1Ј-CH2), 7.05–7.40 (m, 10 H) ppm.
13C NMR: δ = 14.0 (Me), 22.4, 27.9, 30.4, 71.8 (3-CI), 125.4 (2
PhCH), 126.8 (PhCH), 127.4 (PhCH), 127.8 (2 PhCH), 128.2 (2
PhCH), 130.4 (2 PhCH), 130.6 (C), 134.1 (C), 147.8 (C), 155.9 (C)
(one quaternary obscured) ppm. IR (film): ν = 3086, 2923, 2854,
˜
1679, 1458, 1377, 1059 cm–1. MS (EI): m/z (%) = 402 (100) [M+],
360 (22), 359 (95), 105 (95), 77 (92). C20H19IO (402.27): calcd. C
59.7, H 4.8; found C 59.7, H 4.8.
1
m.p. 104–105 °C. H NMR: δ = 0.01 (s, 9 H, 3 Me), 2.74 (br. s, 1
3-Iodo-4,5-diphenyl-2-(thien-2-yl)furan (22b): Following the general
iodocyclisation procedure, reaction between the alkynediol 21d
(0.20 g, 0.62 mmol), sodium hydrogen carbonate (0.166 g,
1.98 mmol) and iodine (0.500 g, 1.98 mmol) gave, after purification
by column chromatography (5% EtOAc/petroleum ether), the thi-
enyl-iodofuran 22b (0.20 g, 71%) as a pale brown, crystalline solid,
H, OH), 2.84 (br. s, 1 H, OH), 4.89 (s, 1 H, 1-H), 7.18–7.46 (m, 10
H) ppm. 13C NMR: δ = 0.0 (3 Me), 81.1 (1-CH), 81.2 (C), 93.2
(C), 105.9 (C), 126.8 (PhCH), 126.9 (PhCH), 127.7 (PhCH), 127.9
(PhCH), 128.3 (PhCH), 129.3 (PhCH), 139.8 (C), 141.6 (C) ppm.
IR (CHCl ): ν = 3378, 2925, 2274, 1602, 1453, 1377, 1250, 1192,
˜
3
1062, 954, 838 cm–1. MS (APCI): m/z = 293 [M+ + H – H2O].
1
m.p. 158–159 °C (from ether/petroleum ether). H NMR: δ = 7.07
C19H22O2Si (310.47): calcd. C 73.5, H 7.1; found C 73.2, H 6.9.
(d, J = 0.8 Hz, 1 H, 3Ј-H), 7.12–7.17 (m, 3 H), 7.26–7.40 (m, 8 H),
7.75 (d, J = 3.5 Hz, 1 H, 5Ј-H) ppm. 13C NMR: δ = 71.5 (3-CI),
125.6 (CH), 125.9 (CH), 127.8 (overlapping CH), 128.0 (C), 128.1
(CH), 128.6 (CH), 128.8 (CH), 129.2 (CH), 130.1 (C), 130.8 (CH),
1,2-Diphenylbut-3-yne-1,2-diol (21c): Tetrabutylammonium fluoride
(4.9 mL of a 1.0  solution in tetrahydrofuran, 4.9 mmol) was
added dropwise to a stirred solution of the foregoing silylated al-
kyne 21b (1.51 g, 4.9 mmol) in tetrahydrofuran (20 mL), cooled in
an ice-water bath. After 20 min, during which time the colour of
the solution changed from yellow to brown, the bulk of the tetra-
hydrofuran was evaporated and the residue taken up in ether and
water (1:1, 20 mL). The resulting layers were separated and the
aqueous layer extracted with diethyl ether (3ϫ20 mL). The com-
bined organic solutions were dried, filtered and evaporated to leave
a dark oil, which was purified by column chromatography (20%
EtOAc/petroleum ether) to give the alkynediol 21c, which crystal-
lised from EtOAc/petroleum ether as a colourless crystalline solid
132.7 (C), 133.9 (C), 148.2 (C), 148.4 (C) ppm. IR (CHCl ): ν =
˜
3
1462, 1376, 1061, 905, 846, 823, 767, 694 cm–1. UV (EtOH): λmax
= 343 nm. MS (APCI): m/z = 429 [M+ + H]. HRMS: calcd. for
C20H14IOS 428.9810; found 428.9811. C20H13IOS (428.29): calcd.
C 56.1, H 3.1; found C 56.2, H 3.2.
1,2-Di(furan-2-yl)-4-(trimethylsilyl)but-3-yne-1,2-diol (26a): Using
exactly the same method for the preparation of the alkynediol 21b
from benzoin and (trimethylsilyl)acetylene, addition of the latter
alkyne to furoin 25 (5.00 g, 26 mmol) with scaling of all the remain-
(0.93 g, 80%), m.p. 98–99 °C [ref.[23] m.p. 112–113 °C]. 1H NMR: ing quantities of reactants and solvents, gave the alkynediol 26a
δ = 2.67 (s, 1 H, 4-H), 2.71 (br. s, 1 H, OH), 2.94 (br. s, 1 H, OH),
(5.85 g, 78%) as a yellow oil and a single diastereoisomer. 1H
4.82 (s, 1 H, 1-H), 7.06–7.22 (m, 8 H), 7.35–7.45 (m, 2 H) ppm. NMR: δ = 0.00 (s, 9 H, 3 MeSi), 2.60 (d, J = 7.5 Hz, 1 H, 1-OH),
13C NMR: δ = 76.2 (4-CH), 76.5 (C), 81.2 (1-CH), 85.0 (C), 126.9 2.96 (br. s, 1 H, 2-OH), 4.93 (d, J = 7.5 Hz, 1 H, 1-H), 6.12–6.14
(PhCH), 128.2 (PhCH), 128.4 (PhCH), 128.6 (PhCH), 129.1
(m, 3 H, 3 furyl-β-H), 6.27 (d, J = 2.7 Hz, 1 H, furyl-β-H), 7.15
(PhCH), 137.5 (C), 139.9 (C) ppm. IR (CHCl ): ν = 3405, 3269, (d, J = 0.8 Hz, 1 H, furyl-α-H), 7.20 (d, J = 0.8 Hz, 1 H, furyl-α-
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Eur. J. Org. Chem. 2007, 5759–5770

β-Iodofurans by 5-endo-dig Cyclisations
H) ppm. 13C NMR: δ = 0.0 (3 MeSi), 71.8 (2-C), 73.6 (1-CH), 92.7 1 H, furyl-3-H), 6.69 (d, J = 3.5 Hz, 1 H, furyl-3-H), 7.04 (d, J =
(C), 102.5 (C), 108.8 (2 CH), 109.6 (CH), 110.6 (CH), 142.5 (CH), 3.5 Hz, 1 H, furyl-3-H), 7.40 (d, J = 2.0 Hz, 1 H, furyl-2-H), 7.49
143.2 (CH), 151.8 (C), 152.5 (C) ppm. IR (CHCl ): ν = 3455, 2959,
(d, J = 1.6 Hz, 1 H, furyl-2-H), 7.50 (d, J = 2.0 Hz, 1 H, furyl-2-
˜
3
2899, 2176, 1655, 1500, 1374, 1224, 1065, 927, 700 cm–1. MS H) ppm. 13C NMR: δ = 68.6 (3-CI), 111.6 (CH), 111.7 (CH), 113.4
(APCI): m/z = 273 [M+ + H – H2O]. C15H18O4Si (290.39): calcd. (CH), 113.5 (CH), 113.9 (C), 114.0 (CH), 119.5 (C), 128.3 (C),
C 62.0, H 6.25; found C 62.4, H 6.4.
145.0 (CH), 145.3 (CH), 145.4 (CH), 146.7 (C), 146.9 (C), 147.4
(C), 147.9 (C) ppm. IR (CHCl ): ν = 1537, 1502, 1217, 1148, 1071,
˜
3
1,2-Di(furan-2-yl)but-3-yne-1,2-diol (26b): Tetrabutylammonium
fluoride (7.8 mL of a 1  solution in tetrahydrofuran, 7.8 mmol)
was added dropwise to a stirred solution of the foregoing silylated
alkynediol 26a (2.25 g, 7.8 mmol) in tetrahydrofuran (30 mL) co-
oled in an ice-water bath. After 20 min, during which time the solu-
tion colour changed from yellow to black, the bulk of the solvent
was evaporated and the residue partitioned between ether (20 mL)
and water (20 mL). The resulting two layers were separated and the
aqueous layer extracted with diethyl ether (2ϫ20 mL). The com-
bined organic solutions were dried and evaporated and the dark
green oily residue separated by column chromatography (20%
EtOAc/petroleum ether) to give the alkynediol 26b (1.15 g, 68%)
1011, 986, 914, 807 cm–1. UV (EtOH): λmax = 277.3, 338.9 nm. MS
(APCI): m/z (%) = 393 (100) [M+ + H]. HRMS: (EI): calcd. for
C16H9IO4 391.9546 (M+); found 391.9550.
2,3,5-Tri(furan-2-yl)furan (29): Sodium carbonate (20 mg,
0.18 mmol) was added to a stirred mixture of 2-furanboronic acid
(10 mg, 0.09 mmol), the iodofuran 28 (37 mg, 0.09 mmol) and tet-
rakis(triphenylphosphane)palladium(0) (10 mg, 9 µmol) in 90%
aqueous ethanol (2 mL). The resulting mixture was refluxed over-
night then evaporated. Column chromatography of the residue (1%
EtOAc/petroleum ether) separated the trifurylfuran 29 (ca. 9 mg,
ca. 40%) as a colourless oil. 1H NMR: δ = 6.42–6.44 (m, 2 H, 2
furyl-4-H), 6.47 (dd, J = 3.5, 1.8 Hz, 1 H, furyl-4-H), 6.61 (d, J =
3.5 Hz, 1 H, furyl-3-H), 6.79–6.83 (m, 3 H), 7.39 (d, J = 1.4 Hz, 1
H, furyl-2-H), 7.42 (d, J = 1.8 Hz, 1 H, furyl-2-H), 7.47 (d, J =
1.4 Hz, 1 H, furyl-2-H) ppm. MS (APCI): m/z (%) = 267 (100) [M+
+ H]. HRMS: calcd. for C16H11O4 267.0657; found 267.0657.
1
as a dark, unstable oil and a single diastereoisomer. H NMR: δ =
2.61 (s, 1 H, 4-H), 2.80 (br. s, 1 H, OH), 3.20 (br. s, 1 H, OH), 5.06
(d, J = 7.0 Hz, 1 H, 1-H), 6.25–6.28 (m, 3 H, 3 furyl-β-H), 6.42 (d,
J = 3.2 Hz, 1 H, furyl-β-H), 7.29 (d, J = 0.8 Hz, 1 H, furyl-α-H),
7.34 (d, J = 0.8 Hz, 1 H, furyl-α-H) ppm. 13C NMR: δ = 71.6 (2-
C), 73.6 (CH), 75.5 (CH), 81.7 (C), 109.2 (CH), 109.5 (CH), 110.8
(CH), 110.9 (CH), 142.9 (CH), 143.3 (CH), 151.5 (C), 152.3 (C)
Acetylide Additions to 2-Silyloxy Esters. General Procedure: Butyl-
lithium (2.2 equiv. of a 2.5  solution in hexanes) was added slowly
to a stirred solution of a 1-alkyne (2.0 equiv.) in dry tetra-
hydrofuran (4 mL/mmol of butyllithium) at –78 °C. After 20 min,
the protected hydroxy ester (1.0 equiv.) was added, diluted with a
minimum of tetrahydrofuran. The progress of the reaction was
monitored by tlc at –78 °C. When complete, typically after ca. 1 h,
the mixture was quenched by the addition of saturated aqueous
ammonium chloride (4 mL/mmol of butyllithium) and the organic
layer separated. The aqueous layer was extracted with diethyl ether
(3ϫ) and the combined organic solutions washed with brine then
dried and the solvents evaporated.
ppm. IR (CHCl ): ν = 3438, 3290, 2983, 2118, 1567, 1462, 1375,
˜
3
1258, 1151, 926, 819 cm–1. MS (APCI): m/z (%) = 201 (100) [M+
+ H – H2O], 187 (90). HRMS: (NH4CI): calcd. for C12H14NO4
236.0923 (M+ + NH4); found 236.0922.
1,2,4-Tri(furan-2-yl)but-3-yne-1,2-diol (27): Copper(I) iodide
(21 mg, 0.11 mmol) was added to a stirred solution of 2-iodo-
furan (0.42 g, 2.29 mmol),[24] the foregoing alkyne-1,2-diol 26b
(0.50 g, 2.29 mmol) and tetrakis(triphenylphosphane)palladium(0)
(0.132 g, 0.11 mmol) in dry, degassed diethylamine (10 mL) at am-
bient temperature and the resulting mixture stirred overnight then
evaporated. Column chromatography of the residue (20% EtOAc/
petroleum ether) gave the trifuryl-alkynediol 27 (0.483 g, 74%) as
Acetylide Additions to 2-Hydroxy Esters. General Procedure: Butyl-
lithium (3.3 equiv. of a 2.5  solution in hexanes) was added slowly
to a stirred solution of a 1-alkyne (3.0 equiv.) in dry tetra-
hydrofuran (4 mL/mmol of butyllithium) at –78 °C. After 0.5 h, the
hydroxy ester (1.0 equiv.) was added and the foregoing general pro-
cedure followed.
1
a red oil. H NMR: δ = 2.63 (d, J = 7.2 Hz, 1 H, 1-OH), 3.03 (br.
s, 1 H, 2-OH), 5.01 (d, J = 7.2 Hz, 1 H, 1-H), 6.14–6.20 (m, 4 H,
4 furyl-β-H), 6.33 (d, J = 3.0 Hz, 1 H, furyl-β-H), 6.46 (d, J =
3.0 Hz, 1 H, furyl-β-H), 7.18 (d, J = 1.8 Hz, 1 H, furyl-α-H), 7.20
(d, J = 0.8 Hz, 1 H, furyl-α-H), 7.22 (d, J = 0.9 Hz, 1 H, furyl-α-
H) ppm. 13C NMR: δ = 72.7 (2-C), 74.1 (1-CH), 91.4 (C), 102.5
(C), 109.5 (CH), 110.0 (CH), 111.2 (CH), 111.3 (CH), 111.7 (C),
117.3 (CH), 136.8 (C), 143.3 (CH), 143.8 (CH), 144.8 (CH), 151.9
7-[(1-tert-Butyldimethylsilyloxy)ethyl]trideca-5,8-diyn-7-ol
(31a):
Following the general procedure, condensation between methyl 2-
(tert-butyldimethylsilyloxy)propanoate (30a)[25] (2.00 g, 9.17 mmol)
and 1-hexyne (2.10 mL, 18.3 mmol) gave the O-silyl diol 31a
(3.21 g, 78%) as a pale yellow oil. 1H NMR: δ = 0.00 (s, 6 H, 2
MeSi), 0.78–0.84 (m, 15 H, tBuSi, 2 Me), 1.20 (d, J = 6.2 Hz, 3 H,
2Ј-Me), 1.25–1.40 (m, 8 H), 2.08–2.14 (m, 4 H), 2.92 (br. s, 1 H,
OH), 3.76 (q, J = 6.2 Hz, 1 H, 1Ј-H) ppm. 13C NMR: δ = 14.0
(Me), 14.1 (Me), 18.4 (CSi), 18.8 (CH2), 18.9 (CH2), 19.2 (2Ј-Me),
22.2 (CH2), 22.4 (CH2), 26.1 (3 Me), 30.8 (CH2), 30.9 (CH2), 68.0
(7-C), 75.7 (1Ј-CH), 78.7 (C), 80.0 (C), 84.6 (C), 85.5 (C) ppm. IR
(C), 153.2 (C) ppm. IR (CHCl ): ν = 3525, 2229, 1573, 1483, 1375,
˜
3
1212, 1149, 1011, 922, 884, 818 cm–1. MS (APCI): m/z (%) = 267
(100) [M+ + H – H2O]. HRMS: (APCI + aq. NaCl) calcd. for
C16H12NaO5 307.0582 (M+ + Na), found 307.0583.
2,4,5-Tri(furan-2-yl)-3-iodofuran (28): Sodium hydrogen carbonate
(0.35 g, 4.22 mmol) was added to a stirred solution of the foregoing
trifuryl-alkyne 27 (0.40 g, 1.40 mmol) in dry ethyl acetate (10 mL)
at ambient temperature. After 10 min, iodine (1.07 g, 4.22 mmol)
was added in one portion and the resulting mixture stirred for 1 h
then quenched by the addition of 10% aqueous sodium sulfite
(10 mL). The organic layer was separated and the aqueous layer
extracted with ethyl acetate (3ϫ10 mL). The combined organic
solutions were washed with brine (20 mL) then dried, filtered
through a pad of silica and evaporated to leave the iodofuran 28
(CHCl ): ν = 3549, 2239, 1631, 1463, 1362, 1255, 1189, 1009, 954,
˜
3
811 cm–1. MS (APCI): m/z (%) = 333 (100) [M+ + H – H2O].
2-Butyl-4-(hex-1-ynyl)-3-iodo-5-methylfuran (32a): Using the gene-
ral iodocyclisation procedure, but carried out entirely at ambient
temperature, cyclisation of the O-silyl diol 31a (1.00 g, 2.85 mmol)
using iodine (2.17 g, 8.57 mmol), followed by workup after 1 h and
column chromatography (10% EtOAc/petroleum ether) gave the
1
1
(0.14 g, 25%) as an unstable red oil. H NMR: δ = 6.38 (dd, J =
iodofuran 32a (0.94 g, 82%) as a yellow oil. H NMR: δ = 0.86 (t,
3.5, 1.6 Hz, 1 H, furyl-4-H), 6.47 (dd, J = 3.5, 2.0 Hz, 1 H, furyl-
4-H), 6.49 (dd, J = 3.5, 2.0 Hz, 1 H, furyl-4-H), 6.58 (d, J = 3.5 Hz,
J = 7.5 Hz, 3 H, Me), 0.92 (t, J = 7.3 Hz, 3 H, Me), 1.25–1.31 (m,
2 H), 1.39–1.41 (m, 2 H), 1.50–1.57 (m, 4 H), 2.08 (s, 3 H, 5-Me),
Eur. J. Org. Chem. 2007, 5759–5770
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5767

S. P. Bew, G. M. M. El-Taeb, S. Jones, D. W. Knight, W.-F. Tan
FULL PAPER
2.54 (t, J = 7.4 Hz, 2 H, CH2), 2.68–2.74 (m, 2 H, CH2) ppm. 13C
26.2 (3 Me), 69.3 (3-C), 81.6 (1Ј-CH), 85.2 (C), 86.0 (C), 87.3 (C),
NMR: δ = 13.7 (Me), 14.3 (Me), 14.6 (Me), 22.0 (CH2), 22.5 (CH2), 88.1 (C), 122.6 (C), 122.7 (C), 127.8 (CH), 128.5 (CH), 128.6 (CH),
27.8 (CH2), 30.6 (CH2), 31.1 (CH2), 49.9 (CH2), 65.8 (3-CI), 87.3 128.7 (CH), 128.9 (CH), 129.0 (CH), 129.1 (CH), 132.1 (CH), 132.2
(C), 110.9 (C), 131.2 (4-C), 147.7 (C), 155.2 (C) ppm. IR (CHCl3): (CH), 139.1 (C) ppm. IR (CHCl ): ν = 3545, 3062, 2928, 2885,
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3
ν = 2954, 2869, 1639, 1565, 1428, 1381, 1137, 1109, 961, 886,
2232, 1573, 1471, 1361, 1176, 1072, 938, 669 cm–1. MS (APCI): m/z
789 cm–1. MS (APCI): m/z (%) = 345 (100) [M+ + H]. HRMS: (%) = 435 (100) [M+ + H – H2O]. HRMS: (NH4CI): calcd. for
calcd. for C15H22IO 345.0715; found 345.0711.
C30H36NO2Si 470.2515 (M+ + NH4); found 470.2515.
˜
7-[(tert-Butyldimethylsilyloxy)phenylmethyl]trideca-5,8-diyn-7-ol 3-Iodo-2,5-diphenyl-4-(phenylethynyl)furan (32d): Using the general
(31b): Following the general procedure, condensation between
methyl
iodocyclisation procedure, but carried out entirely at ambient tem-
perature, cyclisation of the O-silyl diol 31d (1.00 g, 2.21 mmol)
2-(tert-butyldimethylsilyloxy)-2-phenylacetate (30b)[26]
(1.00 g, 3.57 mmol) and 1-hexyne (0.82 mL, 7.14 mmol) gave the using iodine (1.68 g, 6.63 mmol), followed by workup after 1 h and
1
O-silyl diol 31b (1.23 g, 83%) as a pale yellow oil. H NMR: δ =
–0.01 (s, 3 H, MeSi), 0.00 (s, 3 H, MeSi), 0.77–0.84 (m, 15 H, tBuSi,
column chromatography (5% EtOAc/petroleum ether) gave the
iodofuran 32d (0.88 g, 89%) as a yellow solid, which crystallised
2 Me), 1.24–1.41 (m, 8 H), 2.05–2.14 (m, 4 H), 4.84 (s, 1 H, 1Ј-H), from dichloromethane/petroleum ether as needles, m.p. 112–
7.11–7.19 (m, 3 H), 7.36–7.38 (m, 2 H) ppm. 13C NMR: δ = 14.0 113 °C. 1H NMR: δ = 7.50–7.52 (m, 5 H), 7.57–7.61 (m, 4 H),
(Me), 14.1 (Me), 18.3 (CSi), 18.8 (CH2), 18.9 (CH2), 22.3 (CH2), 7.74–7.76 (m, 2 H), 8.23 (d, J = 7.6 Hz, 2 H), 8.30 (d, J = 7.6 Hz,
22.4 (CH2), 26.1 (3 Me), 30.6 (CH2), 30.7 (CH2), 68.5 (7-C), 78.7
2 H) ppm. 13C NMR: δ = 70.9 (3-CI), 83.2 (C), 97.6 (C), 111.8 (C),
(C), 79.5 (C), 81.6 (1Ј-CH),85.8 (C), 86.6 (C), 127.5 (2 CH), 128.5
123.4 (C), 125.3 (CH), 126.7 (CH), 128.8 (CH), 128.9 (CH), 129.0
(p-CH), 128.9 (2 CH), 139.4 (C) ppm. IR (CHCl ): ν = 3552, 2956, (CH), 129.1 (CH), 129.8 (C), 130.0 (C), 131.9 (CH), 150.9 (C),
˜
3
2859, 2235, 1463, 1361, 1252, 1102, 1069, 836, 778, 700 cm–1. MS
(APCI): m/z (%) = 396 (100) [M+ + H – H2O]. HRMS: (NH4CI):
calcd. for C26H44NO2Si 430.3141 (M+ + NH4); found 430.3147.
154.3 (C) ppm. IR (CHCl ): ν = 2923, 1595, 1479, 1377, 1132,
˜
3
1067, 1026, 940, 911, 764, 672 cm–1. MS (APCI): m/z (%) = 447
(100) [M+ + H]. HRMS: calcd. for C24H16IO 447.0246 (M+ + H);
found 447.0235. C24H15IO (446.29): calcd. C 64.6, H 3.4; found C
64.3, H 3.2.
3-[(tert-Butyldimethylsilyloxy)ethyl]-1,5-diphenylpenta-1,4-diyn-3-ol
(31c): Following the general procedure, condensation between
methyl 2-(tert-butyldimethylsilyloxy)propanoate 30a[25] (2.00 g,
9.17 mmol) and phenylacetylene (2.01 mL, 18.3 mmol) and column
chromatography (5% EtOAc/petroleum ether) gave the O-silyl diol
3-(Hex-1-ynyl)nona-4-yne-2,3-diol (31e): Following the general pro-
cedure for condensations between α-hydroxy esters and acetylides,
reaction between methyl 2-hydroxypropanoate (30e) (2.00 g,
19.21 mmol) and 1-hexyne (6.62 mL, 57.63 mmol), followed by col-
umn chromatography (20% EtOAc/petroleum ether), gave the di-
1
31c (2.63 g, 74%) as a pale yellow oil. H NMR: δ = 0.00 (s, 6 H,
2 MeSi), 0.77 (s, 9 H, tBuSi), 1.30 (d, J = 6.2 Hz, 3 H, 2Ј-Me), 3.16
(br. s, 1 H, OH), 4.00 (q, J = 6.2 Hz, 1 H, 1Ј-H), 7.11–7.18 (m, 6 ynyl diol 31e (3.92 g, 86%) as a pale yellow oil. 1H NMR: δ = 0.84
H), 7.30–7.34 (m, 4 H) ppm. 13C NMR: δ = 17.0 (CSi), 17.8 (2Ј-
Me), 24.7 (3 Me), 67.4 (7-C), 74.1 (1Ј-CH), 82.7 (C), 83.7 (C), 85.7 = 6.3 Hz, 3 H, 1-Me), 1.30–1.35 (m, 4 H), 1.42–1.51 (m, 4 H), 2.15–
(C), 87.2 (C), 121.1 (C), 121.2 (C), 127.1 (2 CH), 127.2 (2 CH),
2.28 (m, 4 H, 3Ј-, 6-CH2), 3.75 (q, J = 6.3 Hz, 1 H, 2-H) ppm. 13C
127.5 (CH), 127.6 (CH), 130.7 (2 CH), 130.8 (2 CH) ppm. IR NMR: δ = 13.8 (Me), 13.9 (Me), 17.8 (1-Me), 18.7 (CH2), 18.8
(t, J = 7.2 Hz, 3 H, Me), 0.85 (t, J = 7.2 Hz, 3 H, Me), 1.28 (d, J
(CHCl ): ν = 3536, 3057, 2929, 2885, 2230, 1671, 1573, 1471, 1361, (CH2), 22.3 (CH2), 22.4 (CH2), 30.7 (CH2), 30.8 (CH2), 68.4 (3-C),
˜
3
1255, 1140, 1062, 943, 836 cm–1. MS (APCI): m/z (%) = 373 (100)
[M+ + H – H2O].. HRMS: (NH4CI): calcd. for C25H34NO2Si
408.2359 (M+ + NH4); found 408.2356.
74.8 (2-CH), 77.9 (C), 79.1 (C), 85.0 (C), 86.0 (C) ppm. IR
(CHCl ): ν = 3405, 2958, 2872, 2236, 1465, 1378, 1268, 1187, 1119,
˜
3
930 cm–1. MS (APCI): m/z (%) = 219 (100) [M+ + H – H2O].
HRMS: (NH4CI): calcd. for C15H28NO2 254.2120 (M+ + NH4);
found 254.2125.
3-Iodo-5-methyl-2-phenyl-4-phenylethynylfuran (32c): Using the ge-
neral iodocyclisation procedure, but carried out entirely at ambient
temperature, cyclisation of the O-silyl diol 31c (0.51 g, 1.27 mmol)
using iodine (0.97 g, 3.82 mmol), followed by workup after 1 h and
column chromatography (10% EtOAc/petroleum ether) gave the
iodofuran 32c (0.94 g, 82%) as a yellow solid, which crystallised
from dichloromethane/petroleum ether as needles, m.p. 104–
105 °C. 1H NMR: δ = 2.37 (s, 3 H, 5-Me), 7.17–7.19 (m, 3 H),
7.24–7.27 (m, 3 H), 7.38–7.41 (m, 2 H), 7.81–7.86 (m, 2 H) ppm.
2-Butyl-4-(hex-1-ynyl)-3-iodo-5-methylfuran (32a) from Diol 31e:
Using the general iodocyclisation procedure, but carried out en-
tirely at ambient temperature, cyclisation of the diynyl diol 31e
(0.20 g, 0.84 mmol) using iodine (0.64 g, 2.54 mmol), followed by
workup after 1 h and column chromatography (10% EtOAc/petro-
leum ether) gave the iodofuran 32a (0.27 g, 93%) as a yellow oil,
which showed spectroscopic and analytical data identical to the
13C NMR: δ = 13.8 (5-Me), 67.8 (3-CI), 81.7 (C), 95.5 (C), 112.9 foregoing sample of iodofuran 32a derived from the corresponding
(C), 123.6 (C), 126.3 (CH), 126.4 (CH), 128.5 (CH), 128.7 (CH), O-silyl ether 31a.
130.2 (C), 131.9 (CH), 147.2 (C), 155.9 (C) ppm. IR (CHCl ): ν =
˜
3
2-(Hex-1-ynyl)-1-phenyloct-3-yne-1,2-diol (31f): Following the gene-
ral procedure for condensations between α-hydroxy esters and ace-
tylides, reaction between methyl 2-hydroxy-2-phenylacetate (30f)
(0.50 g, 3.00 mmol) and 1-hexyne (1.03 mL, 9.02 mmol), followed
by column chromatography (20% EtOAc/petroleum ether), gave
2921, 1584, 1555, 1463, 1377, 1265, 1082, 1066, 1022, 985, 916,
758, 670 cm–1. MS (APCI): m/z = 385 [M+ + H]. HRMS: calcd. for
C19H14IO 385.0089 (M+ + H); found 385.0090. C19H13IO (384.22):
calcd. C 59.4, H 3.4; found C 59.2, H 3.5.
1
3-[(tert-Butyldimethylsilyloxy)phenylmethyl]-1,5-diphenyl-1,4-penta-
diyn-3-ol (31d): Following the general procedure, condensation be-
tween methyl 2-(tert-butyldimethylsilyloxy)phenylacetate (30b)[26]
(2.00 g, 7.14 mmol) and phenylacetylene (1.56 mL, 14.3 mmol) gave
the diynyl diol 31f (0.64 g, 72%) as a pale yellow oil. H NMR: δ
= 0.80–0.83 (m, 6 H, 2 Me), 1.25–1.32 (m, 4 H), 1.36–1.44 (m, 4
H), 2.12–2.15 (m, 4 H), 2.77 (br. s, 1 H, OH), 2.92 (d, J = 3.2 Hz,
1 H, 1-OH), 4.70 (d, J = 3.2 Hz, 1 H, 1-H), 7.24–7.29 (m, 3 H),
7.44–7.49 (m, 2 H) ppm. 13C NMR: δ = 13.8 (Me), 13.9 (Me), 18.8
(CH2), 18.9 (CH2), 22.3 (CH2), 22.4 (CH2), 30.6 (CH2), 30.7 (CH2),
1
the O-silyl diol 31d (2.59 g, 80%) as a pale yellow oil. H NMR: δ
= –0.01 (s, 3 H, MeSi), 0.00 (s, 3 H, MeSi), 0.79 (s, 9 H, tBuSi),
3.16 (s, 1 H, OH), 4.85 (s, 1 H, 1Ј-H), 7.13–7.23 (m, 11 H), 7.29– 68.4 (2-C), 78.1 (2-CH), 78.8 (C), 80.4 (1-CH), 87.3 (C), 87.5 (C),
7.31 (m, 2 H), 7.44–7.52 (m, 2 H) ppm. 13C NMR: δ = 18.6 (CSi),
127.8 (2 CH), 128.5 (p-CH), 128.6 (2 CH), 137.8 (C) ppm. IR
5768
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5759–5770

β-Iodofurans by 5-endo-dig Cyclisations
(CHCl ): ν = 3417, 3062, 3032, 2956, 2871, 2235, 1605, 1494, 1378, 3-Iodo-2,5-diphenyl-4-(phenylethynyl)furan 32d from Diol 31h:
˜
3
1299, 1175, 1087, 903, 766 cm–1. MS (APCI): m/z (%) = 281 (100)
Using the general iodocyclisation procedure, but carried out en-
tirely at ambient temperature, cyclisation of the diynyl diol 31h
(0.20 g, 0.59 mmol) using iodine (0.45 g, 1.77 mmol), followed by
workup after 1 h and column chromatography (5% EtOAc/petro-
leum ether) gave the iodofuran 32d (0.245 g, 94%) as a yellow solid,
m.p. 112–113 °C, which showed other spectroscopic and analytical
data identical to the foregoing sample of iodofuran 32d derived
from the corresponding O-silyl ether 31d.
[M+ + H – H2O].
2-Butyl-4-(hex-1-ynyl)-3-iodo-5-phenylfuran 32b from Diol 31f:
Using the general iodocyclisation procedure, but carried out en-
tirely at ambient temperature, cyclisation of the diynyl diol 31f
(0.50 g, 0.84 mmol) using iodine (1.27 g, 5.03 mmol), followed by
workup after 1 h and column chromatography (5% EtOAc/petro-
leum ether) gave the iodofuran 32b (0.59 g, 87%) as a yellow oil.
1H NMR: δ = 0.98 (t, J = 7.3 Hz, 3 H, Me), 1.04 (t, J = 7.3 Hz, 3
H, Me), 1.40–1.46 (m, 2 H), 1.53–1.59 (m, 2 H), 1.69–1.75 (m, 4
H), 2.76 (t, J = 7.6 Hz, CH2), 2.84–2.90 (m, 2 H), 7.34–7.35 (m, 1
H, p-H), 7.40–7.44 (m, 2 m-H), 7.69–7.72 (m, 2 o-H) ppm. 13C
NMR: δ = 14.1 (Me), 14.5 (Me), 22.4 (CH2), 22.6 (CH2), 28.0
(CH2), 30.5 (CH2), 30.8 (CH2), 49.8 (CH2), 69.2 (3-CI), 88.8 (C),
97.3 (C), 111.8 (4-C), 125.3 (CH), 128.2 (CH), 128.3 (CH), 128.9
(CH), 129.1 (CH), 131.2 (C), 147.2 (C), 156.5 (C) ppm. IR
2,5-Diphenyl-3-(phenylselanyl)furan (33): The diol 14a (0.70 g,
2.9 mmol) and anhydrous potassium carbonate (0.48 g, 3.48 mmol)
were added to dry tetrahydrofuran (5 mL) and the resulting suspen-
sion stirred and cooled to –78 °C. Phenylselanyl chloride (0.609 g,
3.19 mmol) was added in one portion and stirring continued at this
temperature for 5 h. Most of the solvent was then evaporated and
the residue dissolved in a mixture of water (20 mL) and ether
(20 mL). The separated aqueous layer was then extracted with di-
ethyl ether (2ϫ20 mL) and the combined organic solutions dried,
filtered and the solvents evaporated. Column chromatography of
the residue (5% ether in pentane) separated the selanylfuran 33
(0.32 g, 29%) as a pale yellow solid, m.p. 52–53 °C (ether/hexane).
1H NMR: δ = 6.65 (s, 1 H, 4-H), 7.15–7.45 (m, 11 H), 7.62 (dd, J
= 7.0 and ca. 1 Hz, 2 o-H), 8.05 (dd, J = 7.5 and ca. 1 Hz, 2 o-H)
(CHCl ): ν = 2954, 2869, 1632, 1602, 1583, 1428, 1378, 1248, 1142,
˜
3
1070, 929, 879 cm–1. MS (APCI): m/z (%) = 407 (100) [M+ + H].
HRMS: calcd. for C20H24IO 407.0872 (M+ + H); found 407.0870.
C20H23IO (406.31): calcd. C 59.1, H 5.7; found C 59.4, H 5.9.
5-Phenyl-3-(phenylethynyl)pent-4-yne-2,3-diol (31g): Following the
general procedure for condensations between α-hydroxy esters and
acetylides, reaction between methyl 2-hydroxypropanoate (30e)
(1.00 g, 9.6 mmol) and phenylacetylene (3.16 mL, 28.8 mmol) fol-
lowed by column chromatography (20% EtOAc/petroleum ether),
gave the diynyl diol 31g (1.78 g, 66%) as a pale yellow, crystalline
solid, m.p. 106–107 °C (from petroleum ether/dichloromethane).
1H NMR: δ = 1.35 (d, J = 6.3 Hz, 3 H, 1-Me), 2.61 (br. s, 1 H,
OH), 3.52 (br. s, 1 H, OH), 3.94 (q, J = 6.3 Hz, 1 H, 2-H), 7.12–
7.16 (m, 6 H), 7.29–7.34 (m, 4 H) ppm. 13C NMR: δ = 18.2 (1-
Me), 69.1 (3-C), 74.9 (2-CH), 85.4 (C), 85.9 (C), 86.3 (C), 87.4 (C),
122.1 (C), 122.2 (C), 128.2 (CH), 128.7 (CH), 129.3 (CH), 129.5
ppm. IR (CHCl ): ν = 3020, 1666, 1466, 1430, 1351, 1215, 1101,
˜
3
1015, 735, 685 cm–1. MS (EI): m/z (%) = 376 (15) [M+], 296 (12),
202 (8), 191 (20), 105 (78), 77 (100). C22H16OSe (375.33): calcd. C
70.4, H 4.2; found C 70.2, H 4.3.
Acknowledgments
We thank the EPSRC Mass Spectrometry Service, University Col-
lege, Swansea for the provision of high resolution mass spectromet-
ric data. Financial support from the Engineering and Physical Sci-
ences Research Council (EPSRC) and the Government of Libya is
also acknowledged.
(CH), 132.5 (CH), 133.4 (CH) ppm. IR (CHCl ): ν = 3478, 2929,
˜
3
2875, 2241, 1636, 1475, 1140, 966, 862 cm–1. MS (APCI): m/z (%)
= 259 (100) [M+ + H – H2O]. C19H16O2 (276.33): calcd. C 82.6, H
5.8; found C 82.6, H 5.9.
[1] For excellent general reviews, see the relevant Chapters in Com-
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3-Iodo-5-methyl-2-phenyl-4-(phenylethynyl)furan 32c from Diol 31g:
Using the general iodocyclisation procedure, but carried out en-
tirely at ambient temperature, cyclisation of the diynyl diol 31g
(1.00 g, 3.62 mmol) using iodine (2.75 g, 10.86 mmol), followed by
workup after 1 h and column chromatography (5% EtOAc/petro-
leum ether) gave the iodofuran 32c (1.29 g, 93%) as a yellow solid,
m.p. 104–105 °C, which showed other spectroscopic and analytical
data identical to the foregoing sample of iodofuran 32c derived
from the corresponding O-silyl ether 31c.
1,4-Diphenyl-2-(phenylethynyl)-3-butyne-1,2-diol (31h): Following
the general procedure for condensations between α-hydroxy esters
and acetylides, reaction between methyl 2-hydroxy-2-phenylacetate
(30f) (2.00 g, 12.03 mmol) and phenylacetylene (3.96 mL,
36.1 mmol) followed by column chromatography (20% EtOAc/pe-
troleum ether), gave the diynyl diol 31h (3.10 g, 76%) as a pale
yellow, crystalline solid, m.p. 160–162 °C (from petroleum ether/
1
dichloromethane). H NMR: δ = 3.13 (br. s, 1 H, OH), 3.24 (br. s,
1 H, OH), 4.97 (s, 1 H, 1-H), 7.21–7.23 (m, 13 H), 7.58–7.60 (m, 2
H) ppm. 13C NMR: δ = 69.2 (2-C), 80.5 (1-CH), 86.4 (C), 86.5 (C),
86.7 (C), 87.0 (C), 122.0 (C), 122.1 (C), 128.1 (CH), 128.5 (CH),
128.7 (CH), 128.8 (CH), 129.0 (CH), 129.3 (CH), 132.2 (CH), 132.3
(CH), 137.3 (C) ppm. IR (CHCl ): ν = 3503, 2914, 2227, 1596,
˜
3
1487, 1326, 1220, 1194, 1156, 1095, 992, 850 cm–1. MS (APCI): m/z
(%) = 321 (100) [M+ + H – H2O]. C24H18O2 (338.41): calcd. C 85.2,
H 5.4; found C 85.4, H 5.6.
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5769

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Received: July 24, 2007
Published Online: September 25, 2007
5770
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5759–5770