An approach to 2,3-dihydropyrroles and β-iodopyrroles based on 5-endo-dig cyclisations

Article abstract of DOI:10.1039/b110751h

A representative series of homopropargylic sulfonamides 19 and 22b have been found to undergo smooth 5-endo-dig cyclisation upon exposure to excess iodine in acetonitrile containing potassium carbonate. The resulting 4-iodo-2,3-dihydropyrroles 23 readily react with two equivalents of DBU in DMF at 20°C to give the corresponding β-iodopyrroles 24 and 26 in excellent yields by the elimination of toluene-p-sulfinic acid. Use of less than two equivalents of base results in some loss of iodine. The iodo-2,3-dihydropyrroles 23 can be used in palladium-catalysed coupling reactions as shown by the efficient formation of the Sonogashira product 29 under mild conditions.

Full text of DOI:10.1039/b110751h

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An approach to 2,3-dihydropyrroles and ꢀ-iodopyrroles based on
5-endo-dig cyclisations
David W. Knight,*a Adele L. Redferna and Jeremy Gilmoreb
1
a Chemistry Department, Cardiff University, P.O. Box 912, Cardiff, UK CF10 3TB
b Eli Lilly and Co. Ltd., The Lilly Research Centre, Erlwood Manor, Windlesham, Surrey,
UK GU20 6PH
Received (in Cambridge, UK) 23rd November 2001, Accepted 23rd January 2002
First published as an Advance Article on the web 8th February 2002
A representative series of homopropargylic sulfonamides 19 and 22b have been found to undergo smooth
5-endo-dig cyclisation upon exposure to excess iodine in acetonitrile containing potassium carbonate. The
resulting 4-iodo-2,3-dihydropyrroles 23 readily react with two equivalents of DBU in DMF at 20 ЊC to give
the corresponding β-iodopyrroles 24 and 26 in excellent yields by the elimination of toluene-p-sulfinic acid.
Use of less than two equivalents of base results in some loss of iodine. The iodo-2,3-dihydropyrroles 23 can
be used in palladium-catalysed coupling reactions as shown by the efficient formation of the Sonogashira
product 29 under mild conditions.
attempts to effect iodocyclisations of homopropargylic alco-
hols 13 have yet to be productive in this sense, leading not to
the anticipated dihydrofurans 14 but rather to the diiodides 15.7
It was therefore very unclear at the outset whether homo-
propargylic sulfonamides 8 would indeed undergo the desired
cyclisations. Herein, we report in full that these are indeed
viable processes which provide a rapid approach to both 4-iodo-
2,3-dihydropyrroles and 4-iodopyrrole-2-carboxylates.8
Introduction
We have recently reported that our stereoselective approaches
to both trans-2,5- and cis-2,5-disubstituted-3-iodopyrrolidines
(2 and 3) using 5-endo-trig cyclisations of homoallylic 11 can be
successfully applied to the elaboration of substituted proline
derivatives 4 and 5.2 While investigating the chemistry of
these, we found conditions for effecting the elimination of the
elements of both hydrogen iodide and toluene-p-sulfinic acid,
leading to high yields of the 5-substituted pyrrole-2-carboxyl-
ates 6.2 That base-induced eliminations were successful was not
particularly surprising, especially as many attempts to displace
the β-iodine atom in the electron-poor pyrrolidines 4 and 5
using a variety of nucleophiles by a projected SN2 mechanism
led instead to elimination products, consisting of mixtures of
2,3- and 2,5-dihydropyrroles 7.2 Further, while this approach
overall is relatively efficient, there are many other seemingly as
effective routes to 5-substituted pyrrole-2-carboxylates 6.3 We
also reasoned that loss of the potentially useful iodide atom was
somewhat wasteful. All of these considerations led us to spec-
ulate that related 5-endo-dig cyclisations of the corresponding
homopropargylic† sulfonamides 8 could lead to synthetically
more useful products 9, given the obvious provisos that such
cyclisations could be achieved and also that the dihydropyrroles
9 were stable. We were encouraged to attempt such a sequence
as, in complete contrast to 5-endo-trig processes, 5-endo-dig
cyclisations are favoured according to Baldwin’s rules.4 Despite
this, such cyclisations have not enjoyed a prominence in the
literature which this fact would suggest they deserve, as has
recently been highlighted by Carreira and co-workers.5 We have
gone some way to addressing this apparent deficiency in syn-
thetic methodology with the finding that alk-3-yne-1,2-diols 10
undergo clean electrophile-induced 5-endo-dig cyclisations to
give highly substituted furans 12; the presumed intermediate
hydroxydihydrofurans 11 have yet to be observed, suggesting
that dehydration to the heteroaromatic nuclei 12 is faster than
cyclisation, at least under the conditions used.6 However,
despite the favoured nature of 5-endo-dig processes, recent
Results and discussion
In view of our previous findings with regard to the preparation
of the iodopyrrolidines 2 and 3,1,2 we chose to once again
attenuate the reactivity of the amine group by employing the
† The IUPAC name for homopropargyl is but-3-ynyl.
622
J. Chem. Soc., Perkin Trans. 1, 2002, 622–628
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b110751h

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geminal β-protons resonating as double doublets between δH
2.5 and 3.0 while the 2-H resonances occurred around δH 4.6–
5.0, also as double doublets. The 13C data were also consistent
with the structures 23, especially the significant shielding of the
quaternary carbon attached to iodine at the 4-position, which
resonated around δC 74–79 ppm due to the heavy atom effect.12
All other spectroscopic and analytical data were consistent with
the proposed structures.
corresponding sulfonamide functions. A particularly con-
venient way to prepare the necessary model precursors, when
having an aromatic substituent at the alkyne terminus, turned
out to feature phase transfer-catalysed alkylation9 of glycinate
imine 16 with propargyl bromide10 to give the propargyl-
glycinate derivative 17 followed by protecting group exchange
via the free amines 18a and the N-tosylglycinate 18b. Finally,
Sonogashira coupling11 with an iodo(hetero)arene, gave the
series of precursor homopropargylic sulfonamides 19 in
respectable overall yields. Attempts to carry out Sonogashira
couplings with the glycinate imine 17 were not successful. An
alkyl-substituted substrate 22b was prepared by C-alkylation of
the enolate of glycinate imine 16 generated using LDA,10 with
the propargylic bromide 20, leading to homologue 21 followed
by a similar protecting group exchange via amine 22a.
Clearly, the incorporation of the iodine atom at an sp2
carbon centre opened up a number of additional synthetic
opportunities not available to the related iodopyrrolidines
(e.g. 4 and 5). Firstly, we thought that elimination to the
pyrrole oxidation level should be straightforward using a base
to trigger the removal of the elements of toluene-p-sulfinic acid,
one of the steps in the formation of pyrrolecarboxylates 6 from
the iodopyrrolidines 4 and 5. Now, of course, it was antici-
pated that the iodine would be retained. It therefore came
as something of a surprise to find that treatment of the
iodo-dihydropyrrole 23a with one equivalent of 1,8-diaza-
bicyclo[5.4.0]undecene (DBU) in hot N,N-dimethylformamide2
led to an excellent recovery of pyrroles, but as an approximately
1 : 1 mixture of the anticipated iodopyrrole 24 and the de-
iodinated analogue 25.2 We reasoned that, somehow, the other
product of elimination, toluene-p-sulfinic acid, was responsible
for this undesired side reaction and therefore carried out the
reaction using two equivalents of DBU in the anticipation of
more rapidly neutralizing the acid. This, coupled with an optim-
ization study, which showed elimination to occur smoothly at
ambient temperature, led to the formation of only the desired
iodopyrroles 24 and 26a–c in excellent isolated yields as shown.
By acting as a proton source, the toluene-p-sulfinic acid could
cause cycloreversion by N-protonation to give salt 27 and
iodine loss, in much the same way as we explained the isomer-
ization of the 2,5-trans-pyrrolidines 2 to the corresponding 2,5-
cis-isomers 3 when cyclisations of the precursors 1 were carried
out under acidic conditions.1,2 Subsequently, the regenerated
homopropargylic sulfonamide 19a could undergo acid-induced
cyclisation to give the 2,3-dihydropyrrole 28; elimination would
then give the observed 5-phenylpyrrole-2-carboxylate 25. In
We were pleased to find that exposure of these four examples
of homopropargylic sulfonamides (19 and 22b) to three equiv-
alents each of iodine and anhydrous potassium carbonate in
dry acetonitrile resulted in relatively slow but clean 5-endo-dig
cyclisation to give, after column chromatography and crystal-
lization in the examples having (hetero)aryl substituents, the
4-iodo-2,3-dihydropyrroles 23a–d in very respectable isolated
yields, as shown. All such products turned out to be stable and
amenable to full characterization, although the 5-ethyl deriv-
ative 23d did begin to decompose if left at ambient temperature
for extended periods. The products 23 displayed a characteristic
ABX pattern for the 2-H and the 3-CH2 spin system, with the
J. Chem. Soc., Perkin Trans. 1, 2002, 622–628
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support of this, exposure of homopropargylic sulfonamides 19
to various proton sources, including toluene-p-sulfinic acid, did
indeed induce an overall 5-endo-dig cyclisation although, as yet,
not as cleanly as in the present case.13 In any event, use of
an additional equivalent of DBU which presumably rapidly
suppresses the amount of free sulfinic acid present during the
elimination, resulted in excellent yields of the iodopyrroles 24
and 26a–c.
pyrrole which would be formed by base-induced elimination of
toluenesulfinic acid was not detected. It therefore seems likely
that many other Pd-catalysed processes will be applicable to
homologation of both the initial dihydropyrroles 23 and the
iodopyrroles 24 and 26.
Conclusions
In conclusion, we have defined a new approach to both 4-iodo-
2,3-dihydropyrroles20 and β-iodopyrroles21 which is relatively
brief and straightforward, using a novel version of the 5-endo-
dig cyclisation. While all the examples reported herein are
substituted with an ester group, this was mostly due to synthetic
expediency during this model study; its relative remoteness
from the points of reaction during cyclisation suggests that
many other homopropargylic sulfonamides should also undergo
such cyclisations. Our original aim of retaining the iodine atom
whilst forming a pyrrole nucleus has therefore been achieved
with the bonus that the intermediate 4-iodo-2,3-dihydro-
pyrroles can be isolated and that both types of compound
seemingly have considerable potential for further elaboration,
especially using palladium-catalysed methods.
Experimental
For general details, see ref. 2.
Methyl 2-[(diphenylmethylene)amino]pent-4-ynoate 17
Methyl 2-[(diphenylmethylene)amino]ethanoate 16 (10.0 g,
39.5 mmol, 1.0 equiv.), potassium carbonate (5.5 g, 39.5 mmol,
1.0 equiv.) and tetrabutylammonium iodide (1.5 g, 3.95 mmol,
0.1 equiv.) were stirred in dry acetonitrile (100 ml) at room
temperature.9 Propargyl bromide (4.70 g, 39.5 mmol, 1.0 equiv.)
was then added and the resulting mixture was heated under
reflux for 6.5 h. The reaction was then allowed to cool, filtered
and concentrated under reduced pressure to give a crude resi-
due which was chromatographed (6 : 1 hexane–ethyl acetate) to
give the imine 17 (8.0 g, 70%) as a colourless solid, mp 51–52 ЊC;
νmax/cmϪ1 3305 (m), 3059 (m), 2950 (m), 1745 (s), 1671 (s), 1451
(m), 1310 (m) and 1220 (m); δH 1.96 (1H, t, J = 2.6, 5-H), 2.80–
2.94 (2H, m, 3-CH2), 3.74 (3H, s, OMe), 4.33 (1H, dd, J = 8.1
and 5.2, 2-H) and 7.26–7.67 (10H, m, Ar-H); δC 23.5 (3-CH2),
52.4 (OMe), 64.0 (2-CH), 70.3 (5-CH), 81.0 (4-C), 128.1, 128.2,
128.5, 128.8, 129.0, 130.6 (all Ar-CH), 136.0, 140.0 (both C),
170.0 (C᎐N) and 171.0 (C᎐O); m/z [EI] 292 (M ϩ Hϩ, 21%), 252
The incorporation of an iodine atom at an unsaturated
carbon suggests a number of strategies for further elaborations,
most notably using palladium-catalysed coupling reactions or
radical-based methods.14 In the area of palladium-induced
couplings, 3,4-dibromopyrroles undergo smooth Kumada-type
displacements with Grignard reagents to give 3,4-dialkyl
(or aryl) pyrroles.15 The same dibromopyrroles also undergo
efficient Suzuki couplings, at least with phenylboronic acid,16
whilst a seemingly less effective alternative features conversion
of a β-iodopyrrole into the corresponding boronic acid.17 Per-
haps surprisingly, it was only very recently that Wang and Scott
reported that β-iodopyrroles also participate in Stille couplings,
although the corresponding chloro or bromo derivatives give
poor yields or fail altogether to undergo couplings with tri-
butylstannyl species.18 Alternatively, β-iodopyrroles can be
converted into the corresponding β-stannyl derivatives which
can then be coupled with aryl bromides.17,19 In the present pro-
ject, we therefore chose only to attempt to establish that the
4-iodo-2,3-dihydropyrrole functionality was compatible with a
palladium-catalysed coupling reaction. The relatively electron
deficient nature of the alkene bond suggested that such reac-
tions should be relatively straightforward and this was indeed
the case. When the dihydropyrrole 23a was exposed to
Sonogashira coupling conditions11 with phenylacetylene, an
excellent yield of the acetylene homologue 29 was isolated after
only two hours at ambient temperature. The corresponding
᎐
᎐
(63), 232 (35), 192 (54), 165 (57), 126 (100), 82 (54) and 58 (63)
[Found: M ϩ Hϩ, 292.1338. C19H18NO2 requires M, 292.1337].
Methyl 2-aminopent-4-ynoate 18a
The imine 17 (8.0 g, 27.5 mmol) was vigorously stirred in 2 M
hydrochloric acid (95 ml) and diethyl ether (135 ml) until the
hydrolysis was complete by TLC (approx. 1 h). The organic
layer was then separated and discarded and the aqueous layer
washed with ether (50 ml), then taken to pH 9 with solid
sodium carbonate and extracted with ether (4 × 50 ml). The
combined organic extracts were dried, filtered and concentrated
under reduced pressure to yield the crude amine 18a (1.9 g,
54%) which was used without further purification in the sub-
sequent tosylation reaction and which showed νmax/cmϪ1 [film]
3289 (s), 2955 (m), 2180 (w), 1748 (s), 1438 (m), 1208 (s), 1150
(m) and 1021 (m); δH 1.60–1.70 (2H, br s, NH2), 2.06 (1H, t,
624
J. Chem. Soc., Perkin Trans. 1, 2002, 622–628

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J = 2.6, 5-H), 2.57–2.68 (2H, m, 3-CH2), 3.64 (1H, dd, J = 5.7
and 5.7, 2-H) and 3.75 (3H, s, OCH3); δC 24.7 (3-CH2), 52.3
(0.21 g, 1.07 mmol, 1.0 equiv.) was added. The crude product
was chromatographed (4 : 1 hexane–ethyl acetate) to give the
acetylene 19b (0.28 g, 76%), as a pale brown solid, mp 92–93 ЊC;
νmax/cmϪ1 3062 (s), 1747 (m), 1430 (w), 1351 (m), 1306 (w), 1268
(m), 1214 (m), 1165 (s), 1119 (w) and 1093 (m); δH 2.42 (3H,
s, Ar-CH3), 2.89 (1H, dd, J = 17.0 and 5.1, 3-Ha), 2.94 (1H, dd,
J = 17.0 and 5.1, 3-Hb), 3.64 (3H, s, OCH3), 4.18 (1H, ddd,
J = 8.8, 5.1 and 5.1, 2-H), 5.48 (1H, d, J = 8.8, NH), 6.36 (1H,
dd, J = 3.3 and 1.9, 4Ј-H), 6.50 (1H, d, J = 3.3, 3Ј-H), 7.29 (2H,
d, J = 8.2, 2 × Ar-H), 7.35 (1H, app br s, 5Ј-H) and 7.69 (2H, d,
J = 8.2, 2 × Ar-H); δC 21.7 (Ar-CH3), 25.1 (3-CH2), 53.0
(OCH3), 54.1 (2-CH), 75.4 (5(4)-C), 87.4 (4(5)-C), 110.8
(4Ј-CH), 115.2 (3Ј-CH), 127.2 (2 × CH), 129.7 (2 × CH), 137.1
(OMe), 53.0 (2-CH), 71.2 (5-CH), 79.4 (4-C) and 174.1 (C᎐O);
᎐
m/z [EI] 163 (Mϩ, 0.01%), 151 (7), 128 (11), 104 (16), 88 (16) and
67 (100).
Methyl 2-(4-tolylsulfonylamino)pent-4-ynoate 18b
The propargylic amine 18a (1.83 g, 14.4 mmol, 1.0 equiv.) was
stirred in dry dichloromethane (37 ml) at room temperature.
Tosyl chloride (3.02 g, 15.8 mmol, 1.1 equiv.) and a crystal of
DMAP were then added, followed by the dropwise addition of
triethylamine (2.42 ml, 17.3 mmol, 1.2 equiv.). The mixture was
stirred overnight at room temperature and then 2 M hydro-
chloric acid (20 ml) was added and the organic phase separated.
The aqueous phase was extracted with dichloromethane (2 ×
20 ml) and the combined organic solutions were washed with
brine (20 ml), dried, filtered and concentrated under reduced
pressure to give the crude product as a brown oil. The oil was
chromatographed (6 : 1 hexane–ethyl acetate) to give the
tosylamide 18b (2.80 g, 69%) as a colourless solid, mp 83 ЊC;
νmax/cmϪ1 3304 (w), 3053 (m), 2184 (w), 1747 (m), 1599 (w),
1441 (w), 1422 (m), 1351 (m), 1286 (m), 1258 (s), 1221 (w), 1165
(s) and 1093 (w); δH, 2.02 (1H, t, J = 2.5, 5-H), 2.36 (3H, s,
Ar-CH3), 2.56–2.67 (2H, m, 3-CH2), 3.55 (3H, s, OCH3), 4.05
(1H, ddd, J = 9.0 and 4.7 and 4.7, 2-H), 5.35 (1H, d, J = 9.0,
NH), 7.23 (2H, d, J = 8.2, 2 × Ar-H) and 7.68 (2H, d, J = 8.2,
2 × Ar-H); δC 21.5 (CH3), 24.1 (3-CH2), 52.9 (OCH3), 53.9
(2-CH), 77.0 (5-CH), 72.3 (4-C), 127.2 (2 × CH), 129.7 (2 ×
(C), 140.0 (C), 143.4 (5Ј-CH), 144.0 (C) and 171.0 (C᎐O); m/z
᎐
[EI] 347 (Mϩ, 4%), 288 (5), 242 (41), 176 (100), 155 (100), 105
(79), 91 (100), 77 (95) and 65 (76) [Found: Mϩ, 347.0828.
C17H17NO5S requires M, 347.0828].
Methyl
5-(2-thienyl)-2-(4-tolylsulfonylamino)pent-4-ynoate
19c. The tosylamide 18b (0.50 g, 1.78 mmol, 1.0 equiv.) was
stirred in diethylamine (12.5 ml) with CuI (0.07 g, 0.36 mmol
0.2 equiv.) and Pd(PPh3)4 (0.21 g, 0.18 mmol, 0.1 equiv.), then
2-iodothiophene (0.37 g, 1.78 mmol, 1.0 equiv.) was added. The
crude product was chromatographed (4 : 1 hexane–ethyl acet-
ate) to give the acetylene 19c (0.46 g, 71%) as a pale brown solid,
mp 100–102 ЊC; νmax/cmϪ1 3056 (s), 2955 (w), 1747 (s), 1599 (w),
1437 (m), 1415 (w), 1350 (s), 1270 (m), 1262 (s), 1220 (m), 1118
(w) and 1093 (m); δH 2.42 (3H, s, Ar-CH3), 2.89 (1H, dd, J =
17.0 and 4.8, 3-Ha), 2.93 (1H, dd, J = 17.0 and 5.4, 3-Hb), 3.64
(3H, s, OCH3), 4.18 (1H, app br s, 2-H), 5.46 (1H, br s, NH),
6.95 (1H, dd, J = 5.1 and 3.6, 4Ј-H), 7.12 (1H, d, J = 3.6, 3Ј-H),
7.22 (1H, d, J = 5.1, 5Ј-H), 7.29 (2H, d, J = 8.2, 2 × Ar-H) and
7.76 (2H, d, J = 8.2, 2 × Ar-H); m/z [EI] 363 (Mϩ, 1%), 304 (2),
242 (21), 192 (76), 177 (21), 155 (100), 20.9 (88), 91 (100), 76.9
(41) and 64.8 (29) [Found: Mϩ, 363.0599. C17H17NO4S2 requires
M, 363.0599] [Found: C, 56.39; H, 4.99; N, 4.01. C17H17NO4S2
requires C, 56.19; H, 4.72; N, 3.86%].
CH), 136.4 (C), 143.0 (C) and 169.7 (C᎐O); m/z [EI] 282
᎐
(M ϩ Hϩ, 20%), 264 (19), 242 (52), 222 (51), 155 (69), 91 (100)
and 65 (74) [Found: M ϩ Hϩ, 282.0800. C13H16NO4S requires
M, 282.0808]; [Found: C, 55.70; H, 5.25; N, 5.03. C13H15NO4S
requires C, 55.50; H, 5.38; N, 4.98%].
Sonogashira reactions: general procedure
The tosylamide 18b (1 mmol, 1.0 equiv.) was stirred in degassed
diethylamine (7 ml) with copper() iodide (0.2 mmol, 0.2 equiv.)
and tetrakis(triphenylphosphine)palladium(0) (0.1 mmol, 0.1
equiv.). The aryl iodide (1 mmol, 1.0 equiv.) was then added and
the reaction was stirred under nitrogen for approximately 3 h,
until complete according to TLC. The reaction mixture was
then concentrated, diluted with ether (10 ml), filtered through
Celite and the filtrate concentrated to give a brown oil which
was purified by column chromatography.
Methyl 2-[(diphenylmethylene)amino]hept-4-ynoate 21
Phosphorus tribromide (2.79 ml, 29.7 mmol, 1.0 equiv.) was
added dropwise to a stirred, ice-cooled solution of pent-2-yn-1-
ol (5.00 g, 59.4 mmol, 2.0 equiv.) and pyridine (0.53 ml) in ether
(110 ml). After stirring overnight at room temperature, the reac-
tion mixture was poured into ice–water (100 ml). The organic
layer was separated and the aqueous layer was extracted with
ether (3 × 50 ml). The combined organic solutions were
dried, filtered and evaporated under reduced pressure to yield
1-bromopent-2-yne 20 as a brown oil (5.50 g, 63%). The product
was reacted immediately without further purification.
Methyl 2-[(diphenylmethylene)amino]ethanoate 16 (4.73 g,
18.7 mmol, 1.0 equiv.), potassium carbonate (2.58 g, 18.7
mmol, 1.0 equiv.) and tetrabutylammonium iodide (0.69 g, 1.87
mmol, 0.1 equiv.) were stirred in acetonitrile (50 ml) at room
temperature. 1-Bromopent-2-yne 20 (18.7 mmol, 1.0 equiv.) was
then added dropwise and the resulting mixture heated under
reflux for 7 h. The mixture was allowed to cool, filtered and
concentrated under reduced pressure to give a crude residue,
which was then chromatographed (6 : 1 hexane–ethyl acetate) to
give the imine 21 (2.60 g, 44%) as a pale yellow oil, νmax/cmϪ1
[film] 3058 (w), 2950 (w), 1741 (s), 1660 (s), 1447 (m), 1318 (m)
and 1277 (s); δH 0.97 (3H, t, J = 7.5, 7-CH3), 2.03 (2H, q, J = 7.5,
6-CH2), 2.61–2.78 (2H, m, 3-CH2), 3.65 (3H, s, OCH3), 4.20
(1H, dd, J = 8.4 and 5.1, 2-H) and 7.17–7.74 (10H, m, Ar-H); δC
12.4 (CH2), 14.0 (CH3), 23.7 (CH2), 52.2 (OCH3), 64.7 (2-H),
75.6 (4(5)-C), 83.6 (5(4)-C), 128.0, 128.2, 128.3, 128.7, 128.9,
Methyl 5-phenyl-2-(4-tolylsulfonylamino)pent-4-ynoate 19a.
The tosylamide 18b (0.50 g, 1.78 mmol, 1.0 equiv.) was stirred
in diethylamine (12.5 ml) with CuI (0.07 g, 0.36 mmol,
0.2 equiv.) and Pd(PPh3)4 (0.21 g, 0.18 mmol, 0.1 equiv.) and
iodobenzene (0.2 ml, 1.78 mmol, 1.0 equiv.) was added. The
crude product was chromatographed (3 : 1 hexane–ethyl acet-
ate) to give the acetylene 19a (0.37 g, 58%), mp 91 ЊC; νmax/cmϪ1
3045 (s), 1747 (s), 1599 (w), 1491 (w), 1443 (w), 1418 (w), 1350
(m) 1219 (w) and 1165 (s); δH 2.41 (3H, s, Ar-CH3), 2.88 (1H,
dd, J = 16.9 and 5.1, 3-Ha), 2.91 (1H, dd, J = 16.9 and 5.1,
3-Hb), 3.64 (3H, s, OCH3), 4.20 (1H, ddd, J = 9.1, 5.1 and 5.1,
2-CH), 5.46 (1H, d, J = 9.1, NH), 7.28–7.38 (7H, m, Ar-H) and
7.62 (2H, d, J = 8.3, 2 × Ar-H); δC 21.6 (Ar-CH3), 25.1 (3-CH2),
52.9 (OCH3), 54.4 (2-CH), 127.2 (3 × CH), 128.4 (2 × CH),
129.7 (2 × CH), 131.7 (2 × CH), 144.0, 152.5, 157.0 (all C) and
171.0 (C᎐O); m/z [EI] 357 (Mϩ, 21%), 242 (49), 186 (67), 155
᎐
(71), 115 (83) and 91 (100) [Found: Mϩ, 357.1035. C19H19NO4S
requires M, 357.1035] [Found: C, 63.62; H, 5.17; N, 3.85.
C19H19NO4S requires C, 63.85; H, 5.36 N, 3.92%].
Methyl 5-(2-furyl)-2-(4-tolylsulfonylamino)pent-4-ynoate 19b.
The tosylamide 18b (0.30 g, 1.07 mmol, 1.0 equiv.) was stirred
in diethylamine (7.5 ml) with CuI (0.04 g, 0.21 mmol, 0.2 equiv.)
and Pd(PPh3)4 (0.12 g, 0.11 mmol, 0.1 equiv.) and 2-iodofuran
130.3 (all Ar-H), 136.0 (C), 139.5 (C). 171.3 (C᎐N) and 171.4
᎐
(C᎐O); m/z [EI] 318 (M Ϫ Hϩ, 49%), 260 (61), 252 (83), 191
᎐
(50), 164 (100), 120 (82) and 90 (33) [Found: M Ϫ Hϩ, 318.1489.
C21H20NO2 requires M, 318.1493].
J. Chem. Soc., Perkin Trans. 1, 2002, 622–628
625

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Methyl 2-aminohept-4-ynoate 22a
(m) and 1028 (m); δH 2.44 (3H, s, Ar-CH3), 2.87 (1H, dd,
J = 16.7 and 3.6, 3-Ha), 2.94 (1H, dd, J = 16.7 and 9.7, 3-Hb),
3.87 (3H, s, OMe), 4.99 (1H, dd, J = 9.7 and 3.6, 2-H) and 7.23–
7.50 (9H, m, Ar-H); δC 21.7 (Ar-CH3), 43.3 (3-CH2), 53.1
(OCH3), 62.0 (2-CH), 73.0 (4-C), 127.7, 127.2, 129.2, 129.5,
129.9 (all Ar-CH), 132.0, 134.6, 144.3, 144.4 (all C), and 171.7
The imine 21 (2.60 g, 8.15 mmol) was vigorously stirred in 2 M
hydrochloric acid (25 ml) and diethyl ether (40 ml) until the
hydrolysis was complete by TLC (approx. 1 h). The organic
layer was then separated and discarded and the aqueous layer
washed with ether (10 ml), then taken to pH 9 with solid
sodium carbonate and extracted with ether (4 × 10 ml). The
combined organic extracts were then dried, filtered and concen-
trated under reduced pressure to yield the crude amine 22a (0.64
g, 51%) which was used without further purification in the sub-
sequent tosylation reaction and which showed νmax/cmϪ1 [film]
3060 (m), 2975 (m), 1743 (s), 1660 (s), 1599 (m), 1447 (m), 1318
(s), 1278 (s) and 1216 (m); δH 1.04 (3H, t, J = 7.5, 7-CH3), 1.62–
1.69 (2H, br s, NH2), 2.13–2.19 (2H, m, 6-CH2), 2.50–2.54 (2H,
m, 3-CH2), 3.50–3.53 (1H, m, 2-H) and 3.69 (3H, s, OCH3); δC
12.2 (CH2), 14.0 (CH3), 25.1 (CH2), 52.0 (OCH3), 53.4 (2-CH),
(C᎐O); m/z [EI] 483 (Mϩ, 92%), 424 (17), 197 (16), 201 (100),
᎐
169 (52), 142 (61), 115 (80), 91 (82) and 65 (60) [Found: Mϩ,
483.0001. C19H18INO4S requires M, 483.0003].
Methyl 5-(2-furyl)-4-iodo-1-(4-tolylsulfonyl)-2,3-dihydropyr-
role-2-carboxylate 23b. The tosylamide 19b (70 mg, 0.20 mmol)
was cyclised according to the general procedure with potassium
carbonate (84 mg, 0.61 mmol, 3.0 equiv.) and iodine (153 mg,
0.61 mmol, 3.0 equiv.). The crude residue was chromato-
graphed (6 : 1 hexane–ethyl acetate) to give the dihydropyrrole
23b (74 mg, 78%) as a pale yellow solid, mp 88–92 ЊC; νmax/cmϪ1
2953 (w), 1742 (s), 1597 (w), 1437 (w), 1361 (s), 1210 (m), 1170
(s), 1089 (m) and 1017 (m); δH 2.45 (3H, s, Ar-CH3), 2.59 (1H,
dd, J = 17.1 and 9.7, 3-Ha), 2.85 (1H, dd, J = 17.1 and 2.3,
3-Hb), 3.82 (3H, s, OMe), 4.83 (1H, dd, J = 9.7 and 2.3, 2-H),
6.50 (1H, dd, J = 3.4 and 1.8, 4Ј-H), 6.89 (1H, d, J = 3.4, 3Ј-H),
7.31 (2H, d, J = 8.2, 2 × Ar-H), 7.47 (1H, app br s, 5Ј-H) and
7.60 (2H, d, J = 8.2, 2 × Ar-H); δC 21.6 (Ar-CH3), 43.5 (3-CH2),
53.1 (OMe), 62.2 (2-CH), 77.6 (4-C), 111.0 (4Ј-CH), 113.9
(3Ј-CH), 127.8 (2 × CH), 129.6 (2 × CH), 133.5 (C), 135.8 (C),
74.0 (4(5)-C), 84.8 (5(4)-C) and 174.0 (C᎐O).
᎐
Methyl 2-(4-tolylsulfonylamino)hept-4-ynoate 22b
The amine 22a (0.50 g, 3.23 mmol, 1.0 equiv.) was stirred in
dichloromethane (10 ml) at room temperature. Tosyl chloride
(0.68 g, 3.55 mmol, 1.1 equiv.) and a crystal of DMAP were
then added, followed by the dropwise addition of triethylamine
(0.54 ml, 3.88 mmol, 1.2 equiv.). The resulting mixture was
stirred overnight at room temperature, then 2 M hydrochloric
acid (10 ml) was added and the organic phase separated. The
aqueous phase was extracted with dichloromethane (2 × 10 ml)
and the combined organic solutions washed with brine (10 ml),
dried, filtered and concentrated under reduced pressure to give
a brown oil. This was chromatographed (4 : 1 hexane–ethyl
acetate) to give the tosylamide 22b (0.72 g, 72%) as a pale oil,
νmax/cmϪ1 3283 (m), 3061 (w), 1745 (s), 1436 (m), 1338 (s), 1219
(m), 1163 (s) and 1092 (s); δH 0.99 (3H, t, J = 7.5, 7-CH3),
1.97–2.05 (2H, m, 6-CH2), 2.61–2.66 (2H, m, 3-CH2), 2.42 (3H,
s, Ar-CH3), 3.58 (3H, s, OCH3), 4.07 (1H, ddd, J = 9.3, 5.0 and
5.0, 2-H), 5.48 (1H, d, J = 9.3, NH), 7.30 (2H, d, J = 8.2, 2 ×
Ar-H) and 7.75 (2H, d, J = 8.2, 2 × Ar-H); δC 12.2 (6-CH2), 13.9
(7-CH3), 21.5 (Ar-CH3), 24.2 (3-CH2), 52.6 (OCH3), 54.4
(2-CH), 72.2 (5(4)-C), 85.9 (4(5)-C), 127.1 (2 × CH), 129.6
143.1 (5Ј-CH), 144.6 (C), 144.8 (C) and 170.6 (C᎐O); m/z [EI]
᎐
473 (Mϩ, 27%), 318 (17), 191 (88), 159 (51), 132 (56), 104 (55)
and 91 (100) [Found: Mϩ, 472.9796. C17H16INO5S requires M,
472.9796] [Found: C, 42.83; H, 3.41; N, 3.10. C17H16INO5S
requires C, 43.13; H, 3.41; N, 2.96%].
Methyl 4-iodo-5-(2-thienyl)-1-(4-tolylsulfonyl)-2,3-dihydro-
pyrrole-2-carboxylate 23c. The tosylamide 19c (0.20 g,
0.55 mmol, 1.0 equiv.) was cyclised according to the general
procedure with potassium carbonate (0.23 g, 1.65 mmol,
3.0 equiv.) and iodine (0.42 g, 1.65 mmol, 3.0 equiv.). The crude
residue was chromatographed (6 : 1 hexane–ethyl acetate) to
give the dihydropyrrole 23c (0.21 g, 76%) as a pale yellow solid,
mp 103–105 ЊC; νmax/cmϪ1 2953 (m), 1744 (s), 1597 (m), 1436
(m), 1362 (s), 1296 (m), 1212 (m), 1169 (s), 1090 (m), 1026 (m)
and 911 (m); δH 2.45 (3H, s, Ar-CH3), 2.67 (1H, dd, J = 17.0 and
9.6, 3-Ha), 2.83 (1H, dd, J = 17.0 and 2.6, 3-Hb), 3.84 (3H, s,
OCH3), 4.91 (1H, dd, J = 9.6 and 2.6, 2-H), 7.05 (1H, dd, J = 5.0
and 3.7, 4Ј-H), 7.28 (2H, d, J = 8.2, 2 × Ar-H), 7.40–7.45 (2H,
m, 3Ј- and 5Ј-H) and 7.58 (2H, d, J = 8.2, 2 × Ar-H); δC 21.6
(Ar-CH3), 43.7 (3-CH2), 53.1 (OCH3), 62.2 (2-CH), 78.7 (4-C),
126.4 (4Ј-CH), 127.7 (3Ј(5Ј)-CH), 127.8 (2 × CH), 129.6 (2 ×
CH), 130.8 (5Ј(3Ј)-CH), 132.6, 133.8, 138.9, 144.6 (all C) and
(2 × CH), 136.8 (C), 143.6 (C) and 170.3 (C᎐O); m/z [EI] 309
᎐
(Mϩ, 7%), 250 (32), 242 (67), 155 (99), 139 (36), 91 (100) and 65
(74) [Found: C, 58.06; H, 6.37; N, 4.37. C15H19NO4S requires C,
58.23; H, 6.19; N, 4.53%].
Iodocyclisation of homopropargylic sulfonamides: general
procedure
The homopropargylic sulfonamide 19a–c or 22b (1 mmol,
1.0 equiv.) was stirred in dry acetonitrile (2 ml) with anhydrous
potassium carbonate (3 mmol, 3 equiv.) at 0 ЊC. Iodine
(3 mmol, 3 equiv.) in acetonitrile (0.6 ml) was added dropwise
and the resulting mixture allowed to warm to room temperature
overnight. The reaction was quenched with saturated aqueous
sodium thiosulfate until the mixture was decolourised and the
organic layer was separated. The aqueous layer was then
extracted with dichloromethane (2 × 5 ml) and the organic
solutions were combined, dried and concentrated under reduced
pressure. The crude product was then purified by column
chromatography.
170.8 (C᎐O); m/z [EI] 489 (Mϩ, 7%), 275 (2), 207 (16), 148 (20),
᎐
121 (16), 91 (100) and 65 (73) [Found: Mϩ, 488.9566.
C17H16INO4S2 requires M, 488.9567].
Methyl 5-ethyl-4-iodo-1-(4-tolylsulfonyl)-2,3-dihydropyrrole-
2-carboxylate 23d. The tosylamide 22b (0.20 g, 0.65 mmol,
1.0 equiv.) was cyclised according to the general procedure with
potassium carbonate (0.27 g, 1.94 mmol, 3.0 equiv.) and iodine
(0.50 g, 1.94 mmol, 3.0 equiv.). The crude residue was chroma-
tographed (6 : 1 hexane–ethyl acetate) to give the dihydropyrrole
23d (0.20 g, 71%) as a brown oil, νmax/cmϪ1 [film] 3500 (w), 2925
(s), 1745 (s), 1598 (w), 1454 (m), 1356 (s), 1215 (m) 1187 (s) and
1090 (m); δH 1.04–1.09 (3H, m, 5b-CH3), 2.38 (3H, s, Ar-CH3),
2.43–2.63 (4H, m, 1Ј-CH2 and 3-CH2), 3.73 (3H, s, OCH3), 4.62
(1H, app s, 2-H), 7.30 (2H, d, J = 8.4, 2 × Ar-H) and 7.66 (2H,
d, J = 8.4, 2 × Ar-H); δC 11.7 (2Ј-CH3), 21.7 (Ar-CH3), 23.5
(1Ј-CH2), 41.9 (3-CH2), 52.9 (OCH3), 62.1 (2-CH), 73.9 (4-C),
127.5 (2 × CH), 129.9 (2 × CH), 134.5, 144.5, 146.9 (all C) and
Methyl 4-iodo-5-phenyl-1-(4-tolylsulfonyl)-2,3-dihydropyrrole-
2-carboxylate 23a. The tosylamide 19a (0.25 g, 0.70 mmol,
1.0 equiv.) was cyclised according to the general procedure with
potassium carbonate (0.29 g, 2.1 mmol, 3.0 equiv.) and iodine
(0.54 g, 2.1 mmol, 3.0 equiv.). The crude residue was chromato-
graphed (6 : 1 hexane–ethyl acetate) to give the dihydropyrrole
23a (0.25 g, 74%) as a pale yellow solid, mp 130–133 ЊC; νmax
/
171.2 (C᎐O); m/z [EI] 435 (Mϩ, 2%), 155 (24), 127 (16), 91 (100),
᎐
cmϪ1 [CHCl3] 3058 (m), 2999 (m), 1740 (s), 1650 (s), 1598 (w),
1443 (m), 1363 (s), 1282 (s), 1245 (m), 1212 (m), 1171 (s), 1091
89 (18), 77 (9) and 65 (61) [Found: M ϩ Hϩ, 436.0080.
C16H19INO4S requires M, 436.0081].
626
J. Chem. Soc., Perkin Trans. 1, 2002, 622–628

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Preparation of ꢀ-iodopyrroles 24 or 26a–c: general procedure
(1 ml) with CuI (4 mg, 0.0208 mmol, 0.2 equiv.) and Pd(PPh3)4
(12 mg, 0.0104 mmol, 0.1 equiv.). Phenylacetylene (11 mg, 0.104
mmol, 1.0 equiv.) was then added and the mixture stirred at
room temperature under nitrogen for 2 h. The reaction was then
concentrated, diluted with ether (5 ml), filtered through Celite
and the filtrate concentrated to give a brown oil. This was puri-
fied by column chromatography (4 : 1 hexane–ethyl acetate) to
give the dihydropyrrole 29 (39 mg, 82%) as a pale yellow solid,
mp 139–141 ЊC; νmax/cmϪ1 2953 (w), 2245 (w), 1756 (s), 1595
(m), 1488 (m), 1365 (s), 1210 (s), 1170 (s), 1089 (m) and 1030
(m); δH 2.43 (3H, s, Ar-CH3), 2.62 (1H, dd, J = 16.3 and 9.6,
3-Ha), 2.72 (1H, dd, J = 16.3 and 2.6, 3-Hb), 3.84 (3H, s, OCH3),
4.90 (1H, dd, J = 9.6 and 2.6, 2-H) and 7.25–7.81 (14H, m,
Ar-H); δC 21.7 (Ar-CH3), 36.5 (3-CH2), 53.1 (OCH3), 62.0
(2-CH), 84.4, 95.5, 108.3, 122.8 (all C), 127.6, 127.7, 128.4,
128.5, 129.2, 129.4, 129.8, 131.3 (all Ar-CH), 131.4 (C), 134.4
To a stirred solution of the dihydropyrrole 23 (1 mmol, 1 equiv.)
in DMF (5 ml) at room temperature was added DBU
(2.1 mmol, 2.1 equiv.) dropwise. The reaction was then stirred at
room temperature until complete by TLC analysis (approx.
2 h). 2 M Hydrochloric acid (5 ml) was added and the mixture
was then extracted with hexane (4 × 20 ml). The combined
organic extracts were dried, filtered and concentrated under
reduced pressure. The crude product was purified by dissolving
it in ethyl acetate and filtering the resulting solution through a
small pad of silica to yield the iodopyrrole 24 or 26a–c.
Methyl 4-iodo-5-phenylpyrrole-2-carboxylate 24. The dihydro-
pyrrole 23a (50 mg, 0.104 mmol, 1.0 equiv.) was treated with
DBU (31 µl, 0.208 mmol, 2.0 equiv.) according to the general
procedure to give the iodopyrrole 24 (45 mg, 90%) as a colour-
less solid, mp 62–65 ЊC; νmax/cmϪ1 3280 (s), 1689 (s), 1463 (m),
1438 (m), 1319 (m), 1257 (m) and 1207 (m); δH 3.83 (3H, s,
OCH3), 7.10 (1H, d, J = 2.6, 3-H), 7.38–7.48 (3H, m, Ar-H),
7.67 (2H, dd, J = 7.2 and 7.2, Ar-H) and 9.57 (1H, br s, NH); δC
51.9 (OCH3), 62.2 (4-C), 124.4 (3-CH), 127.9 (Ar-CH), 128.7
(CH), 144.5 (C), 146.3 (C) and 171.3 (C᎐O); m/z [EI] 457 (Mϩ,
᎐
22%), 302 (75), 270 (82), 243 (75) and 91 (100) [Found: Mϩ,
457.1348. C27H23NO4S requires M, 457.1348].
Acknowledgements
(Ar-CH), 131.2 (C), 137.1 (C) and 162.0 (C᎐O); m/z [EI] 327
᎐
We are very grateful to the EPSRC Mass Spectrometry Service,
University College, Swansea for the provision of high reso-
lution mass spectral data, and to Eli Lilly and Co. Ltd. and the
EPSRC for financial support through the CASE scheme.
(Mϩ, 80%), 295 (51), 267 (14), 140 (100) and 113 (43) [Found:
Mϩ 326.9759. C12H10INO2 requires M, 326.9758].
Methyl 5-(2-furyl)-4-iodopyrrole-2-carboxylate 26a. The
dihydropyrrole 23b (49 mg, 0.104 mmol, 1.0 equiv.) was treated
with DBU (31 µl, 0.208 mmol, 2.1 equiv.) according to the
general method to give the iodopyrrole 26a (28 mg, 85%) as a
colourless solid, mp 72–75 ЊC; νmax/cmϪ1 3282 (m), 2951 (m),
1697 (s), 1508 (m), 1437 (m), 1395 (m), 1317 (m), 1262 (m) and
1203 (m); δH 3.88 (3H, s, OCH3), 6.53 (1H, dd, J = 3.5 and 1.6,
4Ј-H), 7.07 (1H, d, J = 2.7, 3-H), 7.21 (1H, d, J = 3.5, 3Ј-H), 7.47
(1H, d, J = 1.6, 5Ј-H) and 9.45 (1H, br s, NH); δC 51.9 (OCH3),
65.2 (4-C), 107.8, 111.8, 124.5, 142.0 (all Ar-H), 129.0, 136.0,
References
1 A. D. Jones, D. W. Knight and D. E. Hibbs, J. Chem. Soc., Perkin
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2 D. W. Knight, A. L. Redfern and J. Gilmore, J. Chem. Soc., Perkin
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3 For recent contributions, see J. T. Gupton, D. A. Krolikowski, R. H.
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4 J. E. Baldwin, J. Chem. Soc., Chem. Commun., 1976, 734 and 738;
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5 P. Aschwanden, D. E. Frantz and E. M. Carreira, Org. Lett., 2000, 2,
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140.5 (all Ar-C) and 162.5 (C᎐O); m/z [EI] 317 (Mϩ, 79%), 285
᎐
(59), 130 (70), 76 (79) and 56 (100) [Found: Mϩ, 316.9551.
C10H8INO3 requires M, 316.9551].
Methyl 4-iodo-5-(2-thienyl)pyrrole-2-carboxylate 26b. The
dihydropyrrole 23c (51 mg, 0.104 mmol, 1.0 equiv.) was treated
with DBU (31 µl, 0.208 mmol, 2.0 equiv.) according to the
general procedure to give the iodopyrrole 26b (30 mg, 86%) as a
colourless solid, mp 120–124 ЊC; νmax/cmϪ1 3295 (m), 2952 (w),
1688 (s), 1472 (m), 1438 (m), 1317 (m), 1263 (s) and 1204 (s);
δH 3.88 (3H, s, OCH3), 7.08 (1H, d, J = 2.6, 3-H), 7.14 (1H, dd,
J = 5.0 and 3.7, 4Ј-H), 7.38 (1H, d, J = 5.0, 3Ј-H), 7.48 (1H, d,
J = 3.7, 5Ј-H) and 9.66 (1H, br s, NH); δC 51.9 (OCH3), 72.5
(4-C), 124.5, 127.0, 128.0, 128.5 (all Ar-H), 133.4, 135.0, 147.0
6 S. P. Bew and D. W. Knight, Chem. Commun., 1996, 1007; G. M. M.
El-Taeb, A. B. Evans, S. Jones and D. W. Knight, Tetrahedron Lett.,
2001, 42, 5945.
7 A. B. Evans and D. W. Knight, unpublished observations.
8 For a preliminary report, see D. W. Knight, A. L. Redfern and
J. Gilmore, Chem. Commun., 1998, 2207.
(all C) and 169.5 (C᎐O); m/z [EI] 333 (Mϩ, 81%), 301 (87), 174
᎐
(13), 146 (100), 120 (85) and 69 (50) [Found: Mϩ, 332.9322.
9 A. Lopez, M. Moreno-Manas, R. Pleixats, A. Roglans, J. Ezquerra
and C. Pedregal, Tetrahedron, 1996, 52, 8365.
C10H8INO2S requires M, 332.9322].
10 M. J. O’Donnell and R. L. Polt, J. Org. Chem., 1982, 47, 2663.
11 K. Sonogashira, Y. Tohda and N. Hagihara, Tetrahedron Lett., 1975,
4467; K. Sonogashira, Comp. Org. Synth, eds. B. M. Trost and
I. Fleming, Pergamon Press, Oxford, 1991, vol. 3, p. 521.
12 H. Günther, NMR Spectroscopy, 2nd edn., Georg Thieme Verlag,
Stuttgart, 1992; H. Günther, English translation, John Wiley and
Sons Ltd., Chichester, 1995.
13 D. W. Knight and C. M. Sharland, unpublished results.
14 See, for example, M. A. Fagan and D. W. Knight, Tetrahedron Lett.,
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15 N. A. Bumagin, A. F. Nikitina and I. P. Beletskaya, Russ. J. Org.
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16 C. K. Chang and N. Bag, J. Org. Chem., 1995, 60, 7030.
17 A. Alvarez, A. Cuzmán, A. Ruiz, E. Velarde and J. M. Muchowski,
J. Org. Chem., 1992, 57, 1653.
Methyl 5-ethyl-4-iodopyrrole-2-carboxylate 26c. The dihydro-
pyrrole 23d (100 mg, 0.23 mmol, 1.0 equiv.) was treated with
DBU (0.07 ml, 0.46 mmol, 2.0 equiv.) according to the general
procedure to give the iodopyrrole 26c (50 mg, 86%) as a pale
brown oil, νmax/cmϪ1 3279 (s), 2975 (w), 1682 (s), 1489 (s), 1319
(m), 1280 (m) and 1206 (s); δH 1.24 (3H, t, J = 7.6, 2Ј-CH3), 2.66
(2H, q, J = 7.6, 1Ј-CH2), 3.84 (3H, s, OCH3), 6.94 (1H, d,
J = 2.6, 3-H) and 9.28 (1H, br s, NH); δC 13.2 (2Ј-CH3), 21.6
(1Ј-CH2), 51.6 (OCH3), 63.0 (4-C), 122.6 (3-CH), 141.0 (C),
142.0 (C) and 162.0 (C᎐O); m/z [ES] 280 (M ϩ Hϩ, 10%), 204
᎐
(49), 239 (14), 154 (10), 102 (37) and 61 (100) [Found: M ϩ Hϩ,
279.9835. C8H11INO2 requires M, 279.9836].
18 J. Wang and A. I. Scott, Tetrahedron Lett., 1995, 36, 7043.
19 J. Wang and A. I. Scott, Tetrahedron Lett., 1995, 36, 3247.
20 For recently reported alternative approaches to 2,3-dihydropyrroles,
see M. S. Baird, A. G. W. Baxter, A. Hoorfar and I. Jefferies,
J. Chem. Soc., Perkin Trans. 1, 1991, 2575; D. Jacoby, J. P. Celerier,
Methyl 5-phenyl-4-(phenylethynyl)-1-(4-tolylsulfonyl)-2,3-di-
hydropyrrole-2-carboxylate 29. The dihydropyrrole 23a (50 mg,
0.104 mmol, 1.0 equiv.) was stirred in degassed diethylamine
J. Chem. Soc., Perkin Trans. 1, 2002, 622–628
627

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21 For recent developments of methods leading to β-halopyrroles, see:
F. Franco, R. Greenhouse and J. M. Muchowski, J. Org. Chem.,
628
J. Chem. Soc., Perkin Trans. 1, 2002, 622–628