An efficient and selective synthesis of 2,5-substituted pyrroles by gold-catalysed ring expansion of alkynyl aziridines

Article abstract of DOI:10.1016/j.jorganchem.2010.08.040

A range of substituted alkynyl aziridines undergo a ring expansion to afford 2,5-substituted pyrroles under gold catalysis. While effective conditions can be generated from other gold sources, a combination of Ph₃PAuCl and AgOTs generate a cata

Full text of DOI:10.1016/j.jorganchem.2010.08.040

Journal of Organometallic Chemistry 696 (2011) 159e164
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
An efficient and selective synthesis of 2,5-substituted pyrroles by gold-catalysed
ring expansion of alkynyl aziridines
*
Paul W. Davies , Nicolas Martin
School of Chemistry, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
A range of substituted alkynyl aziridines undergo a ring expansion to afford 2,5-substituted pyrroles
under gold catalysis. While effective conditions can be generated from other gold sources, a combination
of Ph3PAuCl and AgOTs generate a catalyst system that provides extremely clean cycloisomerisation
reactions requiring minimal work-up and purification.
Received 31 July 2010
Received in revised form
24 August 2010
Accepted 24 August 2010
Available online 29 September 2010
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
Gold catalysis
Pyrrole
Cycloisomerisation
Counterion
1. Introduction
precursors through choice of solvent and counterion. 2,4-Subs-
tituted pyrroles were formed with ultimate rearrangement of the
Transition-metal catalysed cycloisomerisation strategies have
proven highly applicable for the synthesis of heterocyclic motifs [1].
Attractive aspects of cycloisomerisations include their inherent
substrate efficiency and the generally mild reaction conditions
employed, which for example avoid the need for strong bases/acids.
Additionally, the provision of alternative stratagems to access
valuable target molecules can greatly facilitate synthesis. As there is
often no need to add reagents beyond the solvent, catalyst and
substrate, the cycloisomerisation reactions and their work-up and
purifications are often rendered straightforward and user-friendly.
The pyrrole motif attracts particular attention in methodology
design for its utility as a synthetic building block and widespread
occurrence in target structures, such as functional materials and
biologically-relevant compounds [2]. Within this area we recently
carbonecarbon connectivity by a cascade reaction triggered on ring
expansion (A / C).
Subsequently, several reports have employed
p-acid promoted
ring expansion of alkynyl aziridines to prepare a range of variously
substituted pyrroles (Type A / B) [6,7]. The combination of azir-
idines tethered in some way to alkynes has also been employed
under gold catalysis in reactions such as cyclisationerearrange-
ment [8], and cyclisationesubstitution [9] cascades. Here we report
our studies on the gold-catalysed ring expansion of alkynyl azir-
idines to form 2,5-substituted pyrroles [10].
2. Results and discussion
All the alkynyl aziridines employed in our study were prepared
according to the method of Dai through a convergent coupling of an
imine with a propargylic sulfonium ylide (Scheme 2) [11]. In most
cases a mixture of diastereomers were obtained, with the cis-dia-
stereomer predominating, and were used as such in the subsequent
reactions [12].
Our study commenced with use of 2-(hex-1-ynyl)-3-phenyl-1-
tosylaziridine 1a. Under some standard reaction conditions for
gold-catalysed cycloisomerisation processes (Ph3PAuOTf in non-
coordinating solvent) we observed the unexpected formation of
a mixture of isomers (Scheme 3) [13].
reported
a new pyrrole synthesis by gold-catalysed cyclo-
isomerisation of 1-aryl-2-alkynyl aziridines which features a formal
‘XeH’ addition across an alkyne (Scheme 1) [3]. Ring expansion from
the aziridine onto the adjacent alkyne was promoted by the cationic
gold system Ph3PAuX, where X is a ‘non-coordinating’ counterion
(A / B) [4,5]. Along with this pathway for the preparation of
2,5-substituted pyrroles, we had also shown that a regiodivergent
pathwaycould be accessed from the same 1-aryl-2-alkynyl aziridine
The outcome of thisreactionprovedto behighly dependenton the
nature of either solvent and/or counterion [14]. Less of the product
* Corresponding author. Tel.: þ44 121 414 4408; fax: þ44 121 4144403.
E-mail address: p.w.davies@bham.ac.uk (P.W. Davies).
0022-328X/$ e see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.08.040

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P.W. Davies, N. Martin / Journal of Organometallic Chemistry 696 (2011) 159e164
Scheme 1. Selective synthesis of 2,5 or 2,4-substituted pyrroles.
from the cascade skeletal rearrangement pathway (1 /3) was seen
when the reaction media consisted of a relatively Lewis basic or protic
solvent. Conversely, formation of 3 was favoured in chlorinated
solvents.
Referring to the proposed mechanism for ring expansion (Fig. 1),
the presence of Lewis basic or protic solvents to assist in stabilising
Scheme 3. Survey of reaction conditions.
common intermediate
E and/or in the deprotonation/proto-
Additionally, functionalised substrates bearing aryl bromides and
alkenes can be taken through unscathed [Entries 2e4, 8 and 15].
When trimethylsilylated alkynes 4aec were subjected to the
standard reaction conditions (Scheme 4), quantitative yields of 2-
substituted pyrroles 5aec were isolated. Protodesilylation is
presumably aided by adventitious water [19]. Use of triethylsilyated
species 4d gave equivalent results.
Alkynyl aziridine 6 bearing a deuterium label adjacent to the
aryl group was subjected to the reaction conditions and a quanti-
tative yield of a mixture of isotopomers was obtained (Scheme 5).
Incomplete deuterium incorporation was observed at C-4 which is
consistent with the proposed reaction mechanism. Elimination of
the proton/deuteron from E (Fig. 1) and subsequent intermolecular
capture of proton or deuteron by the vinyl gold unit, provide
opportunity for H/D exchange [20]. Similarly, deuterium incorpo-
ration at C-4 was also observed when non-deuterated alkynyl
aziridine was reacted in D2O washed dichlorethane [21]. No
significant build up of intermediates was observed when a cyclo-
isomerisation reaction was monitored by 1H NMR [22].
demetallation stages appears to aid clean progression along this
pathway [15]. The proclivity of the system to afford 3 by undergoing
an alternate rearrangement pathway from intermediates E/F is
reduced [16,17].
These conditions gave good yields and selectivity, and it is
notable that all the other preparations reported also ultimately
employ ethereal or protic solvents in the reaction media [6].
However, for the formation of 2,5-substituted pyrrole by this route
we discovered that the use of an apparently less active catalyst,
Ph3PAuOTs, provides exquisite selectivity. The 2,5-substituted
product is formed cleanly even in chlorinated solvents (Scheme 3).
The effect of the tosylate on reaction outcome is quite remarkable.
Despite being only present in catalytic quantities it has greater
impact even than solvent on directing the process along the ring
expansion pathway whilst avoiding alternative outcomes, to thus
enable the quantitative formation of a single product. To rationalise
the overall improved relative efficacy of this system against the
more active Ph3PAuOTf system for the formation of 2,5-substituted
pyrroles, we can consider it a consequence of the level of carbo-
cationic character that is generated being insufficient to access the
cascade pathway, and/or the involvement of the more basic tosylate
counterion in proton transfer steps. Alternatively, as a relatively
nucleophilic species, the tosylate could conceivably play a direct
role in the process [18].
The reaction simplicity and the formation of a single product in
quantitative yields engender significant economy and efficiency
over the entire process as, beyond the simple expedient of filtration
through a silica plug, no work-up or purification was required.
These conditions were then applied to a range of alkynyl
aziridines. 1-Aryl-2-alkynyl aziridines were transformed to the
2-aryl-5-substituted pyrroles in quantitative yield with no isomeric
side-product [Table 1, Entries 1e8]. A range of alkyl substituted
species, which are incapable of undergoing the cascade reaction
(A / C), were also tested under the reaction conditions. In all cases
near-quantitative yields were obtained [Entries 9e14].
3. Conclusions
The ring expansion of alkynyl aziridines proceeds smoothly under
a simple reaction system to afford 2,5-substituted pyrroles. The use of
arelativelylowactivitycatalyst, Ph3PAuOTs, gavegreater specificity in
the ring expansion reactions than a combination of a more reactive
system and protic or ethereal solvents. The reaction tolerates alkyl
and aryl substituents both on the alkyne and the aziridine, also
accommodating functionality such as aryl halides and alkenes, and in
all cases pyrroles were formed in near-quantitative yields.
4. Experimental
All experiments were carried out under an inert atmosphere in
dried glassware. NMR: Spectra were recorded on Bruker AC300
The reaction tolerates either alkyl or aryl substituents, or
a mixture thereof, at both the aziridine and the alkyne moiety.
Substrates bearing aryl groups on the alkyne were more prone to
ring expansion than alkyl substituted analogues, proceeding to
completion even at room temperature [Entries 9, 10 and 14].
Scheme 2. General method for the preparation of alkynyl aziridine precursors
(Ref. [11]).
Fig. 1. Mechanistic proposal.

P.W. Davies, N. Martin / Journal of Organometallic Chemistry 696 (2011) 159e164
161
Table 1
Cycloisomerisation to form 2,5-substituted pyrroles.a
Entry
R
R1
Time/h
T/ꢀC
Yieldb/%
Entry
R
R1
Time/h
T/ꢀC
Yieldb/%
1
2
3
4
5
6
7
8
Ph
nBu
3.5
4
4
5
3
3.5
4
3
70
70
70
70
70
70
70
70
>95
>95
>95
>95
>95
>95
95
9
10
11
12
13
14
15
nBu
Ph
12
12
4
3
3
23
23
70
70
70
23
70
>95
>95
>95
>95
>95
>95
95
4-BrC6H4
2-BrC6H4
4-CH3C6H4
Ph
4-CH3C6H4
Ph
nBu
cC6H11
cC6H11
cC6H11
iPr
Ph
nBu
nBu
nBu
cC6H11
cC6H11
Ph
Ph
Ph
iPr
12
12
CH2CH2Ph
4-BrC6H4
iPr
CH2CH]CH2
Ph
>95
a
All reactions are run using 0.2 mmol of substrate using 5 mol% of Ph3PAuCl and AgOTs at 0.2 M concentration at the indicated temperature.
Isolated percentage yields of pyrrole products.
b
(1H ¼ 300 MHz, 13C ¼ 75.5 MHz), Bruker AV300 (1H ¼ 300 MHz,
4.1.3. Hex-5-en-2-ynyldimethylsulfonium bromide
13C ¼ 75.5 MHz), Bruker AV400 (1H ¼ 400 MHz, 13C ¼ 101 MHz),
White solid (35%). 1H NMR (300 MHz, CDCl3):
d
¼ 3.41 (s, 6H),
and Bruker DRX500 (1H ¼ 500 MHz, 13C ¼ 126 MHz) in the solvents
3.70 (m, 2H), 4.80 (s, 2H), 5.47 (dd, J ¼ 11.0, 1.8 Hz, 1H), 5.56 (dd,
indicated; Chemical shifts (d) are given in ppm relative to TMS. The
J ¼ 18.0, 1.8 Hz, 1H), 6.01 (m, 1H); 13C NMR (75 MHz, CDCl3):
solvent signals were used as references and the chemical shifts
converted to the TMS scale (CDCl3: dC h 77.0 ppm; residual CHCl3 in
CDCl3: dH h 7.26 ppm).
Sulfonium salts and alkynyl aziridines were prepared according to
the literature method [11]. For analytical data relating to compounds
in Table 1 Entries 1e6 see Ref [3]. Data for the following compounds
are in accordance to literature values (Table 1 Entries, 10, 11, 14) [6a];
4a [23], 4b [6a], 5b/c [6a], 4c [11], dimethyl(3-(trimethylsilyl)prop-2-
yn-1-yl)sulfonium bromide and dimethyl(3-phenylprop-2-yn-1-yl)
sulfonium bromide correspond to the literature [11].
d
¼ 23.3, 24.6 (2C), 34.3, 76.6, 81.5, 117.5, 133.1; IR (neat): ¼ 3090,
n
3020, 2915, 2191, 1825, 1640, 1323, 1193, 1035, 991, 925, 840, 760,
642; HRMS (TOF ESþ): m/z calcd for C8H13S: 141.0732, found:
141.0740.
4.1.4. Dimethyl(5-phenylpent-2-ynyl)sulfonium bromide
White solid (72%). 1H NMR (300 MHz, CDCl3):
d
¼ 2.65 (tt,
J ¼ 6.9, 2.1 Hz, 2H), 2.84 (t, J ¼ 6.9 Hz, 2H), 2.87 (s, 6H), 4.85 (t,
J ¼ 2.1 Hz, 2H), 7.17e7.24 (m, 3H), 7.26e7.33 (m, 2H); 13C NMR
(75 MHz, CDCl3):
128.4 (2C), 128.7 (2C), 139.6; IR (neat):
1494, 1452, 1410, 1323, 1261, 1206, 1151, 1056, 1005, 939, 742, 701;
d
¼ 20.3, 24.0 (2C), 33.3, 34.0, 66.3, 91.4, 126.8,
n
¼ 2988, 2918, 2231, 1601,
4.1. Propargyl sulfonium salts
HRMS (TOF ESþ): m/z calcd for C13H17S: 205.1051, found: 205.1055.
4.1.1. Dimethyl(3-(triethylsilyl)prop-2-ynyl)sulfonium bromide
4.1.5. Dimethyl(3-(4-bromophenyl)prop-2-ynyl)sulfonium bromide
White solid (60%). 1H NMR (300 MHz, CDCl3):
d
¼ 0.61 (q,
White solid (79%). 1H NMR (300 MHz, CDCl3):
d
¼ 3.39 (s, 6H),
J ¼ 7.7 Hz, 6H), 0.96 (t, J ¼ 7.7 Hz, 9H), 3.21 (s, 6H), 5.06 (s, 2H); 13C
5.51 (s, 2H), 7.44 (d, J ¼ 8.4 Hz, 2H), 7.55 (d, J ¼ 8.4 Hz, 2H); 13C NMR
NMR (75 MHz, CDCl3):
d
¼ 4.0 (3C), 7.4 (3C), 24.4 (2C), 33.7, 90.9,
(75 MHz, CDCl3):
d
¼ 23.9 (2C), 30.2, 79.9, 87.5, 122.6, 122.8, 132.1
95.4; IR (neat):
n
¼ 3013, 2918, 2181,1318,1253,1190,1038, 991, 845,
(2C), 135.6 (2C); IR (neat):
n
¼ 3012, 2929, 2884, 2241, 1628, 1401,
761, 639; HRMS (TOF ESþ): m/z calcd for C11H23SSi: 215.1290, found:
1325, 1221, 1163, 1135, 1112, 1072, 1039, 1001, 982, 840, 805, 778,
722; HRMS (TOF ESþ): m/z calcd for C11H12SBr: 254.9838, found:
254.9845.
215.1291.
4.1.2. (3-Cyclohexylprop-2-ynyl)dimethylsulfonium bromide
White solid (55%). 1H NMR (300 MHz, CDCl3):
d
¼ 1.12e1.85 (m,
10H), 2.44 (m, 1H), 3.18 (s, 6H), 4.95 (s, 2H); 13C NMR (75 MHz,
CDCl3):
¼ 18.0, 24.2 (2C), 24.7 (2C), 25.5, 32.3 (2C), 33.4, 65.1, 96.7;
IR (neat):
4.2. Alkynyl aziridines
d
4.2.1. 2-{Phenyl-3-(4-phenylbut-1-yn-1-yl)-1-(toluene-4-sulfonyl)
aziridine (Table 1, Entry 7)
n
¼ 3001, 2951, 2929, 2889, 2233, 1458, 1419, 1325, 1248,
1187,1153, 1050,1001, 928, 721, 638; HRMS (TOF ESþ): m/z calcd for
Colourless oil (70%, 11:1 cis:trans). 1H NMR (300 MHz, CDCl3):
C11H19S: 183.1202, found: 183.1210.
d
¼ 2.27e2.34 (m, 2H), 2.44 (s, 3H), 2.50e2.66 (m, 2H), 3.63 (dt,
J ¼ 6.9, 1.8 Hz, 1H), 3.95 (d, J ¼ 6.9 Hz, 1H), 6.96e7.01 (m, 2H),
Scheme 4. Reaction of silylated alkynyl aziridines.
Scheme 5. Use of deuterated substrate.

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P.W. Davies, N. Martin / Journal of Organometallic Chemistry 696 (2011) 159e164
7.24e7.27 (m, 3H), 7.30 (s, 5H), 7.34 (d, J ¼ 8.3 Hz, 2H), 7.89 (d,
2230, 1830, 1630, 1323, 1160, 1093, 980, 940, 876, 725; HRMS (TOF
ESþ): m/z calcd for C17H21NO2NaS: 326.1191, found: 326.1182.
J ¼ 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3):
d
¼ 20.8, 21.7, 34.4, 36.2,
46.1, 73.0, 85.9, 126.2, 127.8 (2C), 127.9 (2C), 128.0 (2C), 128.3 (5C),
129.8 (2C), 132.2, 134.8, 140.2, 144.8; IR (neat):
n
¼ 2987, 2931, 2248,
4.2.7. 2-Isopropyl-1-(toluene-4-sulfonyl)-3-((trimethylsilyl)
ethynyl)aziridine (4a)
1597, 1495, 1453, 1384, 1327, 1291, 1233, 1158, 1090, 1021, 875, 814,
742, 695; HRMS (TOF ESþ): m/z calcd for C25H23NO2NaS: 424.1347,
found: 424.1341.
Colourless oil (70%, cis isomer only). 1H NMR (300 MHz, CDCl3):
d
¼ 0.12 (s, 9H), 0.79 (d, J ¼ 6.8 Hz, 3H), 0.98 (d, J ¼ 6.8 Hz, 3H),
1.50e1.60 (m, 1H), 2.45 (s, 3H), 2.49 (dd, J ¼ 6.9, 2.6 Hz, 1H), 3.38 (d,
4.2.2. 2-((4-Bromophenyl)ethynyl)-3-phenyl-1-(toluene-4-
sulfonyl)aziridine (Table 1, Entry 8)
J ¼ 6.9 Hz, 1H), 7.34 (d, J ¼ 8.3 Hz, 2H), 7.84 (d, J ¼ 8.3 Hz, 2H); 13C
NMR (75 MHz, CDCl3):
d
¼ ꢁ0.4 (3C), 18.4, 20.1, 21.7, 28.4, 33.9, 51.0,
Colourless oil (75%, 15:1 cis:trans). 1H NMR (300 MHz, CDCl3):
90.0, 97.9, 128.2 (2C), 129.6 (2C), 134.6, 144.7; IR (neat):
n
¼ 2966,
d
¼ 2.43 (s, 3H), 3.85 (d, J ¼ 6.9 Hz, 1H), 4.09 (d, J ¼ 6.9 Hz, 1H), 7.02
2913, 2178, 1601, 1472, 1405, 1351, 1322, 1308, 1291, 1250, 1154,
1092, 1076, 945, 873, 840, 814, 759; HRMS (TOF ESþ): m/z calcd for
C17H25NO2NaSSi: 358.1273, found: 358.1281.
(d, J ¼ 8.6 Hz, 2H), 7.36e7.31 (m, 9H), 7.92 (d, J ¼ 8.3 Hz, 2H); 13C
NMR (75 MHz, CDCl3):
127.1, 128.0 (2C), 128.3 (2C), 128.6 (2C), 129.4 (2C), 131.5 (2C), 134.7
(2C), 136.9, 137.8, 138.4; IR (neat):
d
¼ 21.7, 26.9, 42.2, 80.0, 92.3, 121.9, 123.1,
n
¼ 3066, 2233, 1599, 1450, 1334,
4.2.8. 2-Isopropyl-1-(toluene-4-sulfonyl)-3-((triethylsilyl)ethynyl)
aziridine (4d)
1233, 1160, 1087, 1023, 885, 818, 745, 698; HRMS (TOF ESþ): m/z
calcd for C23H18NO2NaSBr: 474.0139, found: 474.0145.
Colourless oil (80%, cis isomer only). 1H NMR (300 MHz, CDCl3):
d
¼ 0.55 (q, J ¼ 8.0 Hz, 6H), 0.81 (d, J ¼ 6.7 Hz, 3H), 0.93 (t, J ¼ 8.0 Hz,
4.2.3. 2-Butyl-3-(phenylethynyl)-1-(toluene-4-sulfonyl)aziridine
(Table 1, Entry 9)
9H), 0.98 (d, J ¼ 6.7 Hz, 3H), 1.58e1.65 (m, 1H), 2.44 (s, 3H), 2.51 (dd,
J ¼ 9.7, 6.9 Hz,1H), 3.37 (d, J ¼ 6.9 Hz,1H), 7.33 (d, J ¼ 8.3 Hz, 2H), 7.83
Colourless oil (40%, cis isomer only). 1H NMR (300 MHz, CDCl3):
(d, J ¼ 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3):
¼ 4.1 (3C), 7.3 (3C),
d
d
¼ 0.84 (t, J ¼ 7.0 Hz, 3H), 1.26e1.32 (m, 4H), 1.55e1.75 (m, 2H),
18.5, 20.2, 21.7, 28.5, 34.0, 51.0, 87.5, 99.0,128.1 (2C),129.6 (2C),134.7,
2.44 (s, 3H), 2.63 (dt, J ¼ 13.0, 6.9 Hz, 1H), 3.59 (d, J ¼ 6.9,
144.6; IR (neat):
n
¼ 3047, 2958, 2875, 2230, 1323, 1160, 1093, 876,
1H),7.28e7.41 (m, 7H), 7.87 (d, J ¼ 8.3 Hz, 2H); 13C NMR (75 MHz,
725; HRMS (TOF ESþ): m/z calcd for C20H31NO2NaSSi: 400.1742,
CDCl3):
d
¼ 13.8, 21.6, 22.1, 27.9, 28.7, 34.4, 45.3, 82.0, 84.2,
found: 400.1733.
121.9, 128.0 (2C), 128.2, 128.8 (2C), 129.7 (2C), 131.9 (2C),
134.7, 144.7; IR (neat):
1304,1292,1152, 1087, 934, 842, 809, 753, 730, 715, 688, 672; HRMS
n
¼ 2965, 2930, 2860, 2249, 1601, 1491, 1316,
4.2.9. 2-Deuterio-3-hex-1-ynyl-1-(toluene-4-sulfonyl)-2-p-
tolylaziridine (6)
(TOF ESþ): m/z calcd for C21H23NO2NaS: 376.1347, found: 376.1340.
Colourless oil (77%, 12:1 cis:trans). 1H NMR (300 MHz, CDCl3):
d
¼ 0.76 (t, J ¼ 7.2 Hz, 3H), 1.05e1.18 (m, 2H), 1.22e1.31 (m, 2H), 2.02
4.2.4. 2-Cyclohexyl-3-(cyclohexylethynyl)-1-(toluene-4-sulfonyl)
aziridine (Table 1, Entry 12)
(dt, J ¼ 6.9 Hz, 1.8 Hz, 2H), 2.32 (s, 3H), 2.43 (s, 3H), 3.60 (t,
J ¼ 1.8 Hz,1H), 7.09 (d, J ¼ 8.1 Hz, 2H), 7.21 (d, J ¼ 8.1 Hz, 2H), 7.33 (d,
J ¼ 8.4 Hz, 2H), 7.87 (d, J ¼ 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3):
Colourless oil (51%, 25:1 cis:trans). 1H NMR (300 MHz, CDCl3):
d
¼ 0.85e1.15 (m, 5H), 1.24e1.43 (m, 9H), 1.59e1.78 (m, 8H), 2.43 (s,
d
¼ 13.4, 18.3, 21.2, 21.5, 21.6, 30.0, 36.1, 72.3, 86.6, 127.6 (2C), 127.9
3H), 2.53 (dd, J ¼ 9.6, 6.9 Hz, 1H), 3.35 (dd, J ¼ 6.9, 1.5 Hz, 1H), 7.31
(2C), 128.6 (2C), 129.1, 129.7 (2C), 134.8, 138.0, 144.6; IR (neat):
(d, J ¼ 8.3 Hz, 2H), 7.81 (d, J ¼ 8.3 Hz, 2H); 13C NMR (75 MHz,
n
¼ 2961, 2926, 2874, 2248, 1921, 1598, 1518, 1458, 1410, 1363, 1323,
CDCl3):
d
¼ 21.6, 24.4 (2C), 25.3, 25.4, 25.7, 26.0 (2C), 28.8, 29.0, 32.0
1301, 1181, 1161, 1133, 1090, 1019, 914, 894, 838, 805, 757, 704;
HRMS (TOF ESþ): m/z calcd for C22H24DNO2NaS: 391.1566, found:
391.1563.
(2C), 33.8, 37.2, 49.4, 72.8, 88.9, 128.0 (2C), 129.5 (2C), 134.7, 144.5;
IR (neat):
n
¼ 2967, 2871, 2249, 1598, 1448, 1319, 1153, 1192, 815,
709, 686; HRMS (TOF ESþ): m/z calcd for C23H31NO2NaS: 408.1973,
found: 408.1976.
4.3. Pyrroles
4.2.5. 2-(Cyclohexylethynyl)-3-isopropyl-1-(toluene-4-sulfonyl)
aziridine (Table 1, Entry 13)
4.3.1. General Method for gold-catalysed cyclisation
The catalyst system is prepared by addition of anhydrous 1,2-
dichloroethane (0.5 mL) to Ph3PAuCl (0.01 mmol, 5.0 mg) and AgOTs
(0.01 mmol, 2.8 mg). After stirring for 10 min at room temperature,
a white precipitate of AgCl is observed and a solution of the corre-
sponding acetylenyl aziridine (0.2 mmol) in anhydrous 1,2-dichlo-
roethane (0.5 mL) was added. The reaction mixture was stirred at the
indicated temperature until complete consumption of aziridine was
observed. The solution was filtered through a pad of silica and then
concentrated under reduced pressure to afford the pyrrole.
Colourless oil (50%, 15:1 cis:trans). 1H NMR (300 MHz, CDCl3):
d
¼ 0.77 (d, J ¼ 6.7 Hz, 3H), 0.96 (d, J ¼ 6.7 Hz, 3H), 1.24e1.48 (m,
6H), 1.54e1.80 (m, 5H), 2.44e2.37 (m, 5H), 3.37 (dd, J ¼ 6.9, 1.3 Hz,
1H), 7.31 (d, J ¼ 8.2 Hz, 2H), 7.81 (d, J ¼ 8.2 Hz, 2H); 13C NMR
(75 MHz, CDCl3):
d
¼ 18.5, 20.1, 21.6, 24.5 (2C), 25.7, 28.3, 32.1 (2C),
34.1 (2C), 50.9, 72.6, 89.1, 128.0 (2C), 129.5 (2C), 134.7, 144.5; IR
(neat):
1151, 1088, 946, 899, 876, 866, 813, 801, 775; HRMS (TOF ESþ): m/z
n
¼ 2965, 2927, 2854, 2241, 1598, 1449, 1406, 1314, 1304,
calcd for C20H27NO2NaS: 368.1660, found: 368.1666.
4.3.2. 2-2-Phenethyl-5-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrole
(Table 1, Entry 7)
4.2.6. 2-Isopropyl-3-(pent-4-en-1-ynyl)-1-(toluene-4-sulfonyl)
aziridine (Table 1, Entry 15)
Colourless oil (95%). 1H NMR (300 MHz, CDCl3):
d
¼ 2.38 (s, 3H),
Colourless oil (40%, cis isomer only). 1H NMR (300 MHz, CDCl3):
3.05e3.10 (m, 2H), 3.23e3.28 (m, 2H), 6.06 (d, J ¼ 3.3 Hz, 1H), 6.09
d
¼ 0.81 (d, J ¼ 6.7 Hz, 3H), 0.99 (d, J ¼ 6.7 Hz, 3H), 1.58e1.69 (m,
(d, J ¼ 3.3 Hz,1H), 7.15 (d, J ¼ 8.3 Hz, 2H), 7.21e7.33 (m, 7H), 7.35 (m,
1H), 2.45 (s, 3H), 2.52 (dd, J ¼ 9.8, 6.9 Hz, 1H), 2.95 (dd,
J ¼ 5.2, 1.8 Hz, 2H), 3.41 (dt, J ¼ 6.9, 1.8 Hz, 1H), 5.09 (dd, J ¼ 10.0,
1.7 Hz, 1H), 5.23 (dd, J ¼ 17.0, 1.7 Hz, 1H), 5.70e5.79 (m, 1H), 7.34 (d,
J ¼ 8.3 Hz, 2H), 7.84 (d, J ¼ 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3):
5H); 13C NMR (75 MHz, CDCl3):
d
¼ 21.6, 31.8, 36.3, 113.5, 115.6,
126.0, 126.4 (2C), 127.2 (2C), 127.8, 128.3 (2C), 128.5 (2C), 129.3 (2C),
130.5 (2C),133.2,136.2,138.4,138.8, 141.5,144.3; IR (neat):
n
¼ 3027,
2920, 2851,1596,1494,1452,1363,1295,1170,1098,1071,1028, 908,
809, 759, 729, 694; HRMS (TOF ESþ): m/z calcd for C25H23NO2NaS:
424.1347, found: 424.1340.
d
¼ 18.6, 20.1, 21.6, 23.0, 28.3, 34.0, 51.0, 76.4, 81.6, 116.3, 128.1 (2C),
129.6 (2C), 131.7, 134.7, 144.7; IR (neat):
n
¼ 3089, 3047, 2958, 2875,

P.W. Davies, N. Martin / Journal of Organometallic Chemistry 696 (2011) 159e164
163
4.3.3. 2-(4-Bromophenyl)-5-phenyl-1-(toluene-4-sulfonyl)-1H-
pyrrole (Table 1, Entry 8)
support from Advantage West Midlands (AWM) and part funded by
the European Regional Development Fund (ERDF).
Colourless oil (>95%). 1H NMR (300 MHz, CDCl3):
d
¼ 2.38 (s,
3H), 6.26 (d, J ¼ 3.5 Hz, 2H), 7.12e7.05 (m, 4H), 7.55e7.28 (m, 9H);
13C NMR (75 MHz, CDCl3):
¼ 21.6, 117.3, 118.3, 126.8 (2C), 127.6
(2C), 127.8, 128.7 (2C), 128.8 (2C), 128.9 (2C), 129.5 (2C),133.0, 133.4,
134.3, 134.8, 139.2, 141.9, 144.7; IR (neat):
References
d
[1] For selected reviews of heterocycle synthesis by gold see: (a) N. Patil,
Y. Yamamoto, Chem. Rev. 108 (2008) 3395e3442;
n
¼ 2233, 1705, 1596,
(b) S.F. Kirsch, Synthesis (2008) 3183e3204;
(c) N. Patil, Y. Yamamoto, Arkivoc (2007) 121e141;
(d) H.C. Shen, Tetrahedron 64 (2008) 7847e7870;
1439, 1371, 1176, 1092, 920, 810, 729, 703; HRMS (TOF ESþ): m/z
calcd for C23H18NO2NaSBr: 474.0139, found: 474.0144.
(e) H.C. Shen, Tetrahedron 64 (2008) 3885e3903.
[2] For examples of gold-catalysed pyrrole synthesis see: (a) C.A. Witham,
P. Mauleon, N.D. Shapiro, B.D. Sherry, F.D. Toste, J. Am. Chem. Soc. 129 (2007)
5838e5839;
4.3.4. 2,5-Dicyclohexyl-1-(toluene-4-sulfonyl)-1H-pyrrole (Table 1,
Entry 12)
Colourless oil (>95%). 1H NMR (300 MHz, CDCl3):
d
¼ 1.14e1.40
(b) F.M. Istrate, F. Gagosz, Org. Lett. 9 (2007) 3181e3184;
(c) I.V. Seregin, V. Gevorgyan, J. Am. Chem. Soc. 128 (2006) 12050e12051;
(d) T.J. Harrison, J.A. Kozak, M. Corbella-Pané, G.R. Dake, J. Org. Chem. 71 (2006)
4525e4529;
(e) D.J. Gorin, N.R. Davis, F.D. Toste, J. Am. Chem. Soc. 127 (2005) 11260e11261;
(f) A. Arcadi, S. Di Guiseppe, F. Marinelli, E. Rossi, Tetrahedron: Asymmetry 12
(2001) 2715e2720;
(g) A. Arcadi, S. Di Guiseppe, F. Marinelli, E. Rossi, Adv. Synth. Catal. 343 (2001)
443e446;
(h) A. Saito, T. Konishi, Y. Hanzaw, Org. Lett. 12 (2010) 372e374;
(i) V. Lavallo, G.D. Frey, B. Donnadieu, M. Soleilhavoup, G. Bertrand, Angew.
Chem. Int. Ed. 47 (2008) 5224e5228;
(m, 8H), 1.62e1.72 (m, 8H), 1.90 (d, J ¼ 12.2 Hz, 4H), 2.38 (s, 3H),
3.05 (m, 2H), 5.94 (s, 2H), 7.22 (d, J ¼ 8.3 Hz, 2H), 7.38 (d, J ¼ 8.3 Hz,
2H); 13C NMR (75 MHz, CDCl3):
d
¼ 21.5, 26.2 (2C), 26.8 (4C), 34.8
(4C), 37.3 (2C), 109.4 (2C), 125.5 (2C), 129.7 (2C), 138.2, 143.9, 144.0
(2C); IR (neat):
n
¼ 2924, 2853, 1726, 1681, 1601, 1524, 1497, 1443,
1367, 1358, 1309, 1271, 1195, 1177, 1154, 1120, 1097, 1087, 1069, 1045,
891, 810, 784, 738, 688, 652; HRMS (TOF ESþ): m/z calcd for
C23H18NO2NaSBr: 474.0139, found: 474.0144. HRMS (TOF ESþ): m/z
calcd for C23H31NO2NaS: 408.1973, found: 408.1969.
(j) H.M. Peng, J. Zhao, X. Li, Adv. Synth. Catal. 351 (2009) 1371e1377;
(k) R. Surmont, G. Verniest, N. De Kimpe, Org. Lett. 11 (2009) 2920e2923.
[3] P.W. Davies, N. Martin, Org. Lett. 11 (2009) 2293e2296.
[4] For previous examples of alkynyl epoxide ring expansion to form furans under
gold catalysis see: (a) A.S.K. Hashmi, P. Sinha, Adv. Synth. Catal. 346 (2004)
432e438;
(b) M. Yoshida, M. Al-Amin, K. Matsuda, K. Shishido, Tetrahedron Lett. 49
(2008) 5021e5023.
[5] Selected reviews of gold catalysis: (a) A. Fürstner, P.W. Davies, Angew. Chem.
Int. Ed. 46 (2007) 3410e3449;
4.3.5. 2-Cyclohexyl-5-isopropyl-1-(toluene-4-sulfonyl)-1H-pyrrole
(Table 1, Entry 13)
Colourless oil (>95%). 1H NMR (300 MHz, CDCl3):
d
¼ 1.17 (d,
J ¼ 6.7 Hz, 6H), 1.21e1.49 (m, 4H), 1.52e1.82 (m, 4H), 1.91 (d,
J ¼ 12.1 Hz, 2H), 2.38 (s, 3H), 3.05 (m, 1H), 3.42 (sept, J ¼ 6.7 Hz, 1H),
5.95 (d, J ¼ 3.5 Hz, 1H), 5.98 (d, J ¼ 3.5 Hz, 1H), 7.22 (d, J ¼ 8.4 Hz,
2H), 7.28 (d, J ¼ 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3):
¼ 21.5, 24.0
d
(b) A.S.K. Hashmi, Chem. Rev. 107 (2007) 3180e3211;
(c) D.J. Gorin, F.D. Toste, Nature 446 (2007) 395e403;
(2C), 26.2, 26.7 (2C), 27.5, 34.8 (2C), 37.4, 109.2, 109.4, 125.4 (2C),
ꢀ
(d) E.J. Jimenez-Núnez, A.M. Echavarren, Chem. Rev. 108 (2008) 3326e3350;
129.7 (2C), 138.0, 144.0, 144.5, 145.0; IR (neat):
n
¼ 2968, 2926,
(e) A. Fürstner, Chem. Soc. Rev. 38 (2009) 3208e3221;
(f) J. Li, C. Brouwer, C. He, Chem. Rev. 108 (2008) 3239e3265;
(g) A. Arcadi, Chem. Rev. 109 (2008) 3266e3325.
2853,1681,1598,1528,1493, 1447,1370,1357, 1304,1193, 1180,1167,
1142, 1111, 1095, 1060, 1016, 810, 783, 747, 703, 682; HRMS (TOF
ESþ): m/z calcd for C20H27NO2NaS: 368.1660, found: 368.1676.
[6] (a) D.D. Chen, X.-L. Hou, L.-X. Dai, Tetrahedron Lett. 50 (2009) 6944e6946;
(b) M. Yoshida, M. Al-Amin, K. Shishido, Synthesis (2009) 2454e2466;
(c) X. Du, X. Xie, Y. Liu, J. Org. Chem. 75 (2010) 510e513.
[7] Cyclisation triggered by iodine: M. Yoshida, M. Al-Amin, K. Shishido Tetra-
hedron Lett. 50 (2009) 6268e6270.
[8] X. Zhao, E. Zhang, Y.-Q. Tu, Y.-Q. Zhang, D.-Y. Yuan, K. Cao, C.-A. Fan,
4.3.6. 2-Allyl-5-isopropyl-1-(toluene-4-sulfonyl)-1H-pyrrole (Table
1, Entry 15)
Pale yellow oil (95%). 1H NMR (300 MHz, CDCl3):
d
¼ 1.24 (d,
F.-M. Zhang, Org. Lett. 11 (2009) 4002e4004.
[9] A. Blanc, A. Alix, J.-M. Weibel, P. Pale, Eur. J. Org. Chem. (2010) 1644e1647.
[10] For our initial report and optimisation of 2,5-pyrrole formation by gold cat-
alysed ring-expansion of 1-aryl-2-alkynyl aziridines including Table 1, Entries
1e6, see Ref [3].
[11] A.H. Li, Y.G. Zhou, L.X. Dai, X.L. Hou, L.J. Xia, L. Lin, J. Org. Chem. 63 (1998)
4338e4348.
[12] Attempts to introduce a p-methoxy unit in these systems were ultimately
unsuccessful due to the apparent lability of the alkynyl aziridine.
[13] For the study of solvent and counterion effect on reaction pathway see Ref [3].
[14] Review of ligand effects: D.J. Gorin, B.D. Sherry, F.D. Toste Chem. Rev. 108
(2008) 3351e3378.
J ¼ 6.7 Hz, 6H), 2.44 (s, 3H), 3.50 (sept, J ¼ 6.7 Hz, 1H), 3.60 (dd,
J ¼ 3.6, 1.1 Hz, 2H), 5.11 (m, 1H), 5.16 (m, 1H), 5.85e5.99 (m, 2H),
6.05 (dd, J ¼ 3.4, 1.1 Hz, 1H), 7.31 (d, J ¼ 8.2 Hz, 2H), 7.50 (d,
J ¼ 8.2 Hz, 2H); 13C NMR (75 MHz, CDCl3):
¼ 21.5, 24.0 (2C), 27.3,
d
33.7, 108.9, 111.9, 116.7, 125.7 (2C), 129.8 (2C), 135.2, 135.4, 137.7,
144.2, 145.5; IR (neat):
n
¼ 3089, 3010, 2967, 2871, 1831, 1635, 1597,
1366, 1179, 1189, 980, 925, 818, 706, 686; HRMS (TOF ESþ): m/z
calcd for C17H21NO2NaS: 326.1191, found: 326.1198.
[15] The formation of intermediate E from aziridine can be explained through
several distinct pathways based on the coordination of the alkyne to the gold
catalyst rendering it electrophilic: Stepwise ring-expansion could occur by
aziridine ring opening followed by attack of the nitrogen onto the alkyne; A
direct 3- to 5-ring expansion would result by migration of electron density
4.3.7. 2-Isopropyl-1-(toluene-4-sulfonyl)-1H-pyrrole (5a)
Colourless oil (>95%). 1H NMR (300 MHz, CDCl3):
d
¼ 1.13 (d,
J ¼ 6.7 Hz, 6H), 2.41 (s, 3H), 3.29 (sept, J ¼ 6.7 Hz, 1H), 6.05 (m, 1H),
6.22 (dd, J ¼ 3.4, 3.3 Hz, 1H), 7.26 (dd, J ¼ 3.3, 1.6 Hz, 1H), 7.28 (d,
J ¼ 8.3 Hz, 2H), 7.61 (d, J ¼ 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3):
from the strained aziridine C-N
s-bond to the developing carbocation char-
acter at the alkyne; The aziridine nitrogen could act as an initial nucleophile
to the alkyne-gold complex prior to aziridine ring-opening, though this would
result in increased steric strain from the bulky sulfonamide, developing ring
strain, as well as employing a poor nucleophile, see: S.R. Koepke, R. Kupper,
C.J. Michedja J. Org. Chem. 44 (1979) 2718e2722.
d
¼ 21.6, 23.8 (2C), 26.3, 109.8, 111.4, 122.2, 126.5 (2C), 129.9 (2C),
136.9, 143.1, 144.6; IR (neat):
n
¼ 3010, 2967, 2871, 1597, 1366, 1179,
1189, 812, 704, 682; HRMS (TOF ESþ): m/z calcd for C14H17NO2NaS:
[16] For a recent relevant experimental and computational study on counterion
286.0878, found: 286.0874.
and solvent effects in
a furan synthesis, see: A.S. Dudnik, Y. Xia, Y. Li,
V. Gevorgyan J. Am. Chem. Soc. 132 (2010) 7645e7655.
[17] Review of 1,2 migrations in gold catalysed processes: B. Crone, S.F. Kirsch
Chem. Eur. J. 14 (2008) 3514e3522.
Acknowledgements
[18] Tosylate could act as a nucleophile to either the aziridine or, as suggested by
a reviewer, the metal-activated alkyne. Reversible aziridine ring-opening by
nucleophilic attack at the propargylic position, would result in a species able
to undergo cyclisation and aromatisation. For the effective cyclisations of
equivalent ring-opened species see: (a) A. Aponick, C.-Y. Li, J. Malinge,
E.F. Marques, Org. Lett. 11 (2009) 4624e4627;
Financial support from the University of Birmingham is gratefully
acknowledged. We thank Johnson Matthey plc for a generous loan of
metal salts. This research was part supported through Birmingham
Science City: Innovative Uses for Advanced Materials in the Modern
World (West Midlands Centre for Advanced Materials Project 2), with
(b) M. Egi, K. Azechi, S. Akai, Org. Lett. 11 (2009) 5002e5005 The gold-

164
P.W. Davies, N. Martin / Journal of Organometallic Chemistry 696 (2011) 159e164
catalysed addition of sulfonic acids across alkynes has recently been reported;
[21] Trace amounts of what appears to be pyrrole incorporating deuterium at C-3
were also observed from the reaction of 6. This could arise from a competing
1,2-deuteride shift in E. Proton exchange after pyrrole formation may be
possible although there was no indication of deuterium incorporation when
the pyrrole products of these reactions were treated with cationic gold source
in the presence of D2O washed 1,2-dichlorethane.
[22] Using substrate from Table 1, Entry 14, in the presence of 20 mol% Ph3PAuOTs
in CD2Cl2 at 23 ꢀC: Only traces (<5%, relative to 1 and 2) of unidentified
species were observed on the 1H NMR timescale during the course of the
reaction with overall clean conversion to pyrrole 2.
(c) D.-M. Cui, Q. Meng, J.-Z. Zheng, C. Zhang, Chem. Commun. (2009)
1577e1579 Regioselective tosylate addition to the least hindered end of the
gold-activated alkyne would result in a vinyl gold species. Formation of an
allenyl intermediate by elimination of gold with concomitant ring-opening of
the aziridine provides a viable pathway for formation of the pyrrole, by gold-
promoted ring closure on attack of the charged nitrogen to the alkyne with
subsequent elimination of tosylate.
[19] For an example of desilylation in gold catalysed heterocycle synthesis, see:
ꢁ
A.S.K. Hashmi, E. Kurpejovic, W. Frey, J.W. Bats Tetrahedron 63 (2007) 5879e5885.
[20] Review of evidenced intermediates in gold catalysis: A.S.K. Hashmi Angew.
[23] Chemla: F. Chemla, F. Ferreira, V. Hebbe, E. Stercklen Eur. J. Org. Chem. (2002)
1385e1391.
Chem. Int. Ed. 49 (2010) 5232e5241.