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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-catalysedring expansion of alkynyl aziridines

Paul W. Davies*, Nicolas MartinSchool of Chemistry, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK

a r t i c l e i n f o

Article history:Received 31 July 2010Received in revised form24 August 2010Accepted 24 August 2010Available online 29 September 2010

Keywords:Gold catalysisPyrroleCycloisomerisationCounterion

* Corresponding author. Tel.: þ44 121 414 4408; faE-mail address: p.w.davies@bham.ac.uk (P.W. Dav

0022-328X/$ e see front matter � 2010 Elsevier B.V.doi:10.1016/j.jorganchem.2010.08.040

a b s t r a c t

A range of substituted alkynyl aziridines undergo a ring expansion to afford 2,5-substituted pyrrolesunder gold catalysis. While effective conditions can be generated from other gold sources, a combinationof Ph3PAuCl and AgOTs generate a catalyst system that provides extremely clean cycloisomerisationreactions requiring minimal work-up and purification.

� 2010 Elsevier B.V. All rights reserved.

1. Introduction

Transition-metal catalysed cycloisomerisation strategies haveproven highly applicable for the synthesis of heterocyclic motifs [1].Attractive aspects of cycloisomerisations include their inherentsubstrate efficiency and the generally mild reaction conditionsemployed, which for example avoid the need for strong bases/acids.Additionally, the provision of alternative stratagems to accessvaluable target molecules can greatly facilitate synthesis. As there isoften no need to add reagents beyond the solvent, catalyst andsubstrate, the cycloisomerisation reactions and their work-up andpurifications are often rendered straightforward and user-friendly.

The pyrrole motif attracts particular attention in methodologydesign for its utility as a synthetic building block and widespreadoccurrence in target structures, such as functional materials andbiologically-relevant compounds [2]. Within this area we recentlyreported a new pyrrole synthesis by gold-catalysed cyclo-isomerisation of 1-aryl-2-alkynyl aziridineswhich features a formal‘XeH’ addition across an alkyne (Scheme1) [3]. Ring expansion fromthe aziridine onto the adjacent alkynewas promoted by the cationicgold system Ph3PAuX, where X is a ‘non-coordinating’ counterion(A/ B) [4,5]. Along with this pathway for the preparation of2,5-substituted pyrroles, we had also shown that a regiodivergentpathwaycould be accessed fromthe same1-aryl-2-alkynyl aziridine

x: þ44 121 4144403.ies).

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precursors through choice of solvent and counterion. 2,4-Subs-tituted pyrroles were formed with ultimate rearrangement of thecarbonecarbon connectivity by a cascade reaction triggered on ringexpansion (A/C).

Subsequently, several reports have employed p-acid promotedring expansion of alkynyl aziridines to prepare a range of variouslysubstituted pyrroles (Type A/B) [6,7]. The combination of azir-idines tethered in some way to alkynes has also been employedunder gold catalysis in reactions such as cyclisationerearrange-ment [8], and cyclisationesubstitution [9] cascades. Here we reportour 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 preparedaccording to themethod of Dai through a convergent coupling of animine with a propargylic sulfonium ylide (Scheme 2) [11]. In mostcases a mixture of diastereomers were obtained, with the cis-dia-stereomer predominating, andwere used as such in the subsequentreactions [12].

Our study commenced with use of 2-(hex-1-ynyl)-3-phenyl-1-tosylaziridine 1a. Under some standard reaction conditions forgold-catalysed cycloisomerisation processes (Ph3PAuOTf in non-coordinating solvent) we observed the unexpected formation ofa mixture of isomers (Scheme 3) [13].

Theoutcomeof this reactionproved tobehighlydependenton thenature of either solvent and/or counterion [14]. Less of the product

Scheme 1. Selective synthesis of 2,5 or 2,4-substituted pyrroles.

Scheme 3. Survey of reaction conditions.

P.W. Davies, N. Martin / Journal of Organometallic Chemistry 696 (2011) 159e164160

from the cascade skeletal rearrangement pathway (1/3) was seenwhen the reactionmedia consisted of a relatively Lewis basic or proticsolvent. Conversely, formation of 3 was favoured in chlorinatedsolvents.

Referring to the proposedmechanism for ring expansion (Fig. 1),the presence of Lewis basic or protic solvents to assist in stabilisingcommon intermediate E and/or in the deprotonation/proto-demetallation stages appears to aid clean progression along thispathway [15]. The proclivity of the system to afford 3 by undergoingan alternate rearrangement pathway from intermediates E/F isreduced [16,17].

These conditions gave good yields and selectivity, and it isnotable that all the other preparations reported also ultimatelyemploy ethereal or protic solvents in the reaction media [6].However, for the formation of 2,5-substituted pyrrole by this routewe discovered that the use of an apparently less active catalyst,Ph3PAuOTs, provides exquisite selectivity. The 2,5-substitutedproduct 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 greaterimpact even than solvent on directing the process along the ringexpansion pathway whilst avoiding alternative outcomes, to thusenable the quantitative formation of a single product. To rationalisethe overall improved relative efficacy of this system against themore active Ph3PAuOTf system for the formation of 2,5-substitutedpyrroles, we can consider it a consequence of the level of carbo-cationic character that is generated being insufficient to access thecascade pathway, and/or the involvement of themore basic tosylatecounterion in proton transfer steps. Alternatively, as a relativelynucleophilic species, the tosylate could conceivably play a directrole in the process [18].

The reaction simplicity and the formation of a single product inquantitative yields engender significant economy and efficiencyover the entire process as, beyond the simple expedient of filtrationthrough a silica plug, no work-up or purification was required.

These conditions were then applied to a range of alkynylaziridines. 1-Aryl-2-alkynyl aziridines were transformed to the2-aryl-5-substituted pyrroles in quantitative yield with no isomericside-product [Table 1, Entries 1e8]. A range of alkyl substitutedspecies, which are incapable of undergoing the cascade reaction(A/C), were also tested under the reaction conditions. In all casesnear-quantitative yields were obtained [Entries 9e14].

The reaction tolerates either alkyl or aryl substituents, ora mixture thereof, at both the aziridine and the alkyne moiety.Substrates bearing aryl groups on the alkyne were more prone toring expansion than alkyl substituted analogues, proceeding tocompletion even at room temperature [Entries 9, 10 and 14].

Scheme 2. General method for the preparation of alkynyl aziridine precursors(Ref. [11]).

Additionally, functionalised substrates bearing aryl bromides andalkenes can be taken through unscathed [Entries 2e4, 8 and 15].

When trimethylsilylated alkynes 4aec were subjected to thestandard reaction conditions (Scheme 4), quantitative yields of 2-substituted pyrroles 5aec were isolated. Protodesilylation ispresumably aided by adventitious water [19]. Use of triethylsilyatedspecies 4d gave equivalent results.

Alkynyl aziridine 6 bearing a deuterium label adjacent to thearyl 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 isconsistent with the proposed reaction mechanism. Elimination ofthe proton/deuteron from E (Fig. 1) and subsequent intermolecularcapture of proton or deuteron by the vinyl gold unit, provideopportunity for H/D exchange [20]. Similarly, deuterium incorpo-ration at C-4 was also observed when non-deuterated alkynylaziridine was reacted in D2O washed dichlorethane [21]. Nosignificant build up of intermediates was observed when a cyclo-isomerisation reaction was monitored by 1H NMR [22].

3. Conclusions

The ring expansion of alkynyl aziridines proceeds smoothly undera simple reaction system to afford 2,5-substitutedpyrroles. The use ofa relatively lowactivitycatalyst, Ph3PAuOTs, gavegreater specificity inthe ring expansion reactions than a combination of a more reactivesystem and protic or ethereal solvents. The reaction tolerates alkyland aryl substituents both on the alkyne and the aziridine, alsoaccommodating functionality such as aryl halides and alkenes, and inall cases pyrroles were formed in near-quantitative yields.

4. Experimental

All experiments were carried out under an inert atmosphere indried glassware. NMR: Spectra were recorded on Bruker AC300

Fig. 1. Mechanistic proposal.

Table 1Cycloisomerisation to form 2,5-substituted pyrroles.a

Entry R R1 Time/h T/�C Yieldb/% Entry R R1 Time/h T/�C Yieldb/%

1 Ph nBu 3.5 70 >95 9 nBu Ph 12 23 >952 4-BrC6H4

nBu 4 70 >95 10 cC6H11 Ph 12 23 >953 2-BrC6H4

nBu 4 70 >95 11 cC6H11nBu 4 70 >95

4 4-CH3C6H4nBu 5 70 >95 12 cC6H11

cC6H11 3 70 >955 Ph Ph 3 70 >95 13 iPr cC6H11 3 70 >956 4-CH3C6H4 Ph 3.5 70 >95 14 iPr Ph 12 23 >957 Ph CH2CH2Ph 4 70 95 15 iPr CH2CH]CH2 12 70 958 Ph 4-BrC6H4 3 70 >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.b Isolated percentage yields of pyrrole products.

P.W. Davies, N. Martin / Journal of Organometallic Chemistry 696 (2011) 159e164 161

(1H¼ 300 MHz, 13C¼ 75.5 MHz), Bruker AV300 (1H¼ 300 MHz,13C¼ 75.5 MHz), Bruker AV400 (1H¼ 400 MHz, 13C¼ 101 MHz),and Bruker DRX500 (1H¼ 500 MHz, 13C¼ 126 MHz) in the solventsindicated; Chemical shifts (d) are given in ppm relative to TMS. Thesolvent signals were used as references and the chemical shiftsconverted to the TMS scale (CDCl3: dCh 77.0 ppm; residual CHCl3 inCDCl3: dHh 7.26 ppm).

Sulfonium salts and alkynyl aziridineswere prepared according tothe literature method [11]. For analytical data relating to compoundsin Table 1 Entries 1e6 see Ref [3]. Data for the following compoundsare 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].

4.1. Propargyl sulfonium salts

4.1.1. Dimethyl(3-(triethylsilyl)prop-2-ynyl)sulfonium bromideWhite solid (60%). 1H NMR (300 MHz, CDCl3): d¼ 0.61 (q,

J¼ 7.7 Hz, 6H), 0.96 (t, J¼ 7.7 Hz, 9H), 3.21 (s, 6H), 5.06 (s, 2H); 13CNMR (75 MHz, CDCl3): d¼ 4.0 (3C), 7.4 (3C), 24.4 (2C), 33.7, 90.9,95.4; IR (neat): n¼ 3013, 2918, 2181,1318,1253,1190,1038, 991, 845,761, 639;HRMS (TOF ESþ):m/z calcd for C11H23SSi: 215.1290, found:215.1291.

4.1.2. (3-Cyclohexylprop-2-ynyl)dimethylsulfonium bromideWhite solid (55%). 1H NMR (300 MHz, CDCl3): d¼ 1.12e1.85 (m,

10H), 2.44 (m, 1H), 3.18 (s, 6H), 4.95 (s, 2H); 13C NMR (75 MHz,CDCl3): d¼ 18.0, 24.2 (2C), 24.7 (2C), 25.5, 32.3 (2C), 33.4, 65.1, 96.7;IR (neat): n¼ 3001, 2951, 2929, 2889, 2233, 1458, 1419, 1325, 1248,1187,1153,1050,1001, 928, 721, 638; HRMS (TOF ESþ):m/z calcd forC11H19S: 183.1202, found: 183.1210.

Scheme 4. Reaction of silylated alkynyl aziridines.

4.1.3. Hex-5-en-2-ynyldimethylsulfonium bromideWhite solid (35%). 1H NMR (300 MHz, CDCl3): d¼ 3.41 (s, 6H),

3.70 (m, 2H), 4.80 (s, 2H), 5.47 (dd, J¼ 11.0, 1.8 Hz, 1H), 5.56 (dd,J¼ 18.0, 1.8 Hz, 1H), 6.01 (m, 1H); 13C NMR (75 MHz, CDCl3):d¼ 23.3, 24.6 (2C), 34.3, 76.6, 81.5, 117.5, 133.1; IR (neat): n¼ 3090,3020, 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 bromideWhite solid (72%). 1H NMR (300 MHz, CDCl3): d¼ 2.65 (tt,

J¼ 6.9, 2.1 Hz, 2H), 2.84 (t, J¼ 6.9 Hz, 2H), 2.87 (s, 6H), 4.85 (t,J¼ 2.1 Hz, 2H), 7.17e7.24 (m, 3H), 7.26e7.33 (m, 2H); 13C NMR(75 MHz, CDCl3): d¼ 20.3, 24.0 (2C), 33.3, 34.0, 66.3, 91.4, 126.8,128.4 (2C), 128.7 (2C), 139.6; IR (neat): n¼ 2988, 2918, 2231, 1601,1494, 1452, 1410, 1323, 1261, 1206, 1151, 1056, 1005, 939, 742, 701;HRMS (TOF ESþ): m/z calcd for C13H17S: 205.1051, found: 205.1055.

4.1.5. Dimethyl(3-(4-bromophenyl)prop-2-ynyl)sulfonium bromideWhite solid (79%). 1H NMR (300 MHz, CDCl3): d¼ 3.39 (s, 6H),

5.51 (s, 2H), 7.44 (d, J¼ 8.4 Hz, 2H), 7.55 (d, J¼ 8.4 Hz, 2H); 13C NMR(75 MHz, CDCl3): d¼ 23.9 (2C), 30.2, 79.9, 87.5, 122.6, 122.8, 132.1(2C), 135.6 (2C); IR (neat): n¼ 3012, 2929, 2884, 2241, 1628, 1401,1325, 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.

4.2. Alkynyl aziridines

4.2.1. 2-{Phenyl-3-(4-phenylbut-1-yn-1-yl)-1-(toluene-4-sulfonyl)aziridine (Table 1, Entry 7)

Colourless oil (70%, 11:1 cis:trans). 1H NMR (300 MHz, CDCl3):d¼ 2.27e2.34 (m, 2H), 2.44 (s, 3H), 2.50e2.66 (m, 2H), 3.63 (dt,J¼ 6.9, 1.8 Hz, 1H), 3.95 (d, J¼ 6.9 Hz, 1H), 6.96e7.01 (m, 2H),

Scheme 5. Use of deuterated substrate.

P.W. Davies, N. Martin / Journal of Organometallic Chemistry 696 (2011) 159e164162

7.24e7.27 (m, 3H), 7.30 (s, 5H), 7.34 (d, J¼ 8.3 Hz, 2H), 7.89 (d,J¼ 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3): d¼ 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): n¼ 2987, 2931, 2248,1597, 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.

4.2.2. 2-((4-Bromophenyl)ethynyl)-3-phenyl-1-(toluene-4-sulfonyl)aziridine (Table 1, Entry 8)

Colourless oil (75%, 15:1 cis:trans). 1H NMR (300 MHz, CDCl3):d¼ 2.43 (s, 3H), 3.85 (d, J¼ 6.9 Hz, 1H), 4.09 (d, J¼ 6.9 Hz, 1H), 7.02(d, J¼ 8.6 Hz, 2H), 7.36e7.31 (m, 9H), 7.92 (d, J¼ 8.3 Hz, 2H); 13CNMR (75 MHz, CDCl3): d¼ 21.7, 26.9, 42.2, 80.0, 92.3, 121.9, 123.1,127.1, 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): n¼ 3066, 2233, 1599, 1450, 1334,1233, 1160, 1087, 1023, 885, 818, 745, 698; HRMS (TOF ESþ): m/zcalcd for C23H18NO2NaSBr: 474.0139, found: 474.0145.

4.2.3. 2-Butyl-3-(phenylethynyl)-1-(toluene-4-sulfonyl)aziridine(Table 1, Entry 9)

Colourless oil (40%, cis isomer only). 1H NMR (300 MHz, CDCl3):d¼ 0.84 (t, J¼ 7.0 Hz, 3H), 1.26e1.32 (m, 4H), 1.55e1.75 (m, 2H),2.44 (s, 3H), 2.63 (dt, J¼ 13.0, 6.9 Hz, 1H), 3.59 (d, J¼ 6.9,1H),7.28e7.41 (m, 7H), 7.87 (d, J¼ 8.3 Hz, 2H); 13C NMR (75 MHz,CDCl3):d¼ 13.8, 21.6, 22.1, 27.9, 28.7, 34.4, 45.3, 82.0, 84.2,121.9, 128.0 (2C), 128.2, 128.8 (2C), 129.7 (2C), 131.9 (2C),134.7, 144.7; IR (neat): n¼ 2965, 2930, 2860, 2249, 1601, 1491, 1316,1304,1292,1152,1087, 934, 842, 809, 753, 730, 715, 688, 672; HRMS(TOF ESþ):m/z calcd for C21H23NO2NaS: 376.1347, found: 376.1340.

4.2.4. 2-Cyclohexyl-3-(cyclohexylethynyl)-1-(toluene-4-sulfonyl)aziridine (Table 1, Entry 12)

Colourless oil (51%, 25:1 cis:trans). 1H NMR (300 MHz, CDCl3):d¼ 0.85e1.15 (m, 5H), 1.24e1.43 (m, 9H), 1.59e1.78 (m, 8H), 2.43 (s,3H), 2.53 (dd, J¼ 9.6, 6.9 Hz, 1H), 3.35 (dd, J¼ 6.9, 1.5 Hz, 1H), 7.31(d, J¼ 8.3 Hz, 2H), 7.81 (d, J¼ 8.3 Hz, 2H); 13C NMR (75 MHz,CDCl3): d¼ 21.6, 24.4 (2C), 25.3, 25.4, 25.7, 26.0 (2C), 28.8, 29.0, 32.0(2C), 33.8, 37.2, 49.4, 72.8, 88.9, 128.0 (2C), 129.5 (2C), 134.7, 144.5;IR (neat): n¼ 2967, 2871, 2249, 1598, 1448, 1319, 1153, 1192, 815,709, 686; HRMS (TOF ESþ): m/z calcd for C23H31NO2NaS: 408.1973,found: 408.1976.

4.2.5. 2-(Cyclohexylethynyl)-3-isopropyl-1-(toluene-4-sulfonyl)aziridine (Table 1, Entry 13)

Colourless oil (50%, 15:1 cis:trans). 1H NMR (300 MHz, CDCl3):d¼ 0.77 (d, J¼ 6.7 Hz, 3H), 0.96 (d, J¼ 6.7 Hz, 3H), 1.24e1.48 (m,6H), 1.54e1.80 (m, 5H), 2.44e2.37 (m, 5H), 3.37 (dd, J¼ 6.9, 1.3 Hz,1H), 7.31 (d, J¼ 8.2 Hz, 2H), 7.81 (d, J¼ 8.2 Hz, 2H); 13C NMR(75 MHz, CDCl3): d¼ 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): n¼ 2965, 2927, 2854, 2241, 1598, 1449, 1406, 1314, 1304,1151, 1088, 946, 899, 876, 866, 813, 801, 775; HRMS (TOF ESþ): m/zcalcd for C20H27NO2NaS: 368.1660, found: 368.1666.

4.2.6. 2-Isopropyl-3-(pent-4-en-1-ynyl)-1-(toluene-4-sulfonyl)aziridine (Table 1, Entry 15)

Colourless oil (40%, cis isomer only). 1H NMR (300 MHz, CDCl3):d¼ 0.81 (d, J¼ 6.7 Hz, 3H), 0.99 (d, J¼ 6.7 Hz, 3H), 1.58e1.69 (m,1H), 2.45 (s, 3H), 2.52 (dd, J¼ 9.8, 6.9 Hz, 1H), 2.95 (dd,J¼ 5.2, 1.8 Hz, 2H), 3.41 (dt, J¼ 6.9, 1.8 Hz, 1H), 5.09 (dd, J¼ 10.0,1.7 Hz, 1H), 5.23 (dd, J¼ 17.0, 1.7 Hz, 1H), 5.70e5.79 (m, 1H), 7.34 (d,J¼ 8.3 Hz, 2H), 7.84 (d, J¼ 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3):d¼ 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): n¼ 3089, 3047, 2958, 2875,

2230, 1830, 1630, 1323, 1160, 1093, 980, 940, 876, 725; HRMS (TOFESþ): m/z calcd for C17H21NO2NaS: 326.1191, found: 326.1182.

4.2.7. 2-Isopropyl-1-(toluene-4-sulfonyl)-3-((trimethylsilyl)ethynyl)aziridine (4a)

Colourless oil (70%, cis isomer only). 1H NMR (300 MHz, CDCl3):d¼ 0.12 (s, 9H), 0.79 (d, J¼ 6.8 Hz, 3H), 0.98 (d, J¼ 6.8 Hz, 3H),1.50e1.60 (m, 1H), 2.45 (s, 3H), 2.49 (dd, J¼ 6.9, 2.6 Hz, 1H), 3.38 (d,J¼ 6.9 Hz, 1H), 7.34 (d, J¼ 8.3 Hz, 2H), 7.84 (d, J¼ 8.3 Hz, 2H); 13CNMR (75 MHz, CDCl3): d¼�0.4 (3C), 18.4, 20.1, 21.7, 28.4, 33.9, 51.0,90.0, 97.9, 128.2 (2C), 129.6 (2C), 134.6, 144.7; IR (neat): n¼ 2966,2913, 2178, 1601, 1472, 1405, 1351, 1322, 1308, 1291, 1250, 1154,1092, 1076, 945, 873, 840, 814, 759; HRMS (TOF ESþ): m/z calcd forC17H25NO2NaSSi: 358.1273, found: 358.1281.

4.2.8. 2-Isopropyl-1-(toluene-4-sulfonyl)-3-((triethylsilyl)ethynyl)aziridine (4d)

Colourless oil (80%, cis isomer only). 1H NMR (300 MHz, CDCl3):d¼ 0.55 (q, J¼ 8.0 Hz, 6H), 0.81 (d, J¼ 6.7 Hz, 3H), 0.93 (t, J¼ 8.0 Hz,9H), 0.98 (d, J¼ 6.7 Hz, 3H), 1.58e1.65 (m, 1H), 2.44 (s, 3H), 2.51 (dd,J¼ 9.7, 6.9 Hz,1H), 3.37 (d, J¼ 6.9 Hz,1H), 7.33 (d, J¼ 8.3 Hz, 2H), 7.83(d, J¼ 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3): d¼ 4.1 (3C), 7.3 (3C),18.5, 20.2, 21.7, 28.5, 34.0, 51.0, 87.5, 99.0,128.1 (2C),129.6 (2C),134.7,144.6; IR (neat): n¼ 3047, 2958, 2875, 2230, 1323, 1160, 1093, 876,725; HRMS (TOF ESþ): m/z calcd for C20H31NO2NaSSi: 400.1742,found: 400.1733.

4.2.9. 2-Deuterio-3-hex-1-ynyl-1-(toluene-4-sulfonyl)-2-p-tolylaziridine (6)

Colourless oil (77%, 12:1 cis:trans). 1H NMR (300 MHz, CDCl3):d¼ 0.76 (t, J¼ 7.2 Hz, 3H), 1.05e1.18 (m, 2H), 1.22e1.31 (m, 2H), 2.02(dt, J¼ 6.9 Hz, 1.8 Hz, 2H), 2.32 (s, 3H), 2.43 (s, 3H), 3.60 (t,J¼ 1.8 Hz,1H), 7.09 (d, J¼ 8.1 Hz, 2H), 7.21 (d, J¼ 8.1 Hz, 2H), 7.33 (d,J¼ 8.4 Hz, 2H), 7.87 (d, J¼ 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3):d¼ 13.4, 18.3, 21.2, 21.5, 21.6, 30.0, 36.1, 72.3, 86.6, 127.6 (2C), 127.9(2C), 128.6 (2C), 129.1, 129.7 (2C), 134.8, 138.0, 144.6; IR (neat):n¼ 2961, 2926, 2874, 2248, 1921, 1598, 1518, 1458, 1410, 1363, 1323,1301, 1181, 1161, 1133, 1090, 1019, 914, 894, 838, 805, 757, 704;HRMS (TOF ESþ): m/z calcd for C22H24DNO2NaS: 391.1566, found:391.1563.

4.3. Pyrroles

4.3.1. General Method for gold-catalysed cyclisationThe 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 reactionmixturewas stirred at theindicated temperature until complete consumption of aziridine wasobserved. The solution was filtered through a pad of silica and thenconcentrated under reduced pressure to afford the pyrrole.

4.3.2. 2-2-Phenethyl-5-phenyl-1-(toluene-4-sulfonyl)-1H-pyrrole(Table 1, Entry 7)

Colourless oil (95%). 1H NMR (300 MHz, CDCl3): d¼ 2.38 (s, 3H),3.05e3.10 (m, 2H), 3.23e3.28 (m, 2H), 6.06 (d, J¼ 3.3 Hz, 1H), 6.09(d, J¼ 3.3 Hz,1H), 7.15 (d, J¼ 8.3 Hz, 2H), 7.21e7.33 (m, 7H), 7.35 (m,5H); 13C NMR (75 MHz, CDCl3): d¼ 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): n¼ 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.

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)

Colourless oil (>95%). 1H NMR (300 MHz, CDCl3): d¼ 2.38 (s,3H), 6.26 (d, J¼ 3.5 Hz, 2H), 7.12e7.05 (m, 4H), 7.55e7.28 (m, 9H);13C NMR (75 MHz, CDCl3): d¼ 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): n¼ 2233, 1705, 1596,1439, 1371, 1176, 1092, 920, 810, 729, 703; HRMS (TOF ESþ): m/zcalcd for C23H18NO2NaSBr: 474.0139, found: 474.0144.

4.3.4. 2,5-Dicyclohexyl-1-(toluene-4-sulfonyl)-1H-pyrrole (Table 1,Entry 12)

Colourless oil (>95%). 1H NMR (300 MHz, CDCl3): d¼ 1.14e1.40(m, 8H), 1.62e1.72 (m, 8H), 1.90 (d, J¼ 12.2 Hz, 4H), 2.38 (s, 3H),3.05 (m, 2H), 5.94 (s, 2H), 7.22 (d, J¼ 8.3 Hz, 2H), 7.38 (d, J¼ 8.3 Hz,2H); 13C NMR (75 MHz, CDCl3): d¼ 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): n¼ 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 forC23H18NO2NaSBr: 474.0139, found: 474.0144. HRMS (TOF ESþ):m/zcalcd for C23H31NO2NaS: 408.1973, found: 408.1969.

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): d¼ 1.17 (d,J¼ 6.7 Hz, 6H), 1.21e1.49 (m, 4H), 1.52e1.82 (m, 4H), 1.91 (d,J¼ 12.1 Hz, 2H), 2.38 (s, 3H), 3.05 (m,1H), 3.42 (sept, J¼ 6.7 Hz, 1H),5.95 (d, J¼ 3.5 Hz, 1H), 5.98 (d, J¼ 3.5 Hz, 1H), 7.22 (d, J¼ 8.4 Hz,2H), 7.28 (d, J¼ 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3): d¼ 21.5, 24.0(2C), 26.2, 26.7 (2C), 27.5, 34.8 (2C), 37.4, 109.2, 109.4, 125.4 (2C),129.7 (2C), 138.0, 144.0, 144.5, 145.0; IR (neat): n¼ 2968, 2926,2853,1681,1598,1528,1493,1447,1370,1357,1304,1193,1180,1167,1142, 1111, 1095, 1060, 1016, 810, 783, 747, 703, 682; HRMS (TOFESþ): m/z calcd for C20H27NO2NaS: 368.1660, found: 368.1676.

4.3.6. 2-Allyl-5-isopropyl-1-(toluene-4-sulfonyl)-1H-pyrrole (Table1, Entry 15)

Pale yellow oil (95%). 1H NMR (300 MHz, CDCl3): d¼ 1.24 (d,J¼ 6.7 Hz, 6H), 2.44 (s, 3H), 3.50 (sept, J¼ 6.7 Hz, 1H), 3.60 (dd,J¼ 3.6, 1.1 Hz, 2H), 5.11 (m, 1H), 5.16 (m, 1H), 5.85e5.99 (m, 2H),6.05 (dd, J¼ 3.4, 1.1 Hz, 1H), 7.31 (d, J¼ 8.2 Hz, 2H), 7.50 (d,J¼ 8.2 Hz, 2H); 13C NMR (75 MHz, CDCl3): d¼ 21.5, 24.0 (2C), 27.3,33.7, 108.9, 111.9, 116.7, 125.7 (2C), 129.8 (2C), 135.2, 135.4, 137.7,144.2, 145.5; IR (neat): n¼ 3089, 3010, 2967, 2871, 1831, 1635, 1597,1366, 1179, 1189, 980, 925, 818, 706, 686; HRMS (TOF ESþ): m/zcalcd for C17H21NO2NaS: 326.1191, found: 326.1198.

4.3.7. 2-Isopropyl-1-(toluene-4-sulfonyl)-1H-pyrrole (5a)Colourless oil (>95%). 1H NMR (300 MHz, CDCl3): d¼ 1.13 (d,

J¼ 6.7 Hz, 6H), 2.41 (s, 3H), 3.29 (sept, J¼ 6.7 Hz, 1H), 6.05 (m, 1H),6.22 (dd, J¼ 3.4, 3.3 Hz, 1H), 7.26 (dd, J¼ 3.3, 1.6 Hz, 1H), 7.28 (d,J¼ 8.3 Hz, 2H), 7.61 (d, J¼ 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3):d¼ 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): n¼ 3010, 2967, 2871, 1597, 1366, 1179,1189, 812, 704, 682; HRMS (TOF ESþ):m/z calcd for C14H17NO2NaS:286.0878, found: 286.0874.

Acknowledgements

Financial support from the University of Birmingham is gratefullyacknowledged. We thank JohnsonMatthey plc for a generous loan ofmetal salts. This research was part supported through BirminghamScience City: Innovative Uses for Advanced Materials in the ModernWorld (WestMidlands Centre for AdvancedMaterials Project 2),with

support from Advantage West Midlands (AWM) and part funded bythe European Regional Development Fund (ERDF).

References

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[18] Tosylate could act as a nucleophile to either the aziridine or, as suggested bya reviewer, the metal-activated alkyne. Reversible aziridine ring-opening bynucleophilic attack at the propargylic position, would result in a species ableto undergo cyclisation and aromatisation. For the effective cyclisations ofequivalent ring-opened species see: (a) A. Aponick, C.-Y. Li, J. Malinge,E.F. Marques, Org. Lett. 11 (2009) 4624e4627;(b) M. Egi, K. Azechi, S. Akai, Org. Lett. 11 (2009) 5002e5005 The gold-

P.W. Davies, N. Martin / Journal of Organometallic Chemistry 696 (2011) 159e164164

catalysed addition of sulfonic acids across alkynes has recently been reported;(c) D.-M. Cui, Q. Meng, J.-Z. Zheng, C. Zhang, Chem. Commun. (2009)1577e1579 Regioselective tosylate addition to the least hindered end of thegold-activated alkyne would result in a vinyl gold species. Formation of anallenyl intermediate by elimination of gold with concomitant ring-opening ofthe aziridine provides a viable pathway for formation of the pyrrole, by gold-promoted ring closure on attack of the charged nitrogen to the alkyne withsubsequent elimination of tosylate.

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