Exploiting the σ-phylic properties of cationic gold(i) catalysts in the ring opening reactions of aziridines with indoles

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Exploiting the σ-phylic properties of cationic gold(I) catalysts in the ring

opening reactions of aziridines with indoles

*a

a

Elisabetta Rossi, Giorgio Abbiati, Monica Dell’Acqua, Marco Negrato, Andrea Paganoni and

a

Valentina Pirovano

a

Dipartimento di Scienze Farmaceutiche – Sezione di Chimica Generale e Organica “A. Marchesini”,

Università degli Studi di Milano, Via G. Venezian, 2 – 20133 Milano, Italy.

eꢀmail: elisabetta.rossi@unimi.it

Keywords Gold / Aziridines / Indoles / Tryptamines/ Pyrroloindolines

Abstract

N

A study on the S 2ꢀtype ring opening reactions of aziridines with indoles as nucleophiles is

reported. Under gold(I) catalysis a great variety of tryptamine derivatives were prepared in good to

excellent yields with complete stereocontrol when chiral aziridines were used. We demonstrated

that cationic gold(I) catalysts are superior Lewis acids to the previously reported group 3, 12 and

1

3 metals in term of catalyst loading and reaction yields. Moreover, complete regioselectivity was

observed for 2ꢀphenylꢀNꢀtosylaziridine; whereas, regioselectivity up to 10:1 ratio was observed

with 2ꢀmethylꢀNꢀtosylaziridine. Finally, a preliminary study on the dearomatization reactions

giving rise to pyrroloindolines is also reported.

Introduction

Aziridine nucleophilic ringꢀopening reactions have been recognized for a long time as a precious

1

and reliable tool to introduce the CCN motif in a huge number of substrates. In the specific case

of the indole nucleus, regioselective nucleophilic ringꢀopening of aziridines led to the formation of

tryptamine derivatives, chemical synthesized or naturally occurring drugs/alkaloids with wellꢀ

2

defined and significant biological effects. However, reported examples with indoles as

nucleophiles are relatively rare and involve aziridines bearing an electron withdrawing group at

3

nitrogen (activated aziridines) under (Lewis) acidic catalysis. In particular, the regiochemical

outcome for those reactions involving C2 monosubstituted aziridines largely depends on the

substitution pattern (Scheme 1).

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Scheme 1 Previously reported results on the ring opening reactions of aziridines with indoles.

For example, indoles add regioselectively at the benzylic position of C2 aryl substituted aziridines

3h

3a

3i

under LiClO₄, and Sc(OTf) /Zn(OTf) catalysis, or in the presence of an excess of BF₃

3

2

(

Scheme 1, eq. 1). Moving to alkyl substituted aziridines, mixtures of both conceivable

3

c

regioisomers are isolated using Zn(OTf)

reaction in the presence of an excess of BF

2

as catalyst, and only one report of regioselective

3

i

3

has been reported till now (Scheme 1, eq. 2).

Besides, aziridines 2ꢀcarboxylate have been involved in the synthesis of tryptophan derivatives

3

j

3b

3d

using 1 equivalent of Sc(ClO

data reported in scheme 1, it should be noted that working with chiral C2 substituted aziridines,

enantiomeric pure compounds can be obtained, suggesting the involvement of a S 2ꢀtype

Clearly, enantiomeric pure derivatives have been

obtained in C3 selective ring opening reactions of enantiomeric pure C2 substituted

4

)

3

, Sc(OTf)

3

or Y(OTf)

3

as promoters (Scheme 1, eq. 3). From

N

3

i,3c

mechanism for the ringꢀopening reaction.

3b,3d,3j

aziridines.

Furthermore, several of the reported reactions suffers from some drawbacks, i.e.,

they are performed in the presence of at least stoichiometric amount of Lewis acids, require an

excess of aziridine/indole substrates and/or are limited in scope.

On the other hand, indole is one of the most extensively explored heterocyclic nucleus. A plethora

4

of synthetic methodologies have been developed for the assembly of the indole core as well as for

5

the functionalization of the preformed nucleus. This latter goal has been mainly achieved on the

pyrrole moiety with electrophiles, exploiting the enamineꢀtype reactivity at the C3 carbon atom

and the nucleophilic properties of the nitrogen atom, and, to a lesser extent, with nucleophiles,

reversing the natural reactivity by the insertion of proper substituents at nitrogen or at C2/C3

positions.

Others interconnected and fascinating research areas encompass the dearomative manipulation of

6

the preformed indole ring

for the synthesis of the indolenine core and the

4

e,4h,4k,7

cyclization/cycloaddition reactions for the synthesis of polycyclic indole derivatives,

either

common scaffolds in naturally occurring and bioactive compounds. Over the last years, the

effectiveness of all these transformations has been notably enhanced through the development of

new catalytic and organocatalytic processes.

Considering these results and in step with our latest research reports on the synthesis of polycyclic

8

9

indoles and indole derivatives under gold catalysis, we recognized goldꢀactivated aziridines as

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suitable electrophiles for the simple functionalization and the dearomative reactions of indoles for

the synthesis of βꢀindolylamines and fused pyrrolo[2,3ꢀb]indoles, respectively (Scheme 2).

Scheme 2 Planned gold(I) catalyzed reactions.

Formation of stable complexes via Nꢀcoordination of aziridines with in situ generated

3

triphenylphosphine gold(I) triflate (AuPPh OTf) has been recently described by Lorenz and coꢀ

1

0

workers. These complexes are quite stable and can be isolated and characterized under standard

laboratory conditions. Moreover, in 2007 Wu and coꢀworkers published a gold(III) chloride/silver

1

triflate catalyzed ringꢀopening reaction of aziridines with furan and electronꢀrich arenes. Thus, in

the presence of 1ꢀ5% of AuCl and 3ꢀ15% of AgOTf in nitromethane at room temperature, the

3

reaction affords the corresponding βꢀaryl(furyl)amines in good to excellent yields. Moreover,

several papers dealing with the σꢀphylic properties of gold species have been recently

8

a,12

published.

Results

We started our investigations testing the reactivity of indoles 1a and 1h with racemic 2ꢀphenylꢀNꢀ

tosylaziridine (2a), under conventional Lewis acid, organic acid and under gold catalysis. A

comprehensive review of reaction conditions we tested is summarized in Table 1.

Table 1. Optimization studies for the formation of tryptamine derivatives 3a and 3h.

a

entry indole eq. of 2a

catalyst (mol%)

solvent T, °C time, h yield, %

1

2

3

4

5

6

7

8

9

1a

1h

1a

1h

1a

1h

1a

1h

1.1

1.5

0.6

1.5

1.1

1.5

In(OTf)

Sc(OTf)

Zn(NTf

BF ·OEt (1.5 eq.)

3

(15 mol%)

DCM

DCE

DCM

DCE

rt, 40

rt, 60

ꢀ20

rt

20

0.2

1.5

20

24

20

24

0.5

42

21

3

(15 mol%)

2

)

2

(15 mol%)

48

54

3

2

TfOH (5 mol%)

51

b

BDHP (5 mol%)

80

traces

23

AuCl (5 mol%) AgOTf (15 mol%) CH NO₂

rt

3

AgOTf (5 mol%)

DCM

rt, 40

80

50

AgNTf

2

(5 mol%)

DCE

45

c

10

[Au(PPh )OTf] (5 mol%)

80

61

3

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11

12

13

14

1h

1a

1.5

1.1

[Au(IPr)SbF

6

] (5 mol%)

DCE

80

0.5

79

87

80

98

[Au(JohnPhos)NTf ] (5 mol%)

0.5

4.5

2

[Au(PPh

3

)NTf

2

] (5 mol%)

[Au(JohnPhos)NTf

2

a

Entries 1ꢀ3, 5ꢀ14: reaction conditions: to a solution of indole (0.3 mmol) and aziridine (n equiv.) in the appropriate

solvent (2 mL, 0.15 M), catalyst was added and the mixture was stirred for the stated time and temperature. Entry 4,

see ref. 3i.

b

BDHP = 1,1'ꢀbinaphthylꢀ2,2'ꢀdiyl hydrogenphosphate.

We choose to survey the reactivity of 2ꢀalkynylindole 1h, beside simple and commercially

available 1a, to verify the feasibility of a domino process involving nucleophilic addition of indole

to aziridine and subsequent hydroamination of the triple bond (Table 1, compound in brackets).

However, under tested reaction conditions, this compound has been never isolated or detected in

the crude reaction mixtures. When the reaction works toward the formation of the desired

compounds 3 the only isolated regioisomers arose from the C2 selective ringꢀopening of the

aziridine, compounds 3a and 3h. The structure of 3a was elucidated via 1D and 2D NMR

1

3

experiments. Initially, for comparison, we tested several conventional Lewis acids under

catalytic condition (15 mol%, entries 1ꢀ3). Instead, boron trifluoride was used under the conditions

reported in ref. 3i (entry 4). These first attempts, however, led to the formation of the desired

product in poor or moderate yields. Similar results were obtained in the presence of trifluoroacetic

acid as catalyst, whereas the phosphoric acid (1,1'ꢀbinaphthylꢀ2,2'ꢀdiyl hydrogenphosphate)

resulted essentially ineffective, entries 5ꢀ6. Thus, gold(III) chloride, in the presence of silver

1

triflate as activating agent, was tested under the reaction conditions reported by Wu, entry 7. In

this case, 3a was obtained in 23% yield. 5 mol% silver triflate, silver triflimidate or cationic

gold(I) species resulted more effective, entries 8ꢀ14, and compounds 3a or 3h were isolated in 45ꢀ

9

2

8% yields, with [Au(JohnPhos)NTf ] as catalyst of choice.

With these results in hand, we initially choose to test the scope of the reaction under the conditions

reported in table 1, entry 14, changing the substituents array on the indole nucleus (Scheme 3).

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NHTs

Ph

Ts

N

R²

R

[Au(JohnPhos)(NTf2)] (5 mol%)

+

_R2

R

N

DCE, 80 °C

Ph

N

R¹

1

a-o

2a

R)2a, ee 98%

3a-o

(

(S)3a,c-e,k

NHTs

Ph

NHTs

Ph

NHTs

Ph

Oi-Pr

Me

N

Me

N

H

COMe

3

a, 98%

S)3a, 98%, ee 97%

3b, 95%

3c, 90%

(S)3c, 89%, ee 98%

3d, 97%

(S)3d, 97%, ee 97%

3e, 92%

(S)3e, 88%, ee 94%

(

NHTs

Ph

Me

N

H

Me

3

f, 90%

3g, 69%

3h, 87%

3i, 93%

3j, 80%

NHTs

Ph

F

Ph

CO2Et

CO Et

2

N

H

N

F3C

Et2N

H

3

k, 83%

3l, 97%

3m, 30%

3n, 54%

3o, 54%

(

S)3k, 85%, ee 97%

Scheme 3 Reaction scope with 2ꢀphenylꢀNꢀtosylaziridines 2a and (R)2a.

Product yields ranged from very good to excellent when the reaction was performed with 2ꢀaryl,

2

ꢀalkyl, 2ꢀvinyl, 2ꢀalkynyl and 2ꢀallyl indoles (1a, 1c-f, 1h-j), with NꢀMe protected indoles 1b and

1

g and with indole itself (1k). The introduction of an EWG on the indole phenyl moiety is well

tolerated (1l), whereas in the presence of an EDG, indole 1m, or of when an ethoxycarbonyl group

is linked at C2 of the indole nucleus, indoles 1n and 1o, the corresponding tryptamine derivatives

3

m-o were obtained in moderate yields. Moreover, the reactions of indoles 1a,c-e,k were repeated

in the presence of (R)ꢀ2ꢀphenylꢀNꢀtosylaziridine ((R)2a) yielding the corresponding optical active

compounds (S)3a,c-e,k in enantiomeric excesses comparable to that of the starting aziridine.

Next, we turned our attention to the aziridine nucleus testing the reactivity of Nꢀtosylaziridine (2b)

(Scheme 4).

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Scheme 4 Reaction scope with Nꢀtosylaziridine 2b.

The reaction works well also with the unsubstituted Nꢀtosylaziridine (2b). Tryptamines 3p-t were

obtained in 62ꢀ71% yield using a slight excess (1.2 equivalents) of thermally fragile 2b. Working

with a larger excess of 2b (1.5 or 2.0 equivalents) resulted in the isolation of dirty reaction

products, contaminated by inseparable tarry decomposition compounds arising from 2b.

Then, we focused on the ring opening reactions of racemic 2ꢀmethylꢀNꢀtosylaziridine (2c) with

indoles 1 (Table 2).

Table 2. Ringꢀopening reactions of 2ꢀmethylꢀNꢀtosylaziridine (2c) with indoles 1.

a

entry indole

catalyst (mol%)

solvent T, °C overall yield, % ratio 3/3’

1

2

3

4

5

6

7

8

9

1a

1c

1e

1a

[Au(JohnPhos)(NTf

2

)] (5 mol%)

DCE

DCM

DCE

80

20

80

98

86

92

55

91

31

99

96

27

46

2:1

[Au(JohnPhos)(NTf

)] (5 mol%)

2:1

BF

3

·OEt

2

(1.5 equiv.)

12:1

1.5:1

2:1

[Au(JohnPhos)(SbF )(CH CN)] (5 mol%)

6

3

[Au(PPh

3

)(NTf

2

)] (5 mol%)

[Au(IPr)(NTf

2

)] (5 mol%)

[Au(IPr)(SbF )(CH

6

3

CN)] (5 mol%)

2:1

AuCl/AgOTf (5 mol%)

7:1

10

10:1

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11

12

13

1a

AuCl/AgNTf

AuCl/AgSbF

2

(5 mol%)

DCE

80

70

ꢀ

7:1

ꢀ

6

AgOTf (5 mol%)

a

Entries 1ꢀ3, 5ꢀ9: reaction conditions: to a solution of indole (0.3 mmol) and aziridine (1.1 equiv.) in DCE (2 mL,

.15 M), catalyst was added and the mixture was stirred for the stated time and temperature. Entry 4: see ref. 3i.

0

Entries 10ꢀ13: reaction conditions: to a solution of indole (0.3 mmol) and aziridine (0.15 equiv.) in DCE (2 mL, 0.15

M), catalyst was added and the mixture was stirred at 80°C for 24 h.

Generally, quite unsatisfactory results were obtained working with 2ꢀmethylꢀNꢀtosylaziridine 2c.

The first three experiments (entries 1ꢀ3), performed with indoles 1a,c,e under standard reaction

conditions, resulted in the isolation in excellent overall yields of an inseparable mixture of both

conceivable regioisomeric tryptamines 3u-w and 3’u-w in 2:1 ratios. As reported in the

introduction, regioselectivity in the ringꢀopening reaction of activated 2ꢀalkylaziridines, using

indoles as nucleophiles, is still a challenging objective and only one example of a regioselective

reaction has been reported till now in the presence of an excess (1.5 equiv.) of boron trifluoride

3i

etherate. Thus, we performed the reaction between 1a and 2c under the conditions reported by

Farr and coꢀworkers (entry 4) attaining 3u and 3’u in 12:1 ratio. Next, with the aim to improve the

regioisomeric ratios between 3 and 3’ under catalytic conditions, we tested several cationic gold(I)

complexes varying both the ligands and the counterions (entries 5ꢀ8) achieving quite disappointing

results. Better results could be obtained in the presence of simple gold(I) salts such as gold(I)

triflate, generated in situ by mixing equimolecular amounts of gold(I) chloride and silver triflate.

Thus, the reaction gave rise to compounds 3u and 3’u in 7:1 ratio (entry 9). Yield and

regioisomeric ratio comparable to those obtained with boron trifluoride could be obtained working

in the presence of 2 equivalents of indole 1a (entry 10). A brief screening on the silver salts nature

6 2

was then performed revealing that AuCl/AgSbF and AuCl/AgNTf were the catalysts of choice to

achieve 3u and 3’u in 70% yield and 7:1 ratio (entries 11ꢀ12). A control experiment performed

with silver triflate as catalyst failed to give the desired compound (entry 13). Structures and ratios

13

between the two regioisomers were assigned via NMR analysis. A control reaction between

indole 1a and aziridine (S)2c under the reaction conditions reported in table 2, entry 12 resulted in

the isolation of a mixture of (R)3u (94% ee) and 3’u in 68% overall yield (10:1 ratio) (Scheme 5).

NHTs

Ph

NHTs

Me

Ts

N

Me

Ph

AuCl/AgSbF6 (5 mol%)

DCE, 80 °C, 24 h

Ph

+

N

Me (S)

N

0

.15 M

H

68%

10:1

1a

(S)2c, ee 99.9%

(R)3u, ee 94%

(S)3'u, ee nd

Scheme 5 Gold(I) catalyzed reaction of indole 1a and aziridine (S)2c.

Moreover, several additional experiments were performed with indole 1a and aziridines 2d-f

Scheme 6).

(

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Scheme 6 Gold(I) catalyzed reaction of indole 1a and aziridines 2d-f.

Under standard reaction conditions indole 1a reacts with aziridines 2d and 2e giving rise to

tryptamines 3x-y in low to moderate yields, beside unreacted 1a. Moreover, the same reaction

performed in the presence of aziridine 2f resulted in the isolation of unreacted 1a (45%) alongside

a mixture of unidentified compounds.

Finally, we want to report our preliminary results on the dearomative domino addition/annulation

reactions between N,3ꢀdimethylindole 1p, Nꢀbenzylꢀ3ꢀmethylindole 1q, 2,3ꢀdimethylindole 1r and

3

ꢀallylꢀNꢀmethylindole 1s with aziridines 2a and 2b, under cationic [Au(JohnPhos)(NTf

2

)] gold(I)

catalysis (Scheme 7).

1

4

Excellent results on related dearomative reactions, involving unsubstituted aziridine,

1

5

16

symmetrically C2/C3 substituted aziridines or C2 substituted aziridines , have been recently

reported.

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Scheme 7 Dearomative domino addition/annulation reactions.

Under cationic gold(I) catalysis, the dearomatization reactions of indoles 1p-r with aziridine 2a

proceeded in moderate yields giving rise to the corresponding diastereoisomeric

dihydropyrroloindolines (±)4a-c and (±)4’a-c as racemic mixtures. Diastereoisomers (±)4a/(±)4’a

and (±)4c/(±)4’c could be separated by column chromatography and the structures established by

16

comparison with reported data for (±)4a and (±)4’a and by 2D NOESY experiments for (±)4c

and (±)4’c. Diastereoisomers (±)4b/(±)4’b were characterized as a mixture via NMR and by

1

6

comparison with reported data. Reactions with indoles 1p-q were repeated also in the presence

of chiral aziridine (R)2a giving rise to enantiomeric enriched diastereoisomers 4a (96% ee) and

4

’a (96% ee) / 4b (99% ee) and 4’b (99% ee). 4a/4’a and 4b/4’b were evaluated as mixtures via

1

3,17

chiral HPLC analysis, after chromatographic purification.

Working with indole 1p and aziridine 2b, the indoline 4d was obtained in 55% yield after

optimization of the reaction conditions. In particular, the reactions performed under standard

conditions (ratio indole/aziridine 1:1.2, 0.15 M solution in dichloroethane) at 80 and at 120°C

under conventional heating or at temperatures ranging from 120 to 150 °C under microwaves

irradiation gave unsatisfactory results (yields 18ꢀ39%, scheme 7, entries 1ꢀ4). A brief optimization

study on the reagents ratios and reaction concentration revealed that doubling the equivalents of

2

b has no effect on the product yield (scheme 7, entry 5). On the other hand, working with two

equivalents of indole 1p, at 0.3 M and 0.6 M concentrations, the desired compound could be

isolated in 45% and 55% yields, respectively (scheme 7, entries 6ꢀ7). Under optimized reaction

conditions, 3ꢀallylꢀNꢀmethylindole (1s) was tested in the dearomative reaction giving rise to

indoline 4e in 45% yield.

Discussion

As a general remark it can be stated that cationic gold(I) complexes are active catalysts in the ringꢀ

opening reactions of activated aziridine with indoles as nucleophiles. In particular,

[

2

Au(JohnPhos)NTf ] is the catalyst of choice for the ringꢀopening reactions performed with 2ꢀ

phenylꢀNꢀtosylaziridine 2a. Thus, the nucleophilic attack of indoles 1a-o, through C3 carbon

atom, occurs regioselectively at the C2 of the aziridine ring, yielding the corresponding tryptamine

derivatives 3a-o in excellent yields with a catalyst loading of only 5 mol%. Moreover, the ringꢀ

opening reactions provide racemic mixtures when performed with achiral aziridine 2a and is

stereospecific employing the chiral aziridine (R)2a as starting material. Based on these

experimental results and literature reports, a reaction mechanism can be postulated for the ringꢀ

1

0,18

opening reactions of 2a and (R)2a with indoles 1 (Scheme 8). Therefore, azaphilic

activation

of aziridine by cationic gold(I) catalyst produces an activated complex (I). Then the indole 1

attacks regioselectively at the benzylic carbon of I producing a new intermediate II via a Friedelꢀ

Craftꢀtype reaction. Rearomatization and protodeauration steps conclude the catalytic cycle

affording 3 and restoring the catalyst.

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Scheme 8 Proposed reaction mechanism.

The stereospecificity attained with (R)2a accounts for the intermediacy of a strongly polarized

specie like I, reacting with 1 via S 2ꢀtype mechanism. Besides, the intermediacy of a zwitterionic

specie III, scheme 7, can be disregarded as it would provide racemic 3 by S 1ꢀtype mechanism.

Unfortunately, the same regioselectivity was not observed in the ringꢀopening reactions involving

ꢀmethylꢀNꢀtosylaziridine (2b) under [Au(JohnPhos)NTf ] catalysis. As reported in the literature

N

2

and confirmed by our experiments (see Table 2), boron trifluoride is able to almost

regioselectively address the nucleophilic attack at the more hindered carbon atom of the aziridine

ring. It seems that an excess of a hard Lewis acid like boron trifluoride is essential to establish a

strong interaction within both reacting substrates and to trigger the reaction toward the C2

3

i,19

selective ringꢀopening reaction path.

Instead, cationic gold(I) complexes in catalytic amount

weakly interacts with the aziridine nitrogen and, in the absence of a strong directing group like a

phenyl ring in aziridine 2a, the reaction outcomes is driven by steric and electronic issues making

possible two opposite reaction paths. Both of them involve ringꢀopening reaction of the aziridine

2

b, respectively at C2 and C3, affording mixtures of both conceivable tryptamines 3 and 3’. In line

with these observations, it is worth to note that using 5 mol% of more electrophilic naked cationic

gold salts improve the regioisomeric ratio between 3u and 3’u. Importantly, [Au(JohnPhos)NTf

2

]

catalyst results effective also in the dearomative reactions of C3 substituted indoles. In this latter

case, a reaction intermediate analogous to II, scheme 8, evolves by intramolecular amination

reaction and regeneration of the catalyst.

Conclusions

2

In this work we established the high efficiency of cationic gold(I) catalyst [Au(JohnPhos)(NTf )]

in the ring opening reactions of 2ꢀphenylꢀNꢀtosylaziridine 2a and (R)2a with indoles as

nucleophiles. In particular, we gathered a large collection of tryptamine derivatives in high yields,

with complete stereochemical control and at a catalyst loading of only 5 mol%. To the best of our

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knowledge, only sporadic examples of related Lewis acid catalyzed reactions have been reported

3

h,3a,3i

till now.

Furthermore, it should be pointed out that, depending on the nature of the Lewis

acid employed, previously reported reactions could suffer from lack of stereocontrol due to

16a

racemization of the starting aziridine during the reaction course. The results obtained with 2a,

beside those obtained with Nꢀtosylaziridine itself (2b), represent the key strength of our work. In

contrast, less exciting results have been achieved with 2ꢀmethylꢀNꢀtosylaziridine (2c) and in the

dearomative domino addition/annulation reactions. In the first case, we observed a lack of

regiochemical control even if nearly quantitative reaction yields could be obtained. Dearomative

reactions giving rise to pyrroloindoline derivatives, beside excellent stereocontrol, present several

drawbacks. Moderate yields and low diastereoselection are the main weak points that must be

addressed and further efforts in these directions are ongoing in our laboratory. Also the results

reported for aziridines 2d-f in scheme 6 could represent a good starting point for further

investigations.

Experimental

General Experimental Details

All chemicals and solvents are commercially available and were used after distillation or treatment

with drying agents. Silica gel F254 thinꢀlayer plates were employed for thinꢀlayer chromatography

(TLC). Silica gel 40–63 micron/60 Å was employed for flash column chromatography. Melting

points were measured with a Perkinꢀ Elmer DSC 6 calorimeter at a heating rate of 5 °C/min and

1

13

are uncorrected. H and CꢀNMR spectra were determined with a VarianꢀGemini 200, a Bruker

00 or 500 Avance spectrometers at room temperature in CDCl , CD Cl or d ꢀacetone with

3

2

6

residual solvent peaks as the internal reference. The APT sequence was used to distinguish the

methine and methyl carbon signals from those arising from methylene and quaternary carbon

atoms. Twoꢀdimensional NMR experiments were performed, where appropriate, to aid the

assignment of structures. Lowꢀresolution MS spectra were recorded with a ThermoꢀFinnigan LCQ

advantage AP electrospray/ion trap equipped instrument using a syringe pump device to directly

inject sample solutions. Microwave promoted reactions were performed with a singleꢀmode

Personal Chemistry microwave synthesizer “Emrys Creator,” using sealed glass vessels. The

temperature was detected with an infrared sensor. Indoles 1a, 1e, 1k, 1n, 1o, 1p, 1r are

commercially available and were used without any further purification. Indoles 1b-d, and 1l are

9

,20

known compounds and were prepared as reported in literature. Indoles 1q and 1s are a known

2

1

22

23

compound and were prepared according to literature procedure. Indole 1h and indoles 1i, 1j

were prepared according to the procedures reported in ref. 9 and 20 (see below). Indoles 1f and 1g

24,8b

were prepared as reported in ref. 24 and 8b, respectively.

Indole 1m is a new compound and

was prepared as reported below. Aziridines 2a-f are known compounds and were prepared

2

5

according to standard procedures. AuCl

3 3

, AuCl [Au(PPh )Cl], [Au(JohnPhos)Cl], [Au(IPr)Cl],

AgNTf , AgOTf, In(OTf) , Zn(NTf) and TfOH were purchased from commercial suppliers and

2

3

2

6

used as received, the rest of the gold catalysts were prepared according to literature procedures.

Preparation and characterization data for compounds 1h-j, m

Organic & Biomolecular Chemistry

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2

20

2

-(phenylethynyl)-1H-indole (1h) . Ethyl 2ꢀ(phenylethynyl)ꢀ1Hꢀindoleꢀ1ꢀcarboxylate (0.84 g,

2

2 3

.9 mmol) was dissolved in MeOH (20 mL). Solid K CO (0.40 g, 2.9 mmol) was added and the

mixture stirred for 2 h at 40 °C. Then the solvent was removed in vacuum and the residue

dissolved in H O/EtOAc 1:1 (50 mL). The two phases were separated and the aqueous layer was

2

extracted with EtOAc (2 x 15mL). The combined organic layers were dried over Na SO , filtered

2

4

and concentrated in vacuum to yield the 2ꢀ(phenylethynyl)ꢀ1Hꢀindole (1h) (0.59 g, 94%) as a

1

yellow solid. H-NMR (200 MHz, CD

2

Cl

2

): δ 8.39 (s, 1H), 7.59 (m, 3H), 7.40 (m, 4H), 7.27 (t, J

13

=

6.9 Hz, 1H), 7.15 (t, J = 7.3 Hz, 1H), 6.87 (s, 1H). C-NMR (50 MHz, CD

2 2

Cl ): δ 136.5 (C),

1

31.6 (2 x CH), 128.9 (CH), 128.7 (2 x CH), 128.0 (C), 123.8 (CH), 122.8 (C), 120.9(CH), 120.7

+

(CH), 119.0 (C), 111.0 (CH), 108.8 (CH), 92.6 (C), 81.8 (C). ESI-MS m/z 218 (M+H , 100). Data

are in agreement with those reported in ref. 22.

2

-(pent-1-yn-1-yl)-1H-indole (1i). To well stirred solution of ethyl 2ꢀ(((trifluoromethyl)

20

sulfonyl)oxy)ꢀ1Hꢀindoleꢀ1ꢀcarboxylate (1.0 g, 2.96 mmol) and pentꢀ1ꢀyne (0.24 g, 3.55 mmol)

in dry DMF (12 mL), Pd(PPh (4 mol%, 132 mg, 0.12 mmol), CuI (2 mol%, 11.3 mg, 0.06

mmol) and Et N (8.25 mL, 59.2 mmol) were added. The mixture was then stirred at room

temperature until disappearing of starting materials (c.a. 1 h) and then diluted with HCl 0.1 M

100 mL). Aqueous phase was extracted with EtOAc (3 x 50 mL); the combined organic phases

were washed with brine (1 x 50 mL), dried over Na SO , filtered and concentrated in vacuum.

3 4

)

3

(

2

4

Purification by column chromatography (Hex/EtOAc 98:2) yielded ethyl 2ꢀ(pentꢀ1ꢀynꢀ1ꢀyl)ꢀ1Hꢀ

1

indoleꢀ1ꢀcarboxylate (0.72 g, 95%) as a yellow oil. H-NMR (200 MHz, CDCl

3

): δ 8.13 (d, J =

8

7

2

.2 Hz, 1H), 7.48 (m, 1H), 7.37ꢀ7.17 (m, 2H), 6.82 (s, 1H), 4.51 (q, J = 7.1 Hz, 2H), 2.48 (t, J =

.1 Hz, 2H), 1.68 (sextet, J = 7.1 Hz, 2H), 1.49 (t, J = 7.1 Hz, 3H), 1.08 (t, J = 7.3 Hz, 3H). Ethyl

ꢀ(pentꢀ1ꢀynꢀ1ꢀyl)ꢀ1Hꢀindoleꢀ1ꢀcarboxylate (0.72 g, 2.82 mmol) was dissolved in MeOH (19 mL).

Solid K

that time, the solvent was removed in vacuum and the residue was dissolved in H

50 mL). The two phases were separated and aqueous layer was extracted with EtOAc (2 x 15mL).

The combined organic layers were dried over Na SO , filtered and concentrated in vacuum to

2

CO

3

(0.39 g, 2.82 mmol) was added and the mixture was stirred for 2 h at 40 °C. After

2

O/EtOAc 1:1

(

2

4

1

yield the 2ꢀ(pentꢀ1ꢀynꢀ1ꢀyl)ꢀ1Hꢀindole (1i) (0.49 g, 94%) as a brown wax. H-NMR (200 MHz,

CDCl ): δ 8.09 (s, 1H), 7.56 (m, 1H), 7.35ꢀ7.02 (m, 3H), 6.66 (d, J = 1.3 Hz, 1H), 2.44 (t, J = 7.0

Hz, 2H), 1.63 (sextet, J = 7.1 Hz, 2H), 1.07 (t, J = 7.3 Hz, 3H). C-NMR (50 MHz, CDCl

3

13

3

): δ

1

9

36.0 (C), 128.1 (C), 123.2 (CH), 120.8 (CH), 120.5 (CH), 119.8 (C), 110.8 (CH), 107.7 (CH),

+

3.9 (C), 73.4 (C), 22.3 (CH

2

), 21.8 (CH

2

), 13.8 (CH

3

). ESI-MS m/z 182 (MꢀH , 100).

2

3

20

2

-allyl-1H-indole (1j) . Ethyl 2ꢀallylꢀ1Hꢀindoleꢀ1ꢀcarboxylate (0.25 g, 1.11 mmol) was

dissolved in MeOH (8 mL) and K

for 30 min at 40 °C. After that time, the solvent was removed in vacuum and the residue was

dissolved in H O/EtOAc 1:1 (15 mL). The two phases were separated and aqueous layer was

extracted with EtOAc (2 x 5 mL). The combined organic layers were dried over Na SO , filtered

and concentrated in vacuum to yield 2ꢀallylꢀ1Hꢀindole (1j) (0.11 g, 60%) as a white solid. H-

NMR (200 MHz, CDCl ): δ 7.89 (s, 1H), 7.54 (d, J = 6.8 Hz, 1H), 7.36ꢀ7.00 (m, 3H), 6.28 (s,

H), 6.00 (m, 1H), 5.21 (m, 2H), 3.55 (d, J = 6.3 Hz, 2H). Data are in agreement with those

reported in ref. 23.

2 3

CO (0.15 g, 1.11 mmol) was added. The mixture was stirred

2

4

1

3

1

N,N-diethyl-1H-indol-6-amine (1m). A solution of NaOH 2M (3.7 mL, 7.49 mmol) was added to

2

7

a stirring solution of 6ꢀ(N,Nꢀdiethylamino)ꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀindole (200 mg, 0.61 mmol)

Page 13 of 26

Organic & Biomolecular Chemistry

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DOI: 10.1039/C6OB00672H

in 7 mL of MeOH and heated at 85 °C under a nitrogen atmosphere. The reaction mixture was

stirred for 24 h until no more starting product was detectable by TLC analysis. Methanol was

removed under reduced pressure and the crude product was poured into H O (25 mL) and

2

extracted with EtOAc (4 × 20 mL), washed with brine and dried over Na SO . The solvent was

2

4

removed under reduced pressure and then the residue was purified by flash chromatography over a

silica gel column using Hex/EtOAc (7:3) to afford the N,Nꢀdiethylꢀ1Hꢀindolꢀ6ꢀamine (1m) (95

1

mg, 83%) as pale brown oil. H-NMR (200 MHz, CDCl

3

): δ 7.87 (s, 1H), 7.47 (d, J = 9.1 Hz,

1

H), 7.01 (m, 1H), 6.78 (m, 2H), 6.42 (m, 1H), 3.36 (q, J = 7.0 Hz, 4H), 1.16 (t, J = 7.0 Hz, 6H).

1

3

C-NMR (C

6 6

D , 50 MHz): δ 145.2 (C), 138.0 (C), 121.7 (CH), 121.3 (CH), 120.9 (C), 110.7

+

(CH), 102.4 (CH), 96.3 (CH), 45.7 (2 x CH ), 12.7 (2 x CH ). ESI-MS m/z 189 (M+H , 100).

2 3

Preparation and characterization data for compounds 3a-t, (S)3a, (S)3c-e, (S)3k, 3x-y

Representative procedure for gold(I)-catalyzed ring opening of N-tosyl aziridines (procedure

A). To a N

or 1.2 equiv.) in DCE (0.15 M), [Au(JohnPhos)(NTf

stirred at 80 °C for 0.5ꢀ5 h. Solvent was then removed in vacuum and the residue purified by

column chromatography (SiO ) to yield the corresponding product 3a-t, (S)3a, (S)3c-e, (S)3k.

2

ꢀflushed solution of indole 1a-o (1.0 equiv.) and Nꢀtosyl aziridine 2a, (R)2a or 2b (1.1

2

)] (5 mol%) was added and the mixture was

2

4

-methyl-N-(2-phenyl-2-(2-phenyl-1H-indol-3-yl)ethyl)benzenesulfonamide (3a). Procedure A

was followed using 2ꢀphenylꢀ1Hꢀindole (1a) (58 mg, 0.3 mmol), 2ꢀphenylꢀ1ꢀtosylaziridine (2a)

90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL).

(

2

Purification of the crude by column chromatography (Hex/EtOAc 8:2) yielded 3a (137 mg, 98%)

1

as a white solid (m.p.: 165ꢀ167 °C). H NMR (300 MHz, CDCl

3

): δ 8.27 (s, 1H), 7.54ꢀ7.38 (m,

8

2

8

1

H), 7.32ꢀ7.09 (m, 9H), 6.97 (t, J = 7.5 Hz, 1H), 4.49 (dd, J = 10.7, 6.1 Hz, 1H), 4.24 (dd, J = 9.1,

1

.8 Hz, 1H), 3.84ꢀ3.62 (m, 2H), 2.42 (s, 3H). H NMR (300 MHz, CDCl

3 2

+ D O): δ 7.54ꢀ7.38 (m,

H), 7.32ꢀ7.09 (m, 9H), 6.97 (t, J = 7.5 Hz, 1H), 4.49 (dd, J = 10.7, 6.1 Hz, 1H), 3.80 (dd, J =

13

2.2, 6.1 Hz, 1H), 3.70 (dd, J = 10.9, 12.0 Hz, 1H), 2.41 (s, 3H). C NMR (50 MHz,

): δ 143.4 (C), 141.9 (C), 138.0 (C), 136.5 (C), 136.4 (C), 132.4 (C), 129.8 (2 x CH), 129.1

2 x CH), 128.9 (2 x CH), 128.8 (2 x CH), 128.6 (CH), 127.9 (2 x CH), 127.3 (C), 127.2 (2 x CH),

CDCl

(

3

1

2

6

26.9 (CH), 122.7 (CH), 120.4 (CH), 120.3 (CH), 111.8 (CH), 109.7 (C), 46.9 (CH

2

), 42.5 (CH),

+

1.8 (CH

.00; found C 74.38, H 5.78, N 5.86.

3 26 2 2

). ESI-MS m/z 465 (MꢀH , 100). Calcd. for C29H N O S [466.59]: C 74.65, H 5.62, N

(S)-4-methyl-N-(2-phenyl-2-(2-phenyl-1H-indol-3-yl)ethyl)benzenesulfonamide

((S)3a).

Procedure A was followed using (R)ꢀ2ꢀphenylꢀ1ꢀtosylaziridine ((R)2a). (S)3a was obtained in 98%

yield and 97% ee. (S)3a was analyzed via chiralꢀHPLC in comparison with racemic 3a, see

supporting information (HPLC section) for details.

4

-methyl-N-(2-(1-methyl-2-phenyl-1H-indol-3-yl)-2-phenylethyl)benzenesulfonamide

Procedure A was followed using 1ꢀmethylꢀ2ꢀphenylꢀ1Hꢀindole (1b) (62 mg, 0.3 mmol), 2ꢀphenylꢀ

ꢀtosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in

DCE (2 mL). Purification of the crude by column chromatography (Hex/EtOAc 8:2) yielded 3b

(3b).

1

2

Organic & Biomolecular Chemistry

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DOI: 10.1039/C6OB00672H

1

(

=

137 mg, 95%) as a white thick oil. H-NMR (300 MHz, CDCl

3

): δ 7.55ꢀ7.12 (m, 17H), 6.95 (t, J

1

3

7.0 Hz, 1H), 4.25 (dd, J = 10.6, 6.6 Hz, 1H), 3.72ꢀ3.51 (m, 5H), 2.44 (s, 3H). C-NMR (75

MHz, CDCl ): δ 143.6 (C), 142.2 (C), 140.9 (C), 137.8 (C), 136.6 (C) 131.5 (C), 131.2 (2 x CH),

3

1

4

30.0 (2 x CH), 129.0 (CH), 128.9 (2 x CH), 128.8 (2 x CH), 128.0 (2 x CH), 127.5 (2 x CH),

26.9 (CH), 126.2 (C), 122.3 (CH), 120.2 (CH), 120.1 (CH), 110.3 (C), 110.2 (CH), 46.9 (CH ),

2

+

2.8 (CH), 31.3 (CH ), 21.9 (CH ). ESI-MS m/z 503 [M + Na , 100]. Calcd. for C H N O S

3

30 28

2

[

480.63]: C 74.97, H 5.87, N 5.83; found C 75.29, H 5.71, N 5.97.

N-(2-(2-(4-isopropoxyphenyl)-1H-indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide

3c). Procedure A was followed using 2ꢀ(4ꢀisopropoxyphenyl)ꢀ1Hꢀindole (1c) (75.4 mg, 0.3

mmol), 2ꢀphenylꢀ1ꢀtosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg,

.015 mmol) in DCE (2 mL). Purification of the crude by column chromatography (Hex/EtOAc

(

2

0

8

1

:2) yielded 3c (142 mg, 90%) as a white solid (m.p.: 75ꢀ78 °C). H-NMR (200 MHz,

): δ 8.18 (s, 1H), 7.50ꢀ7.36 (m, 3H), 7.32ꢀ7.08 (m, 11H), 6.97ꢀ6.85 (m, 3H), 4.59 (hept, J =

.0 Hz, 1H), 4.45 (dd, J = 10.7, 6.2 Hz, 1H), 4.22 (dd, J = 9.0, 2.9 Hz, 1H), 3.84ꢀ3.55 (m, 2H),

CDCl

3

6

2

13

.40 (s, 3H), 1.39 (d, J = 6.2 Hz, 3H), 1.37 (d, J = 6.0 Hz, 3H). C-NMR (50 MHz,

): δ 158.5 (C), 143.3 (C), 142.0 (C), 138.0 (C), 136.5 (C), 136.3 (C), 130.1 (2 x CH), 129.8

2 x CH), 128.8 (2 x CH), 127.9 (2 x CH), 127.4 (C), 127.2 (2 x CH), 126.9 (CH), 124.4 (C),

CDCl

(

3

1

22.4 (CH), 120.3 (CH), 120.1 (CH), 116.3 (2 x CH), 111.4 (CH), 109.1 (C), 70.3 (CH), 46.8

+

(CH ), 42.4 (CH), 22.3 (CH ), 22.2 (CH ), 21.7 (CH ). ESI-MS m/z 523 [M – H , 100]. Calcd. for

2 3 3 3

C H N O S [524.67]: C 73.25, H 6.15, N 5.34; found: C 73.02, H 6.27, N 5.49.

32

2

3

(S)-N-(2-(2-(4-isopropoxyphenyl)-1H-indol-3-yl)-2-phenylethyl)-4-

methylbenzenesulfonamide ((S)3c). Procedure A was followed using (R)ꢀ2ꢀphenylꢀ1ꢀ

tosylaziridine ((R)2a). (S)3c was obtained in 89% yield and 98% ee. (S)3c was analyzed via chiralꢀ

HPLC in comparison with racemic 3c, see supporting information (HPLC section) for details.

N-(2-(2-(3-acetylphenyl)-1H-indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide

Procedure A was followed using 1ꢀ(3ꢀ(1Hꢀindolꢀ2ꢀyl)phenyl)ethanone (1d) (70.6 mg, 0.3 mmol),

ꢀphenylꢀ1ꢀtosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015

(3d).

2

mmol) in DCE (2 mL). Purification of the crude by column chromatography (Hex/EtOAc 7:3)

1

yielded 3d (148 mg, 97%) as a yellowish solid (m.p.: 77ꢀ79 °C). H-NMR (200 MHz,

CDCl ): δ 8.92 (s, 1H), 7.89 (m, 2H), 7.64 ꢀ7.05 (m, 14H), 6.96 (t, J = 7.2, 1H), 4.48 (m, 2H), 3.75

3

1

3

(

3

m, 2H), 2.42 (s, 3H), 2.37 (s, 3H). C NMR (50 MHz, CDCl ): δ 198.2 (C), 143.5 (C), 141.8

C), 137.7 (C), 136.8 (C), 136.7 (C), 136.6 (C), 133.3 (CH), 133.0 (C), 129.8 (2 x CH), 129.3

CH), 128.9 (2 x CH), 128.9 (CH), 128.0 (2 x CH), 127.3 (C), 127.2 (2 x CH), 127.1 (CH), 122.9

CH), 120.5 (CH), 120.3 (CH), 112.0 (CH), 110.4 (C), 47.1 (CH

2 3

), 43.0 (CH), 26.8 (CH ), 21.7

+

CH ). 1 CH is overlapping probably with 2xCH at 128.0. ESI-MS m/z 507 [M – H , 100].

3

ar

Calcd. for C H N O S [508.63]: C 73.20, H 5.55, N 5.51; found: C 73.58, H. 5.41, N. 5.62.

31

28

2

3

(

S)-N-(2-(2-(3-acetylphenyl)-1H-indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide

(S)3d). Procedure A was followed using (R)ꢀ2ꢀphenylꢀ1ꢀtosylaziridine ((R)2a). (S)3d was

obtained in 97% yield and 97% ee. (S)3d was analyzed via chiralꢀHPLC in comparison with

racemic 3d, see supporting information (HPLC section) for details.

4

-methyl-N-(2-(2-methyl-1H-indol-3-yl)-2-phenylethyl)benzenesulfonamide (3e). Procedure A

was followed using 2ꢀmethylꢀ1Hꢀindole (1e) (39.4 mg, 0.3 mmol), 2ꢀphenylꢀ1ꢀtosylaziridine (2a)

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2

(90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL).

Purification of the crude by column chromatography (Hex/EtOAc 8:2) yielded 3e (112 mg, 92%)

1

as a white solid (m.p.: 147ꢀ150 °C). H-NMR (200 MHz, CDCl

3

): δ 7.97 (s, 1H), 7.62 (d, J = 8.3

Hz, 2H), 7.31ꢀ7.08 (m, 9H), 6.90 (t, J = 7.4 Hz, 1H), 4.41 (dd, J = 10.4, 6.1 Hz, 1H), 4.33 (dd, J =

8

3

9

.9, 2.9 Hz, 1H), 3.84 (ddd, J = 12.1, 9.1, 6.2, 1H), 3.61 (ddd, J = 12.1, 10.6, 3.2, 1H), 2.45 (s,

1

H), 2.33 (s, 3H). H-NMR (200 MHz, CDCl

3

+ D

2

O): δ 7.62 (d, J = 8.3 Hz, 2H), 7.31ꢀ7.08 (m,

H), 6.90 (t, J = 7.4 Hz, 1H), 4.41 (dd, J = 10.5, 6.1 Hz, 1H), 4.33 (dd, J = 8.9, 2.9 Hz, 1H), 3.83

13

(

dd, J = 12.1, 6.1, 1H), 3.60 (dd, J = 12.1, 10.6, 1H), 2.45 (s, 3H), 2.32 (s, 3H). C NMR (50

MHz, CDCl ): δ 143.7 (C), 141.7 (C), 136.7 (C), 135.8 (C), 133.9 (C), 130.0 (2 x CH), 128.8 (2 x

CH), 127.9 (2 x CH), 127.3 (2 x CH), 127.2 (C), 126.8 (CH), 121.4 (CH), 119.8 (CH), 118.9

3

(

–

6

CH), 111.1 (CH), 109.2 (C), 46.6 (CH ), 42.3 (CH), 21.8 (CH ), 12.2 (CH ). ESI-MS m/z 403 [M

H , 100]. Calcd. for C H N O S [404.52]: C 71.26, H 5.98, N 6.93; found: C 71.48, H 6.02, N

24 24 2 2

.80.

2 3 3

+

4

-methyl-N-(2-phenyl-2-(2-vinyl-1H-indol-3-yl)ethyl)benzenesulfonamide (3f). Procedure A

was followed using ethyl 2ꢀvinylꢀ1Hꢀindole (1f) (42.9 mg, 0.3 mmol), 2ꢀphenylꢀ1ꢀtosylaziridine

2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL).

(

2

Purification of the crude by column chromatography (Hex/EtOAc 3:1) yielded 3f (112 mg, 90%)

1

as a white solid (m.p.: 130ꢀ132 °C). H-NMR (200 MHz, CDCl ): δ 8.23 (s, 1H), 7.60 (d, J = 8.3

3

Hz, 2H), 7.32ꢀ7.14 (m, 10H), 6.88 (ddd, J = 8.2, 6.9, 1.1 Hz, 1H), 6.69 (dd, J = 17.5, 11.3 Hz,

1

H), 5.52 (d, J = 17.6 Hz, 1H), 5.28 (d, J = 11.3 Hz, 1H), 4.49 (dd, J = 10.3, 6.1 Hz, 1H), 4.30 (dd,

13

J = 8.7, 3.4 Hz, 1H), 3.87 (m, 1H), 3.62 (m, 1H), 2.43 (s, 3H). C-NMR (50 MHz,

CDCl ): δ 143.6 (C), 141.1 (C), 136.9 (C), 136.7 (C), 134.3 (C), 129.9 (2 x CH), 128.8 (2 x CH),

27.8 (2 x CH), 127.3 (2 x CH), 127.2 (C), 126.9 (CH), 125.3 (CH), 123.4 (CH), 120.3 (CH),

20.1 (CH), 113.6 (CH ), 113.0 (C), 111.3 (CH), 46.5 (CH ), 41.8 (CH), 21.8 (CH ). ESI-MS m/z

39 [M + Na , 100]. Calcd. for C25 S [416.54]: C 72.09, H 5.81, N 6.73; C 72.37, H 5.88,

3

1

4

2

3

+

24 2 2

H N O

N 6.72.

(E)-4-methyl-N-(2-(1-methyl-2-(4-methylstyryl)-1H-indol-3-yl)-2-

phenylethyl)benzenesulfonamide (3g). Procedure A was followed using ethyl (E)ꢀ1ꢀmethylꢀ2ꢀ(4ꢀ

methylstyryl)ꢀ1Hꢀindole (1g) (74.2 mg, 0.3 mmol), 2ꢀphenylꢀ1ꢀtosylaziridine (2a) (90.2 mg, 0.33

mmol) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the

2

crude by column chromatography (Hex/EtOAc 8:2) yielded 3g (108 mg, 69%) as a yellow wax.

1

H-NMR (200 MHz, CDCl

3

): δ 7.55 (d, J = 8.3 Hz, 2H), 7.37ꢀ7.10 (m, 14H), 6.94 (m, 2H), 6.64

(

d, J = 16.5 Hz, 1H), 4.58 (dd, J = 10.5, 6.3 Hz, 1H), 4.30 (dd, J = 8.8, 3.1 Hz, 1H), 3.84ꢀ3.59 (m,

13

5

H), 2.39 (s, 3H), 2.34 (s, 3H). C-NMR (50 MHz, CDCl

3

): δ 143.4 (C), 142.2 (C), 138.6 (C),

1

38.1 (C), 137.7 (C), 136.7 (C), 135.7 (CH), 134.1 (C), 129.8 (2 x CH) , 129.7 (2 x CH), 128.9 (2

x CH), 128.0 (2 x CH), 127.3 (2 x CH), 126.9 (CH), 126.8 (2 x CH), 126.6 (C), 122.4 (CH), 120.1

(

CH), 119.8 (CH), 115.7 (CH), 110.7 (C), 109.8 (CH), 47.0 (CH

2

), 43.2 (CH), 31.1 (CH

3

), 21.6

+

(CH

3

3 32 2 2

), 21.5 (CH ). ESI-MS m/z 519 [M – H , 100]. Calcd. for C33H N O S [520.68]: C 76.12, H

6

.19, N 5.38; found C 76.23, H 6.02, N 5.49.

4

-methyl-N-(2-phenyl-2-(2-(phenylethynyl)-1H-indol-3-yl)ethyl)benzenesulfonamide

(3h).

Procedure A was followed using 2ꢀ(phenylethynyl)ꢀ1Hꢀindole (1h) (65.2 mg, 0.3 mmol), 2ꢀ

phenylꢀ1ꢀtosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015

mmol) in DCE (2 mL). Purification of the crude by column chromatography (Hex/EtOAc 8:2)

2

Organic & Biomolecular Chemistry

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1

6

yielded 3h (128 mg, 87%) as a yellowish solid (m.p.: 190ꢀ192 °C). H-NMR (200 MHz, d -

Acetone): δ 10.59 (s, 1H), 7.70 (d, J = 8.3 Hz, 2H), 7.57ꢀ7.41 (m, 8H), 7.39ꢀ7.09 (m, 7H), 6.99 (t,

J = 7.0 Hz, 1H), 6.49 (t, J = 5.5 Hz, 1H), 4.74 (t, J = 8.0 Hz, 1H), 4.08ꢀ3.80 (m, 2H), 2.34 (s, 3H).

1

3

C-NMR (50 MHz, d -Acetone): δ 143.0 (C), 142.6 (C), 138.4 (C), 136.9 (C), 131.3 (2 x CH),

6

1

29.7 (2 x CH), 128.9 (2 x CH), 128.5 (2 x CH), 128.2 (2 x CH), 127.1 (2 x CH), 126.8 (C), 126.6

(

CH), 123.5 (CH), 123.0 (C), 121.4 (C), 119.9 (CH), 119.5 (CH), 116.8 (C), 111.5 (CH), 95.0 (C),

2.3 (C), 46.8 (CH ), 43.5 (CH), 20.7 (CH ). 1 CHar is missing, probably overlapping. ESI-MS

m/z 489 [M – H , 100]. Calcd. for C31 S [490.62]: C 75.89, H 5.34, N 5.71; found: C

8

2

3

+

26 2 2

H N O

7

6.22, H 5.28, N 5.93.

4

-methyl-N-(2-(2-(pent-1-yn-1-yl)-1H-indol-3-yl)-2-phenylethyl)benzenesulfonamide

(3i).

Procedure A was followed using 2ꢀ(pentꢀ1ꢀynꢀ1ꢀyl)ꢀ1Hꢀindole (1i) (55 mg, 0.3 mmol), 2ꢀphenylꢀ

ꢀtosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in

1

2

DCE (2 mL). Purification of the crude by column chromatography (Hex/EtOAc 5:1) yielded 3i

1

(

127 mg, 93%) as a white solid (m.p.: 126ꢀ128 °C). H-NMR (200 MHz, CDCl

3

): δ 8.06 (s, 1H),

7

8

.60 (d, J = 8.3 Hz, 2H), 7.31ꢀ7.07 (m, 9H), 6.92 (t, J = 6.7 Hz, 2H), 4.48 (m, 2H), 3.80 (dd, J =

.1, 6.3 Hz, 2H), 2.47ꢀ2.29 (m, 5H), 1.71ꢀ1.53 (m, 2H), 1.02 (t, J = 7.3 Hz, 3H). C-NMR (50

13

MHz, CDCl ): δ 143.4 (C), 141.4 (C), 137.2 (C), 135.9 (C), 129.8 (2 x CH), 128.8 (2 x CH), 128.0

3

(2 x CH), 127.3 (2 x CH), 127.0 (CH), 126.5 (C), 123.6 (CH), 120.3 (CH), 119.3 (CH), 118.4 (C),

1

18.0 (C), 111.1 (CH), 97.4 (C), 72.7 (C), 46.5 (CH ), 43.0 (CH), 22.2 (CH ), 21.8 (CH ), 21.7

2

3

+

(CH ), 13.9 (CH ). ESI-MS m/z 455 [M – H , 100]. Calcd. for C H N O S [456.60]: C 73.65, H

2 3 28 28 2 2

6

.18, N 6.14; C 73.37, H 6.12, N 6.26.

N-(2-(2-allyl-1H-indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide (3j). Procedure A

was followed using ethyl 2ꢀallylꢀ1Hꢀindole (1j) (47.2 mg, 0.3 mmol), 2ꢀphenylꢀ1ꢀtosylaziridine

2

(2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL).

Purification of the crude by column chromatography (Hex/EtOAc 7:3) yielded 3j (103 mg, 80%)

1

as a white wax. H NMR (200 MHz, CDCl ): δ 7.99 (s, 1H), 7.60 (d, J = 8.2, 2H), 7.37ꢀ7.03 (m,

3

1

0H), 6.89 (t, J = 7.5, 1H), 5.87 (m, 1H), 5.2ꢀ 5.05 (m, 2H), 4.42 (dd, J = 10.4, 6.2 Hz, 1H), 4.31

13

(

dd, J = 9.0, 3.4 Hz, 1H), 3.82 (m, 1H), 3.59 (m, 1H), 3.42 (d, J = 6.4 Hz, 2H), 2.43 (s, 3H). C

NMR (50 MHz, CDCl ): δ 143.6 (C), 141.5 (C), 136.9 (C), 136.0 (C), 135.2 (C), 134.7 (CH),

29.9 (2 x CH), 128.7 (2 x CH), 127.9 (2 x CH), 127.3 (2 x CH), 127.2 (C), 126.8 (CH), 121.7

CH), 119.9 (CH), 119.3 (CH), 117.9 (C), 111.2 (CH), 109.7 (CH), 46.6 (CH ), 42.2 (CH), 31.0

S [430.57]: C 72.53, H

3

1

(

2

+

CH

2 3 26 2 2

), 21.7 (CH ). ESI-MS m/z 429 [M – H , 100]. Calcd. for C26H N O

6

.09, N 6.51; found: C 72.87, H 5.99, N 6.61.

N-(2-(1H-indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide (3k). Procedure A was

followed using 1Hꢀindole (1k) (51.4 mg, 0.3 mmol), 2ꢀphenylꢀ1ꢀtosylaziridine (2a) (90.2 mg, 0.33

mmol) and [Au(JohnPhos)(NTf2)] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the

crude by column chromatography (Hex/EtOAc 8:2) yielded 3k (100 mg, 83%) as a white solid

1

(

m.p.:185ꢀ188°C). H-NMR (200 MHz, DMSOꢀd

6

): δ 10.86 (s, 1H), 7.62 (dd, J = 8.1, 1.5 Hz,

2

3

H), 7.39ꢀ7.05 (m, 10H), 7.00 (t, J = 8.2 Hz, 1H), 6.85 (t, J = 7.9 Hz, 1H), 4.27 (t, J = 7.7 Hz, 1H),

13

.35ꢀ3.19 (m, 2H), 2.32 (s, 3H). C-NMR (50 MHz, DMSOꢀd ): δ 143.6 (C), 143.1 (C), 138.3

6

(

C), 136.9 (C), 130.2 (2 x CH), 128.9 (2 x CH), 128.7(2 x CH), 127.2 (2 x CH), 127.1 (C), 126.8

CH), 122.8 (CH), 121.7 (CH), 119.0 (CH), 116.1 (C), 112.1 (CH), 48.2 (CH ), 43.3 (CH), 21.6

2

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+

(

CH

3

). ESI-MS m/z 391 [M – H , 100]. Calcd. for C23

H

22

N

2

O

2

S [390.50]: C 70.74, H 5.68, N

7

.17; found C 70.99, H 5.75, N 7.01.

S)-N-(2-(1H-indol-3-yl)-2-phenylethyl)-4-methylbenzenesulfonamide ((S)3k). Procedure A

was followed using (R)ꢀ2ꢀphenylꢀ1ꢀtosylaziridine ((R)2a). (S)3k was obtained in 85% yield and

7% ee. (S)3k was analyzed via chiralꢀHPLC in comparison with racemic 3k, see supporting

information (HPLC section) for details.

-methyl-N-(2-phenyl-2-(2-phenyl-6-(trifluoromethyl)-1H-indol-3-

yl)ethyl)benzenesulfonamide (3l). Procedure A was followed using 2ꢀphenylꢀ6ꢀ(trifluoromethyl)ꢀ

Hꢀindole (1l) (78.4 mg, 0.3 mmol), 2ꢀphenylꢀ1ꢀtosylaziridine (2a) (90.2 mg, 0.33 mmol) and

Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude by

(

9

4

1

[

2

column chromatography (Hex/EtOAc 8:2) yielded 3l (156 mg, 97%) as a white solid (m.p.: 201ꢀ

1

2

(

03 °C). H-NMR (200 MHz, CDCl

3

): δ 8.64 (s, 1H), 7.68 (s, 1H), 7.46ꢀ7.34 (m, 7H), 7.32ꢀ6.99

13

m, 9H), 4.49 (dd, J = 10.7, 6.0 Hz, 1H), 4.13 (m, 1H), 3.69 (m, 2H), 2.40 (s, 3H). C-NMR (50

MHz, CDCl ): δ 143.6 (C), 141.2 (C), 140.6 (C), 136.4 (C), 135.3 (C), 131.6 (C), 129.8 (2 x CH),

29.5 (C), 129.2 (2 x CH), 129.1 (CH), 129.0 (2 x CH), 128.9 (2 x CH), 127.8 (2 x CH), 127.1 (2

x CH), 125.2 (q, J = 271 Hz, C), 124.6 (q, J = 32 Hz, C), 120.4 (CH), 116.9 (q, J = 3.5 Hz, CH),

10.5 (C), 109.1 (q, J = 4.3 Hz, CH), 46.8 (CH ), 42.2 (CH), 21.6 (CH ). ESI-MS m/z 533 [M –

S [534.60]: C 67.40, H 4.71, N 5.24; found: C 67.76; H 4.80, N

3

1

2

3

+

H , 100]. Calcd. for C30

25 3 2 2

H F N O

5

.31.

N-(2-(6-(diethylamino)-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide (3m). Procedure A

was followed using N,Nꢀdiethylꢀ1Hꢀindolꢀ6ꢀamine (1m) (56.50 mg, 0.3 mmol), 2ꢀphenylꢀ1ꢀ

tosylaziridine (90.2 mg, 0.33 mmol) (2a) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in

2

DCE (2 mL). Purification of the crude by column chromatography (Hex/EtOAc 8:2) yielded 3m

1

(

41 mg, 30%) as a white solid (m.p.: 54ꢀ56°C). H NMR (C

6

D

6

, 200 MHz): δ 7.45 (d, J = 8.4 Hz,

1

6

2

H), 7.36 (d, J = 8.1 Hz, 2H), 7.19ꢀ7.12 (m, 3H), 6.98ꢀ6.89 (m, 4H), 6.58 (d, J = 8.1 Hz, 2H),

.26ꢀ6.22 (m, 2H), 5.41 (t, J = 7.0 Hz, 1H), 4.73 (bs, 1H), 3.94ꢀ3.84 (m, 1H), 3.47ꢀ3.36 (m, 1H),

13

6 6

.77 (q, J = 7.0 Hz, 4H), 1.83 (s, 3H), 0.86 (t, J = 7.0 Hz, 6H). C NMR (C D , 50 MHz): δ 145.0

(

C), 142.3 (C), 140.9 (C),137.3 (C), 135.1 (C), 129.3 (2 x CH), 129.0 (2 x CH), 127.1 (2 x CH),

26.8 (C), 126.7 (2 x CH), 124.6 (CH), 121.6 (C), 120.4 (CH), 116.1 (CH), 102.3 (CH), 49.5

CH ), 45.8 (2 x CH ), 40.7 (CH), 20.9 (CH ), 12.8 (2 x CH ). 1 CHar is missing, probably

overlapping. ESI-MS m/z 484 [M + Na , 100], 462 [M + H , 60]. Calcd for C27 S: C

1

(

2

3

+

31 3 2

H N O

7

0.25, H 6.77, N 9.10; found C 70.15, H 6.53, N 9.07.

Ethyl

3-(2-(4-methylphenylsulfonamido)-1-phenylethyl)-1H-indole-2-carboxylate

(3n).

Procedure A was followed using ethyl 1H-indoleꢀ2ꢀcarboxylate (1n) (56.7 mg, 0.3 mmol), 2ꢀ

phenylꢀ1ꢀtosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015

2

mmol) in DCE (2 mL). Purification of the crude by column chromatography (Hex/EtOAc 8:2)

1

yielded 3n (75 mg, 54%) as a white solid (m.p.: 175ꢀ177 °C). H-NMR (200 MHz,

CDCl

3

): δ 9.19 (s, 1H), 7.58 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.2 Hz, 1H), 7.32 – 7.10 (m, 9H),

6

4

.91 (t, J = 7.0 Hz, 1H), 5.39 (dd, J = 10.0, 6.1 Hz, 1H), 4.88 (m, 1H), 4.28 (q, J = 7.1 Hz, 2H),

13

.00ꢀ3.70 (m, 2H), 2.39 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H). C-NMR (50 MHz, CDCl ): δ 162.3

3

(C), 143.4 (C), 141.1 (C), 136.9 (C), 136.4 (C), 129.7 (2 x CH), 128.7 (2 x CH), 127.9 (2 x CH),

1

27.2 (2 x CH), 126.9 (CH), 126.5 (C), 125.7 (CH), 124.8 (C), 122.0 (CH), 121.9 (C), 120.8 (CH),

12.5 (CH), 61.6 (CH ), 46.6 (CH ), 41.6 (CH), 21.7 (CH ), 14.5 (CH ). ESI-MS m/z 461 [M –

2

3

Organic & Biomolecular Chemistry

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+

H , 100]. Calcd. for C26

26 2 4

H N O S [462.56]: C 67.51, H 5.67, N 6.06; found: 67.88, H. 5.52, N.

6

.19.

Ethyl

3o). Procedure A was followed using ethyl 5ꢀfluoroꢀ1Hꢀindoleꢀ2ꢀcarboxylate (1o) (62.2 mg, 0.3

mmol), 2ꢀphenylꢀ1ꢀtosylaziridine (2a) (90.2 mg, 0.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg,

5-fluoro-3-(2-(4-methylphenylsulfonamido)-1-phenylethyl)-1H-indole-2-carboxylate

(

2

0

8

.015 mmol) in DCE (2 mL). Purification of the crude by column chromatography (Hex/EtOAc

:2) yielded 3o (75 mg, 54%) as a white solid (m.p.: 125ꢀ127 °C). H-NMR (200 MHz,

1

CDCl

3

): δ 9.27 (s, 1H), 7.79 (d, J = 8.3 Hz, 1H), 7.57 (d, J = 8.3 Hz, 2H), 7.35ꢀ7.12 (m, 7H), 6.99

(td, J = 9.0, 2.4 Hz, 1H), 6.78 (dd, J = 9.9, 2.3 Hz, 1H), 5.33 (dd, J = 5.9, 10.4 Hz, 1H), 4.90 (m,

1

H), 4.29 (q, J = 7.1 Hz, 2H), 3.89 (dt, J = 12.7, 6.4 Hz, 1H), 3.69 (td, J = 11.8, 4.6 Hz, 1H), 2.40

13

3

(s, 3H), 1.37 (t, J = 7.1 Hz, 3H). C NMR (50 MHz, CDCl ): δ 162.0 (C), 157.8 (d, JC-F = 237

Hz, C), 143.5 (C), 140.7 (C), 136.7 (C), 133.0 (C), 129.8 (2 x CH), 128.8 (2 x CH), 127.8 (2 x

CH), 127.1 (2 x CH), 127.0 (CH), 126.4 (C), 121.7 (d, JC-F = 5.5 Hz, C), 114.9 (d, JC-F = 27 Hz,

CH), 113.5 (d, JC-F = 9.4 Hz, CH), 106.3 (d, JC-F = 24 Hz, CH), 61.7 (CH

2

), 46.2 (CH

). ESI-MS m/z 479 [M – H , 100]. Calcd. for C26

480.55]: C 64.98, H 5.24, N 5.83; found: C 64.72, H 5.38, N 5.91.

2

), 41.3

+

(

CH), 21.7 (CH

3

), 14.5 (CH

3

2 4

H25FN O S

[

4

-methyl-N-(2-(2-phenyl-1H-indol-3-yl)ethyl)benzenesulfonamide (3p). Procedure A was

followed using 2ꢀphenylꢀ1H-indole (1a) (58 mg, 0.3 mmol), 1ꢀtosylaziridine (2b) (71 mg, 0.36

mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification

2

of the crude by column chromatography (Hex/EtOAc 8:2) yielded 3p (77 mg, 66%) as a white

1

solid (m.p.: 129ꢀ130 °C). H-NMR (200 MHz, CDCl

3

): δ 8.16 (s, 1H), 7.58 (d, J = 8.3 Hz, 2H),

7

.51ꢀ7.33 (m, 7H), 7.27ꢀ7.03 (m, 4H), 4.40 (t, J = 6.0 Hz, 1H), 3.26 (m, 2H), 3.07 (m, 2H), 2.39

1

3

(

s, 3H). C-NMR (50 MHz, CDCl

29.8 (2 x CH), 129.2 (2 x CH), 128.8 (C), 128.4 (2 x CH), 128.2 (CH), 127.2 (2 x CH), 122.8

CH), 120.2 (CH), 119.0 (CH), 111.2 (CH), 108.6 (C), 43.4 (CH ), 25.2 (CH ), 21.7 (CH ). ESI-

S [390.50]: C 70.74, H 5.68, N 7.17; found C

3

): δ 143.4 (C), 137.1 (C), 136.1(C), 135.9 (C), 132.8 (C),

1

(

2

3

+

22 2 2

MS m/z 389 [M – H , 100]. Calcd. for C23H N O

7

0.95, H 5.56, N 7.01.

N-(2-(2-(4-isopropoxyphenyl)-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide

Procedure A was followed using 2ꢀ(4ꢀisopropoxyphenyl)ꢀ1Hꢀindole (1c) (75.3 mg, 0.3 mmol), 1ꢀ

tosylaziridine (2b) (71 mg, 0.36 mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015

(3q).

2

mmol) in DCE (2 mL). Purification of the crude by column chromatography (Hex/EtOAc 8:2)

1

yielded 3q (96 mg, 71%) as a white solid (m.p.: 54ꢀ55 °C). H-NMR (200 MHz, CDCl

3

): δ 8.12

(s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.44ꢀ7.31 (m, 4H), 7.22ꢀ7.01 (m, 4H), 6.93 (d, J = 8.9 Hz, 2H),

4

.59 (hept, J = 6.0 Hz, 1H), 4.41 (t, J = 6.1 Hz, 1H), 3.26 (m, 2H), 3.04 (m, 2H), 2.39 (s, 3H), 1.38

13

(d, J = 6.1 Hz, 6H). C-NMR (50 MHz, CDCl ): δ 158.1 (C), 143.3 (C), 137.1 (C), 136.1 (C),

3

1

35.9 (C), 129.8 (2 x CH), 129.6 (2 x CH), 128.9 (C), 127.2 (2 x CH), 124.8 (C), 122.4 (CH),

20.1 (CH), 118.7 (CH), 116.4 (2 x CH), 111.1 (CH), 107.7 (C), 70.3 (CH), 43.4 (CH ), 25.2

2

+

(CH

2

), 22.3 (CH

3

), 21.7 (CH

3

). ESI-MS m/z 447 [M – H , 100]. Calcd. for C26

H

28

N

O

2 3

S [448.58]:

C 69.62, H 6.29, N 6.25; found C 69.86, H 6.32, N 6.18.

N-(2-(2-(3-acetylphenyl)-1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide (3r). Procedure A

was followed using 1ꢀ(3ꢀ(1Hꢀindolꢀ2ꢀyl)phenyl)ethanone (1d) (70.6 mg, 0.3 mmol), 1ꢀ

tosylaziridine (2b) (71 mg, 0.36 mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf

2

)] (11.6 mg, 0.015

mmol) in DCE (2 mL). Purification of the crude by column chromatography (Hex/EtOAc 7:3)

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1

yielded 3r (80 mg, 62%) as a yellowish solid (m.p.: 52.5ꢀ54 °C). H-NMR (200 MHz,

CDCl ): δ 8.59 (s, 1H), 8.06 (m, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.62ꢀ7.30

m, 5H), 7.27ꢀ7.01 (m, 4H), 4.80 (t, J = 6.1 Hz, 1H), 3.27 (m, 2H), 3.08 (m, 2H), 2.58 (s, 3H),

3

(

1

3

2

1

.37 (s, 3H). C-NMR (50 MHz, CDCl ): δ 198.4 (C), 143.5 (C), 137.8 (C), 137.1 (C), 136.3 (C),

3

34.7 (C), 133.3 (C), 132.8 (CH), 129.8 (2 x CH), 129.5 (CH), 128.7 (C), 127.9 (CH), 127.8 (CH),

27.2 (2 x CH), 123.1 (CH), 120.3 (CH), 119.1 (CH), 111.5 (CH), 109.3 (C), 43.5 (CH ), 26.9

2

+

(CH

3

), 25.5 (CH

2

), 21.7 (CH

3

). ESI-MS m/z 431 [M – H , 100]. Calcd. for C25

H

24

N

O

2 3

S [432.53]:

C 69.42, H 5.59, N 6.48; found C 69.83, H 5.47, N 6.22.

4

-methyl-N-(2-(2-methyl-1H-indol-3-yl)ethyl)benzenesulfonamide (3s). Procedure A was

followed using 2ꢀmethylꢀ1H-indole (1e) (39.4 mg, 0.3 mmol), 1ꢀtosylaziridine (2b) (71 mg, 0.36

mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification

2

of the crude by column chromatography (Hex/EtOAc 8:2) yielded 3s (70 mg, 71%) as a white

1

wax. H-NMR (200 MHz, CDCl

3

): δ 7.82 (s, 1H), 7.62 (d, J = 8.3 Hz, 2H), 7.33ꢀ7.16 (m, 4H),

7

.14ꢀ6.96 (m, 2H), 4.31 (t, J = 6.2 Hz, 1H), 3.22 (m, 2H), 2.90 (m, 2H), 2.40 (s, 3H), 2.35 (s, 3H).

1

3

C-NMR (50 MHz, CDCl

3

): δ 143.5 (C), 137.1 (C), 135.6 (C), 132.7 (C), 129.8 (2 x CH), 128.4

), 24.9

2 3 3 20 2 2

CH ), 21.7 (CH ), 11.8 (CH ). ESI-MS m/z 327 [M – H , 65]. Calcd. for C18H N O S [328.43]:

(

C), 127.2 (2 x CH), 121.4 (CH), 119.6 (CH), 117.8 (CH), 110.7(CH), 107.3 (C), 43.4 (CH

2

+

C 65.83, H 6.14, N 8.53; found C 66.11, H 6.00, N 8.77.

N-(2-(1H-indol-3-yl)ethyl)-4-methylbenzenesulfonamide (3t). Procedure A was followed using

Hꢀindole (1k) (35.1 mg, 0.3 mmol), 1ꢀtosylaziridine (2b) (71 mg, 0.36 mmol, 1.2 equiv.) and

1

[

Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude by

2

1

column chromatography (Hex/EtOAc 9:1) yielded 3t (65 mg, 69%) as a white wax. H-NMR

(

200 MHz, CDCl

H), 3.28 (m, 2H), 2.93 (m, 2H), 2.40 (s, 3H). C-NMR (50 MHz, CDCl

C), 136.7 (C), 129.8 (2 x CH), 127.2 (2 x CH), 122.9 (CH), 122.4 (CH), 119.7 (CH), 118.7 (CH),

3

): δ 8.03 (s, 1H), 7.64 (d, J = 8.3 Hz, 3H), 7.45ꢀ6.92 (m, 7H), 4.38 (t, J = 5.9 Hz,

13

1

(

1

3

): δ 143.5 (C), 137.1

+

2 2 3

11.8 (C), 111.6 (CH), 43.3 (CH ), 25.7 (CH ), 21.7 (CH ). ESI-MS m/z 313 [M – H , 100].

Calcd. for C17 S [314.40]: C 64.94, H 5.77, N 8.91; found C 65.19, H 5.83, N 8.87.

18 2 2

H N O

benzyl (2-(2-phenyl-1H-indol-3-yl)ethyl)carbamate (3x). Procedure A was followed using 2ꢀ

phenylꢀ1Hꢀindole (1a) (58 mg, 0.3 mmol), benzyl aziridineꢀ1ꢀcarboxylate (2d) (64 mg, 0.36

mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification

2

of the crude by column chromatography (Hex/EtOAc 9:1) yielded 3x (63 mg, 57%) as a white

1

solid (m.p.: 46ꢀ48 °C). H NMR (300 MHz, CDCl

1

3

): δ 8.26 (s, 1H), 7.69ꢀ7.12 (m, 14H), 5.05 (s,

1

3

H), 4.84 (t, J = 6.0 Hz, 1H), 3.53 (q, J = 6.8 Hz, 2H), 3.13 (t, J = 7.1 Hz, 2H). C NMR (75

MHz, CDCl ): δ 156.6 (C), 136.9 (C), 136.1 (C), 135.7 (C), 133.1 (C), 129.2 (C), 129.2 (2 x CH),

3

1

28.7 (CH), 128.3 (4 x CH), 128.2 (2 x CH), 128.1 (CH), 122.7 (CH), 120.1 (CH), 119.3 (CH),

+

11.2 (CH), 109.8 (C), 66.7 (CH ), 41.8 (CH ), 25.3 (CH ). ESI-MS m/z 393 [M + Na , 75], 371

2

+

[

M + H , 100]. Calcd. for C H N O [370.44]: C 77.81, H 5.99, N 7.56; found C 77.69, H 5.87,

24 22 2 2

N 7.68.

4

-methyl-N-(2-(2-phenyl-1H-indol-3-yl)cyclohexyl)benzenesulfonamide (3y). Procedure A was

followed using 2ꢀphenylꢀ1Hꢀindole (1a) (58 mg, 0.3 mmol), 7ꢀtosylꢀ7ꢀazabicyclo[4.1.0]heptane

2e) (91 mg, 0.36 mmol, 1.2 equiv.) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2

(

2

mL). Purification of the crude by column chromatography (Hex/EtOAc 8:2) yielded 3y (35 mg,

1

2

6%) as a white wax. H NMR (300 MHz, CDCl ): δ 8.02 (s, 1H), 7.51ꢀ7.39 (m, 5H), 7.29ꢀ7.18

3

Organic & Biomolecular Chemistry

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DOI: 10.1039/C6OB00672H

(

m, 2H), 7.15ꢀ7.08 (m, 3H), 6.84ꢀ6.77 (m, 3H), 4.15 (m, 1H), 3.43 (m, 1H), 2.83 (ddd, J = 12.2,

1

3

1

0.8, 4.1, 1H), 2.52 (m, 1H), 2.30 (s, 3H), 1.88 (m, 3H), 1.30 (m, 4H). C NMR (75 MHz,

): δ 142.6 (C), 136.4 (2 x C), 136.0 (C), 132.7 (C), 129.3 (2 x CH), 129.2 (2 x CH), 129.0 (2

x CH), 128.6 (CH), 126.6 (2 x CH), 122.1 (CH), 120.3 (CH), 119.7 (CH), 112.5 (C), 111.3 (CH),

6.3 (CH), 41.7 (CH), 35.0 (CH ), 32.5 (CH ), 26.2 (CH ), 25.3 (CH ), 21.8 (CH ) (one

quaternary carbon is missing, probably overlapped with one negative signal, CH). ESI-MS m/z

CDCl

3

5

2

3

+

4

6

44 [M + H , 100]. Calcd. for C27

.12, N 6.41.

28 2 2

H N O S [444.59]: C 72.94, H 6.35, N 6.30; found C 72.86, H

Representative procedures for the ring opening reactions of 2-methyl-N-tosyl aziridine (2c

and (S)2c) – see table 2 for details.

Table 2, entries 1, 2, 3 general procedure. To a N ꢀflushed solution of indole 1a,c,e (1.0 equiv.)

2

and 2ꢀmethylꢀNꢀtosyl aziridine (2c) (1.1 equiv.) in DCE (0.15 M), [Au(JohnPhos)(NTf

2

)] (5

mol%) was added and the mixture was stirred at 80 °C for 24 h. Solvent was then removed in

vacuum and the residue was purified by column chromatography (SiO ) to yield the corresponding

2

product 3u-w/3’u-w as inseparable mixtures.

4

-methyl-N-(2-(2-phenyl-1H-indol-3-yl)propyl)benzenesulfonamide (3u) and 4-methyl-N-(1-

2-phenyl-1H-indol-3-yl)propan-2-yl)benzenesulfonamide (3’u). General procedure was

followed using 1Hꢀindole 1a (39.0 mg, 0.2 mmol), aziridine 2c (46.5 mg, 0.22 mmol) and

Au(JohnPhos)(NTf )] (7.75 mg, 0.01 mmol) in DCE (2 mL). Purification of the crude by column

(

[

2

chromatography (Hex/EtOAc 8:2) yielded 3u/3’u (79.3 mg, 98%) in 2:1 ratio as a white solid.

Ratio and identity of the two regioisomers were established via 1D and 2D NMR analysis. See

+

copy of original spectra enclosed in the supporting information. ESI-MS m/z 403 [M – H , 100].

3

i

Reported data are in agreement with those reported in literature.

N-(2-(2-(4-isopropoxyphenyl)-1H-indol-3-yl)propyl)-4-methylbenzenesulfonamide (3v) and

N-(1-(2-(4-isopropoxyphenyl)-1H-indol-3-yl)propan-2-yl)-4-methylbenzenesulfonamide (3’v).

General procedure was followed using 1Hꢀindole 1c (75.4 mg, 0.3 mmol), aziridine 2c (69.7 mg,

0

2

.33 mmol) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the

crude by column chromatography (Hex/EtOAc 8:2) yielded 3v/3’v (120 mg, 86%) in 2:1 ratio as a

pink solid. Ratio and identity of the two regioisomers were established by analogy with 3u/3’u via

1

H NMR analysis. See copy of original spectra enclosed in the supporting information. ESI-MS

+

m/z 461 [M – H , 100].

4

-methyl-N-(2-(2-methyl-1H-indol-3-yl)propyl)benzenesulfonamide (3w) and 4-methyl-N-(1-

2-methyl-1H-indol-3-yl)propan-2-yl)benzenesulfonamide (3’w). General procedure was

followed using 1Hꢀindole 1e (39.5 mg, 0.3 mmol), aziridine 2c (69.7 mg, 0.33 mmol) and

Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL). Purification of the crude by

(

[

2

column chromatography (Hex/EtOAc 8:2) yielded 3w/3’w (94.4 mg, 92%) in 2:1 ratio as a pink

thick oil. Ratio and identity of the two regioisomers were established by analogy with 3u/3’u via

1

H NMR analysis. See copy of original spectra enclosed in the supporting information. ESI-MS

+

m/z 341 [M – H , 100].

Page 21 of 26

Organic & Biomolecular Chemistry

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DOI: 10.1039/C6OB00672H

Table 2, entry 4. To a solution of 1Hꢀindole 1a (58.0 mg, 0.3 mmol) and aziridine 2c (42.3 mg,

.2 mmol) in DCM (1 mL) boron trifluoride etherate (0.04 mL, 0.3 mmol) was added at room

0

temperature over a period of 10 min. The solution was stirred for 24 h. and quenched with 5%

aqueous NaHCO solution (1 mL). The two phases were separated and aqueous layer was

3

extracted with DCM (2 x 1mL). The combined organic layers were dried over Na SO , filtered

2

4

and concentrated in vacuum. Purification by column chromatography (Hex/EtOAc 8:2) yielded 3u

and 3’u (43 mg, 55%) as inseparable mixture in 12:1 ratio as a white solid. Reported data refers to

1

major isomer and are in agreement with those reported in ref. 3i. H-NMR (200 MHz,

CDCl ): δ 8.10 (s, 1H), 7.49ꢀ7.30 (m, 9H), 7.26ꢀ7.15 (m, 3H), 6.99 (t, J = 7.3 Hz, 1H), 4.18 (d, J =

3

1

3

7

.1 Hz, 1H), 3.32 (m, 3H), 2.40 (s, 3H), 1.39 (d, J = 5.9 Hz, 3H). C NMR (50 MHz,

CDCl ): δ 143.2 (C), 136.7 (C), 136.5 (2 x C), 132.8 (C), 129.7 (2 x CH), 129.1 (2 x CH), 129.0 (2

x CH), 128.4 (CH), 127.1 (2 x CH), 126.7 (C), 122.5 (CH), 120.0 (CH), 119.9 (CH), 112.9 (C),

3

+

1

2 3 3

11.5 (CH), 48.1 (CH ), 31.8 (CH), 21.7 (CH ), 19.0 (CH ). ESI-MS m/z 427 [M + Na , 100].

2 6

Table 2, entry 12. To a N ꢀflushed solution of AuCl (2.3 mg, 0.01 mmol) and AgSbF (3.4 mg,

0

.01 mmol) in DCE (1.33 mL), indole 1a (77.3 mg, 0.4 mmol) and aziridine 2c (42.3 mg, 0.20

mmol) were added and the mixture was stirred for 24 h at 80 °C. Solvent was then removed in

vacuum and the residue was purified by column chromatography (Hex/EtOAc 8:2) yielding

3

u/3’u (51 mg, 70%) as inseparable mixture in 7:1 ratio as a white solid. Ratio and identity of the

1

two regioisomers were established via H NMR analysis and are in agreement with those reported

in ref. 12. See the enclosed copy of original spectra. The same reaction was performed using (S)ꢀ2ꢀ

methylꢀ1ꢀtosylaziridine ((S)2c). The purified reaction mixture was analyzed via chiralꢀHPLC, see

supporting information (HPLC section) for details.

Preparation and characterization data for compounds (±)4a-d and (±)4’a-c

(

±)-3a,8-dimethyl-3-phenyl-1-tosyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole ((±)4a and

±)4’a). Procedure A was followed using 1,3ꢀdimethylꢀindole (1p) (87.1 mg, 0.6 mmol), aziridine

2

a (197 mg, 0.72 mmol) and [Au(JohnPhos)(NTf )] (23.3 mg, 0.03 mmol) in DCE (4 mL).

Purification of the crude by column chromatography (Hex/DCM 1:1) yielded progressively (±)4a

and (±)4’a (170 mg, overall yield 68%, ratio 60:40 ) as white solids (m.p.: (±)4a 115ꢀ117.2 °C;

1

6 1

(

8

7

±)4’a 173ꢀ176 °C). (±)4a : H NMR (300 MHz, CDCl

3

): δ 7.86 (d, J = 8.3 Hz, 2H), 7.42 (d, J =

.0 Hz, 2H), 7.29ꢀ7.23 (m, 3H), 7.05 (dt, J = 7.7, 1.3 Hz, 1H), 6.85 (d, J = 6.2, 2H), 6.39 (d, J =

.8 Hz, 1H), 6.31 (t, J = 7.4 Hz, 1H), 5.60 (d, J = 7.4 Hz, 1H), 5.40 (s, 1H), 3.80 (dd, J = 12.2, 6.5

Hz, 1H), 3.42 (t, J = 12.4 Hz, 1H), 3.07 (s, 3H), 2.76 (dd, J = 12.6, 6.5 Hz, 1H), 2.50 (s, 3H), 1.31

1

3

(

s, 3H). C NMR (75 MHz, CDCl

3

): δ 151.2 (C), 144.2 (C), 137.6 (C), 136.1 (C), 130.3 (2 x

CH), 129.2 (2 x CH), 129.0 (C), 128.8 (CH), 128.3 (2 x CH), 127.9 (CH), 127.7 (2 x CH), 125.8

(

CH), 116.8 (CH), 105.4 (CH), 91.5 (CH), 57.1 (C), 55.4 (CH), 51.6 (CH

2

), 31.7 (CH

3

), 26.4

+

(CH ), 22.0 (CH ). ESI(+)-MS (m/z %): 441 (100) [M + Na] . Calcd. for C25H N O S [418.56]:

3 3 26 2 2

1

6b

1

C 71.74, H 6.26, N 6.69; found C.71.92, H 6.16, N 6.85. (±)4’a : H NMR (300 MHz,

CDCl ): δ 7.90 (d, J = 8.2 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 7.38ꢀ7.24 (m, 3H), 7.19 (t, J = 7.6

3

Hz, 1H), 6.96 (dd, J = 6.6, 2.9 Hz, 2H), 6.67 (t, J = 7.4 Hz, 1H), 6.56 (dd, J = 7.1, 3.5 Hz, 2H),

Organic & Biomolecular Chemistry

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DOI: 10.1039/C6OB00672H

5

.10 (s, 1H), 3.89ꢀ3.76 (m, 2H), 3.61 (dd, J = 11.0, 8.0 Hz, 1H), 3.06 (s, 3H), 2.50 (s, 3H), 0.53 (s,

13

3

H). C NMR (75 MHz, CDCl ): δ 149.5 (C), 144.4 (C), 135.7 (C), 135.5 (C), 133.0 (C), 130.2

3

(

1

2 x CH), 129.1 (2 x CH), 129.0 (CH), 128.5 (2 x CH), 128.2 (2 x CH), 127.8 (CH), 122.7 (CH),

18.2 (CH), 107.9 (CH), 94.8 (CH), 54.5 (C), 52.9 (CH ), 52.4 (CH), 33.2 (CH ), 22.0 (CH ), 16.9

). ESI-MS m/z 419 [M + H , 100]. Calcd. for C25 S [418.56]: C 71.74, H 6.26, N

.69; found: C 71.88, H 6.02, N 6.98.

2

3

+

(CH

3

26 2 2

H N O

6

8

-benzyl-3a-methyl-3-phenyl-1-tosyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole ((±)4b and

(

0

±)4’b). Procedure A was followed using indole 1p (132.7 mg, 0.6 mmol), aziridine 2a (196.8 mg,

.72 mmol) and [Au(JohnPhos)(NTf )] (23.3 mg, 0.03 mmol) in DCE (4 mL). Purification of the

crude by column chromatography (Hex/EtOAc 9:1) yielded (±)4b and (±)4’b as inseparable

2

1

3,14

1

mixture (187 mg, overall yield 63%, ratio 60:40, white solid). (±)4b

/(±)4’b: H-NMR (300

MHz, CDCl ): by comparison with NMR data in ref 16b, signals marked in blue and red can be

3

attributed to (±)4b and (±)4’b, respectively. Signals in black are superimposed hydrogens. δ 7.76

(m, 4H), 7.46ꢀ7.20 (m, 20H), 7.08 (dt, J = 1.6, 7.5 Hz, 1H), 7.03ꢀ6.94 (m, 3H), 6.87 (dd, J = 1.6,

7

.7 Hz, 2H), 6.65 (t, J = 7.2 Hz, 1H), 6.60 (dd, J = 1.6, 7.3 Hz, 1H), 6.42 (d, J = 7.9 Hz, 1H), 6.35

(

d, J = 7.9 Hz, 1H), 6.30 (dt, J = 0.8, 7.4 Hz, 1H), 5.60 (dd, J = 1.1, 7.4 Hz, 1H), 5.52 (s, 1H), 5.45

s, 1H), 4.77 (AB, J = 16.2 Hz, 2H), 4.75 (AB, J = 16.5 Hz, 2H), 3.81ꢀ3.90 (m, 3H), 3.53 (t, J =

9

1

9

.3 Hz, 1H), 3.53 (t, J = 12.6 Hz, 1H), 2.79 (dd, J = 12.7, 6.4 Hz, 1H), 2.48 (s, 3H), 2.46 (s, 3H),

1

3

.27 (s, 3H), 0.58 (s, 3H). C-NMR (75 MHz, CDCl ): δ 150.3, 148.7, 144.2, 144.1, 139.2, 138.9,

3

37.3, 136.00, 135.7, 135.2, 132.9, 130.1, 130.0, 129.1 129.0, 128.8, 128.7, 128.7, 128.6, 128.4,

28.2, 128.0, 127.7, 127.6, 127.6, 127.4, 127.2, 127.0, 126.0, 122.5, 117.9, 116.7, 108.0, 105.6,

2.5, 90.1, 57.1, 55.5, 54.8, 52.8, 52.7, 51.4, 49.9, 48.3, 29.9, 26.66, 21.9, 17.0. ESI-MS m/z 495

+

[

M + H , 100].

(

±)-3a,8a-dimethyl-3-phenyl-1-tosyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole ((±)4c and

±)4’c). Procedure A was followed using 2,3ꢀdimethylꢀ1Hꢀindole (1r) (43.6 mg, 0.3 mmol),

2

aziridine 2a (90.2 mg, 0.33.) and [Au(JohnPhos)(NTf )] (11.6 mg, 0.015 mmol) in DCE (2 mL).

Purification of the crude by column chromatography (Hex/EtOAc 98:2ꢀ9:1ꢀ8:2) yielded

progressively (±)4’c and (±)4c (69 mg, overall yield 55%, ratio (±)4c/(±)4’c 70:30) as white

1

solids (m.p: (±)4c 177ꢀ179 °C; (±)4’c 145ꢀ147 °C). (±)4c: H-NMR (300 MHz, CDCl

3

): δ 7.72

(

d, J = 8.1 Hz, 2H), 7.41ꢀ6.95 (m, 8H), 6.56 (t, J = 7.8 Hz, 1H), 6.46 (t, J = 7.3 Hz, 1H), 5.92 (d, J

13

=

7.4 Hz, 1H), 5.42 (bs, 1H), 3.58ꢀ3.32 (m, 3H), 2.39 (s, 3H), 1.84 (s, 3H), 1.22 (s, 3H). C-NMR

): δ 148.2 (C), 143.3 (C), 139.1 (C), 137.6 (C), 135.6 (C), 129.7 (2 x CH), 129.6

2 x CH), 128.3 (2 x CH), 127.9 (CH), 127.7 (CH), 127.3 (2 x CH), 126.1 (CH), 118.4 (CH),

09.2 (CH), 91.9 (C), 59.5 (C), 51.4 (CH), 50.6 (CH ), 23.5 (CH ), 22.7 (CH ), 21.7 (CH ). ESI-

S [418.56]: C 71.74, H 6.26, N 6.69; found: C

1.95, H 6.02, N 6.81. (±)4’c: H-NMR (300 MHz, CDCl ): δ 7.80 (d, J = 8.3 Hz, 2H), 7.32ꢀ7.23

m, 5H), 7.15ꢀ7.08 (m, 2H), 7.06 (dd, J = 7.6, 1.1 Hz, 1H), 6.99 (d, J = 6.8 Hz, 1H), 6.76 (dt, J =

(75 MHz, CDCl

3

(

1

2

3

+

26 2 2

MS m/z 419 [M +H , 100]. Calcd. for C25H N O

1

7

(

3

7

2

1

5

.4, 0.8 Hz, 1H), 6.58 (d, J = 7.8 Hz, 1H), 5.26 (bs, 1H), 3.70 (dd, J = 7.5, 2.1 Hz, 1H), 3.47 (m,

1

3

H), 2.43 (s, 3H), 1.72 (s, 3H), 0.93 (s, 3H). C-NMR (75 MHz, CDCl

39.3 (C), 137.3 (C), 135.0 (C), 129.9 (2 x CH), 129.1 (2 x CH), 128.7 (CH), 128.5 (2 x CH),

27.9 (2 x CH), 127.5 (CH), 122.8 (CH), 119.4 (CH), 109.5 (CH), 92.3 (C), 59.8 (C), 52.6 (CH ),

1.6 (CH), 24.1 (CH ), 21.9 (CH ), 19.7 (CH ). ESI-MS m/z 419 [M + H , 100]. Calcd. for

3

): δ 146.9 (C), 143.6 (C),

2

+

3

C H N O S [418.56]: C 71.74, H 6.26, N 6.69; found: C 71.90, H 6.11, N 6.58.

25

26

2

Page 23 of 26

Organic & Biomolecular Chemistry

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DOI: 10.1039/C6OB00672H

Reactions between indoles 1p-q and aziridine (R)2a. The reactions between indoles 1p-q and

aziridine (R)2a were performed as reported above for the reactions with racemic 2a. Crude

reaction mixtures were purified through a short pad of silica gel giving rise to pure mixtures of

4

(

a/4’a and 4b/4’b which were evaluated via chiral HPLC analysis, in comparison with racemic

±)4a/(±)4’a and (±)4b/(±)4’b, respectively, see supporting information (HPLC section) for

details.

(

±)-(3a,8a-cis)-3a,8-dimethyl-1-tosyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole

Entry 7, scheme 6. In a nitrogen flushed vial a solution of aziridine 2b (39.5 mg, 0.2 mmol) and

Au(JohnPhos)(NTf )] (7.7 mg, 0.01 mmol) in DCE (0.6 mL) was prepared. Then a solution of

((±)4d).

[

2

indole 1p (58.1 mg, 0.4 mmol) in DCE (0.7 mL) was added and the mixture stirred for 1 min

under nitrogen. The vial was then sealed and heated at 150 °C for 1h in a singleꢀmode microwave

synthesizer. The solvent was removed at reduced pressure and the resulting crude was purified by

1

flash column chromatography, affording indoline (±)4d (38 mg, 55%) as a white wax. H-NMR

(

6

200 MHz, CDCl

.92 (d, J = 7.2 Hz, 1H), 6.65 (t, J = 7.3 Hz, 1H), 6.40 (d, J = 7.8 Hz, 1H), 5.12 (s, 1H), 3.61ꢀ3.47

m, 1H), 3.13ꢀ2.95 (m, 4H), 2.45 (s, 3H), 1.93 (ddd, J = 12.4, 5.8, 2.7 Hz, 1H), 1.39 (m, 1H), 1.14

3

): δ 7.78 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 7.9 Hz, 2H), 7.10 (t, J = 7.6 Hz, 1H),

(

1

3

s, 3H). C-NMR (50 MHz, CDCl ): δ 150.2 (C), 143.8 (C), 137.1 (C), 133.4 (C), 130.0 (2 x

3

CH), 128.7 (CH), 127.5 (2 x CH), 122.1 (CH), 117.9 (CH), 106.2 (CH), 91.3 (CH), 53.3 (C), 48.7

+

(

CH ), 39.7 (CH ), 31.6 (CH ), 24.6 (CH ), 21.7 (CH ). ESI-MS m/z 365 [M + Na , 38]. Calcd.

2 2 3 3 3

for C H N O S [342.46]: C 66.64, H 6.48, N 8.18; found: C 66.86, H 6.33, N 8.01.

19

22

2

(

±)-(3a,8a-cis)-3a-allyl-8-methyl-1-tosyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole ((±)4e).

Entry 8, scheme 6. In a nitrogen flushed vial a solution of aziridine 2b (39.5 mg, 0.2 mmol) and

Au(JohnPhos)(NTf )] (7.7 mg, 0.01 mmol) in DCE (0.6 mL) was prepared. Then a solution of

[

2

indole 1s (68.5 mg, 0.4 mmol) in DCE (0.7 mL) was added and the mixture stirred for 1 min under

nitrogen. The vial was then sealed and heated at 150 °C for 1h in a singleꢀmode microwave

synthesizer. The solvent was removed at reduced pressure and the resulting crude was purified by

1

flash column chromatography, affording indoline (±)4e (33 mg, 45%) as a white wax. H-NMR

(

300 MHz, CD

2

Cl

H), 6.94 (dd, J = 7.3.1.3 Hz, 1H), 6.65 (td, J = 7.3, 1.0 Hz, 1H), 6.40 (dd, J = 7.9, 0.7 Hz, 1H),

.42 (m, 1H), 5.16 (s, 1H), 4.97 (m, 1H), 4.92 (m, 1H), 3.60 (m, 1H), 2.96 (m, 4H), 2.47 (s, 3H),

2

): δ 7.77 (d, J = 8.3 Hz, 2H), 7.39 (d, J = 7.9 Hz, 2H), 7.10 (td, J = 7.7, 1.3 Hz,

1

5

2

13

2 2

.30 (m, 1H), 2.06 (m, 1H), 1.87 (m, 1H), 1.42 (m, 1H). C-NMR (75 MHz, CD Cl ): δ 151.1

(

1

(

[

C), 144.1 (C), 137.1 (C), 134.1 (CH), 131.6 (C), 130.1 (2 x CH), 128.7 (CH), 127.4 (2 x CH),

22.8 (CH), 118.1 (C), 117.5 (CH), 105.8 (CH), 88.4 (CH), 57.3 (C), 48.4 (CH ), 42.7 (CH ), 37.8

CH ), 31.3 (CH ), 21.5 (CH ). ESI-MS m/z 391 [M + Na , 100]. Calcd. for C H N O S

2

+

2

3

21 24

2

368.49]: C 68.45, H 6.56, N 7.60; found: C 68.40, H 6.59, N 7.55.

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