Photopromoted Entry to Benzothiophenes, Benzoselenophenes, 3H-Indoles, Isocoumarins, Benzosultams, and (Thio)flavones by Gold-Catalyzed Arylative Heterocyclization of Alkynes

Title: Photopromoted Entry to Benzothiophenes, Benzoselenophenes,

3H-Indoles, Isocoumarins, Benzosultams, and (Thio)Flavones by

Gold-Catalyzed Arylative Heterocyclization of Alkynes

Authors: Pedro Almendros, Benito Alcaide, Eduardo Busto, Fernando

Herrera, Carlos Lazaro-Milla, and Amparo Luna

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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700427

Link to VoR: http://dx.doi.org/10.1002/adsc.201700427

10.1002/adsc.201700427

Advanced Synthesis & Catalysis

FULL PAPER

DOI: 10.1002/adsc.200((will be filled in by the editorial sttaff))

Photopromoted Entry to Benzothiophenes, Benzoselenophenes,

3H-Indoles, Isocoumarins, Benzosultams, and (Thio)flavones by

Gold-Catalyzed Arylative Heterocyclization of Alkynes

Benito Alcaide,^a* Pedro Almendros,^b* Eduardo Busto,^aFernando Herrera,^aCarlos

Lázaro-Milla,^aand Amparo Luna^a

a

Grupo de Lactamas y Heterociclos Bioactivos, Departamento de Química Orgánica I, Unidad Asociada al CSIC,

Facultad de Química, Universidad Complutense de Madrid, 28040 Madrid, Spain, Fax: (+34) 91-3944103, E-mail:

alcaideb@quim.ucm.es

Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas, IQOG-CSIC, Juan de la

b

Cierva 3, 28006 Madrid, Spain, Fax: (+34) 91-5644853, E-mail: Palmendros@iqog.csic.es

Received: ((will be filled in by the editorial staff))

Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.200######.((Please

delete if not appropriate))

Abstract: Visible light-promoted and gold-photoredox thiochromen-4-ones (thioflavones). Moreover, the utility of

catalyzed reactions of heteroatom (N, S, Se, O) tethered functionalized 3H-indoles as precursors for further

alkynes with arenediazonium salts selectively reacted to build elaboration has been demonstrated with the switchable and

vicinal diaryl-substituted 2H-benzo[e][1,2]thiazine 1,1- facile preparation of 1H-indoles, 2-oxindoles, and 3-

dioxides

(benzosultams),

benzoselenophenes, oxindolines.

benzothiophenes, 4H-chromen-4-ones (flavones), 3H-

indoles, 1H-isochromen-1-ones (isocoumarins), and 4H-

Keywords: alkynes; cyclization; gold; heterocyclic

compounds; synthetic methods

use of ligands and bases. Besides, the incorporation of

aryl substituents to the heterocyclic core is performed

by the use of aryl halides, which are not always readily

available. Aiming to surmount these deficiencies, we

were motivated to include diazonium salts and visible

light in a comprehensive gold-catalyzed arylative

heterocycle formation. Due to environmental concerns,

the development of a photocatalyzed arylative

synthesis at room temperature may be a great

achievement. We wish to describe herein the unique

use of diazonium salts as a radical source in the

cooperative gold-photoredox catalyzed synthesis of

benzo-fused heterocycles (Scheme 1).^[6]

Introduction

Homogeneous gold catalysis has been developed as a

potent tool in the field of synthetic organic chemistry.

Particularly attractive is the activation of alkenes,

alkynes and allenes by cationic gold(I) species.^[1]

However, Au(I)/Au(III) catalytic cycles cannot be

accessed through the traditional gold(I)-catalyzed

processes, and super-stoichiometric amounts of a

strong oxidant are required for surpassing the high

redox potential Au(I)/Au(III).^[2]Taking into account

the above limitations, it is not surprising that gold-

catalyzed cross-coupling strategies are a less explored

field. Glorius and, later, Toste developed a smart

strategy for avoiding the drawback of the inclusion of

strong oxidants,^[3]which takes advantage of a

photoredox catalyst and a diazonium salt.^[4]Hashmi

and Barriault developed gold-only photoredox

chemistry through the use of dinuclear complexes of

gold as photoredox catalysts.^[5]

On the other hand, the widespread presence of

heterocycles in both natural products and synthetic

drugs as well as in advanced materials, explains the

interest in the preparation of these cyclic frameworks.

This area is clearly dominated by palladium catalysis,

which usually demands elevated temperatures and the

1

10.1002/adsc.201700427

Advanced Synthesis & Catalysis

When the loading of PPh₃AuCl was increased from 10

mol% to 20 mol%, it resulted in just a little

improvement of the yield (95%) (entry 5, Table 1).

Decreasing the amount of PPh₃AuCl from 10 mol% to

5 mol% produced an appreciable reduction of the yield

(64%) (entry 6, Table 1). Inferior results were obtained

when the reaction was carried out in presence of other

photoactive

complexes

such

as

[Ir(ppy)₂(dtbbpy)](PF₆)₂] (ppy = 2-phenylpyridine;

dtbbpy = 4,4’-di-tert-butyl-2,2’-bipyridine) (entry 4,

Table 1). Also, alternative gold(I) sources such as

[AuClIPr]

(IPr

=

1,3-bis(2,6-

and

diisopropylphenyl)imidazol-2-ylidene)

[(Ph₃P)AuNTf₂] were inefficient (entries 1 and 2,

Table 1).

Table 1. Screening of reaction conditions for

benzothiophene

formation

through

light-driven

gold/photoredox-co-catalyzed diarylative thiacyclization.^[a]

Scheme 1. Dual gold- and photoredox-catalyzed

heterocyclization reactions: Previous and current strategies.

TMS = Trimethylsilyl.

Results and Discussion

Entry

Gold Catalyst

Photocatalyst^[b]

Yield (%)^[c]

1

2

3

4

5

6

7

[IPrAuCl]

[Ru]

[Ir]

–

(2-Ethynylphenyl)(methyl)sulfane 1a-H-SMe and

phenyldiazonium salt 2a were chosen as model

substrates to examine their reactivity under

cooperative gold and photoredox catalysis.^[7]Our aim

[(Ph₃P)AuNTf₂]

[(PPh₃)AuCl]

[(PPh₃)AuCl]^[d]

[(PPh₃)AuCl]^[e]

[(PPh₃)AuCl]

–

94

63

95

64

5^[f]

was the in situ generation of

a

methyl[2-

[Ru]

(arylethynyl)phenyl]sulfane from a gold-catalyzed

sila-Sonogashira-type coupling, which can be further

trapped by the nucleophile sulfur with a concomitant

second arylation in a domino sequence. This premise

deals with difficulties and presents an initial challenge

because the photoredox gold-catalyzed arylation of

sulfur derivatives has not yet been reported. Besides,

we need that the starting material undergoes a

relatively fast coupling at the alkyne site, in

comparison with the heterocyclization event. Substrate

1a-H-SMe provided benzothiophene 3a-S in a

promising 27% yield. A significant improvement was

detected with the use of TMS-capped alkyne 1a-Si-

SMe,^[8]which was considered as viable precursor in

the synthesis of 2,3-diaryl benzothiophenes. We

initiated our optimization studies using various gold(I)

complexes and the ruthenium salt [Ru(bpy)₃](PF₆)₂]

(bpy = 2,2’-bipyridine) as shown in Table 1. After the

evaluation of different conditions, PPh₃AuCl (10

mol%) in combination with [Ru(bpy)₃](PF₆)₂] (2.5

mol%) provided an impressive yield (94%) of 2,3-

diphenyl benzothiophene 3a-S (entry 3, Table 1).

^[a]Unless otherwise noted, all reactions were carried out in

methanol/acetonitrile (3:1) at room temperature.

^[b][Ru] = [Ru(bpy)₃](PF₆)₂]. [Ir] = [Ir(ppy)₂(dtbbpy)](PF₆)₂].

^[c]Yield of pure, isolated product with correct analytical and

spectral data.

^[d]Catalyst loading of 20 mol%.

^[e]Catalyst loading of 5 mol%.

^[f]The reaction was carried out in DMF.

We applied the above reaction conditions to

differently functionalized arenediazonium salts 2

(Scheme 2). Substitution was tolerated in the

diarylative thiacyclizations of 1a-Si-SMe, with the

presence at the arenediazonium salt of electron

withdrawing groups (CO₂Et, CF₃) as well as halogens

(Br) and weakly electron donating groups (Me). The

results depicted in the above Scheme show the

effectiveness of this methodology for the smooth

2

10.1002/adsc.201700427

Advanced Synthesis & Catalysis

preparation of a variety of 2,3-diaryl benzothiophenes

CF₃) failed to give the desired indole. Instead, alkenes

7 were formed (Scheme 5). Apparently, the electron

poor aryl alkyne intermediate disfavors the

aminocyclization with the azide moiety and the

competitive intermolecular nucleophilic addition of

methanol dominates.

3-S.^[9]

Scheme 2. Cooperative gold-photoredox catalysis for the

synthesis of 2,3-diaryl benzothiophenes 3-S.

Scheme 4. Cooperative gold-photoredox catalysis for the

synthesis of 2,3-diaryl 3H-indoles 6. [a] For a full

conversion, the complex was added in two separated

portions with a 30 min spacing.

To further probe the scope and versatility of the

arylative carbon−chalcogen cyclization reaction,

trimethyl[(2-methylselanylphenyl)ethynyl]silane 1a-

Si-SeMe was used to react with phenyldiazonium salt

2a under the optimized conditions for the formation of

2,3-diaryl benzothiophenes 3-S. As depicted in

Scheme 3, the diarylation/C−Se bond formation

sequence

proceeded

to

afford

2,3-diaryl

benzoselenophene 3a-Se, but less efficiently.

Precursor 1a-Si-SeMe reacted well with several

arenediazonium salts 2 bearing diverse substitution

and gave rise under mild conditions to the desired

selenoheterocycles 3-Se, a type of organic molecules

which are prevalent both in drugs and in advanced

materials (Scheme 3).

Scheme 5. Cooperative gold-photoredox catalysis for the

diarylative hydroalkoxylation of (ethynyl)azidobenzene 4a-

Si with strongly deactivated arenediazonium salts.

Next, under the optimized reaction conditions, the

reactivities of several TMS-(ethynyl)azidobenzenes 4-

Si with arenediazonium salt 2b were examined

(Scheme 6). The power of this methodology was

further demonstrated with the use of different alcohols

(ethanol, 2-propanol, tert-butanol, and methanol-d₃)

instead of methanol to give adducts 6ab-Et, 6ab-iPr,

6ab-tBu, and 6ab-CD₃(Scheme 6). Besides, several

substituents could be incorporated to the starting

materials, which grants for the formation of a variety

of functionalized 3H-indoles. The reaction yields (¹H

NMR) were excellent before purification because no

side-products were detected when the starting material

was fully converted. However, partial decomposition

was observed on sensitive 3H-indoles 6 during

chromatographic purification.

Scheme 3. Cooperative gold-photoredox catalysis for the

synthesis of 2,3-diaryl benzoselenophenes 3-Se.

Continuing to explore different functionalities at

the TMS-protected alkynes and taking into account

that the azide moiety is a versatile nitrogen source,^[10]

we decided to test azidobenzene-tethered alkynes.^[11]

The above reaction conditions for TMS-sulfane 1a-Si-

SMe

was

also

applicable

for

TMS-

(ethynyl)azidobenzene 4a-Si,^[12]but it exhibited

different reactivity. The lack of formation of expected

2,3-diaryl 1H-indoles of type 5 was observed, which

should point to a marked directing effect of the

heteroatomic nucleophile functionality. In view of the

structure of adduct 6a, the participation of methanol as

a nucleophile is apparent. Noteworthy, this interesting

reactivity switch allowed the obtention of

functionalized 3H-indoles 6aa–ah through

a

diarylative aminocyclization/hydroalkoxylation

Scheme 6. Cooperative gold-photoredox catalysis for the

synthesis of differently substituted 2,3-diaryl 3H-indoles 6.

[a] For a full conversion, the complex was added in two

separated portions with a 30 min spacing.

sequence (Scheme 4). Halogenated or weakly

activated arenediazonium salts turned out to be

suitable coupling partners. However, diazonium salts

having strong electron withdrawing groups (NO₂and

3

10.1002/adsc.201700427

Advanced Synthesis & Catalysis

benzo-fused heterocycles. For the investigation of the

scope of the sequence, a pair of potential precursors,

esters 10-Si and sulfonamide 11-Si, was prepared.

Interestingly, isocoumarins 12 were obtained in fair

yields by the light-driven gold/photoredox-co-

catalyzed double arylation/oxycyclization of 2-

[(trimethylsilyl)ethynyl]benzoates 10-Si (Scheme 9).

Notably, regioisomeric five-membered heterocycles

were not detected, highlighting the exquisite

selectivity of the sequence. Starting from 2-

[(trimethylsilyl)ethynyl]benzenesulfonamide 11-Si,

the same diarylative protocol afforded benzosultams

13 with satisfactory yields (Scheme 10). It is apparent

that in esters 10-Si and sulfonamide 11-Si the 6-endo

oxy- and aza-cyclizations paths are favoured because

competitive 5-exo heterocyclizations are not involved.

To fully exploit the potential of this methodology,

we reacted [(2-azidophenyl)ethynyl]trimethylsilane

4a-Si with a pair of different diazonium salts 2. Initial

Hiyama coupling of TMS-precursor 4a-Si with the

first diazonium salt

2

provided 1-azido-2-

(arylethynyl)benzene intermediates. Without the need

of isolation, these intermediates afforded the final

differently diarylated 3H-indoles 6 after a second

coupling with another diazonium salt (Scheme 7).

Thus, TMS-(ethynyl)azidobenzene 4a-Si acts as a

versatile building block for the double crossed

diarylation reaction, and allows for the preparation of

crossover adducts in a convenient and modular way.

Scheme 9. Cooperative gold-photoredox catalysis for the

synthesis of 3,4-diaryl- isocoumarins 12. [a] For a full

conversion, the complex was added in two separated

portions with a 30 min spacing.

Scheme 7. Cooperative gold-photoredox catalysis for the

crossed preparation of 2,3-diaryl 3H-indoles 6.

Besides, the utility of 3-alkoxy-2,3-diaryl-3H-

indoles 6 as precursors for further elaboration has been

demonstrated with the controlled preparation of N-

unprotected indoles 5, 2-oxindoles 8 and 3-

oxindolines 9 through base- or acid-promoted

rearrangement reactions (Scheme 8).^[13]Possibly, the

driving-force of these reorganizations may be related

to the gain in stability associated with the 1H-indole,

indolinone and indolone formation.

Scheme 10. Cooperative gold-photoredox catalysis for the

synthesis of 3,4-diaryl-benzosultams 13.

Having in hand (trimethylsilyl)prop-2-yn-1-one

14-Si, we attempted the double arylation with

arenediazonium salt 2a under the above reaction

conditions. However, absence of reaction was

observed (Scheme 11), which shows that the

contiguous ketone group in the (trimethylsilyl)ethyne

moiety is critical for the suppression of any Hiyama-

Sonogashira reaction. Efforts to modified either the

gold catalyst or the diazonium salt led to no

improvement in reactivity. We decided to implement

our planned synthesis of benzo-fused heterocycles

replacing the TMS group by an aryl substituent.

Convincing confirmation for the negative effect of the

alkynone framework on the sila-coupling but not on

the heterocyclization event, was definitively obtained

Scheme 8. Synthetic transformations of 3-methoxy-2,3-

diaryl-3H-indoles 6.

With thia-, selena-, and azido-(TMS-

ethynyl)benzenes 1a-Si-SMe, 1a-Si-SeMe, and 4-Si

found to be compatible with the diarylative five-

membered heterocyclization reaction, structurally

different precursors were investigated to further

expand the scope of the reaction to six-membered

by

the

fruitful

accomplishment

of

the

monoarylative/heterocyclization in aryl-terminated

alkynone 14-Ph by which synthesis of 4H-chromen-4-

ones 15 has been attained (Scheme 11). The succcesful

cyclization of the heteroatom-linked alkynone core

4

10.1002/adsc.201700427

Advanced Synthesis & Catalysis

was further confirmed by the light-driven

effectively produced. Apparently, the silicon/gold

interchange is preferred to the amino-auration. Then,

Si–Au transmetallation should produce gold acetylide

species 20, which suffers reductive elimination paired

gold/photoredox-co-catalyzed

arylative

thiacyclization reaction of the sulfa-derivative 16-Ph

with several diazonium salts 2 to afford 4H-

thiochromen-4-ones 17 (Scheme 12). The detected

regiochemistry of both ring closures (6-endo oxy- and

thia-cyclizations) is in agreement with the results of

Schemes 9 and 10.

to

aryl

transfer

and

releases

2-

(arylethynyl)azidobenzenes 4-Ar and the gold(I) salt,

closing the first gold catalytic cycle (bottom catalytic

cycle). The formation of 3-alkoxy-2,3-diaryl-3H-

indoles 6 from 2-(arylethynyl)azidobenzenes 4-Ar

requires the participation of the organogold(III)

species 19 in the azacyclization event. According to

the aforementioned comments, a second molecule of

arenediazonium salt 2 affords the corresponding aryl

radical helped by light and the photoredox catalyst (top

catalytic cycle, right side). The N atom attack to the

terminal carbon of the triple bond with respect to the

azide moiety is facilitated in intermediate 4-Ar-

Au(III) by the coordination of arylgold(III) species 19

with the alkyne functionality of 4-Ar. After the 5-

endo-dig azacyclization, the aryl transfer from the Au

atom to the C3 indole carbon lead to intermediate 1H-

indoles 22. In concert, the gold(I) precatalyst is

regenerated in this pathway (top catalytic cycle, left

side). The formation of 3-alkoxy-2,3-diaryl-3H-

indoles 6 requires the further attack of the alcohol with

concomitant nitrogen releases.

Scheme 11. Cooperative gold-photoredox catalysis for the

synthesis of 3-aryl-flavones 15.

Scheme 12. Cooperative gold-photoredox catalysis for the

synthesis of 3-aryl-thioflavones 17.

Despite that Hashmi^[14]and Shi^[15]have

independently shown that no photoredox catalysts are

required for related reactions, a control experiment

verified that our reactions operates through

[Ru(bpy)₃](PF₆)₂photoredox. Indeed, starting either

from 1a-Si-SMe or 4a-Si no reaction occurred in the

absence of the photosensitizer. The critical role of light

in the domino reaction was probed when precursors

1a-Si-SMe or 4a-Si were recovered when the reactions

were run with all the reagents but without irradiation.

A tentative mechanistic proposal for the generation of

3-alkoxy-2,3-diaryl-3H-indoles

6

from

2-

4-Si,

[(trimethylsilyl)ethynyl]azidobenzenes

diazonium salts 2 and light under dual gold-

photoredox cocatalysis is summarized in Scheme 13.

Initially, irradiation of the Ru(II)-based photoredox

catalyst results in the formation of an aryl radical from

diazonium salts 2 after extrusion of dinitrogen (bottom

catalytic cycle, right side). This key reactive species is

able to be coupled with the gold(I) precatalyst to allow

the formation of unstable organogold(II) intermediate

18, which rapidly evolves to the cationic

organogold(III) derivative 19, a strong electrophile,

through the oxidative action of Ru(III) and

concomitant liberation of [Ru(bpy)₃](PF₆)₂into the

catalytic cycle. Next, TMS-(ethynyl)azidobenzenes 4-

Si enter the gold catalytic sequence (bottom catalytic

cycle, left side), forming complexes 4-Si-Au(III)

through alkyne coordination with the gold complex.

Either the transmetallation of the C(sp)–Si bond or the

nucleophilic attack from the azide group can be

Scheme 13. Rationalization for the gold-photoredox

cocatalyzed preparation of 3-alkoxy-2,3-diaryl-3H-indoles

5

10.1002/adsc.201700427

Advanced Synthesis & Catalysis

6 from TMS-(ethynyl)azidobenzenes 4-Si and diazonium

salts 2.

mixtures gave analytically pure compounds. The addition of

Et₃N (2%) to the eluent was neccesary for the purification

of acid sensitive 3H-indoles 6. Spectroscopic and analytical

data for pure forms of compounds 1a-Si-SMe, 1a-Si-SeMe,

4a–f-Si, 10a–c-Si, and 11-Si follow.^[16]

Conclusions

2,3-Diaryl benzothiophene 3a-S. From 22 mg (0.10 mmol)

of TMS-alkyne 1a-Si-SMe, and after chromatography of the

In conclusion, visible light-promoted and gold-

photoredox catalyzed reactions of heteroatom(N, S, Se, residue using hexanes as eluent, gave compound 3a-S (27

1

O)-tethered alkyne derivatives with diazonium salts

are totally selective to build in a controlled manner

vicinal diaryl-substituted 2H-benzo[e][1,2]thiazine

1,1-dioxides (benzosultams), benzoselenophenes,

benzothiophenes, 4H-chromen-4-ones (flavones), 3H-

indoles, 1H-isochromen-1-ones (isocoumarins), and

4H-thiochromen-4-ones (thioflavones). Besides, the

usefulness of 3H-indoles has been probed with the

facile and divergent synthesis of 1H-indoles, 2-

oxindoles and 3-oxindolines.

mg, 94%) as a colorless solid; m.p. 107–109 ºC; H NMR

(300 MHz, CDCl₃, 25 ^oC) δ: 7.85–7.79 (m, 1H, CH^Ar), 7.54–

7.50 (m, 1H, CH^Ar), 7.31–7.15 (m, 12H, 12CH^Ar); ¹³C NMR

(75 MHz, CDCl₃, 25 ºC) : 141.2 (C^Ar-q), 139.9 (C^Ar-q),

139.2 (C^Ar-q), 135.8 (C^Ar-q), 134.6 (C^Ar-q), 133.6 (C^Ar-q),

130.8 (2CH^Ar), 130.0 (2CH^Ar), 129.0 (2CH^Ar), 128.7

(2CH^Ar), 128.1 (CH^Ar), 127.7 (CH^Ar), 124.9 (CH^Ar), 124.8

(CH^Ar), 123.7 (CH^Ar), 122.4 (CH^Ar); IR (CHCl₃, cm^–1):

1599, 1436; HRMS (ES): calcd for C₂₀H₁₅S [M + H]⁺:

287.0889; found: 287.0898.

2,3-Diaryl benzothiophene 3b-S. From 35 mg (0.16 mmol)

of TMS-alkyne 1a-Si-SMe, and after chromatography of the

residue using hexanes as eluent, gave compound 3b-S (60

Experimental Section

1

General methods: H NMR and ¹³C NMR spectra were

mg, 86%) as a colorless solid; m.p. 175–177 ºC; H NMR

o

recorded on a Bruker Avance AVIII-700 with cryoprobe,

Bruker AMX-500, or a Bruker AMX-500, or a Bruker

Avance-300 spectrometers. NMR spectra were recorded in

CDCl₃solutions, except otherwise stated. Chemical shifts

are given in ppm relative to TMS (¹H, 0.0 ppm), or CDCl₃

(¹H, 7.27 ppm; ¹³C, 76.9 ppm), or C₆D₆(¹H, 7.16 ppm; ¹³C,

128.0 ppm). Low and high resolution mass spectra were

taken on an AGILENT 6520 Accurate-Mass QTOF LC/MS

spectrometer using the electrospray mode (ES) unless

otherwise stated. IR spectra were recorded on a Bruker

Tensor 27 spectrometer. All commercially available

compounds were used without further purification.

(300 MHz, CDCl₃, 25 C) δ: 7.89 (m, 1H, CH^Ar), 7.56 (m,

3H, 3CH^Ar), 7.40 (m, 4H, 4CH^Ar), 7.19 (m, 4H, 4CH^Ar); ¹³

C

NMR (75 MHz, CDCl₃, 25 ºC) : 140.3 (C^Ar-q), 138.8 (C^Ar-

^q), 138.6 (C^Ar-q), 134.1 (C^Ar-q), 132.9 (C^Ar-q), 132.3 (C^Ar-q),

132.1 (2CH^Ar), 132.0 (2CH^Ar), 131.7 (2CH^Ar), 131.1

(2CH^Ar), 124.9 (CH^Ar), 124.8 (CH^Ar), 123.1 (CH^Ar), 122.3

(C^Ar-q), 122.2 (CH^Ar), 121.8 (C^Ar-q); IR (CHCl₃, cm^–1):

1533, 1484; HRMS (ES): calcd for C₂₀H₁₃Br₂S [M + H]⁺:

442.9099; found: 442.9087.

2,3-Diaryl benzoselenophene 3d-Se. From 26 mg (0.10

mmol) of TMS-alkyne 1a-Si-SeMe, and after

chromatography of the residue using hexanes as eluent, gave

compound 3d-Se (28 mg, 60%) as a colorless solid; m.p.

General procedure for the photopromoted gold-

catalyzed twofold arylation reaction of hetero-subtituted

1

o

140–142 ºC; H NMR (300 MHz, CDCl₃, 25 C) δ: 8.08–

TMS-(ethynyl)benzenes 1a-Si-SMe, 1a-Si-SeMe, 4a–f-Si, 8.04 (m, 1H, CH^Ar), 7.67–7.63 (m, 1H, CH^Ar), 7.47–7.30 (m,

10a–c-Si, or 11-Si with diazonium salts 2. Preparation of

2,3-diaryl benzothiophenes 3-S, 2,3-diaryl

8H, 8CH^Ar), 7.21–7.17 (m, 2H, 2CH^Ar), 2.56 (s, CH₃), 2.46

(s, CH₃); ¹³C NMR (75 MHz, CDCl₃, 25 ºC) : 143.8 (C^Ar-

^q), 143.2 (C^Ar-q), 140.2 (C^Ar-q), 137.4 (C^Ar-q), 136.9 (C^Ar-q),

135.9 (C^Ar-q), 133.8 (C^Ar-q), 133.4 (C^Ar-q), 130.4 (2CH^Ar),

129.7 (2CH^Ar), 129.4 (2CH^Ar), 129.1 (2CH^Ar), 125.6 (CH^Ar),

125.2 (CH^Ar), 124.6 (2CH^Ar); ⁷⁷Se NMR (95 MHz, CDCl₃,

benzoselenophenes 3-Se, 3-alkoxy-2,3-diaryl-3H-indoles

6, 3,4-diaryl-isocoumarins 11, and 3,4-diaryl-

benzosultams 13. In a Schlenk tube in the absence of light

at –78 ºC under argon atmosphere, Ph₃PAuCl (10 mol %)

and [Ru(bpy)_3](PF₆)₂(2.5 mol %) were sequentially added

to a solution of the corresponding arene diazonium salt 2

(6.0 equiv) in a mixture of MeOH/MeCN (3:1, 5.0 mL).

o

25 C) δ: 528.9 (s, 1Se); IR (CHCl₃, cm^–1): 1506, 1439,

810; HRMS (ES): calcd for C₂₂H₁₉Se [M + H]⁺: 363.0647;

found: 363.0632.

Then,

a

solution

of

the

appropriate

2-

[(trimethylsilyl)ethynyl]benzene 1a-Si-SMe, 1a-Si-SeMe,

4a–f-Si, 10a–c-Si, or 11-Si (1.0 mmol) in MeOH/MeCN

(3:1, 2.5 mL) was added dropwise and the reaction was

stirred at –78 ºC for 5 min. For a full conversion in the case

of azides 4, at the beginning the gold salt was added in two

separated portions with a 30 min spacing. The reaction

mixture was then warmed to room temperature and stirred

under irradiation from visible light source (21 W fluorescent

light bulb installed in a tool box). After disappearance of the

starting material (TLC), the reaction mixture was

concentrated under reduced pressure. Chromatography of

the residue using hexanes/ethyl acetate or hexanes/toluene

2,3-Diaryl benzoselenophene 3e-Se. From 26 mg (0.10

mmol) of TMS-alkyne 1a-Si-SeMe, and after

chromatography of the residue using hexanes as eluent, gave

compound 3e-Se (21 mg, 52%) as a colorless solid; m.p.

198–200 ºC; H NMR (300 MHz, CDCl₃, 25 C) δ: 7.97–

7.94 (m, 1H, CH^Ar), 7.52–7.49 (m, 1H, CH^Ar), 7.42–7.27 (m,

4H, 4CH^Ar), 7.26–7.17 (m, 6H, 6CH^Ar); ¹³C NMR (75 MHz,

CDCl₃, 25 ºC) : 143.0 (C^Ar-q), 142.3 (C^Ar-q), 140.5 (C^Ar-q),

135.6 (C^Ar-q), 134.9 (C^Ar-q), 134.4 (C^Ar-q), 133.8 (C^Ar-q),

133.6 (C^Ar-q), 131.9 (2CH^Ar), 131.0 (2CH^Ar), 129.1 (2CH^Ar),

128.7 (2CH^Ar), 125.5 (CH^Ar), 125.4 (CH^Ar), 125.2 (CH^Ar),

125.0 (CH^Ar); ⁷⁷Se NMR (95 MHz, CDCl₃, 25 ^oC) δ: 538.9

1

o

6

10.1002/adsc.201700427

Advanced Synthesis & Catalysis

(s, 1Se); IR (CHCl₃, cm^–1): 1484, 1089, 833; HRMS (ES):

calcd for C₂₀H₁₃Cl₂Se [M + H]⁺: 402.9554; found: 402.9570.

137.6 (C^Ar-q), 135.9 (d, J_CF= 1.0 Hz, C^Ar-q), 135.0 (CH^Ar),

131.7 (2CH^Ar), 131.0 (q, J_CF= 32.7 Hz, C^Ar-q-CF₃), 130.8 (q,

J_CF= 32.8 Hz, C^Ar-q-CF₃), 129.9 (CH^Ar), 129.5 (2CH^Ar),

129.0 (CH^Ar), 126.3 (q, J_CF= 3.7 Hz, 2CH^Ar), 125.2 (CH^Ar),

125.1 (q, J = 3.8 Hz, 2CH^Ar), 123.8 (q, J_CF= 272.4 Hz, CF₃),

123.6 (q, J_CF= 272.4 Hz, CF₃), 120.5 (C^Ar-q), 116.90 (C=C),

103.4 (CH^Ar); ¹⁹F NMR (282 MHz, CDCl₃, 25 ^oC): –62.9 (s,

3F, CF₃), –63.2 (s, 3F, CF₃); IR (CHCl₃, cm^–1): 1735

(C=O); HRMS (ES): calcd for C₂₃H₁₃F₆O₂[M + H]⁺:

435.0814; found: 435.0814.

3-Alkoxy-2,3-diaryl-3H-indole 6ab. From 30 mg (0.14

mmol) of TMS-azide 4a-Si, and after chromatography of the

residue using hexanes/Et₂O (97:3) containing NEt₃(2%) as

eluent, gave compound 6ab (40 mg, 63%) as a yellow oil;

¹H NMR (500 MHz, CDCl₃, 25 ^oC) δ: 7.97 (m, 2H, 2CH^Ar),

7.68 (d, 1H, J = 7.7 Hz, CH^Ar), 7.51 (m, 2H, 2CH^Ar), 7.41

(m, 1H, CH^Ar), 7.37 (m, 2H, 2CH^Ar), 7.22 (d, 1H, J = 6.6

Hz, CH^Ar), 7.19 (m, 2H, 2CH^Ar), 7.11 (d, 1H, J = 6.9 Hz,

CH^Ar), 3.06 (s, 3H, OCH₃); ¹³C NMR (125 MHz, CDCl₃, 25

ºC) : 177.2 (N=C), 153.2 (C^Ar-q), 139.7 (C^Ar-q), 138.3 (C^Ar-

^q), 131.9 (2CH^Ar), 130.2 (CH^Ar), 130.0 (C^Ar-q), 129.9

(2CH^Ar), 127.2 (CH^Ar), 126.4 (C^Ar-q), 126.2 (2CH^Ar), 123.4

(CH^Ar), 121.7 (C^Ar-q), 121.6 (CH^Ar), 92.9 (OC^q), 52.6

(OCH₃); IR (CHCl₃, cm^–1): 1728 (N=C), 1079 (C-O);

HRMS (ES): calcd for C₂₁H₁₆Br₂NO [M + H]⁺: 455.9593;

found: 455.9601.

3,4-Diaryl-isocoumarin 12bb. From 41 mg (0.11 mmol) of

TMS-alkyne 10b-Si, and after chromatography of the

residue using hexanes/ethyl acetate (95:5) as eluent, gave

compound 12bb (37 mg, 72%) as a colorless solid; m.p.

142–144 ºC; ¹H NMR (300 MHz, CDCl₃, 25 ^oC) δ: 8.06 (dd,

1H, J = 8.3, 2.8 Hz, CH^Ar), 7.60 (m, 2H, 2CH^Ar), 7.39 (m,

3H, 3 CH^Ar), 7.16 (m, 5H, 5CH^Ar); ¹³C NMR (75 MHz,

CDCl₃, 25 ºC) : 162.0 (d, J_CF= 251.5 Hz, C^Ar-q-F), 163.7

(d, J_CF= 3.5 Hz, C=O), 149.5 (d, J_CF= 2.6 Hz, C=C), 134.7

(d, J_CF= 2.7 Hz, C^Ar-q), 132.7 (2CH^Ar), 132.6 (2CH^Ar), 131.4

(2CH^Ar), 131.2 (C^Ar-q), 130.6 (2CH^Ar), 127.7 (d, J_CF= 7.8

Hz, CH^Ar), 123.8 (C^Ar-q), 123.3 (C^Ar-q), 123.1 (d, J_CF= 22.8

Hz, CH^Ar), 122.9 (C^Ar-q), 122.2 (d, J_CF= 8.2 Hz, C^Ar-q),

115.5 (d, J_CF= 0.9 Hz, C=C), 115.3 (d, J_CF= 23.3 Hz, CH^Ar);

3-Alkoxy-2,3-diaryl-3H-indole 6ab-CD₃. The reaction

was runned in CD₃OD instead MeOH. From 30 mg (0.14

mmol) of azide 4a-Si, and after chromatography of the

residue using hexanes/Et₂O (97:3) as eluent containing NEt₃

(2%), gave compound 6ab-CD₃(38 mg, 59%) as a yellow

o

¹⁹F NMR (282 MHz, CDCl₃, 25 C): –110.31 (s, 1F, C–F);

1

o

oil; H NMR (300 MHz, CDCl₃, 25 C) : 7.87 (m, 2H,

2CH^Ar), 7.58 (d, 1H, J = 7.7 Hz, CH^Ar), 7.41 (m, 2H,

2CH^Ar), 7.29 (m, 3H, 3CH^Ar), 7.10 (m, 2H, 2CH^Ar), 7.01 (d,

1H, J = 6.8 Hz, CH^Ar); ¹³C NMR (75 MHz, CDCl₃, 25 ºC)

: 177.2 (N=C), 153.3 (C^Ar-q), 139.7 (C^Ar-q), 138.3 (C^Ar-q),

131.9 (2CH^Ar), 130.2 (CH^Ar), 130.1 (C^Ar-q), 129.9 (2CH^Ar),

127.2 (CH^Ar), 126.4 (C^Ar-q), 126.2 (2CH^Ar), 123.4 (CH^Ar),

121.7 (C^Ar-q), 121.6 (CH^Ar), 92.9 (OC^q); D(²H) NMR (107

IR (CHCl₃, cm^–1): 1737 (C=O); HRMS (ES): calcd for

C₂₁H₁₁Br₂FO₂[M + H]⁺: 472.9183; found: 472.9192.

3,4-Diaryl-benzosultam 13e. From 26 mg (0.10 mmol) of

TMS-alkyne 11-Si, and after chromatography of the residue

using hexanes/ethyl acetate (8:2) as eluent, gave compound

1

13e (28 mg, 68%) as a colorless oil; H NMR (300 MHz,

o

MHz, CDCl₃, 25 C) : 3.04; IR (CHCl₃, cm^–1):  1723

CDCl₃, 25 C) δ: 8.00–7.96 (m, 1H, CH^Ar), 7.55–7.53 (m,

(N=C), 1076 (C-O); HRMS (ES): calcd for C₂₁H₁₃D₃Br₂NO

2H, 2CH^Ar), 7.30–7.28 (m, 3H, 3CH^Ar), 7.24–7.22 (m, 4H,

[M + H]⁺: 458.9782; found: 458.9784.

2CH^Ar), 7.15 (d, 2H, J = 7.9 Hz, 2CH^Ar), 2.99 (s, CH₃); ¹³

C

NMR (75 MHz, CDCl₃, 25 ºC) : 140.0 (C^Ar-q), 134.9 (C^Ar-

^q), 134.1 (C^Ar-q), 133.6 (C^Ar-q), 133.4 (C^Ar-q), 132.5 (2CH^Ar),

132.3 (C^Ar-q), 131.8 (CH^Ar), 131.6 (C^Ar-q), 131.3 (2CH^Ar),

128.6 (2CH^Ar), 128.5 (2CH^Ar), 128.2 (CH^Ar), 127.0 (CH^Ar),

123.4 (C^Ar-q), 122.0 (CH^Ar), 34.5 (CH₃); IR (CHCl₃, cm^–1):

1588 (C=C), 1485, 1337 (O=S=O); HRMS (ES): calcd for

C₂₁H₁₆Cl₂NO₂S [M + H]⁺: 416.0273; found: 416.0277.

3,4-Diaryl-isocoumarin 12ad. From 40 mg (0.18 mmol) of

TMS-alkyne 10a-Si, and after chromatography of the

residue using hexanes/ethyl acetate (95:5) as eluent, gave

compound 12ad (41 mg, 70%) as a colorless solid; m.p.

165–167 ºC; ¹H NMR (300 MHz, CDCl₃, 25 ^oC) δ: 8.39 (d,

1H, J = 7.8 Hz, CH^Ar), 7.62 (m, 1H, CH^Ar), 7.50 (t, 1H,

CH^Ar), 7.19 (m, 7H, 7CH^Ar), 7.01 (m, 2H, 2CH^Ar), 2.43 (s,

3H, CH₃), 2.30 (s, 3H, CH₃); ¹³C NMR (75 MHz, CDCl₃, 25

ºC) : 162.4 (C=O), 150.9 (C=C), 139.2 (C^Ar-q), 139.0 (C^Ar-

^q), 137.8 (C^Ar-q), 134.5 (CH^Ar), 131.4 (C^Ar-q), 131.0 (2CH^Ar),

130.1 (C^Ar-q), 129.8 (2CH^Ar), 129.4 (CH^Ar), 129.0 (2CH^Ar),

128.6 (2CH^Ar), 127.8 (CH^Ar), 125.3 (CH^Ar), 120.3 (C^Ar-q),

116.3 (C=C), 21.3 (CH₃), 21.2 (CH₃); IR (CHCl₃, cm^–1):

1715 (C=O); HRMS (ES): calcd for C₂₃H₁₉O₂[M + H]⁺:

327.1380; found: 327.1388.

3,4-Diaryl-benzosultam 13g. From 26 mg (0.10 mmol) of

TMS-alkyne 11-Si, and after chromatography of the residue

using hexanes/ethyl acetate (8:2) as eluent, gave compound

1

13g (25 mg, 66%) as a colorless oil; H NMR (300 MHz,

o

CDCl₃, 25 C) δ: 7.92–7.89 (m, 1H, CH^Ar), 7.48–7.46 (m,

2H, 2CH^Ar), 7.31–7.25 (m, 3H, 3CH^Ar), 7.20–7.05 (m, 2H,

2CH^Ar), 7.02–6.91 (m, 4H, 4CH^Ar), 2.94 (s, CH₃); ¹³C NMR

(75 MHz, CDCl₃, 25 ºC) : 162.5 (d, 1H, J_CF= 250.0 Hz,

C^Ar-q-F), 162.0 (d, 1H, J_CF= 250.0 Hz, C^Ar-q-F), 140.3 (C^Ar-

^q), 133.7 (C^Ar-q), 132.9 162.0 (d, 2H, J_CF= 8.3 Hz, 2CH^Ar),

131.9 (d, 2H, J_CF= 8.3 Hz, 2CH^Ar), 131.8 (CH^Ar), 131.6

(C^Ar-q), 131.5 (C^Ar-q), 130.0 (C^Ar-q), 128.0 (CH^Ar), 127.0

(CH^Ar), 123.4 (C^Ar-q), 121.9 (CH^Ar), 115.2 (d, 4H, J_CF= 22.3

Hz, 4CH^Ar), 34.4 (s, CH₃); ¹⁹F NMR (282 MHz, CDCl₃, 25

^oC): –111.4 (s, 1F, C–F), –114.3 (s, 1F, C–F); IR (CHCl₃,

cm^–1): 1585 (C=C), 1487, 1335 (O=S=O); HRMS (ES):

calcd for C₂₁H₁₆F₂NO₂S [M + H]⁺: 384.0864; found:

384.0860.

3,4-Diaryl-isocoumarin 12af. From 35 mg (0.15 mmol) of

TMS-alkyne 10a-Si, and after chromatography of the

residue using hexanes/ethyl acetate (95:5) as eluent, gave

compound 12af (44 mg, 68%) as a colorless solid; m.p. 155–

157 ºC; ¹H NMR (300 MHz, CDCl₃, 25 ^oC) δ: 8.45 (dd, 1H,

J = 7.9, 1.3 Hz, CH^Ar), 7.71 (m, 3H, 3CH^Ar), 7.60 (m, 1H,

CH^Ar), 7.50 (m, 2H, 2CH^Ar), 7.43 (m, 4H, 4CH^Ar), 7.13 (d,

1H, J = 7.8 Hz, CH^Ar); ¹³C NMR (75 MHz, CDCl₃, 25 ºC)

: 161.4 (C=O), 149.7 (C=C), 137.7 (d, J_CF= 1.3 Hz, C^Ar-q),

7

10.1002/adsc.201700427

Advanced Synthesis & Catalysis

General procedure for the photopromoted gold-

catalyzed cross double arylation reaction of TMS-

(ethynyl)azidobenzene 4a-Si with diazonium salts 2.

Preparation of crossed-3-methoxy-2,3-diaryl-3H-indoles

6aag–6aeb. In a Schlenk tube in the absence of light at –78

ºC under argon atmosphere, Ph₃PAuCl (5 mol %) and

[Ru(bpy)_3](PF₆)₂(2.5 mol %) were sequentially added to a

solution of the first arene diazonium salt 2 (1.5 equiv) in a

mixture of MeOH/MeCN (3:1, 4.0 mL). Then, a solution of

the 2-[(trimethylsilyl)ethynyl]azidobenzene 4a-Si (1.0

mmol) in MeOH/MeCN (3:1, 1.5 mL) was added dropwise

and the reaction was stirred at –78 ºC for 5 min. The reaction

mixture was then warmed to room temperature and stirred

under irradiation from visible light source (21 W fluorescent

light bulb installed in a tool box). After disappearance of the

starting material (TLC, 20–30 min), Ph₃PAuCl (5 mol %)

and a solution of the second arene diazonium salt 2 (6.0

equiv) in a mixture of MeOH/MeCN (3:1, 2.5 mL) were

sequentially added. The resulting reaction mixture was

stirred at rt under irradiation from visible light source (21 W

fluorescent light bulb installed in a tool box). After

disappearance of the starting material (TLC), the reaction

mixture was concentrated under reduced pressure.

Chromatography of the residue using hexanes/ethyl acetate

or hexanes/toluene mixtures gave analytically pure

compounds. The addition of Et₃N (2%) to the eluent was

neccesary for the purification of acid sensitive 3H-indoles 6.

Spectroscopic and analytical data for pure forms of crossed

adducts 6 follow.

General

procedure

for

the

base-catalyzed

rearrangement reaction of 3-methoxy-2,3-diaryl-3H-

indoles 6. Preparation of 2,3-diaryl-1H-indoles 5. A

solution of the corresponding 3H-indole 6 (1 mmol) in

ethanolic potash (115 mL, KOH 1 M in EtOH) was stirred

under microwave heating (105 ºC) until the complete

disappearance of the starting material (TLC, typically 12 h).

After this time, the reaction was cooled down to 0 ºC and

neutralized with HCl (3 M) until pH 7. The aqueous phase

was extracted with EtOAc (3 × 20 mL), the organic phases

combined, dried over MgSO₄and the solvent removed by

distillation under reduced pressure. Chromatography of the

residue eluting with ethyl acetate/hexanes mixtures gave

analytically pure adducts 5.

2,3-Diaryl-1H-indole 5ab. From 20 mg (0.043 mmol) of

3H-indole 6ab, and after chromatography of the residue

using hexanes/DCM (8:2) as eluent, gave compound 5ab

(13 mg, 71%) as a colorless solid; m.p. 175-177 ºC; H

NMR (300 MHz, CDCl₃, 25 C) : 8.21 (s, 1H, NH), 7.62

1

o

(d, 1H, J = 7.9 Hz, CH^Ar), 7.47 (m, 5H, 5CH^Ar), 7.27 (m,

5H, 5CH^Ar), 7.17 (m, 1H, CH^Ar); ¹³C NMR (75 MHz, CDCl₃,

25 ºC) : 135.9 (C^Ar-q), 133.7 (C^Ar-q), 133.0 (C^Ar-q), 132.0

(2CH^Ar), 131.8 (2CH^Ar), 131.6 (2CH^Ar), 131.2 (C^Ar-q), 129.6

(2CH^Ar), 128.3 (C^Ar-q), 123.2 (CH^Ar), 122.1 (C^Ar-q), 120.8

(CH^Ar), 120.4 (C^Ar-q), 119.4 (CH^Ar), 114.3 (C^Ar-q), 111.0

(CH^Ar); IR (CHCl₃, cm^–1):  3417 (N-H); HRMS (ES): calcd

for C₂₀H₁₄Br₂N [M + H]⁺: 425.9487; found: 425.9484.

General

procedure

for

the

acid-catalyzed

3-Methoxy-2,3-diaryl-3H-indole 6abe. From 30 mg (0.14

mmol) of TMS-azide 4a-Si, and after chromatography of the

residue using hexanes/Et₂O (97:3) containing NEt₃(2%) as

eluent, gave compound 6abe (35 mg, 61%) as a yellow oil;

¹H NMR (300 MHz, CDCl₃, 25 ^oC) : 7.99 (m, 2H, 2CH^Ar),

7.59 (d, 1H, J = 7.7 Hz, CH^Ar), 7.42 (m, 2H, 2CH^Ar), 7.32

(td, 1H, J = 7.6, 1.3 Hz, CH^Ar), 7.15 (m, 5H, 5CH^Ar), 7.02

(d, 1H, J = 7.3 Hz, CH^Ar), 2.98 (s, 3H, OCH₃); ¹³C NMR

(75 MHz, CDCl₃, 25 ºC) : 177.3 (N=C), 153.3 (C^Ar-q),

139.8 (C^Ar-q), 137.7 (C^Ar-q), 133.5 (C^Ar-q), 131.9 (2CH^Ar),

130.1 (CH^Ar), 130.0 (C^Ar-q), 129.9 (2CH^Ar), 129.0 (CH^Ar),

127.2 (CH^Ar), 126.3 (C^Ar-q), 125.9 (2CH^Ar), 123.4 (CH^Ar),

121.6 (CH^Ar), 92.9 (OC^q), 52.6 (OCH₃); IR (CHCl₃, cm^–1):

 1693 (N=C), 1085 (C-O); HRMS (ES): calcd for

C₂₁H₁₆BrClNO [M + H]⁺: 412.0098; found: 412.0115.

rearrangement reaction of 3-methoxy-2,3-diaryl-3H-

indoles 6. Preparation of 2-oxindoles 8. A solution of the

corresponding 3H-indole 6 (1 mmol) in ethanolic sulfuric

acid (115 mL, H₂SO₄0.4 M in EtOH) was stirred under

microwave heating (125 ºC) until the complete

disappearance of the starting material (TLC, typically 12 h).

After this time, the reaction was cooled down to 0 ºC and

neutralized with NaHCO₃(aqueous saturated solution) until

pH 7. The aqueous phase was extracted with EtOAc (3 × 10

mL), the organic phases combined, dried over MgSO₄and

the solvent removed by distillation under reduced pressure.

Chromatography of the residue eluting with ethyl

acetate/hexanes mixtures gave analytically pure adducts 8.

3,3-Diaryl-2-oxindole 8ab. From 20 mg (0.043 mmol) of

3H-indole 6ab, and after chromatography of the residue

using hexanes/AcOEt (97:3 → 80:20) as eluent, gave

3-Methoxy-2,3-diaryl-3H-indole 6aeb. From 30 mg (0.14

mmol) of TMS-azide 4a-Si, and after chromatography of the

residue using hexanes/Et₂O (97:3) containing NEt₃(2%) as

eluent, gave compound 6aeb (33 mg, 57%) as a yellow oil;

¹H NMR (300 MHz, CDCl₃, 25 ^oC) : 8.04 (m, 2H, 2CH^Ar),

7.38 (d, 1H, J = 7.7 Hz, CH^Ar), 7.38 (m, 5H, 5CH^Ar), 7.21

(m, 3H, 3CH^Ar), 7.11 (d, 1H, J = 7.3 Hz, CH^Ar), 3.07 (s, 3H,

OCH₃); ¹³C NMR (75 MHz, CDCl₃, 25 ºC) : 177.1 (N=C),

153.3 (C^Ar-q), 139.7 (C^Ar-q), 138.3 (C^Ar-q), 137.7 (C^Ar-q),

131.9 (2CH^Ar), 130.1 (CH^Ar), 129.7 (2CH^Ar), 129.6 (C^Ar-q),

128.9 (2CH^Ar), 127.1 (CH^Ar), 126.2 (2CH^Ar), 123.4 (CH^Ar),

121.6 (C^Ar-q), 121.5 (CH^Ar), 92.9 (OC^q), 52.6 (OCH₃).; IR

(CHCl₃, cm^–1):  1726 (N=C), 1087 (C-O); HRMS (ES):

calcd for C₂₁H₁₆BrClNO [M + H]⁺: 412.0098; found:

412.0087.

1

compound 8ab (14 mg, 72%) as a colorless oil; H NMR

(500 MHz, CDCl₃, 25 ^oC) : 8.48 (s, 1H, NH), 7.44 (m, 4H,

4CH^Ar), 7.28 (t, 1H, J = 7.6 Hz, CH^Ar), 7.16 (m, 5H, 5CH^Ar),

7.09 (t, 1H, J = 7.6 Hz, CH^Ar), 6.98 (d, 1H, J = 7.8 Hz,

CH^Ar). ¹³C NMR (125 MHz, CDCl₃, 25 ºC) : 178.8 (C=O),

140.2 (2C^Ar-q), 139.9 (C^Ar-q), 132.4 (C^Ar-q), 131.7 (4CH^Ar),

130.1 (4CH^Ar), 128.8 (CH^Ar), 126.1 (CH^Ar), 123.2 (CH^Ar),

121.9 (2C^Ar-q), 110.5 (CH^Ar), 61.0 (C^q-C=O). IR (CHCl₃,

cm^–1): 3222 (N-H), 1711 (C=O); HRMS (ES): calcd for

C₂₀H₁₄Br₂NO [M + H]⁺: 441.9437; found: 441.9446.

General

procedure

for

the

acid-catalyzed

rearrangement reaction of 3-methoxy-2,3-diaryl-3H-

indoles 6. Preparation of 3-oxindolines 9. A solution of

the corresponding 3H-indole 6 (1 mmol) in ethanolic

8

10.1002/adsc.201700427

Advanced Synthesis & Catalysis

sulfuric acid (115 mL, H₂SO₄0.2 M in EtOH) was stirred

under microwave heating (95 ºC) until the complete

disappearance of the starting material (TLC, typically 12 h).

After this time, the reaction was cooled down to 0 ºC and

neutralized with NaHCO₃(aqueous saturated solution) until

pH 7. The aqueous phase was extracted with EtOAc (3 × 10

mL), the organic phases combined, dried over MgSO₄and

the solvent removed by distillation under reduced pressure.

Chromatography of the residue eluting with ethyl

acetate/hexanes mixtures gave analytically pure adducts 9

along with compounds 8 as minor components.

(CH₃); IR (CHCl₃, cm^–1): 1712 (C=O), 1639 (C=O), 1270;

HRMS (ES): calcd for C₂₄H₁₉O₄[M + H]⁺: 371.1278; found:

371.12826.

3-Aryl-flavone 15f. From 21 mg (0.10 mmol) of aryl-

terminated alkynone 14-Ph, and after chromatography of

the residue using hexanes/ethyl acetate (95:5) as eluent,

gave compound 15f (25 mg, 69%) as a colorless solid; m.p.

144–145 ºC; ¹H NMR (500 MHz, CDCl₃, 25 ^oC) δ: 8.31 (dd,

1H, J = 7.6 Hz, J = 1.5 Hz, CH^Ar), 7.76–7.73 (m, 2H,

2CH^Ar), 7.57 (d, 1H, J = 8.6 Hz, CH^Ar), 7.49–7.46 (m, 1H,

1CH^Ar), 7.40–7.31 (m, 5H, 5CH^Ar); ¹³C NMR (125 MHz,

CDCl₃, 25 ºC) : 176.8 (C=O), 162.1 (C=C), 159.0 (C^Ar-q),

136.8 (C^Ar-q), 134.0 (CH^Ar), 131.7 (2CH^Ar), 130.5 (CH^Ar),

129.5 (2CH^Ar), 129.6 (q, J_CF= 32.0 Hz, C^Ar-q), 128.3

(2CH^Ar), 126.5 (CH^Ar), 125.4 (CH^Ar), 125.4 (q, J_CF= 4.3

Hz, 2CH^Ar), 124.1 (q, J_CF= 272.0 Hz, CF₃), 123.3 (C^Ar-q),

121.7 (C^Ar-q), 118.0(CH^Ar); ¹⁹F NMR (282 MHz, CDCl₃, 25

^oC): –62.9 (s, 3F, CF₃); IR (CHCl₃, cm^–1): 1638 (C=O),

1377; HRMS (ES): calcd for C₂₂H₁₄F₃O₂[M + H]⁺:

367.0904; found: 367.0947.

2,2-Diaryl-3-oxindoline 9ab. From 20 mg (0.043 mmol) of

3H-indole 6ab, and after chromatography of the residue

using hexanes:AcOEt (97:3) as eluent, gave compound 9ab

1

(10 mg, 51%) yellow oil; H NMR (500 MHz, CDCl₃, 25

^oC) : 7.66 (d, 1H, J = 7.7 Hz, CH^Ar), 7.53 (t, 1H, J = 7.7

Hz, CH^Ar), 7.46 (m, 4H, 4CH^Ar), 7.25 (m, 4H, 4CH^Ar), 6.94

(m, 2H, 2CH^Ar), 5.09 (s, 1H, NH). ¹³C NMR (125 MHz,

CDCl₃, 25 ºC) : 199.8 (C=O), 159.9 (C^Ar-q), 139.7 (2C^Ar-q),

138.0 (CH^Ar), 131.8 (4CH^Ar), 129.1 (4CH^Ar), 125.6 (CH^Ar),

122.4 (2C^Ar-q), 120.3 (CH^Ar), 119.8 (C^Ar-q), 112.7 (CH^Ar),

74.0 (NC^q). IR (CHCl₃, cm^–1): 3450 (N-H), 1686

(C=O)HRMS (ES): calcd for C₂₀H₁₄Br₂NO [M + H]⁺:

441.9437; found: 441.9453.

3-Aryl-thioflavone 17b. From 35 mg (0.14 mmol) of aryl-

terminated alkynone 16-Ph, and after chromatography of

the residue using hexanes/ethyl acetate (95:5) as eluent,

gave compound 17b (33 mg, 61%) as a colorless solid; m.p.

155–157 ºC; ¹H NMR (300 MHz, CDCl₃, 25 ^oC) δ: 8.50 (d,

1H, J = 7.7 Hz, CH^Ar), 7.52 (m, 3H, 3CH^Ar), 7.20 (m, 7H,

7CH^Ar), 6.91 (m, 2H, 2CH^Ar); ¹³C NMR (75 MHz, CDCl₃,

25 ºC) : 179.2 (C=O), 150.8 (C=C), 137.2 (C^Ar-q), 136.6

(C^Ar-q), 134.5 (C^Ar-q), 134.4 (C=C), 132.8 (2CH^Ar), 131.6

(CH^Ar), 131.1 (C^Ar-q), 130.9 (2CH^Ar), 129.5 (CH^Ar), 129.3

(CH^Ar), 129.2 (2CH^Ar), 128.5 (2CH^Ar), 127.8 (CH^Ar), 125.8

(CH^Ar), 121.4 (C^Ar-q); IR (CHCl₃, cm^–1): 1617 (C=O),

1589 (C=C); HRMS (ES): calcd for C₂₁H₁₄BrOS [M + H]⁺:

392.9943; found: 392.9935.

General procedure for the photopromoted gold-

catalyzed monoarylation reaction of aryl-terminated

alkynones 14-Ph or 16-Ph with diazonium salts 2.

Preparation of 3-aryl-flavones 15 and 3-aryl-

thioflavones 17. In a Schlenk tube in the absence of light at

–78 ºC under argon atmosphere, Ph₃PAuCl (10 mol %) and

[Ru(bpy)_3](PF₆)₂(2.5 mol %) were sequentially added to a

solution of the corresponding arene diazonium salt 2 (3.0

equiv) in a mixture of MeOH/MeCN (3:1, 3 mL). Then, a

solution of the appropriate aryl-terminated alkynone 14-Ph

or 16-Ph (1.0 mmol) in MeOH/MeCN (3:1, 2.5 mL) was

added dropwise and the reaction was stirred at –78 ºC for 5

min. The reaction mixture was then warmed to room

temperature and stirred under irradiation from visible light

source (21 W fluorescent light bulb installed in a tool box).

After disappearance of the starting material (TLC), the

reaction mixture was concentrated under reduced pressure.

Chromatography of the residue using hexanes/ethyl acetate

or hexanes/toluene mixtures gave analytically pure

compounds. Spectroscopic and analytical data for pure

forms of compounds 15 and 17 follow.

3-Aryl-thioflavone 17e. From 31 mg (0.12 mmol) of aryl-

terminated alkynone 16-Ph, and after chromatography of

the residue using hexanes/ethyl acetate (95:5) as eluent,

gave compound 17e (28 mg, 68%) as a colorless solid; m.p.

154–156 ºC; ¹H NMR (500 MHz, CDCl₃, 25 ^oC) δ: 8.58 (d,

1H, J = 7.8 Hz, CH^Ar), 7.62 (m, 3H, 3CH^Ar), 7.28 (m, 3H,

3CH^Ar), 7.21 (m, 4H, 4CH^Ar), 7.05 (2CH^Ar); ¹³C NMR (125

MHz, CDCl₃, 25 ºC) : 179.3 (C=O), 150.8 (C=C), 137.2

(C^Ar-q), 136.6 (C^Ar-q), 134.4 (C^Ar-q), 134.0 (C=C), 133.1 (C^Ar-

^q), 132.5 (2CH^Ar), 131.6 (CH^Ar), 131.2 (C^Ar-q), 129.6 (CH^Ar),

129.3 (CH^Ar), 129.2 (2CH^Ar), 128.5 (2CH^Ar), 128.0 (2CH^Ar),

127.8 (CH^Ar), 125.8 (CH^Ar); IR (CHCl₃, cm^–1): 1617

(C=O), 1588 (C=C); HRMS (ES): calcd for C₂₁H₁₃ClOS [M

+ H]⁺: 349.0448; found: 349.0457.

3-Aryl-flavone 15c. From 21 mg (0.10 mmol) of aryl-

terminated alkynone 14-Ph, and after chromatography of

the residue using hexanes/ethyl acetate (95:5) as eluent,

gave compound 15c (24 mg, 66%) as a colorless solid; m.p.

127–129 ºC; ¹H NMR (300 MHz, CDCl₃, 25 ^oC) δ: 8.32 (dd,

1H, J = 7.6 Hz, J = 1.5 Hz, CH^Ar), 8.00 (d, 2H, J = 8.3 Hz,

2CH^Ar), 7.77–7.71 (m, 1H, 1CH^Ar), 7.56 (d, 1H, J = 8.6 Hz,

1CH^Ar), 7.49–7.27 (m, 8H, 8CH^Ar), 4.38 (q, 2H, J = 6.5 Hz,

CH₂), 1.40 (t, 3H, J = 6.5 Hz, CH₃); ¹³C NMR (75 MHz,

CDCl₃, 25 ºC) : 176.8 (C=O), 166.4 (C=O), 161.8 (C=C),

155.9 (C^Ar-q), 137.8 (C^Ar-q), 133.8 (CH^Ar), 132.8 (C^Ar-q),

131.3 (2CH^Ar), 130.3 (CH^Ar), 129.5 (2CH^Ar), 129.4 (C^Ar-q),

129.3 (2CH^Ar), 128.2 (2CH^Ar), 126.3 (CH^Ar), 125.2 (CH^Ar),

123.3 (C^Ar-q), 122.1 (C^Ar-q), 118.0 (CH^Ar), 60.9 (CH₂), 14.3

Acknowledgements

Financial support from the MINECO and FEDER (Projects

CTQ2015-65060-C2-1-P and CTQ2015-65060-C2-2-P) is

gratefully acknowledged. F. H. and C. L.-M. thank UCM and

MINECO, respectively, for predoctoral contracts. E. B. thanks

MINECO for a postdoctoral contract. We thank Imanol Burgos for

preliminary studies.

9

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Advanced Synthesis & Catalysis

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[16] Experimental procedures as well as full spectroscopic

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Experimental Section are described in the Supporting

Information. It contains compound characterization data,

experimental procedures, and copies of NMR spectra for

all new compounds.

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Advanced Synthesis & Catalysis

FULL PAPER

Photopromoted Entry to Benzothiophenes,

Benzoselenophenes, 3H-Indoles, Isocoumarins,

Benzosultams, and (Thio)Flavones by Gold-

Catalyzed Arylative Heterocyclization of Alkynes

Adv. Synth. Catal. 2017, 359, Page – Page

Benito Alcaide,* Pedro Almendros,* Eduardo

Busto, Fernando Herrera, Carlos Lázaro-Milla, and

Amparo Luna

12

Article Doi

Photopromoted Entry to Benzothiophenes, Benzoselenophenes, 3H-Indoles, Isocoumarins, Benzosultams, and (Thio)flavones by Gold-Catalyzed Arylative Heterocyclization of Alkynes

DOI: 10.1002/adsc.201700427

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