Synthesis of carbazoles and 1,2-dihydrocarbazoles by domino 'twofold Heck/6π-electrocyclization' reactions of di-, tri- and tetrabromoindoles

Tetrahedron 67 (20 1 1 ) 5304e5318

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Tetrahedron

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Synthesis of carbazoles and 1,2-dihydrocarbazoles by domino ‘twofold

Heck/6p-electrocyclization’ reactions of di-, tri- and tetrabromoindoles

a

a,

b

a

ꢀ

ꢁ

Munawar Hussain , Serge-Mitherand Tengho Toguem , Rasheed Ahmad , Ðặng Thanh Tung ,

Ingo Knepper ^a, Alexander Villinger ^a, Peter Langer ^a

,c,

*

a

€

Institut fur Chemie, Universitat Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany

^bDepartment of Petroleum Technology, University of Karachi, University Road, Karachi 75270, Pakistan

c

€

Leibniz-Institut fur Katalyse e. V. an der Universitat Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany

a r t i c l e i n f o

a b s t r a c t

Article history:

Di-, tri- and tetra-alkenylindoles were prepared by palladium(0)-catalyzed Heck cross-coupling reactions

of di-, tri- and tetrabromo-N-methylindoles. The reactions were carried out at 90 ^ꢀC using a novel biaryl

monophosphine ligand developed by Buchwald and co-workers. 1,2-Dihydrocarbazoles were formed by

Received 18 March 2011

Received in revised form 3 May 2011

Accepted 5 May 2011

a domino ‘twofold Heck/6p-electrocyclization’ when the reaction was carried out at higher temperature.

Available online 14 May 2011

The regioselectivity of the Heck reaction of 2,3,6-tribromo-N-methylindoles was in favour of carbon

atoms C-2 and C-3. The 1,2-dihydrocarbazoles were transformed, by Pd/C-catalyzed dehydrogenation,

into the corresponding carbazoles in high yield.

Keywords:

Carbazoles

Catalysis

Cyclizations

Indoles

Heck reaction

Palladium

1. Introduction

A number of synthetic approaches to carbazoles have been

reported. In recent years, transition metal catalyzed reactions have

Carbazole is a natural product isolated for the ﬁrst time from

coal tar in 1872 by Graebe and Glaser. Carbazole derivatives are of

signiﬁcant pharmacological relevance because of their antifungal,

antibiotic and antitumour activities. Simple carbazole alkaloids

were isolated in the 1960s as natural products from plant sources.

Murrayafoline A and murrayaquinone B are examples of naturally

occurring carbazoles and carbazolequinones isolated from the root

bark of Murraya euchrestifolia Hayata (Fig. 1).^1,2

been extensively used for the synthesis of carbazoles. For example,

a general approach to carbazoles relies on iron-mediated cycliza-

tion reactions (stoichiometric use of iron complexes).^1dLater,

a catalytic approach to carbazoles has been developed, which is

based on BuchwaldeHartwig reactions of aryl halides with anilines

and subsequent oxidative cyclizations.³Carbazoles have been also

prepared by palladium-catalyzed cyclization of anilines with

1,2-dihaloalkenes,

a domino reactions recently developed by

Ackermann and Althammer.⁴Classic syntheses of carbazoles in-

clude, for example, DielseAlder reactions of 2- or 3-vinylindoles

with various dienophiles.⁵Carbazoles have also been prepared by

O

Me

thermal

6p-electrocyclization reactions of 2,3-di(alkenyl)in-

MeO

doles.^6,7The scope of this method was severely limited by the fact

that the synthesis of the precursors, 2,3-di(alkenyl)indoles, was

complicated and required many steps. Acceptor-substituted 2,3-

di(alkenyl)indoles were prepared by Pd(II)-catalyzed reactions of

carbon atom C-3 of 2-formylindoles with alkenes to form 2-formyl-

3-vinylindoles. The aldehyde group was subsequently transformed

into an alkenyl group by means of a Wittig reaction. Attempts to

prepare 2,3-di(alkenyl)indoles by double Wittig reaction of 2,3-

diformyl-N-methylindole proved to be unsuccessful, due to the

unstable nature of the bis-aldehyde and low yields.

N

H

O

N

H

OMe

Murrayaquinone B

Murrayafoline A

Fig. 1. Carbazoles isolated from the root bark of Murraya euchrestifolia Hayata.

* Corresponding author. Fax: þ49 381 4986412; e-mail address: peter.langer@

uni-rostock.de (P. Langer).

doi:10.1016/j.tet.2011.05.014

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

5305

De Meijere and co-workers described an efﬁcient annulations

DMF at 90 ^ꢀC for 36 h. Recently, Li and Wang reported¹⁶that trie-

thanolamine represents an efﬁcient and reusable combined base,

ligand, and solvent for palladium(0)-catalyzed Heck reactions. The

application of these conditions to the reaction of 2a with acrylate

3g proved to be successful and resulted in the formation of 4g in

63% yield.

process based on twofold Heck reactions of 1,2-dibromocycloalk-1-

enes and subsequent 6p

-electrocyclizations.⁸In recent years, we

have applied this approach to a variety of heterocyclic substrates.⁹

Recently, we have reported preliminary results related to the syn-

thesis of carbazoles by domino twofold Heck/electrocyclization/

dehydrogenation reactions.^9aHerein, we wish to report full details

and a signiﬁcant extension of the preparative scope. With regard to

our preliminary communication, we also report, for the ﬁrst time,

Heck reactions of 2,3,5,6-tetrabromo-N-methylindole. Bis-

Sonogashira reactions proved to be not general, due to the highly

unstable nature of the 2,3-bis(alkynyl)indoles. The chemistry

reported herein is of considerable synthetic usefulness because

positions 2 and 3 of the carbazole system cannot be directly

accessed by functionalization reactions of carbazole derivatives. In

fact, the substituted carbazole derivatives reported herein are not

readily available by other methods.

CO₂R

N

i or ii

Br

Me

4a,c-g

CO₂R

3a-h

Br

CO₂R

N

Me

2a

iii

N

2. Results and discussion

Me

5a-d,f

Our starting point was the synthesis of various brominated in-

dole derivatives. The reaction of N-methylindole (1) with copper(II)

bromide has been reported to afford 2,3-dibromo-N-methylindole

(2a) in 64% yield.¹⁰We were able to increase the yield of 2a to 90%

by reaction of N-methylindole (1) with NBS (2.1 equiv) in THF

(ꢁ78 ^ꢀC, 4 h) (Scheme 1). During the optimization, it proved to be

important to add NBS portionwise. Dibromide 2a and 2,3,6-

tribromo-N-methylindole (2b) are natural products^11e14and 2a

has been previously converted into 2b by bromination (Br₂, CHCl₃)

in 70e80% yield.¹⁴Our goal was to develop a direct synthesis of 2b.

After some experimentation, we have found that 2b can be pre-

pared in 94% yield by reaction of 1 with NBS (3.1 equiv) in THF

(ꢁ78 ^ꢀC, 4 h). During the optimization, it proved to be mandatory to

carry out the reaction at low temperature and to add NBS in small

portions. A complex mixture was obtained when NBS was added at

room temperature. The reaction of 1 with NBS (5.0 equiv) in THF

(ꢁ78 ^ꢀC, 1 h, then reﬂux for 4 h) afforded 2,3,5,6-tetrabromo-N-

methylindole (2c) in 78% yield.

Scheme 2. Synthesis of 4bee and 5aed,f. Conditions: i, for 4bee: Pd(OAc)₂(5 mol %),

SPhos (10 mol %), NEt₃, DMF, 90 ^ꢀC, 36 h; ii, for 4e: Pd(OAc)₂(5 mol %), N(CH₂CH₂OH)₃

(3 mL), 90 ^ꢀC, 36 h; iii, Pd(OAc)₂(5 mol %), SPhos (10 mol %), NEt₃(8.0 equiv), DMF,

120 ^ꢀC, 48 h.

Table 1

Optimization of the reaction conditions for the synthesis of 4c,f

Entry Catalyst

Temp % (4c)^a

(^ꢀC)

% (4f)^a

1

Pd(PPh₃)₄(5 mol %)

90

Complex Complex

mixture

65

mixture

71

2

3

4

5

Pd(OAc)₂(5 mol %), XPhos (10 mol %)

Pd(OAc)₂(5 mol %), SPhos (10 mol %)

Pd(OAc)₂(3 mol %), SPhos (6 mol %)

90

100

90

72

78

d^b

Complex Complex

mixture

6

7

Pd(OAc)₂(2 mol %), SPhos (4 mol %)

100

120

d^c

5c (77%)

5f (85%)

a

Yields of isolated products; all reactions were carried out in DMF using NEt₃as

base (36 h).

b

Mixture of 4c,f and 5c,f, respectively (TLC).

Approx. 50% conversion (estimated by TLC).

Br

c

i

Br

Table 2

N

Synthesis of 4a,ceg and 5aec,e,f,h

Me

2a (90%)

1

4,5

3

R

% (4)^a

%(5)^a

a

b

c

d

e

f

a

b

c

d

e

f

Me

77

d^b

72

d^b

77

78

76

d^b

69

93

77

66

81

85

d^b

79

iii

ii

Et

ⁿBu

ⁱBu

ⁿHex

^tBu

Br

g

h

g

h

ⁱOct

Br

(CH₂)₂NMe₂

N

Me

Br

a

Yields of isolated products based on 2a.

Experiment was not carried out.

b

Me

2b (94%)

2c (78%)

Scheme 1. Bromination of N-methylindole (1); conditions: i, NBS (2.1 equiv), THF,

ꢁ78 ^ꢀC, 4 h; ii, NBS (3.1 equiv), THF, ꢁ78 ^ꢀC, 4 h, then 20 ^ꢀC, 14 h; iii, NBS (5.0 equiv),

THF, ꢁ78 ^ꢀC, 1 h, then reﬂux, 4 h.

PCy₂

iPr

PCy₂

iPr

MeO

OMe

The Heck reaction of 2a with acrylates 3a,ceg afforded the 2,3-

di(alkenyl)indoles 4a,ceg in good yields (Scheme 2, Tables 1 and 2).

The best yields were obtained when the reactions were carried out

using Pd(OAc)₂(5 mol %) and SPhos (10 mol %) developed by

Buchwald and Billingsley (Fig. 2).¹⁵Lower catalyst loading resulted

in complex mixtures (Table 1). The reactions were carried out in

iPr

₂= XPhos

L₁= SPhos

L

Fig. 2. Structures of ligands (L) SPhos and XPhos.

5306

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

When the reaction of 2a with acrylates 3aec,e,f,h was carried

out at 120 ^ꢀC instead of 90 ^ꢀC, the 1,2-dihydrocarbazoles 5aec,e,f,h

were formed by a domino ‘twofold Heck/6 -electrocyclization’

p

cyclization. The initially formed 2,3-dihydrocarbazoles undergo

a sigmatropic rearrangement into the more stable 1,2-dihydro

carbazoles. The structure of 5b was independently conﬁrmed by

an X-ray crystal structure analysis (Fig. 3).¹⁷

Fig. 4. Crystal structure of 6a.

(intermediate B), base-mediated conjugate addition to give in-

termediate C, and subsequent aromatization by elimination of HCN.

The structure of 7 was independently conﬁrmed by X-ray crystal

structure analysis (Fig. 5).

CN

Br

Fig. 3. Ortep plot of 5f.

CN

Br

N

Me

i

N

Me

The dehydrogenation of 1,2-dihydrocarbazoles to carbazoles

was next studied. Pindur reported the synthesis of 2,3-

di(methoxycarbonyl)-N-phenylsulfonylcarbazole by reaction of

the corresponding 1,2-dihydrocarbazole with DDQ, albeit, in only

18% yield.⁵We have obtained equally disappointing results. The

reaction of 1,2-dihydrocarbazole 5b with DDQ afforded carbazole

6b in only 20% yield. After some optimization of the conditions, we

have achieved a dramatic increase of the yield (100%) using Pd/C

(10 mol %) as the catalyst (xylene, reﬂux) (Scheme 3, Table 3). The

structure of carbazole 6a was independently conﬁrmed by X-ray

crystal structure analysis (Fig. 4).

2a

7 (49%)

CN

N

Me

N

Me

A

C

NEt₃

CN

CO₂R

N

CO₂R

Me

B

i

Scheme 4. Possible mechanism of the formation of 7. Conditions: i, Pd(OAc)₂(5 mol %),

N

Me

SPhos (10 mol %), NEt₃, DMF, 120 ^ꢀC, 48 h.

N

Me

5a-c,f

6a-d (100%)

Scheme 3. Synthesis of carbazole 6aed; conditions: i, Pd/C (10 mol %), xylene, reﬂux,

48 h.

Table 3

Synthesis of 6aed

5

6

R

% (6)^a

b

c

e

f

a

b

c

Et

100

ⁿBu

ⁿHex

^tBu

d

a

Yields of isolated products based on 5aed.

Fig. 5. Crystal structure of 7.

The reaction of 2,3,6-tribromo-N-methylindole (2b) with acry-

late 3f (90 ^ꢀC, 36 h) afforded the di(alkenyl)indole 9 in 75% yield

(Scheme 5). The structure was conﬁrmed by 2D NMR experiments

(NOESY, HMBC). The formation of 9 can be explained by Heck re-

action of 2b at carbon C-2, which is most electron-deﬁcient. Due to

The Pd(OAc)₂/SPhos-catalyzed reaction of 2a with acrylonitrile

(120 ^ꢀC, 48 h) afforded the unexpected carbazole 7 in 49% yield

(Scheme 4). The formation of 7 can be explained by twofold Heck

reaction of 2a to give intermediate A, electrocyclization

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

5307

Table 4

the electron-withdrawing effect of the 2-(alkoxycarbonyl)alkenyl

Synthesis of 11a,eeh, 12aeg and 13aec,e

substituent, carbon C-3 becomes more electron-deﬁcient and, as

a consequence, more reactive than C-6. It was earlier noted¹⁸that

Suzuki reactions of N-TBDS-protected 3,6-dibromoindole pro-

ceeded by ﬁrst attack on position C-6. This might also explain the

observation that the reaction of 2,3-dibromoindole 2a with only

1 equiv of acrylate mainly results in the formation of 2,3-di[2-

(alkoxycarbonyl)ethenyl]indole 4 and starting material, except for

the case of acrylate 3i where 8 was isolated in 35% yield along with

4i. Product 8 was an unstable compound and at room temperature

it underwent decomposition within 24 h providing a dark brown

coloured material, probably due to the loss of Br (Scheme 5).

Therefore, pure compounds of type 8 could not be isolated. The

Pd(OAc)₂/L-catalyzed reaction of 2b with acrylate 3f, carried out at

120 rather than 90 ^ꢀC, afforded the 1,2-dihydrocarbazole 10 in 73%

yield (Scheme 6).

11,12,3

R

% (11)^a

% (12)^a

% (13)^a

a

b

c

d

e

f

Me

69

d^b

74

76

73

64

79

100

d^b

Et

67þ10^c

ⁿBu

95

ⁱBu

72

74

79

ⁿHex

^tBu

100

d^b

g

h

ⁱOct

ⁿOctadec

74

d^b

a

Yields of isolated products based on 2b.

Experiment was not carried out.

Compound 14 was isolated as a by-product in 10%.

b

c

Br

CO₂R

3i

CO₂R

Br

N

i

Me

2a

8 (R = 2-Ethylhexyl): 35% + 4i

Scheme 5. Synthesis of 8. Conditions: i, Pd(OAc)₂(5 mol %), SPhos (10 mol %), NEt₃,

DMF, 90 ^ꢀC, 24 h.

CO₂R

Fig. 6. Crystal structure of 12c.

Along with 12b, a side product 14 was also isolated, which was

N

formed by reduction of carbon atom C-2 or C-3 (Fig. 7). The

structure of the product could not be unambigiously conﬁrmed.

Br

Me

9 (R = tBu): 75%

CO₂R

i

Br

CO₂R

CO₂Et

Br

3d,f

CO₂Et

N

Me

CO₂R

Br

ii

2b

N

OR

N

Me

10 (R = iBu): 73%

N

EtO₂C

Me

EtO₂C

Scheme 6. Synthesis of 9 and 10. Conditions: i, Pd(OAc)₂(5 mol %), SPhos (10 mol %),

NEt₃, DMF, 90 ^ꢀC, 24 h; ii, Pd(OAc)₂(5 mol %), SPhos (10 mol %), NEt₃, DMF, 120 ^ꢀC, 48 h .

Fig. 7. Possible structures of side product 14 derived from 12b.

The Heck reaction of 2b with an excess of acrylates 3 (90 ^ꢀC,

36 h) afforded the 2,3,6-tris(alkenyl)indoles 11a,eeh in good yields

(Scheme 7, Table 4). 7-Alkenyl-1,2-dihydrocarbazoles 12aeg were

isolated when the cross-coupling reactions of 2b with 3 were car-

ried out at 120 instead of 90 ^ꢀC. The structure of 12c was in-

dependently conﬁrmed by X-ray crystal structure analysis (Fig. 6).

The dehydrogenation of 12aec,e, carried out using Pd/C (10 mol %)

in reﬂuxing xylene, afforded the carbazoles 13aec,e.

The Pd(OAc)₂/SPhos-catalyzed reaction of 2,3,5,6-tetra-

bromoindole 2c with an excess of acrylates 3 (120 ^ꢀC, 48 h) afforded

the 6,7-di(alkenyl)-1,2-dihydrocarbazoles 15aeh in good yields

(Scheme 8, Table 5). The Pd/C-catalyzed dehydrogenation of

CO₂R

Br

CO₂R

RO₂C

CO₂R

Br

CO₂R

Br

3

Br

N

Me

Br

N

Me

i

N

Me

N

2b

Me

2c

CO₂R

15

ii

11a,e-h

RO₂C

CO₂R

iii

i

3

CO₂R

RO₂C

CO₂R

N

Me

N

Me

N

Me

iii

Me

13a-c,e

RO₂C

16

12a-g

RO₂C

17

Scheme 8. Synthesis of 15aeh, 16aed,g and 17b,c,e,g. Conditions: i, Pd(OAc)₂

(5 mol %), SPhos (10 mol %), NEt₃, DMF, 120 ^ꢀC, 48 h; ii, Pd/C (10 mol %), xylene, reﬂux,

2 d, iii, Pd(OAc)₂(5 mol %), SPhos (10 mol %), NEt₃, DMF, 90 ^ꢀC, 36 h.

Scheme 7. Synthesis of 11a,eeh, 12aeg and 13aec,e. Conditions: i, Pd(OAc)₂(5 mol %),

SPhos (10 mol %), NEt₃, DMF, 90 ^ꢀC, 36 h; ii, Pd(OAc)₂(5 mol %), SPhos (10 mol %), NEt₃,

DMF, 120 ^ꢀC, 48 h; iii, Pd/C (10 mol %), xylene, reﬂux, 48 h.

5308

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

Table 5

In conclusion, we have reported the synthesis of di-, tri- and

Synthesis of 15aeh, 16aed and 1b,c,e,g

tetra-alkenylindoles by palladium(0)-catalyzed Heck cross-

coupling reactions of di-, tri- and tetrabromo-N-methylindoles.

The reactions were carried out at 90 ^ꢀC using a novel biaryl

monophosphine ligand developed by Buchwald and co-workers.

1,2-Dihydrocarbazoles were formed by a domino ‘twofold Heck/

a

15,16,17

R

% (15)

% (16) ^a

% (17)^a

d^b

a

b

c

d

e

f

Me

68

86

71

72

80

71

74

100

d^b

100

d^b

100

d^b

Et

76

ⁿBu

71

ⁱBu

d^b

88

6p-electrocyclization’ when the reaction was carried out at 120

^tBu

rather than 90 ^ꢀC. The regioselectivity of the Heck reaction of 2,3,6-

tribromo-N-methylindoles was in favour of carbon atoms C-2 and

C-3. Some of the 1,2-dihydrocarbazoles prepared were trans-

formed, by Pd/C-catalyzed dehydrogenation, into the correspond-

ing carbazoles in high yield.

ⁿHex

d^b

75

g

h

2-Ethylhexyl

ⁱOct

d^b

a

Yields of isolated products.

Experiment was not carried out.

b

3. Experimental section

12aed,g afforded the carbazoles 13aed,g in quantitative yield. An

electrocyclization involving the alkenyl groups attached to carbon

atoms C-5 and C-6 was not observed. This can be explained by the

aromaticity of the benzene ring, which would be interrupted by the

electrocyclization. Tetra-alkenylated indoles 17b,c,e,g could be

successfully prepared when the reaction was performed at 90 in-

stead of 120 ^ꢀC. Side-product 18 was isolated in 7% yield along with

17b, due to reduction of carbon atoms C-2 and C-3 (Fig. 8).

3.1. Synthesis of 2,3-dibromo-N-methylindole (2a)

To a THF solution (20 mL) of N-methylindole 1 (1.0 mL, 8.0 mmol)

was portionwise added NBS (3.30 g, 18.4 mmol) at ꢁ78 ^ꢀC and the

solution was stirred at this temperature for 4 h. To the solution was

added water (25 mL). The organic and the aqueous layer were sep-

arated and the latter was extracted with CH₂Cl₂(3ꢂ25 mL). The

combined organic layers were washed with a saturated aqueous

solution of NaHCO₃, dried (Na₂SO₄), ﬁltered and concentrated in

vacuo. The residue was puriﬁed by ﬂash silica column chromatog-

raphy (pure heptanes) to yield 2a as a colourless solid (1.83 g, 90%).

3.2. Synthesis of 2,3,6-tribromo-N-methylindole (2b)

To a THF solution (50 mL) of N-methylindole (1) (2.0 mL,

16.0 mmol) was portionwise added NBS (9.40 g, 52.8 mmol) at

ꢁ78 ^ꢀC and the solution was stirred at this temperature for 4 h and

then at 20 ^ꢀC for 14 h. To the solution was added water (25 mL). The

organic and the aqueous layer were separated and the latter was

extracted with CH₂Cl₂(3ꢂ30 mL). The combined organic layers

were washed with a saturated aqueous solution of NaHCO₃, dried

(Na₂SO₄), ﬁltered and concentrated in vacuo. The residue was pu-

riﬁed by ﬂash silica column chromatography (pure heptanes) to

yield 2b as a colourless solid (5.50 g, 94%).

Fig. 8. Structure of side product 18 derived from 17b.

An alternative synthetic approach to carbazoles based on two-

fold Sonogashira reactions of 2,3-dibromoindole 2a with acetylenes

and subsequent Bergman cyclization was next studied. The Sono-

gashira reaction of 2a with phenylacetylene, in the presence of

Pd(OAc)₂(5 mol %) and XPhos (10 mol %), provided the unstable

bis-alkynylated indole 19c in 60% yield (Scheme 9). The product

proved to be very unstable and rapidly decomposed. It was not

possible to prepare other derivatives because they decomposed

under the conditions of their preparation. All attempts to induce

a thermal Bergman cyclization of 19 by heating in the presence of

dihydrobenzene to prepare carbazole 20 failed (decomposition). All

efforts to achieve a regioselective alkynylation of 2a using 1.0 equiv

of acetylene also failed.

3.3. Synthesis of 2,3,5,6-tetrabromo-N-methylindole (2c)

To a THF solution (100 mL) of N-methylindole (1) (4.9 mL,

38.0 mmol) was portionwise added NBS (33.80 g, 190.0 mmol) at

ꢁ78 ^ꢀC and the solution was stirred at this temperature for 1 h and

then under reﬂux for 4 h. To the solution was added water (50 mL).

The organic and the aqueous layer were separated and the latter

was extracted with CH₂Cl₂(3ꢂ50 mL). The combined organic layers

were washed with a saturated aqueous solution of NaHCO₃, dried

(Na₂SO₄), ﬁltered and concentrated in vacuo. The residue was pu-

riﬁed by ﬂash silica column chromatography (pure heptanes) to

yield 2c as a colourless solid (13.20 g, 78%). ¹H NMR (250 MHz,

Ph

Br

Ph

Br

¼3.70 (s, 3H, NCH₃), 7.60 (s, 1H, ArH), 7.70 (s, 1H, ArH). ¹³

C

Ph

CDCl₃):

NMR (62 MHz, CDCl₃):

117.2, 118.4 (C), 123.1 (CH), 127.4, 135.7 (C).

d

N

i

N

d

¼32.7 (NCH₃), 91.9 (C), 114.4 (CH), 116.4,

Me

2a

Me

19

(60%)

3.4. General procedure A for Heck cross-coupling reactions

Ph

Bergman

In a pressure tube (glass bomb) a suspension of Pd(OAc)₂(12 mg,

0.05 mmol, 5 mol %) and SPhos (L₁) (41 mg, 0.10 mmol) in DMF

(5 mL) was purged with argon and stirred at 20 ^ꢀC to get a yellowish

or brownish transparent solution. To the stirred solution were

added the brominated indole 2aec (1.0 mmol), NEt₃and the ac-

rylate. The reaction mixture was stirred at 90 ^ꢀC for 36 h. The so-

lution was cooled to 20 ^ꢀC, poured into H₂O and CH₂Cl₂(25 mL

each), and the organic and the aqueous layer were separated. The

Ph

N

Me

20

Scheme 9. Bis-alkynylation of 2a. i, Pd(OAc)₂(5 mol %), XPhos (10 mol %), phenyl-

acetylene (2.5 equiv), CuI (10 mol %), (ⁱPr)₂NH, 120 ^ꢀC, 36 h.

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

5309

latter was extracted with CH₂Cl₂(3ꢂ25 mL). The combined organic

layers were washed with H₂O (3ꢂ20 mL), dried (Na₂SO₄), and

concentrated in vacuo. The residue was puriﬁed by chromatogra-

phy (ﬂash silica gel, heptanes/EtOAc).

following general procedure A, as a yellowish highly viscous oil

(299 mg, 78%, E/Z¼7:3). ¹H NMR (250 MHz, CDCl₃):

¼1.50 (s, 18H,

d

6CH₃), 3.70 (s, 3H, NCH₃), 6.20 (d, 1H, J¼16.0 Hz, ArH), 6.40 (d, 1H,

J¼16.0 Hz, ArH), 7.20e7.30 (m, 3H, ArH), 7.60 (d, 1H, J¼15.8 Hz, ArH),

7.70 (d, 1H, J¼16.0 Hz, ArH), 8.00 (d, 1H, J¼7.9 Hz, ArH). ¹³C NMR

3.5. Synthesis of 2,3-bis(alkenyl)-N-methylindoles 4

(75 MHz, CDCl₃):

d

¼27.2, 27.3 (3CH₃), 30.1 (NCH₃), 79.0, 80.2 (CeO),

108.6 (CH), 112.8 (C), 117.2, 120.2, 120.6, 123.8 (CH), 124.5 (C), 125.4,

129.2,134.7(CH),135.9,137.2(C),164.4,166.3(C]O). IR(KBr):

¼2964,

2930 (w),1722,1710,1693,1680,1613,1469,1453,1391,1366 (m),1281,

3.5.1. Dimethyl 3,3⁰-(1-methyl-1H-indole-2,3-diyl)diacrylate (4a).

Starting with Pd(OAc)₂(12 mg, 5 mol %) and SPhos (L₁) (41 mg,

10 mol %), brominated indole 2a (288 mg,1.0 mmol) 4a was isolated

n

1258, 1144, 1090, 1017 (s), 845 (m), 797, 741 (s), 663, 563 (w) cm^ꢁ1

.

as yellow oil (231 mg, 77%). ¹H NMR (250 MHz, CDCl₃):

d¼3.53 (s,

GCeMS (EI, 70 eV): m/z (%)¼383 (M^þ, 39), 271 (13), 227 (84), 226

(100), 225 (52), 208 (31), 182 (69), 167 (54), 152 (21), 57 (79), 41 (42).

HRMS (EI, 70 eV): calcd for C₂₃H₂₉NO₄[M]^þ: 383.20911; found:

383.20905.

3H, CH₃O), 3.75 (s, 3H, CH₃O), 3.78 (s, 3H, CH₃N), 6.25 (d, 1H,

J¼15.9 Hz), 6.49 (d, 1H, J¼15.8 Hz), 6.8e7.3(m, 3H, ArH), 7.70 (d, 1H,

ArH), 7.82 (d, 1H, J¼16.6 Hz), 7.93 (d, 1H, J¼16.6 Hz). ¹³C NMR

(62 MHz, CDCl₃):

116.1, 120.2, 120.8 (CH), 124.2 (C), 131.3, 135.6 (CH), 136.3, 137.1 (C),

143.2 (CH),166.4,168.2 (CO). IR (KBr):

1433 (s), 1410, 1372, 1341 (m), 1269, 1190, 1165, 1132 (s), 1035, 1013,

967 (m), 739 (s), 648, 560 (w) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼

299 (M^þ, 60), 240 (67), 209 (64),181 (100),120 (32), 77 (19), 41 (19).

HRMS (ESI-TOF): m/z calcd for C₁₇H₁₈NO₄[MþH]^þ: 300.12303;

found: 383.12291.

d

¼31.2 (CH₃CN), 51.3, 51.5 (CH₃O), 109.7 (C), 110.0,

3.5.5. Bis(6-methylheptyl) 3,3⁰-(1-methyl-1H-indole-2,3-diyl)diacry-

late (4g). Product 4g was prepared starting with 2a (289 mg,

1.0 mmol), isooctyl acrylate (3g) (0.52 mL, 2.5 mmol), Pd(OAc)₂

(11 mg, 5 mol %), SPhos (10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF

(5 mL) at 90 ^ꢀC for 36 h following general procedure A, as a yellow oil

n

¼2948, 2841 (w),1702,1618,

(377 mg, 76%). ¹H NMR (250 MHz, CDCl₃):

d

¼0.60e0.90 (m, 12H,

4CH₃),1.00e1.40 (m,12H, 6CH₂),1.50e1.60 (m, 6H, aliphatic), 3.80 (s,

3H, NCH₃), 4.10 (t, 2H, J¼6.7 Hz, CH₂O), 4.20 (t, 2H, J¼6.8 Hz, CH₂O),

6.40 (d, 1H, J¼16.1 Hz, ArH), 6.50 (d, 1H, J¼16.0 Hz, ArH), 7.10e7.20

(m, 3H, ArH), 7.80 (d, 1H, J¼15.7 Hz, ArH), 7.80 (br d, 1H, J¼7.6 Hz,

3.5.2. Dibutyl 3,3⁰-(1-methyl-1H-indole-2,3-diyl)diacrylate (4c).

Product 4c was prepared starting with 2a (289 mg, 1.0 mmol), butyl

acrylate (3c) (0.36 mL, 2.5 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos

(10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at 90 ^ꢀC for 24 h

following general procedure A, as a brownish oil (276 mg, 72%). ¹H

ArH), 7.90 (d,1H, J¼15.7 Hz, ArH). ¹³C NMR (62 MHz, CDCl₃):

¼13.0,

d

14.6 (CH₃), 21.5, 24.5, 27.5 (CH₂) 29.5 (NCH₃), 45.5 (CH₂), 63.7, 63.8

(CH₂O), 108.1 (C), 108.7 (CH), 115.7, 120.0, 120.4, 123.2 (CH), 124.5,

125.0 (C),127.6,130.1,134.3 (CH),137.3 (C),165.3,167.0 (CO). IR (KBr):

NMR (250 MHz, CDCl₃):

d

¼0.90 (t, 6H, J¼7.1 Hz, 2CH₃),1.30e1.40 (m,

4H, 2CH₂), 1.60e1.70 (m, 4H, 2CH₂), 3.70 (s, 3H, NCH₃), 4.10 (t, 2H,

J¼6.3 Hz, CH₂O), 4.20 (t, 2H, J¼6.3, 2CH₂O), 6.30 (d,1H, J¼16.1 Hz, CH),

6.50 (d, 1H,, J¼15.8 Hz, CH), 7.20e7.40 (m, 3H, ArH), 7.80 (d, 1H,

J¼16.1 Hz, CH), 7.80 (br d, 1H, J¼8.0 Hz, ArH), 7.90 (d, 1H, J¼15.8 Hz,

n

¼2955, 2927, 2871 (m), 1709, 1620, 1465 (s), 1367, 1280, 1235 (m),

1164 (s), 1132, 1048, 969, 849, 818 (w), 740 (s), 662, 561 (w) cm^ꢁ1

.

GCeMS (EI, 70 eV): m/z (%)¼495 ([M]^þ, 32), 337 (16), 281 (14), 253

(10), 252 (22), 226 (100), 208 (75), 182 (45). HRMS (EI, 70 eV): calcd

for C₃₁H₄₅NO₄[M]^þ: 495.33431; found: 495.33390.

CH). ¹³C NMR (62 MHz, CDCl₃):

d¼13.7, 13.8 (CH₃), 19.2, 19.3 (CH₂),

30.8, 30.9 (CH₂), 31.2 (NCH₃), 64.2, 64.9 (CH₂O), 110.0 (CH), 114.1 (C),

116.6,121.1, 122.0, 124.7, 124.8 (CH),125.5 (C),131.1, 136.5 (CH),136.8,

3.6. Synthesis of bis(2-ethylhexyl) 3,3⁰-(1-methyl-1H-indole-

139.0 (C), 166.2, 168.0 (CO). IR (KBr):

n

¼2957, 2932, 2872 (m), 1706,

2,3-diyl)diacrylate (4i)

1616, 1466 (s), 1364, 1326 (w), 1274, 1235, 1165 (s), 1132, 1115, 1061,

1046, 1027, 968, 844, 8215 (m), 739 (s), 561 (w) cm^ꢁ1. MS (EI, 70 eV):

m/z (%)¼383 (M^þ, 3), 381 (62), 325 (13), 308 (06), 269 (09), 252 (100),

225 (08). HRMS (EI, 70 eV): calcd for C₂₃H₂₉NO₄[M]^þ: 383.20911;

found: 383.208695.

Product 4i was prepared starting with 2a (289 mg, 1.0 mmol),

2-ethylhexyl acrylate (0.27 mL, 1.25 mmol) (0.52 mL, 2.5 mmol),

Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %), NEt₃(1.10 mL,

8.0 mmol), DMF (5 mL) at 90 ^ꢀC for 24 h following general pro-

cedure A, as a yellow oil (50 mg, 10%þ35% 8). ¹H NMR (250 MHz,

3.5.3. Dihexyl 3,3⁰-(1-methyl-1H-indole-2,3-diyl)diacrylate (4e).

Product 4e was prepared starting with 2a (289 mg,1.0 mmol), hexyl

acrylate (3e) (0.44 mL, 2.5 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos

(10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at 90 ^ꢀC for 36 h

following general procedure A, as a deep yellow highly viscous oil

CDCl₃):

d

¼0.90 (t, 12H, J¼7.5 Hz, 4CH₃), 1.20e1.40 (m, 16, 8CH₂),

1.20e1.60 (m, 2H, CH), 3.80 (s, 3H, NCH₃), 4.00e4.10 (m, 4H, CH₂O),

6.30 (d, 1H, J¼16.0 Hz, ArH), 6.50 (d, 1H, J¼16.0 Hz, ArH), 7.20e7.30

(m, 3H, ArH), 7.80 (d,1H, J¼16.0 Hz, ArH), 7.90 (d,1H, J¼8.1 Hz, ArH),

8.00 (d, 1H, J¼15.9 Hz, ArH). ¹³C NMR (75 MHz, CDCl₃):

¼11.0, 11.1,

d

(337 mg, 77%). ¹H NMR (250 MHz, CDCl₃):

d

¼0.80 (t, 6H, J¼7.8 Hz,

14.0 (CH₃), 22.9, 23.0, 23.8, 24.0, 28.9, 29.0, 30.4, 30.5 (CH₂), 31.2

(CH₃CN), 38.8, 38.9 (CH-aliphatic), 66.8, 67.6 (CH₂O), 109.0 (CH), 113

(C), 115.7, 121.2, 122.0, 123.5, 123.6 (CH), 124.5 (C), 131.1, 135.5 (CH),

2CH₃), 1.20e1.40 (m, 16H, 8CH₂), 3.70 (s, 3H, NCH₃), 4.20 (t, 4H,

J¼6.8 Hz, 2CH₂O), 6.20 (d,1H, J¼16.0 Hz, ArH), 6.50 (d,1H, J¼15.9 Hz,

ArH), 7.10e7.30 (m, 3H, ArH), 7.70 (d,1H, J¼15.8 Hz, ArH), 7.80 (d, 2H,

J¼8.1 Hz, ArH), 7.90 (d, 1H, J¼16.0 Hz, ArH). ¹³C NMR (62 MHz,

135.8, 138.0 (C), 165.3, 167.0 (CO). IR (KBr):

n

¼3052 (w), 2957, 2927,

2872, 2858 (m), 1706, 1620 (s), 1464 (m), 1411, 1378, 1352, 1339 (w),

1280, 1250, 1235 (m), 1165 (s), 1132, 1031, 1016, 1016, 968 (m), 850,

818, 766 (w), 740 (s), 655, 561 (w) cm^ꢁ1. GCeMS (EI, 70 eV): m/z

(%)¼595 ([M]^þ, 60), 367 (9), 337 (15), 269 (10), 253 (15), 226 (72),

208 (100), 151 (13). HRMS (EI, 70 eV): calcd for C₃₁H₄₅NO₄[M]^þ:

495.33431; found: 495.33712.

CDCl₃):

d

¼13.0 (2CH₃), 21.4, 21.5, 24.4, 24.8, 27.3, 27.7 (CH₂), 29.9

(NCH₃), 30.3, 30.5 (CH₂), 63.5, 64.2 (CH₂O), 109.7 (CH), 113.0 (C),

120.0,120.2,121.0,123.2,1236 (CH),124.5 (C),130.1,134.2 (CH),135.5,

138.0 (C), 165.2, 166.9 (CO). IR (KBr):

n

¼2955, 2929, 2857 (m), 1712

(s), 1625, 1529, 1467, 1360, 1283, 1238 (w), 1170 (s), 1133, 1049, 972,

916 (w), 735 (s) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼439 ([M]^þ, 44),

338 (06), 310 (28), 252 (11), 226 (100), 208 (68), 182 (84). HRMS (EI,

70 eV): calcd for C₂₇H₃₇NO₄[M]^þ: 439.27171; found: 439.270972.

3.6.1. (E)-2-Ethylhexyl 3-(3-bromo-1-methyl-1H-indol-2-yl)acrylate

(8). Product 8 (138 mg, 35%) was isolated along with 4i (50 mg,

10%) as a light brown oil (138 mg, 35%þ10% of 4i). ¹H NMR

3.5.4. Di(tert-butyl) 3,3⁰-(1-methyl-1H-indole-2,3-diyl)diacrylate (4f).

Product 4f was synthesized starting with 2a (289 mg, 1.0 mmol), tert-

butyl acrylate (3f) (0.37 mL, 2.5 mmol), Pd(OAc)₂(11 mg, 5 mol %),

SPhos (10 mol%), NEt₃(1.10mL, 8.0mmol), DMF (5mL) at 90^ꢀCfor36h

(250 MHz, CDCl₃):

d

¼0.87 (t, J¼7.3, 6H, 2CH₃), 1.18e1.45 (m, 8H),

1.53e1.66 (m, 1H), 3.75 (s, 3H, CH₃N), 4.08 (dd, J¼0.8, 6.0 Hz, 2H,

CH₂O), 6.80 (d, 1H, J¼16.2 Hz, CH), 7.08e7.15 (m, 1H, ArH),

7.22e7.25 (m, 2H, ArH), 7.48e7.52 (m, 1H, ArH), 7.774 (d, 1H,

5310

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

J¼16.3 Hz, CH). ¹³C NMR (75.5 MHz, CDCl₃):

d

¼9.8, 13.1 (CH₃), 22.0,

1.0 mmol), butyl acrylate (0.36 mL, 2.5 mmol), Pd(OAc)₂(11 mg,

22.9, 27.8, 29.5 (CH₂), 30.2 (CH), 37.9 (NCH₃), 66.2 (CH₂O), 95.0 (C),

108.8, 119.1, 119.4, 120.0, 124.0 (CH), 126.2, 129.8 (C), 130.0 (CH),

5 mol %), SPhos (10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (mL) at

120 ^ꢀC for 48 h according to general procedure B, as a yellow highly

137.0 (C), 166.2 (CO). IR (KBr):

n

¼2956, 2926, 2871, 2858 (m), 1706

viscous oil (294 mg, 77%). ¹H NMR (250 MHz, CDCl₃):

d

¼0.80 (t, 3H,

(s), 1625, 1462, 1372, 1325, 1260, 1233, 1207 (m), 1167 (s), 1014, 930,

J¼7.3 Hz, CH₃), 0.90 (t, 3H, J¼7.4 Hz, CH₃), 1.10e1.30 (m, 2H, CH₂),

1.30e1.50 (m, 4H, 2CH₂), 1.60e1.70 (m, 2H, CH₂), 3.00 (dd, 1H_a,

J¼8.6, 17.0 Hz, H-1), 3.60 (dd, 1H_b, J¼2.3, 17.0 Hz, H-1), 3.70 (s, 3H,

NCH₃), 3.80e4.00 (m, 2H, CH₂O), 4.00 (dd, 1H_a, J¼2.3, 8.3 Hz, H-2),

4.20 (t, 2H, J¼6.6 Hz, CH₂O), 7.00e7.20 (m, 3H, ArH), 7.50e7.60 (m,

767 (w), 738 (m) cm^ꢁ1. HRMS (ESI^þ): calcd for C₂₀H₂₆BrNO₂(M^þ,

[

⁷⁹Br]): 391.11469; found: 391.11433, calcd for C₂₀H₂₆BrNO₂(M^þ,

⁸¹Br]): 393.11263; found: 393.11453.

3.7. General procedure B for Heck cross-coupling reactions

1H, ArH), 7.90 (s, 1H, H-4). ¹³C NMR (62 MHz, CDCl₃):

d

¼13.6 (CH₃),

13.8 (CH₃), 19.0, 19.3, 23.8 (CH₂), 29.8 (CH₃N), 30.5, 31.0 (CH₂), 39.0

(CH, C-2), 64.2, 65.0 (CH₂O), 109.4 (C), 109.6 (CH), 116.5 (C), 118.0,

121.0, 121.8 (CH), 125.2 (C), 132.1 (CH), 138.0, 139.7 (C), 167.4, 173.4

In a pressure tube (glass bomb) a suspension of Pd(OAc)₂

(12 mg, 0.05 mmol) and SPhos (L₁) (41 mg, 0.10 mmol) in DMF

(5 mL) was purged with argon and stirred at 20 ^ꢀC to get a yel-

lowish or brownish transparent solution. To the stirred solution

were added the brominated indole 2aec (1.0 mmol), NEt₃(1.1 mL,

8.0 mmol) and the acrylate (1.25 equiv per Br). The reaction

mixture was stirred at 120 ^ꢀC for 48 h. The solution was cooled to

20 ^ꢀC, poured into H₂O and CH₂Cl₂(25 mL each), and the organic

and the aqueous layer were separated. The latter was extracted

with CH₂Cl₂(3ꢂ25 mL). The combined organic layers were

washed with H₂O (3ꢂ20 mL), dried (Na₂SO₄), and concentrated in

vacuo. The residue was puriﬁed by chromatography (ﬂash silica

gel, heptanes/EtOAc).

(CO). IR (KBr):

n

¼2956, 2932, 2872 (m), 1709 (s), 1629, 1599, 1559,

1562 (w), 1500, 1464, 1387, 1362, 1340, 1325 (m), 1257, 1222 (s),

1131, 1106, 1077, 1045, 1015 (m), 950, 902, 843, 830, 783, 765 (w),

742, 720 (m), 632, 608, 561 (w) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼

383 ([M]^þ, 46), 310 (06), 282 (34), 226 (87), 208 (67), 182 (100), 152

(13). HRMS (EI, 70 eV): m/z calcd for C₂₃H₂₉NO₄[M]^þ: 383.20911;

found: 383.20824.

3.8.4. Diisobutyl 9-methyl-2,9-dihydro-1H-carbazole-2,3-dic

arboxylate (5d). Starting with Pd(OAc)2 (12 mg, 0.05 mmol) and

SPhos (41 mg, 0.10 mmol), isobutyl acrylate (0.36 mL, 2.5 mmol),

brominated indole 2a (288 mg, 1.0 mmol) 5d was following general

procedure B, and was isolated as yellow oil (252 mg, 66%). ¹H NMR

3.8. Synthesis of 2,3-dihydrocarbazoles 5

(250 MHz, CDCl₃):

d

¼0.73 (d, 6H, J¼7.6 Hz, 2CH₃), 0.76 (d, 6H,

3.8.1. Dimethyl 9-methyl-2,9-dihydro-1H-carbazole-2,3-dic

arboxylate (5a). Starting with Pd(OAc)₂(12 mg, 5 mol %), SPhos

(41 mg, 10 mol %), methyl acrylate (0.26 mL, 2.5 mmol), brominated

indole 2a (288 mg, 1.0 mmol) 5a was isolated as yellow oil (206 mg,

J¼7.6 Hz, 2CH₃), 0.88e0.92 (m, 2H, CH), 3.01 (dd, 1H, J¼8.5, 17.3 Hz,

C(1)), 3.03 (dd, 1H, J¼2.7, 17.2 Hz, C(1)), 3.68 (d, 2H, J¼7.6 Hz, CH₂O),

3.72 (d, 2H, J¼7.7 Hz, CH₂O), 3.96 (s, 3H, CH₃N), 4.05 (dd, 1H, J¼2.4,

8.8 Hz C (2)), 7.09e7.21 (m, 4H, ArH), 7.92 (s, 1H, C(4)). ¹³C NMR

69%). ¹H NMR (300 MHz, CDCl₃):

C(1)); 3.50 (dd, 1H, J¼2.6, 17.2 Hz, H-1), 3.52 (s, 3H, CH₃N), 3.63 (s,

3H, CH₃O); 3.76 (s, 3H, CH₃O), 4.01 (dd, 1H, J¼2.4, 8.7 Hz, C(2)),

7.08e7.22 (m, 4H, ArH), 7.92 (s, 1H, C(4)). ¹³C NMR (62 MHz, CDCl₃):

d

¼2.99 (dd, 1H, J¼8.6, 17.0 Hz,

(250 MHz, CDCl₃):

(CH₃N), 51.6 (CH₂O), 51.8 (CH₂O), 109.1 (C), 109.3, 118.0 (CH), 118.6

(C), 120.3, 121.5 (CH), 125.0 (C), 130.3 (CH), 137.8, 139.5 (C), 166.8,

d

¼18.1, 18.3 (2CH₃), 23.2 (CH₂), 29.7 (C(2)H), 38.7

172.6 (CO). IR (KBr):

n

¼2958, 2927, 2872 (w), 1727, 1464, 1263, 1194,

d

¼23.9 (CH₂), 29.8 (C(4)H), 38.8 (CH₃N). 51.6 (CH₃O), 52.5 (CH₃O),

109.3, 109.6 (CH), 115.7, 117.9 (CH), 117.3, 121.0, 121.9 (CH), 125.1 (C),

132.7 (CH), 138.0, 139.8 (C), 167.7, 173.8 (CO). IR (KBr):

1158 (m), 1029, 1010 (m), 737 (s), 711, 660, 573 (w) cm^ꢁ1. GCeMS

(EI, 70 eV): m/z (%)¼383 (M^þ, 60), 309 (21), 282 (54), 226 (100), 208

(80), 182 (77), 167 (22). HRMS: m/z calcd for C₂₃H₂₉NO₄[M]^þ:

383.2098; found: 383.20933.

n

¼2949, 2845

(w),1720,1692 (s),1605,1524,1467,1434,1270 (m), 1234,1241,1191

(s), 1048, 750 (m) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼299 (M^þ, 58),

268 (6), 240 (73), 208 (92), 181 (100), 152 (31), 104 (5), 76 (22).

HRMS: m/z calcd for C₁₇H₁₈NO₄[MþH]^þ300.12303; found:

300.122761.

3.8.5. Dihexyl 9-methyl-2,9-dihydro-1H-carbazole-2,3-dicarboxylate

(5e). Compound 5e was synthesized starting with 2a (289 mg,

1.0 mmol), hexyl acrylate (0.44 mL, 2.5 mmol), Pd(OAc)₂(11 mg,

5 mol %), SPhos (10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (mL) at

120 ^ꢀC for 48 h following general procedure B, as a yellowish solid

3.8.2. Diethyl 9-methyl-2,9-dihydro-1H-carbazole-2,3-dicarboxylate

(5b). Product 5b was prepared starting with 2a (289 mg,

1.0 mmol), ethyl acrylate (0.27 mL, 2.5 mmol), Pd(OAc)₂(11 mg,

5 mol %), SPhos (10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (mL) at

120 ^ꢀC for 48 h according to general procedure B, as a yellow solid

(357 mg, 81%), mp 107e109 ^ꢀC. ¹H NMR (250 MHz, CDCl₃):

d

¼0.70

(t, 3H, J¼7.0 Hz, CH₃), 0.80 (t, 3H, J¼7.0 Hz, CH₃), 1.10e1.20 (m, 6H,

3CH₂), 1.20e1.50 (m, 8H, 4CH₂), 1.60e1.70 (m, 2H, CH₂), 3.00 (dd,

1H_a, J¼8.8, 17.1 Hz, H-1), 3.50 (dd, 1H_b, J¼2.3, 17.1 Hz, H-1), 3.60 (s,

3H, NCH₃), 3.80e4.00 (m, 2H, CH₂O), 4.00 (dd, 1H_a, J¼2.4, 8.8 Hz, H-

2), 4.10 (t, 2H, J¼6.8 Hz, CH₂O), 7.00e7.20 (m, 3H, ArH), 7.50e7.60

(303 mg, 93%), mp 100e103 ^ꢀC. ¹H NMR (250 MHz, CDCl₃):

d¼1.10

(s, 3H, CH₃), 1.30 (s, 3H, CH₃), 2.90 (dd, 1H_a, J¼8.8, 17.1 Hz, H-1), 3.50

(dd, 1H_b, J¼2.6, 17.2 Hz, H-1), 3.60 (s, 3H, NCH₃), 3.90e4.10 (m, 3H,

H_aand CH₂O), 4.20 (q, J¼7.1, 13.5 Hz, 2H, CH₂O), 7.10e7.20 (m, 3H,

ArH), 7.50e7.60 (m, 1H, ArH), 7.90 (s, 1H, H-4). ¹³C NMR (75 MHz,

(m, 1H, ArH), 7.90 (s, 1H, H-4). ¹³C NMR (75 MHz, CDCl₃):

d

¼12.9,

13.0 (CH₃), 21.5, 21.6, 22.8, 24.4, 24.8, 27.4, 27.9 (CH₂), 28.7 (NCH₃),

30.3, 30.5 (CH₂), 38.0 (CH, C-4), 63.5, 64.2 (CH₂O), 108.3(C), 108.5

(CH), 115.5 (C), 116.9, 120.0, 121,0 (CH), 124.1 (C), 131.0 (CH), 137.0,

CDCl₃):

d

¼13.0 (CH₃), 13.5 (CH₃), 22.8 (CH₂), 28.7 (CH, C-4), 37.7

(NCH₃), 59.3 (CH₂O), 60.1 (CH₂O), 108.3 (C), 108.6 (CH), 115.4 (C),

116.9, 120.0, 120.8 (CH), 124.1(C), 131.2 (CH), 137.0, 138.6 (C), 166.3,

138.7 (C), 166.4, 172.3 (CO). IR (KBr):

n¼2953, 2928, 2857 (m), 1724,

1691 (s), 1615, 1605, 1526, 1465, 1392, 1311, 1307, 1268 (m), 1223,

1180 (s),1086,1046 (m), 915, 835, 767 (w), 738 (s), 653, 626, 546 (w)

cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼439 ([M]^þ, 41), 310 (30), 226

(100), 208 (68), 182 (84), 152(08). HRMS (EI, 70 eV): calcd for

C₂₇H₃₇NO₄[M]^þ: 439.27171; found: 439.27110.

172.3 (CO). IR (KBr):

n

¼2981, 2928, 2854 (w), 1725(s), 1629, 1599

(w), 1470, 1454 (m), 1372, 1261, 1238 (s), 1109, 1079, 147 (m), 787,

747, 723, 608, 561 (w) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼325

([Mꢁ2]^þ(carbazole), 89), 280 (13), 252 (100), 208 (07), 179 (13).

HRMS (ESI^þ): calcd for C₁₉H₁₉NO₄[Mꢁ2]^þ(carbazole): 325.13141;

found: 325.13161.

3.8.6. Di-tert-butyl 9-methyl-2,9-dihydro-1H-carbazole-2,3-dic

arboxylate (5f). Compound 5f was prepared starting with 2a

(367 mg, 1.0 mmol), tert-butyl acrylate (0.37 mL, 2.5 mmol),

Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %), NEt₃(1.1^ꢀmL,

3.8.3. Dibutyl 9-methyl-2,9-dihydro-1H-carbazole-2,3-dicarboxylate

(5c). Product 5c was prepared starting with 2a (289 mg,

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

5311

8.0 mmol), DMF (mL) at 120 ^ꢀC for 48 h according to general pro-

(12), 152 (9). HRMS: m/z calcd for C₁₉H₁₉NO₄[M]^þ: 325.13141;

found: 325.131001.

cedure B, as a light brown solid (325 mg, 85%), mp 105e107 ^ꢀC. ¹H

NMR (250 MHz, CDCl₃):

d

¼1.30 (s, 9H, 3CH₃),1.50 (s, 9H, 3CH₃), 2.90

(dd, 1H_a, J¼8.9, 17.1 Hz, H-1), 3.50 (dd, 1H_b, J¼2.5, 17.1 Hz, H-1), 3.60

(s, 3H, NCH₃), 3.90 (dd, 1H_a, J¼2.1, 8.9 Hz, H-2), 7.00e7.10 (m, 2H,

ArH), 7.10e7.20 (m, 1H, ArH), 7.50e7.60 (m, 1H, ArH), 7.80 (s, 1H, H-

3.10.2. Dibutyl 9-methyl-9H-carbazole-2,3-dicarboxylate

(6b). Product 6b was prepared starting with 5c (100 mg,

0.26 mmol), following general procedure C, as a light yellow solid

4). ¹³C NMR (75 MHz, CDCl₃):

d

¼23.6 (CH₂), 27.9 (3CH₃), 28.4

(99 mg, 100%). ¹H NMR (250 MHz, CDCl₃):

d

¼0.90 (t, 3H, J¼7.4 Hz,

(3CH₃), 29.7 (CH, C-4), 39.7 (CH₃N), 79.7 (CeO), 81.0 (CeO), 109.2

CH₃), 0.90 (t, 3H, J¼7.3 Hz, CH₃), 1.30e1.50 (m, 4H, 2CH₂), 1.60e1.80

(m, 4H, 2CH₂), 3.80 (s, 3H, NCH₃), 4.30 (t, 2H, J¼6.8 Hz, CH₂O), 4.30

(t, 2H, J¼6.7 Hz, CH₂O), 7.20e7.30 (m, 1H, ArH), 7.30e7.40 (m, 1H,

ArH), 7.40e7.50 (m, 1H, ArH), 7.60 (s, 1H, H-1), 8.00e8.10 (m, 1H,

(C), 109.5 (CH), 118.0 (CH), 118.7 (C), 120.7, 121.5 (CH), 125.2 (C),

130.6 (CH), 137.9, 139.6 (C), 166.8, 172.5 (CO). IR (KBr):

n

¼3049,

2973, 2930 (w), 1712 (s), 1614, 1598, 1470, 1455, 1390 (m), 1365,

1272, 1242, 1152, 1128, 1110 (s), 1046, 1014 (w), 872, 846, 836 (m),

747, 739 (s), 666, 597, 550 (w) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼

383 ([M]^þ, 7), 325 (54), 269 (100), 252 (86), 225 (80), 207 (44), 179

(82). HRMS (EI, 70 eV): calcd for C₂₃H₂₉NO₄[M]^þ: 383.20966;

found: 383.20855.

ArH), 8.40 (s, 1H, H-4). ¹³C NMR (62 MHz, CDCl₃):

d

¼13.7, 13.8 (CH₃),

19.2, 19.3 (CH₂), 29.4 (NCH₃), 30.6, 30.8 (CH₂), 65.3, 65.7 (CH₂O),

109.0, 109.1, 120.2, 121.0 (CH), 121.7, 122.2 (C), 122.4 (CH), 123.6 (C),

127.1 (CH), 131.1, 141.5, 142.1 (C), 167.9, 169.4 (CO). IR (KBr):

n

¼2956,

2931, 2871 (w),1709 (s),1464, 1387,1362,1340,1325 (m) 1255,1221

(s), 1131, 1106, 1077, 1045 (m), 950, 902, 843, 829 (w), 784, 743, 721

(m), 632, 608, 561 (w) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼381(M^þ,

56), 308 (15), 280 (100), 224 (87), 212 (27), 206 (77), 180 (10), 152

(11). HRMS (EI, 70 eV): calcd for C₂₃H₂₇NO₄[M]^þ: 381.19401; found:

381.19422.

3.8.7. Bis[2-(dimethylamino)ethyl] 9-methyl-2,9-dihydro-1H-carba-

zole-2,3-dicarboxylate (5h). Compound 5h was synthesized start-

ing with 2a (289 mg, 1.0 mmol), 2-(diethylamino)ethyl acrylate

(0.38 mL, 2.5 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %),

NEt₃(1.10 mL, 8.0 mmol), DMF (mL) at 120 ^ꢀC for 48 h following

general procedure B, as a yellow highly viscous oil (326 mg, 79%). ¹H

3.10.3. Dihexyl 9-methyl-9H-carbazole-2,3-dicarboxylate (6c).

Starting with 5e (100 mg) following general procedure C, as a yel-

NMR (250 MHz, CDCl₃):

d

¼2.10 (s, 6H, 2CH₃), 2.30 (s, 6H, 2CH₃),

3.00 (dd, 1H_a, J¼8.8, 17.1 Hz), 3.50e3.60 (m, 4H, NCH₃and H_b-1),

4.00e4.10 (m, 5H, 2NCH₂and H_a-2), 3.30 (t, 4H, J¼6.3 Hz, 2CH₂O),

7.10e7.20 (m, 3H, ArH), 7.50 (dd, 1H, J¼2.3, 8.5 Hz, ArH), 7.90 (s, 1H,

low oil (99 mg, 100%). ¹H NMR (300 MHz, CDCl₃):

d

¼0.82 (t, 3H,

J¼7.1 Hz, CH₃), 0.83 (t, 3H, J¼7.0 Hz, CH₃), 1.24e1.30 (m, 8H, 4CH₂),

1.33e1.40 (m, 4H, 2CH₂), 1.66e1.73 (m, 4H, 2CH₂), 3.75 (s, 3H,

CH₃N), 4.26 (t, 2H, J¼6.7 Hz, CH₂O), 4.28 (t, 2H, J¼6.7 Hz, CH₂O),

7.17e7.23 (m,1H, ArH), 7.32 (d,1H, J¼8.2 Hz, ArH), 7.42e7.47 (m,1H,

ArH), 7.53 (s, 1H, ArH), 8.01 (d, 1H, J¼7.8 Hz, ArH), 8.42 (s, 1H, ArH).

H-4). ¹³C NMR (62 MHz, CDCl₃):

d¼23.8 (CH₂, C-1), 29.8 (NCH₃),

38.9 (CH, C-2), 45.5, 45.8 (2CH₃), 57.3, 57.9 (NCH₂), 62.3, 63.2

(CH₂O), 109.3 (C), 109.6 (CH), 115.7 (C), 117.9, 121.1, 122.0 (CH), 125.1

(C), 132.8 (CH), 138.0, 139.8 (C), 167.2, 173.1 (CO). IR (KBr):

n

¼2943,

¹³C NMR (62.9 MHz, CDCl₃):

28.6, 28.7 (CH₂), 28.7 (CH₃N), 31.5, 30.6 (CH₂) 65.6, 66.0 (CH₂O),

109.0, 109.1, 120.1, 120.9 (CH), 121.7, 122.2 (C), 122.3 (CH), 123.6 (C),

d

¼14.0 (2CH₃), 22.6 (2CH₂), 25.7, 25.7,

2857, 2820, 2769 (w), 1691, 1614, 1525, 1455 (s), 1394, 1370, 1332,

1286 (m), 1225, 1166 (s), 1130, 1097 (m), 1031 (s), 954, 919, 835 (w),

739 (s), 627 (w) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼413 ([M]^þ, 13),

297 (98), 252 (06), 227 (04), 225 (13), 208 (56), 180 (17), 58 (100).

HRMS (EI, 70 eV): calcd for C₂₃H₃₁N₃O₄[M]^þ: 413.23091; found:

413.230881.

127.1 (CH), 131.1, 141.4, 142.1 (C), 167.8, 169.3 (CO). IR (KBr):

n

¼3054,

2953, 2928, 2856 (w), 1712 (s), 1629, 1599, 1561, 1501 (w), 1466 (m),

1387 (w), 1363, 1340, 1325 (m), 1257, 1222 (s), 1132 (m), 1108 (s)

1079, 1046, 1015, 981, 907 (m), 867, 883 (w), 785, 766 (m), 729, 722

(s), 646 (m), 633, 609, 561 (w) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼

437 (M^þ, 41), 353 (10), 252 (100), 225 (10),182 (84),152(08). HRMS:

m/z calcd for C₂₇H₃₅NO₄[M]^þ: 437.25661; found: 437.25410.

3.9. General procedure C for the transformation of 1,2-

dihydrocarbazoles to carbazoles

3.10.4. Di-tert-butyl 9-methyl-9H-carbazole-2,3-dicarboxylate

(6d). Starting with 5f (100 mg) following general procedure C, as

To solution of xylene (5 mL) were added the 1,2-dihy-

drocarbazole (100 mg) and Pd/C (10 mg,10 mol %). The solution was

stirred under reﬂux for 48 h under argon atmosphere. The reaction

mixture was ﬁltered and the ﬁltrate was concentrated in vacuo.

a light yellow oil (99 mg, 100%). ¹H NMR (300 MHz, CDCl₃):

d

¼1.57

(s, 9H, 3CH₃), 1.58 (s, 9H, 3CH₃), 3.78 (s, 3H, CH₃N); 7.17e7.23 (m,

1H, ArH), 7.33 (d, 1H, J¼8.2 Hz, ArH), 7.42e7.47 (m, 1H, ArH), 7.50

(s,1H, ArH), 8.03 (d, 1H, J¼7.8 Hz, ArH), 8.33 (s,1H, ArH). ¹³C NMR

(75 MHz, CDCl₃):

(CeO), 81.8 (CeO), 109.0, 109.1, 119.0, 120.9, 122.0 (CH), 122.4, 123.2,

d

¼28.1 (3CH₃), 28.3 (3CH₃), 29.4 (CH₃N). 81.2

3.10. Synthesis of 3,4-di-substituted carbazoles 6

123.8 (C), 126.8 (CH), 132.8, 141.3, 142.2 (C), 167.0, 168.4 (CO). IR

(KBr):

n

¼2975, 2929, 2849 (w), 1713 (s), 1702, 1628, 1596, 1562,

3.10.1. Diethyl

9-methyl-9H-carbazole-2,3-dicarboxylate

(6a).

1530, 1503, 1475, 1455, 1390 (w), 1365, 1337, 1324, 1269, 1251, 1228,

1165, 1129, 1108 (s), 1079, 1046, 1014, 955, 895, 876, 863, 834, 800,

Starting with 5b (100 mg) following general procedure C, 6a was

prepared as a light yellow oil (99 mg, 100%). ¹H NMR (300 MHz,

787, 777, 763, 756, 738, 718 (m), 666, 634, 598, 565, 555 (w) cm^ꢁ1

.

CDCl₃):

d

¼1.31 (t, 3H, J¼7.1 Hz, CH₃), 1.33 (t, 3H, J¼7.1 Hz, CH₃), 3.81

EI^þ(70 eV): m/z (%)¼381 ([M]^þ, 27), 325 (5), 270 (13), 269 (100),

251 (48), 252 (33), 225 (8), 207 (10), 179 (35). HRMS: m/z calcd for

C₂₃H₂₈NO₄[MþH]^þ: 382.20128; found: 382.20055.

(s, 3H, CH₃N), 4.32 (q, 2H, J¼7.2 Hz, CH₂O), 4.43 (q, 2H, J¼7.2 Hz,

CH₂O), 7.21e7.31 (m, 1H, ArH), 7.32e7.41 (m, 1H, ArH), 7.40e7.51

(m, 1H, ArH), 7.60 (s,1H, ArH), 8.00e8.11 (m, 1H, ArH), 8.51 (s, 1H,

ArH). ¹³C NMR (62 MHz, CDCl₃):

d

¼13.2, 13.3 (CH₃), 28.4 (CH₃N),

3.11. Synthesis of 2-(2-cyanoethyl)-9-methyl-9H-carbazole-3-

carbonitrile (7)

60.3 (CH₂O), 60.7 (CH₂O), 108.0, 108.1, 119.2, 120.0 (CH) 120.6, 121.2

(C), 121.4 (CH), 122.7, (C), 126.1 (CH), 130.1, 140.5, 141.2 (C), 166.8,

168.2 (CO). IR (KBr):

n

¼2916 (w), 1713, 1702, 1628, 1599, 1559, 1499,

Product 7 was prepared, starting with 2a (289 mg, 1.0 mmol),

Pd(OAc)₂(11 mg, 5 mol %), acrylonitrile (0.17 mL, 2.5 mmol), SPhos

(10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ^ꢀC for 48 h

according to general procedure B, as a light yellow crystals (127 mg,

1475, 1447, 1427 (m), 1392, 1372, 1339, 1328 (s), 1254, 1240, 1227

(w), 1124, 1106, 1080, 1047, 1030, 953, 913, 868, 835, 794, 781, 765,

748, 725, 664, 656, 626, 590, 556 (s) cm^ꢁ1. GCeMS (EI, 70 eV): m/z

(%)¼325 (M^þ, 95), 280 (12), 253 (21), 252 (100), 251 (5), 208 (7), 179

49%), mp 185e187 ^ꢀC. ¹H NMR (300 MHz, CDCl₃):

d¼2.80 (t, 2H,

5312

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

J¼7.1 Hz, CH₂), 3.30 (t, 2H, J¼7.1 Hz, CH₂), 3.80 (s, 3H, NCH₃),

7.20e7.30 (m, 1H, ArH), 7.30 (s, 1H, H-1), 7.40 (d, 1H, J¼8.2 Hz, ArH),

7.40e7.50 (m, 1H, ArH), 8.00 (d, 1H, J¼7.9 Hz, ArH), 8.30 (s, 1H, H-4).

following general procedure D, as a yellowish highly viscous oil

(264 mg, 69%). ¹H NMR (250 MHz, CDCl₃):

d¼3.60 (s, 3H, CH₃O),

3.70 (s, 3H, OCH₃), 3.70 (s, 3H, NCH₃), 3.80 (s, 3H, OCH₃), 6.20 (d, 1H,

J¼16.1 Hz, ArH), 6.40 (d, 1H, J¼15.9 Hz, ArH), 6.40 (d, 1H, J¼15.9 Hz,

ArH), 7.20e7.40 (m, 2H, ArH), 7.70 (d, 1H, J¼15.9 Hz, ArH), 7.80 (d,

1H, J¼16.2 Hz, ArH), 7.80 (dd, 1H, J¼1.3, 7.5 Hz, ArH), 7.90 (d, 1H,

¹³C NMR (75 MHz, CDCl₃):

d

¼18.0 (CH₂), 28.4 (NCH₃), 30.0 (CH₂),

100.4 (C), 108.2, 108.9 (CH), 117.6, 118.1 (CN), 119.6, 119.7 (CH), 120.6,

121.2 (C), 125.1, 126.3 (CH), 137.1, 140.8, 141.9 (C). IR (KBr):

n

¼2914,

2852 (w), 2206 (s), 1631, 1597, 1557, 1504, 1464, 1432, 1366, 1330,

1320, 1264, 1253 (m), 1112, 1153, 1014, 966, 898 (w), 844, 800, 767,

754 (s), 725, 666, 652, 550, 530 (w) cm^ꢁ1. GCeMS (EI, 70 eV): m/z

(%)¼259 ([M]^þ, 53), 243 (23), 198 (100), 152 (68), 112 (38). HRMS

(EI, 70 eV): calcd for C₁₇H₁₃N₃[M]^þ: 259.11095; found: 259.11041.

J¼15.9 Hz, ArH). ¹³C NMR (75 MHz, CDCl₃):

¼29.4 (CH₃CN), 51.0,

d

52.1, 52.2 (OCH₃), 108.7 (C), 110.6, 115.0, 115.3, 119.3, 119.4, 123.0

(CH), 125 (C), 128.9 (CH), 129.0 (C), 134.2 (CH), 136.3, 137.1 (C), 143.2

(CH), 164.4, 165.6, 166.1 (CO). IR (KBr):

n

¼3028, 2950, 2848 (w),

1710, 1615, 1606 (s), 1298, 1283 (m), 1163, 1138 (s), 1037, 973 (m),

842, 781, 767, 746, 628, 606, 585 (w) cm^ꢁ1. GCeMS (EI, 70 eV): m/z

(%)¼383 (M^þ, 60), 352 (07), 324 (64), 292 (100), 265 (32), 234 (19),

204 (19). HRMS (EI, 70 eV): calcd for C₂₁H₂₁NO₆[M]^þ: 383.13634;

found: 383.136074.

3.12. Synthesis of 6-bromo-2,3-bis(alkenyl)-N-methylindole 9

3.12.1. Di(tert-butyl) 3,3⁰-(6-bromo-1-methyl-1H-indole-2,3-diyl)di-

acrylate (9). Product 9 was prepared starting with 2b (368 mg,

1.0 mmol) and tert-butyl acrylate (0.37 mL, 2.5 mmol), Pd(OAc)₂

(11 mg, 5 mol %), SPhos (10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF

(5 mL) at 90 ^ꢀC for 24 h following general procedure A, as a yellow

solid (276 mg, 75%), mp 148e152 ^ꢀC. The structure was conﬁrmed

by 2D NMR analysis (NOESY, HMBC). ¹H NMR (250 MHz, CDCl₃):

3.13.2. Trihexyl

3,3⁰,3⁰⁰-(1-methyl-1H-indole-2,3,6-triyl)triacrylate

(11d). Product 11d was prepared starting with 2b (367 mg,

1.0 mmol), n-hexyl acrylate (0.66 mL, 3.75 mmol), Pd(OAc)₂(11 mg,

5 mol %), SPhos (10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at

90 ^ꢀC for 36 h following general procedure A, as a yellow highly

d

¼1.50 (s, 18H, 6CH₃), 3.70 (s, 3H, NCH₃), 6.20 (d, 1H, J¼16.1 Hz,

viscous oil (437 mg, 74%). ¹H NMR (250 MHz, CDCl₃):

d

¼0.80 (t, 9H,

ArH), 6.30 (d, 1H, J¼16.1 Hz, ArH), 7.20 (d, 1H, J¼8.4 Hz, ArH), 7.20

(dd, 1H, J¼1.7, 8.6 Hz, ArH), 7.20 (d, J¼1.5 Hz, 1H, ArH), 7.80 (d, 1H,

J¼16.1 Hz), 7.70 (d, 1H, J¼15.9 Hz, ArH). ¹³C NMR (75 MHz, CDCl₃):

J¼6.6 Hz, 3CH₃), 1.10e1.30 (m, 16H, 8CH₂), 1.60e1.70 (m, 8H, 4CH₂),

3.80 (s, 3H, NCH₃), 3.90 (t, J¼6.7 Hz, 2H, CH₂), 4.10e4.30 (m, 4H,

2CH₂), 6.20 (d,1H, J¼16.0 Hz, ArH), 6.40 (d,1H, J¼15.9 Hz, ArH), 6.50

(d, 1H, J¼16.0 Hz, ArH), 7.20e7.40 (m, 2H, ArH), 7.70 (d, 1H,

J¼15.9 Hz, ArH), 7.70 (d, 1H, J¼16.1 Hz, ArH), 7.80 (d, 1H, J¼8.9 Hz,

d

¼28.0 (2CH₃), 28.2 (2CH₃), 28.3 (2CH₃), 31.3 (NCH₃), 81.0, 81.3

(CeO), 113.0 (CH), 113.8, 118.0 (C), 118.9, 122.3 (CH), 124.3 (C), 124.9,

127.0, 129.8, 135.2 (CH), 137.0, 139.0 (C), 165.2, 167.0 (C]O). IR

ArH), 7.90 (d, 1H, J¼16.0 Hz, ArH). ¹³C NMR (62 MHz, CDCl₃):

¼14.0

d

(KBr):

n

¼3090, 2978, 2929 (w),1709,1674,1633,1615 (s),1470, 1454

(3CH₃), 22.6, 25.7, 28.7 (3CH₂), 31.3 (CH₃N), 31.5 (3CH₂), 64.0, 64.7,

65.3 (CH₂O), 109.5 (C), 110.5, 117.3, 117.6 (CH), 117.6(C), 120.3, 120.4,

125.3 (CH), 126.9, 129.6 (C), 130.6, 136.0 (CH), 137.3, 138.0 (C) 143.9

(m), 1365, 1278, 1252, 1147 (s), 1064, 1038 (w), 970, 948 (m), 843,

829, 805 (s), 772, 757, 737, 640, 589 (w) cm^ꢁ1. MS (EI, 70 eV): m/z

(%)¼461 ([M^þ, ⁷⁹Br] 13), 349 (16), 331 (17), 305 (46), 259 (35), 225

(100),181 (97), 57 (38). HRMS (EI, 70 eV): calcd for C₂₃H₂₈BrNO₄[M,

⁷⁹Br]^þ: 461.11962; found: 461.11828.

(CH), 165.0, 166.1, 167.7 (CO). IR (KBr):

n

¼2953, 2927, 2857 (m),

1703, 1610 (s), 1560, 1530 (w), 1465, 1269, 1241, 1204 (m), 1160 (s),

1037, 979, 906, 845, 808, 764, 724, 609, 583 (w) cm^ꢁ1. MS (EI,

70 eV): m/z (%)¼593 (M^þ, 90), 492 (12), 463 (69), 406 (29), 380

(100), 362 (74), 336 (14), 278 (25), 234 (69). HRMS (EI, 70 eV): calcd

for C₃₆H₅₁NO₆[M]^þ: 593.37109; found: 593.36965.

3.12.2. Di(isobutyl) 7-bromo-9-methyl-2,9-dihydro-1H-carbazole-

2,3-dicarboxylate (10). Product 10 was synthesized starting with 2b

(367 mg, 1.0 mmol), iso-butyl acrylate (0.36 mL, 2.5 mmol),

Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %), NEt₃(1.10 mL,

8.0 mmol), DMF (5 mL) at 120 ^ꢀC for 48 h according to general

procedure A, as a yellowish highly viscous oil (335 mg, 73%). ¹H

3.13.3. Tris(tert-butyl)

3,3⁰,3⁰⁰-(1-methyl-1H-indole-2,3,6-triyl)tri-

acrylate (11f). Product 11f was synthesized starting with 2b

(367 mg, 1.0 mmol), tert-butyl acrylate (0.55 mL, 3.75 mmol),

Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %), NEt₃(1.10 mL,

8.0 mmol), DMF (5 mL) at 90 ^ꢀC for 36 h following general pro-

cedure A, as a yellow oil (387 mg, 76%). ¹H NMR (250 MHz, CDCl₃):

NMR (250 MHz, CDCl₃):

d

¼0.70 (d, 6H, J¼6.7 Hz, 2CH₃), 0.80 (d, 6H,

J¼6.7 Hz, 2CH₃), 1.60e1.80 (m, 1H, CH), 1.90e2.00 (m, 1H, CH), 3.50

(dd, 1H_a, J¼2.1, 17.2 Hz, H-1), 3.60 (s, 3H, NCH₃), 3.70 (dd, 2H, J¼3.6,

6.6 Hz, CH₂O), 3.90 (dd, 2H, J¼0.7, 6.5 Hz, CH₂O), 3.90 (dd, 1H_b,

J¼0.7, 6.5 Hz, H-1), 4.00 (dd, 1H_a, J¼2.0, 8.6 Hz, H-2), 7.20 (dd, 1H,

J¼1.6, 8.4 Hz, ArH), 7.30 (d, 1H, J¼1.4 Hz, ArH), 7.40 (d, 1H, J¼8.4 Hz,

d

¼1.50 (s, 9H, 3CH₃), 1.50 (s, 18H, 6CH₃), 3.80 (s, 3H, NCH₃), 6.20 (d,

1H, J¼16.1 Hz, ArH), 6.40 (d, 1H, J¼15.8 Hz, ArH), 6.40 (d, 1H,

J¼16.1 Hz, ArH), 7.30 (dd, 1H, J¼1.0, 8.4 Hz, ArH), 7.40 (s, 1H, ArH),

7.70 (d, 1H, J¼16.1 Hz, ArH), 7.80 (d, 1H, J¼16.1 Hz, ArH), 7.80 (d, 1H,

J¼16.1 Hz, ArH), 7.90 (d, 1H, J¼8.5 Hz, ArH). ¹³C NMR (75.5 MHz,

ArH), 7.80 (s, 1H, H-4). ¹³C NMR (75 MHz, CDCl₃):

d¼18.8,18.9 (CH₃),

19.3 (2CH₃), 23.7 (CH₂), 27.6, 28.0 (CH), 29.9 (NCH₃), 38.8 (CH, C-2),

70.6, 71.2 (CH₂O), 109.4 (C), 112.7 (CH), 115.2, 117.5 (C), 119.1 (CH),

123.9 (C), 124.1, 131.3 (CH), 138.8, 140.2 (C), 167.2, 173.1 (CO). IR

CDCl₃):

d¼28.1 (3CH₃), 28.2 (3CH₃), 28.3 (3CH₃), 31.2 (NCH₃), 80.1,

80.4, 81.4 (CeO), 110.6 (CH), 114.0 (C), 118.9, 119.5, 121.2, 121.4 (CH),

(KBr):

n

¼3052, 2948, 2867 (w), 1728, 1703, 1664, 1588, 1573, 1473,

127.0 (C), 127.2, 129.9 (CH), 130.9 (C), 135.3 (CH), 138.3, 139.0 (C),

1435 (s), 1392, 1379, 1325 (m), 1269, 1244, 1189, 1140, 1079,1040 (s),

998, 975, 934, 904, 872, 853, 813 (w), 776, 736, 691 (s), 660, 646,

608, 576, 562 (m) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼461 ([M,

⁷⁹Br]^þ, 5), 436 (54), 389(10), 299 (100), 267 (70), 225 (12), 178 (17).

HRMS (EI, 70 eV): calcd for C₂₃H₂₈BrNO₄[M, ⁷⁹Br]^þ: 461.12017;

found: 461.12020.

144.0 (CH), 165.2, 166.4, 167.0 (CO). IR (KBr):

n¼2976, 2931 (w),

1699, 1621, 1614 (s), 1455, 1391, 1366 (m), 1306, 1280, 1252, 1140 (s),

1038, 975, 844, 809, 763, 729, 609 (m), 584 (w) cm^ꢁ1. MS (EI, 70 eV):

m/z (%)¼509 (M^þ, 10), 453 (04), 395 (06), 352 (13), 339 (100), 321

(53), 311 (06), 295 (38), 265 (32), 234 (29), 204 (12). HRMS (EI,

70 eV): calcd for C₃₀H₃₉NO₆[M]^þ: 509.27719; found: 509.27692.

3.13. Synthesis of 2,3,6-tris(alkenyl)-N-methylindoles 11

3.13.4. Tris(6-methylheptyl) 3,3⁰,3⁰⁰-(1-methyl-1H-indole-2,3,6-triyl)

triacrylate (11g). Product 11g was synthesized starting with 2b

(367 mg, 1.0 mmol), Pd(OAc)₂(11 mg, 5 mol %), isooctyl acrylate

(0.79 mL, 3.75 mmol), SPhos (10 mol %), NEt₃(1.10 mL, 8.0 mmol),

DMF (5 mL) at 90 ^ꢀC for 36 h following general procedure A, as

3.13.1. Trimethyl 3,3⁰,3⁰⁰-(1-methyl-1H-indole-2,3,6-triyl)triacrylate

(11a). Product 11a was prepared starting with 2b (368 mg,

1.0 mmol), methyl acrylate (0.34 mL, 3.75 mmol), Pd(OAc)₂(11 mg,

5 mol %), SPhos (10 mol %), DMF (5 mL), NEt₃(1.10 mL, 8.0 mmol)

and tert-butyl acrylate (0.3 mL, 3.3 mmol), at 90 ^ꢀC for 36 h

a yellow oil (493 mg, 73%). ¹H NMR (250 MHz, CDCl₃):

d

¼0.60e1.80

(m, 45H, aliphatic protons), 3.80 (s, 3H, NCH₃), 4.00e4.30 (m, 6H,

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

5313

3CH₂O), 6.30 (d, 1H, J¼15.7 Hz, ArH), 6.40 (d, 1H, J¼16.4 Hz, ArH),

6.50 (d, 1H, J¼16.1 Hz, ArH), 7.30e7.40 (m, 2H, ArH), 7.70 (d, 1H,

J¼16.1 Hz, ArH), 7.80 (br d,1H, J¼8.7 Hz, ArH), 7.80 (d,1H, J¼16.8 Hz,

ArH), 7.80 (d, 1H, J¼15.9 Hz, ArH). ¹³C NMR (62.9 MHz, CDCl₃):

2CH₂O), 6.40 (d, 1H, J¼15.9 Hz), 7.30 (m, 2H, ArH), 7.50 (d, 1H,

J¼8.5 Hz, ArH), 7.70 (d, 1H, J¼15.8 Hz), 7.80 (s, 1H, H-4). ¹³C NMR

(62 MHz, CDCl₃):

d

¼14.0 (CH₃), 14.4 (CH₃), 14.5 (CH₃), 23.8 (CH₂),

29.8 (NCH₃), 38.8 (CH, C-2), 60.3 (CH₂O), 60.4 (CH₂O), 61.2 (CH₂O),

109.6 (C), 110.2, 115.9 (CH), 117.4 (C), 118.2, 120.8 (CH), 126.7, 128.3

(C), 131.5 (CH), 138.1, 141.8 (C), 145.7 (CH), 167.1, 167.3, 173.0 (CO).

d¼13.0, 14.6, 15.2 (CH₃), 20.1, 22.9, 24.5, 25.9, 26.7, 27.5 (CH₂), 31.2

(NCH₃), 45.6 (CH₂), 63.0, 63.8, 65.6 (CH₂O), 110.6 (CH), 114 (C), 117.0,

117.9, 121.3, 121.4, 125.3 (CH), 126.9, 130.7 (C), 130.9, 136.0 (CH),

IR (KBr):

n

¼2979, 2931 (m), 1731, 1697, 1606 (s), 1475, 1274 (m),

138.3, 139.0 (C), 145 (CH), 165.9, 167.3, 167.7 (CO). IR (KBr):

n

¼2955,

1227, 1168 (s), 1034, 982, 962, 852, 811, 771, 710 (s), 605, 582 (w)

cm^ꢁ1. MS (EI, 70 eV): m/z (%)¼425 (M^þ, 76), 380 (12), 352 (100),

324 (23), 306 (98), 279 (77), 262 (30), 251 (16), 234 (92), 206 (22).

HRMS (EI, 70 eV): calcd for C₂₄H₂₇NO₆[M]^þ: 425.18329; found:

425.18236.

2927, 2870 (m), 1705, 1623 (s), 1561, 1533 (w), 1463 (s), 1380 (w),

1267, 1234, 1161 (s), 1036, 977, 845, 808, 768, 740, 609 (w) cm^ꢁ1. MS

(EI, 70 eV): m/z (%)¼677 (M^þ, 90), 563 (16), 519 (60), 436 (38), 408

(69), 390 (59), 295 (30), 278 (34), 252 (22), 226 (06), 208 (10), 194

(11). HRMS (EI, 70 eV): calcd for C₄₂H₆₃NO₆[M]^þ: 677.46499;

found: 677.463279.

3.14.3. Dibutyl 7-(3-butoxy-3-oxoprop-1-enyl)-9-methyl-2,9-

dihydro-1H-carbazole-2,3-dicarboxylate (12c). Product 12c was

prepared, following general procedure B, starting with 2b (367 mg,

1.0 mmol), Pd(OAc)₂(11 mg, 5 mol %), n-butyl acrylate (0.53 mL,

3.75 mmol), SPhos (10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL)

at 120 ^ꢀC for 48 h as a yellow solid (483 mg, 95%), mp 112e114 ^ꢀC.

3.13.5. (2E,2⁰E,2⁰⁰E)-trioctadecyl 3,3⁰,3⁰⁰-(1-methyl-1H-indole-2,3,6-

triyl)triacrylate (11h). Starting with Pd(OAc)₂(12 g, 5 mol %) and

SPhos (41 mg, 0.10 mmol), brominated indole 2b (367 mg,

1.0 mmol), 11h was isolated as a yellow oil (702 mg, 64%). ¹H NMR

(300 MHz, CDCl₃):

d

¼0.80 (t, 9H, J¼7.6 Hz, 3CH₃), 0.91e1.21 (m,

¹H NMR (250 MHz, CDCl₃):

d¼0.80 (t, 3H, J¼7.3 Hz, CH₃), 0.90 (t, 3H,

96H, 48CH₂), 3.62e3.75 (m, 4H, 2CH₂O), 3.79 (s, 3H, CH₃N), 3.82 (t,

2H, J¼6.9 CH₂O), 6.24 (d, 1H, J¼16.1 Hz, CH), 6.43 (d, 1H, J¼15.9 Hz,

CH), 6.42 (d, 1H, J¼15.9 Hz, CH), 7.23e7.43 (m, 2H, ArH), 7.72 (d, 1H,

J¼15.9 Hz, CH), 7.83 (d, 1H, J¼16.2 Hz, CH), 7.88 (dd, 1H, J¼1.3,

7.5 Hz, ArH), 7.95 (d,1H, J¼15.9 Hz, CH). ¹³C NMR (75.5 MHz, CDCl₃):

J¼7.3 Hz, CH₃), 0.90 (t, 3H, J¼7.3 Hz, CH₃), 1.10e1.30 (m, 2H, CH₂),

1.30e1.50 (m, 6H, 3CH₂), 1.60e1.70 (m, 4H, 2CH₂), 3.00 (dd, 1H_a,

J¼8.6, 17.2 Hz, H-1), 3.60 (dd, 1H_b, J¼2.2, 17.2 Hz, H-1), 3.70 (s, 3H,

NCH₃), 3.80e4.00 (m, 2H, CH₂O), 4.00 (dd, 1H_a, J¼1.9, 8.6 Hz, H-2),

4.10e4.20 (m, 4H, 2CH₂O), 6.40 (d,1H, J¼15.8 Hz, CH), 7.20e7.30 (m,

2H, ArH), 7.50 (d, 1H, J¼8.3 Hz, ArH), 7.70 (d, 1H, J¼16.1 Hz, ArH),

d

¼14.1 (CH₃), 22.6 (CH₂), 28.4e29.6 (CH₂), 32.8 (CH₃CN), 63.9, 64.6,

65.2 (CH₂O), 108.7 (C), 110.5, 114.2, 115.3, 117.3, 121.3, 123.0 (CH),

125.4 (C), 128.9 (CH), 129.0 (C), 134.2 (CH), 138.3, 139.0 (C), 144.8

(CH), 166.0, 167.1, 167.7 (CO). GCeMS (EI, 70 eV): m/z (%)¼1097

(M^þ,9), 801 (2), 575 (7), 228 (4), 189 (5), 97 (21), 69 (27), 44 (100).

HRMS (ESI^ꢁ): m/z calcd for C₇₂H₁₂₃NO₆[M]^þ: 1097.93504; found:

1097.935219.

7.80 (s,1H, H-4). ¹³C NMR (75 MHz, CDCl₃):

d

¼13.6 (CH₃),13.7 (CH₃),

13.8 (CH₃), 19.0 (CH₂), 19.2 (CH₂), 19.3 (CH₂), 24.0 (CH₂), 29.9 (CH₃),

30.4 (CH₂), 30.8 (CH₂), 31.0 (CH₂), 38.8 (NCH₃), 64.3 (CH₂O), 64.4

(CH₂O), 65.1 (CH₂O), 109.7 (C), 110.2, 116.0 (CH), 117.6 (C), 118.2,

120.8 (CH), 126.7, 128.4 (C), 131.4 (CH), 138.2, 141.8 (C), 145 (CH),

167.2, 167.5, 173.1 (CO). IR (KBr):

n

¼2954, 2931 (m), 1721, 1703, 1676

(s), 1469, 1277 (m), 1219, 1167 (s), 1042, 998, 960, 854 (w), 821, 770,

735 (m), 605, 582, 553 (w) cm^ꢁ1. MS (EI, 70 eV): m/z (%)¼509 ([M]^þ,

78), 436 (14), 408 (72), 378 (20), 352 (100), 334 (94), 308 (18), 278

(31), 234 (94). HRMS (EI, 70 eV): calcd for C₃₀H₃₉NO₆[M]^þ:

509.27719; found: 509.276955.

3.14. Synthesis of 6-alkenyl-2,3-dihydrocarbazoles 12

3.14.1. Dimethyl 7-(3-methoxy-3-oxoprop-1-enyl)-9-methyl-2,9-

dihydro-1H-carbazole-2,3-dicarboxylate (12a). Compound 12a was

prepared starting with 2b (367 mg, 1.0 mmol), methyl acrylate

(0.34 mL, 3.75 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %),

NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ^ꢀC for 48 h according to

general procedure B, as a brownish highly viscous oil (302 mg, 79%).

3.14.4. Di(isobutyl) 7-(3-isobutoxy-3-oxoprop-1-enyl)-9-methyl-2,9-

dihydro-1H-carbazole-2,3-dicarboxylate (12d). Product 12d was

prepared starting with 2b (367 mg, 1.0 mmol), iso-butyl acrylate

(0.54 mL, 3.75 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %),

NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ^ꢀC for 48 h following

general procedure B, as a yellow solid (363 mg, 72%). ¹H NMR

¹H NMR (250 MHz, CDCl₃):

d

¼3.00 (dd, 1H_a, J¼8.5, 17.3 Hz, H-1),

3.50 (s, 3H, NCH₃), 3.60 (dd, 1H_b, J¼2.4, 17.3 Hz, H-1), 3.60 (s, 3H,

OCH₃), 3.70 (s, 3H, OCH₃), 3.80 (s, 3H, OCH₃), 4.00 (dd, 1H_a, J¼2.4,

8.8 Hz, H-2), 6.40 (d, 1H, J¼15.9 Hz, ArH), 7.30e7.40 (m, 2H, ArH),

7.50 (d, 1H, J¼8.6 Hz, ArH), 7.70 (d, 1H, J¼15.9 Hz, ArH), 7.90 (s, 1H,

(250 MHz, CDCl₃):

d¼0.70 (d, 6H, J¼6.7 Hz, 2CH₃), 0.90 (dd, 12H,

J¼3.4, 6.7 Hz, 4CH₃), 1.70e1.80 (m, 1H, CH), 1.90e2.00 (m, 2H, CH),

3.00 (dd, 1H_a, J¼8.7, 17.2 Hz, H-1), 3.60 (dd, 1H_b, J¼2.0, 17.2 Hz, H-

1), 3.60e3.70 (m, 5H, NCH₃and CH₂O), 3.90e4.00 (m, 4H, 2CH₂O),

4.10 (dd, 1H_a, J¼2.0, 8.5 Hz, H-2), 6.20 (d, 1H, J¼15.8 Hz, ArH), 7.30

(d, 1H, J¼8.4 Hz, ArH), 7.40 (s, 1H, ArH), 7.60 (d, 1H, J¼8.2 Hz, ArH),

7.80 (d, 1H, J¼15.9 Hz, ArH), 7.90 (s, 1H, H-4). ¹³C NMR (75 MHz,

H-4). ¹³C NMR (75 MHz, CDCl₃):

d¼23.0 (CH₂), 29.7 (CH, C-4), 38.7

(NCH₃), 51.6 (OCH₃), 51.8 (OCH₃), 52.6 (OCH₃), 108.7, 110.4 (CH),

114.6, 115.9 (CH), 117.3, 120.0 (CH), 125.8, 127.4, 131.0 (CH), 137.2,

141.0, 145.0 (CH), 166.5, 166.8, 172.5 (C). IR (KBr):

n

¼2999, 2950,

2846 (w), 1709 (s), 1628, 1605, 1270, 1231, 1188, 1166, 1110, 1040,

1060 (m), 973, 803 (s), 778 (s), 727 (m) cm^ꢁ1. GCeMS (EI, 70 eV): m/

z (%)¼383 [M]^þ, 353 (69), 323 (61), 293 (40), 284 (51), 189 (31), 102

(100), 77 (22). HRMS (EI, 70 eV): calcd for C₂₁H₂₁NO₆[M]^þ:

383.13689; found: 383.13632.

CDCl₃):

d

¼18.8 (CH₃), 18.9 (CH₃), 19.2 (2CH₃), 19.3 (2CH₃), 23.9

(CH₂), 27.6, 27.9, 28.0 (CH), 29.9 (NCH₃), 38.8 (CH, C-2), 70.5, 70.6,

71.2 (CH₂O), 109.7 (C), 110.3, 116.3 (CH), 117.6 (C), 118.2, 120.9 (CH),

126.7, 128.4 (C), 131.3 (CH), 138.2, 141.9 (C), 145.7(CH), 167.1, 167.5,

173.0 (CO). IR (KBr):

n

¼2956, 2872 (w), 1715, 1693 (s), 1633, 1608,

3.14.2. Diethyl 7-(3-ethoxy-3-oxoprop-1-enyl)-9-methyl-2,9-

dihydro-1H-carbazole-2,3-dicarboxylate (12b). Product 12b was

synthesized starting with 2b (367 mg, 1.0 mmol), ethyl acrylate

(0.41 mL, 3.75 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %),

NEt₃(1.1^ꢀmL, 8.0 mmol), DMF (5 mL) at 120 ^ꢀC for 48 h following

general procedure B, as yellowish highly viscous oil (285 mg, 67%).

1529, 1494, 1468, 1454, 1392, 1375, 1355, 1309, 1278 (m), 1228,

1205, 1166 (s), 1110, 1086, 1038, 1017, 989 (m), 942, 930, 852, 832,

799, 779, 756, 731, 705, 650, 615, 600, 550 (w) cm^ꢁ1. GCeMS (EI,

70 eV): m/z (%)¼507 ([Mꢁ2]^þ(carbazole), 100), 451 (36), 407 (22),

378 (78), 352 (29), 278 (18), 251 (11), 234 (25), 204 (12). HRMS (EI,

70 eV): calcd for C₃₀H₃₇NO₆[Mꢁ2]^þ(carbazole): 507.26154;

found: 507.26138.

¹H NMR (250 MHz, CDCl₃):

d¼1.10 (t, 3H, J¼7.3 Hz, CH₃), 1.20 (t,

3H, J¼7.1 Hz, CH₃), 1.30 (t, 3H, J¼7.0 Hz, CH₃), 3.00 (dd, 1H_a, J¼8.8,

17.2 Hz, H-1), 3.50 (dd, 1H_b, J¼2.4, 17.2 Hz, H-1), 3.60 (s, 3H, NCH₃),

3.80e4.10 (m, 3H and 1H_a, H-2 and CH₂O), 4.10e4.30 (m, 4H,

3.14.5. Dihexyl 7-(3-(hexyloxy)-3-oxoprop-1-enyl)-9-methyl-2,9-

dihydro-1H-carbazole-2,3-dicarboxylate (12e). Product 12e was

5314

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

prepared, starting with 2b (367 mg, 1.0 mmol), n-hexyl acrylate

(0.66 mL, 3.75 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %),

NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ^ꢀC for 48 h following

general procedure B, as a yellowish highly viscous oil (435 mg, 74%).

519 (44), 434 (60), 408 (99), 390 (81), 234 (44). HRMS (EI, 70 eV):

calcd for C₄₂H₆₃NO₆[M]^þ: 677.46499; found: 677.46337.

3.15. Synthesis of 6-alkenylcarbazoles 13

¹H NMR (300 MHz, CDCl₃):

d¼0.70 (t, 3H, J¼6.9 Hz, CH₃), 0.80 (t, 3H,

J¼6.3 Hz, CH₃), 0.80 (t, 3H, J¼6.9 Hz, CH₃), 1.00e1.20 (m, 6H, 3CH₂),

1.20e1.40 (m, 14H, 7CH₂), 1.60e1.70 (m, 4H, 2CH₂), 3.00 (dd, 1H_a,

J¼8.6, 17.1 Hz, H-1), 3.60 (dd, 1H_b, J¼2.1, 17.1 Hz, H-1), 3.70 (s, 3H,

NCH₃), 3.80e4.00 (m, 2H, CH₂O), 4.00 (dd, 1H_a, J¼2.1, 8.7 Hz, H-2),

4.10 (t, 2H, J¼6.8 Hz, CH₂O), 4.20 (t, 2H, J¼6.8 Hz, CH₂O), 6.40 (d, 1H,

J¼15.8 Hz, ArH), 7.30 (d,1H, J¼8.4 Hz, ArH), 7.30 (s,1H, ArH), 7.50 (d,

1H, J¼8.1 Hz, ArH), 7.70 (d, 1H, J¼16.0 Hz, CH), 7.80 (s, 1H, H-4). ¹³C

3.15.1. (E)-Dimethyl 7-(3-methoxy-3-oxoprop-1-enyl)-9-methyl-9H-

carbazole-2,3-dicarboxylate (13a). Starting with 12a (100 mg) fol-

lowing general procedure C, 13a was isolated as a yellow oil (98 mg,

100%). ¹H NMR (300 MHz, CDCl₃):

d

¼3.77 (s, 3H, CH₃N), 3.83 (s, 3H,

CH₃O), 3.89 (s, 3H, CH₃O), 3.91 (s, 3H, CH₃O), 6.51 (d, 1H J¼16.0 Hz),

7.44 (d, 1H, J¼8.2 Hz, ArH), 7.49 (s, 1H, ArH), 7.59 (s, 1H, ArH), 7.82

(d, 1H, J¼16.0 Hz, ArH), 8.03 (d, 1H, J¼8.1 Hz, ArH), 8.48 (s, 1H, ArH).

NMR (62 MHz, CDCl₃):

d

¼13.9 (CH₃), 14.0 (2CH₃), 22.4 (CH₂), 22.5

¹³C NMR (62.9 MHz, CDCl₃):

109.2, 109.3, 118.0, 120.1, 121.3 (CH) 121.7 (C), 122.9 (CH), 123.3,

123.9, 131.4, 133.5, 142.3, 142.4 (C), 145.3 (CH), 167.4, 168.0, 169.4

d

¼29.5 (CH₃N), 51.8, 52.5, 52.8 (CH₃O),

(2CH₂), 23.9, 25.4, 25.6, 25.7, 28.4, 28.7, 28.8 (CH₂), 29.9 (NCH₃),

31.3, 31.4, 31.5 (CH₂), 38.8, (C(2)H), 64.5, 64.7, 65.3 (CH₂O),109.7 (C),

110.2, 116.0 (CH), 117.6 (C), 118.2, 120.8 (CH), 126.7, 128.4 (C), 131.4

(CH), 138.1, 141.8 (C), 145,7 (CH), 167.1, 167.4, 173.1 (CO). IR (KBr):

(CO). IR (KBr):

n

¼3047, 3004, 2917, 2848 (w), 1708 (s), 1627 (m),

1563, 1498 (w), 1431 (m), 1376 (w), 1351, 1314 (m), 1272, 1259, 1245,

1232,1173,1110 (s),1080,1039, 974, 964 (m), 930, 900, 881 (w), 839,

826,803, 777, 760 (m), 747, 729 (w), 711, 653, 603, 584 (m), 551(w)

cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼381 ([M]^þ, 100), 351 (16), 350

(80), 204 (11), 159 (42), 145 (22). HRMS: m/z calcd for C₂₁H₁₉NO₆

[M]^þ: 381.12069; found: 381.120947.

n

¼2954, 2928, 2857 (m), 1715, 1695, 1629, 1605 (s), 1558, 1527, 1488

(w), 1471 (w), 1395, 1303, 1278 (m), 1245, 1228 (w), 1162 (s), 974,

908, 848, 821, 754, 730, 700, 607, 592 (w) cm^ꢁ1. MS (EI, 70 eV): m/z

(%)¼593 ([M]^þ, 62), 492 (09), 464 (41), 406 (07), 380 (100), 362

(72), 336 (08), 278 (20), 251 (9), 234 (53). HRMS (EI, 70 eV): calcd

for C₃₆H₅₁NO₆[M]^þ: 593.37109; found: 593.37046.

3.15.2. (E)-Diethyl 7-(3-ethoxy-3-oxoprop-1-enyl)-9-methyl-9H-car

bazole-2,3-dicarboxylate (13b). Starting with 12b (100 mg) fol-

lowing general procedure C, 13b was prepared as a yellow oil

3.14.6. Di(tert-butyl) 7-(3-tert-butoxy-3-oxoprop-1-enyl)-9-methyl-

2,9-dihydro-1H-carbazole-2,3-dicarboxylate (12f). Product 12f was

synthesized starting with 2b (367 mg, 1.0 mmol), Pd(OAc)₂(11 mg,

(98 mg, 100%). ¹H NMR (300 MHz, CDCl₃):

d¼1.23 (t, 3H, J¼7.1 Hz,

5

mol %), tert-butyl acrylate (0.55 mL, 3.75 mmol), SPhos

CH₃), 1.31 (t, 3H, J¼7.1 Hz, CH₃), 1.32 (t, 3H, J¼7.1 Hz, CH₃), 3.81 (s,

3H, CH₃N), 4.20 (q, 2H, J¼7.0 Hz, CH₂O), 4.31 (q, 2H, J¼7.0 Hz, CH₂O),

4.31 (q, 2H, J¼7.0 Hz, CH₂O), 6.51 (d, 1H, J¼15.7 Hz), 7.40 (d, 1H,

J¼7.9 Hz, ArH), 7.41 (s, 1H, ArH), 7.51 (s, 1H, ArH), 7.80 (d, 1H,

J¼15.7 Hz), 8.02 (d, 1H, J¼7.9 Hz, ArH), 8.41 (s, 1H, ArH). ¹³C NMR

(10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ^ꢀC for

48 h following general procedure B, as a yellow oil (401 mg, 79%).

¹H NMR (250 MHz, CDCl₃):

d¼1.30 (s, 9H, 3CH₃), 1.40 (s, 9H, 3CH₃),

1.50 (s, 9H, 3CH₃), 3.00 (dd, 1H_a, J¼8.7, 17.1 Hz, H-1), 3.60 (dd, 1H_b,

J¼2.2, 17.1 Hz, H-1), 3.70 (s, 3H, NCH₃), 3.90 (dd, 1H_a, J¼2.2, 8.7 Hz,

H-2), 6.30 (d, 1H, J¼16.0 Hz, ArH), 7.30 (dd, 1H, J¼1.2, 8.2 Hz, ArH),

7.30 (s, 1H, ArH), 7.50 (d, 1H, J¼8.2 Hz, ArH), 7.60 (d, 1H, J¼15.9 Hz,

(62 MHz, CDCl₃):

60.5, 61.4, 61.8 (CH₂O), 109.0, 109.2, 118.4, 120.0, 121.3 (CH), 122.1

(C), 122.7 (CH), 123.1, 123.8, 131.7, 133.4, 142.2, 142.3 (C), 145.0 (CH),

d

¼14.1 (CH₃), 14.3 (CH₃), 14.4 (CH₃), 29.4 (CH₃N),

ArH), 7.70 (s, 1H, H-4). ¹³C NMR (75 MHz, CDCl₃):

d¼23.6 (CH₂),

167.0, 167.5, 169.0 (CO). IR (KBr):

n

¼2979, 2849 (m), 1703 (s), 1628,

27.9, 28.2, 28.3 (3CH₃), 29.8 (NCH₃), 39.6 (CH, C-2), 78.9, 79.2, 80.1

(CeO), 108.5 (C), 109.9, 116.7, 117.2 (CH), 118.6, (C), 119.6 (CH),

125.6, 127.3 (C), 130 (CH), 137.1, 140.7 (C), 143.8 (CH), 165.5, 165.7,

1604, 1560, 1498, 1473, 1391, 1373, 1343, 130 (m), 1258, 1240, 1227

(s), 1173, 1108, 1078, 1039, 975 (m), 908, 874, 842, 804 (w), 779, 730,

664, 606, 585 (s) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼423 ([M]^þ, 99),

378 (6), 349 (41), 322 (6), 162 (7), 153 (100), 139 (58). HRMS: m/z

calcd for C₂₄H₂₅NO₆[M]^þ: 423.16764; found: 423.16659.

171.2 (C]O). IR (KBr):

n

¼2976, 2931 (w), 1705 (s), 1631, 1612, 1469,

1461, 1454, 1391 (w), 1366, 1277, 1255 (m), 1147 (s), 1113, 1080,

1041, 980, 846, 812, 791, 765, 608 (w) cm^ꢁ1. MS (EI, 70 eV): m/z

(%)¼509 ([M]^þ, 02), 507 (33), 451 (51), 395 (39), 378 (15), 339 (95),

321 (100), 295 (17), 277 (34), 249 (80), 204 (12), 176 (5). HRMS (EI,

70 eV): calcd for C₃₀H₃₇NO₆([Mꢁ2H]^þcarbazole): 507.26154;

found: 507.26178.

3.15.3. (E)-Dibutyl 7-(3-butoxy-3-oxoprop-1-enyl)-9-methyl-9H-car

bazole-2,3-dicarboxylate (13c). Starting with 12c (100 mg) follow-

ing general procedure C, 13c was prepared as a yellow oil (99 mg,

100%). ¹H NMR (300 MHz, CDCl₃):

d

¼0.81 (t, 3H, J¼7.4 Hz, CH₃), 0.91

(t, 3H, J¼7.4 Hz, CH₃), 0.93 (t, 3H, J¼7.4 Hz, CH₃), 1.10e1.31 (m, 2H,

CH₂), 1.31e1.52 (m, 6H, 3CH₂), 1.57e1.71 (m, 4H, 2CH₂), 3.71 (s, 3H,

CH₃N), 4.22 (t, 2H, J¼6.9 Hz, CH₂O), 4.31 (t, 2H, J¼6.6 Hz, CH₂O),

4.34 (t, 2H, J¼6.6 Hz, CH₂O), 6.52 (d, 1H, J¼16.1 Hz, CH), 7.42 (d, 1H,

J¼8.5 Hz, ArH), 7.51 (s, 1H, ArH), 7.62 (s, 1H, ArH), 7.80 (d, 1H,

J¼15.3 Hz, CH), 8.01 (d,1H, J¼7.6 Hz, ArH), 8.51 (s,1H, ArH). ¹³C NMR

3.14.7. Bis(6-methylheptyl) 9-methyl-7-(3-(6-methylheptyloxy)-3-

oxoprop-1-enyl)-2,9-dihydro-1H-carbazole-2,3-dicarboxylate

(12g). Compound 12g was synthesized starting with 2b (367 mg,

1.0 mmol), isooctyl acrylate (0.79 mL, 3.75 mmol), Pd(OAc)₂(11 mg,

5 mol %), SPhos (10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at

120 ^ꢀC for 48 h following general procedure B, as a yellow oil

(62.9 MHz, CDCl₃):

30.7, 30.8 (CH₂), 64.5, 65.4, 65.8 (CH₂O), 109.1, 109.2, 118.4, 120.1,

121.3 (CH), 122.3 (C), 122.7 (CH), 123.2, 123.9, 131.8, 133.5, 142.3,

d

¼13.8 (3CH₃), 19.3 (3CH₂), 29.5 (CH₃N), 30.6,

(501 mg, 74%). ¹H NMR (250 MHz, CDCl₃):

d

¼0.60e1.80 (m, 45H,

aliphatic), 3.00 (dd, 1H_a, J¼8.9, 17.2 Hz, H-1), 3.60e3.70 (m, 4H, 1ꢂ

H_b-1 and NCH₃), 3.90e4.30 (m, 7H, 3CH₂O and H_a-2), 6.40 (d, 1H,

J¼15.9 Hz, ArH), 7.30e7.40 (m, 2H, ArH), 7.50 (d, 1H, J¼8.8 Hz, ArH),

7.80 (d, 1H, J¼16.4 Hz), 7.90 (s, 1H, H-4). ¹³C NMR (75 MHz, CDCl₃):

142.4 (C), 145.0 (CH), 167.1, 167.6, 169.1 (CO). IR (KBr):

n

¼2931 (w),

1706, 1627, 1602, 1563, 1500, 1455, 1387, 1343 (w), 1258 (m), 1223,

1163, 1106, 1077, 1038, 977, 901, 843, 810, 779, 738, 715, 663, 609,

583 (s) cm^ꢁ1. MS (EI, 70 eV): m/z (%)¼507 ([M]^þ, 100), 434 (6), 378

(33), 332 (7), 278 (4). HRMS: m/z calcd for C₃₀H₃₇NO₆[M]^þ:

507.26154; found: 507.26156.

d

¼12.2 (2CH₃), 14.1 (2CH₃), 14.4 (2CH₃), 19.6, 23.4, 29.1 (CH₂), 25.0,

27.0 (CH), 29.9 (CH₃N), 31.9 (CH), 38.8 (CH, C-2), 46.5, 46.6, 46.7

(CH₂), 64.9, 65.0, 65.3 (CH₂O), 108.7 (C), 109.2, 115.0 (CH), 116.6 (C),

117.2, 119.9 (CH), 125.7, 127.6 (C), 130.4 (CH), 137.2, 140.9 (C), 145.7

(CH), 166.1, 166.5, 172.1 (CO). IR (KBr):

n

¼2955, 2927 (w), 1704, 1631,

3.15.4. (E)-Dihexyl 7-(3-(hexyloxy)-3-oxoprop-1-enyl)-9-methyl-9H-

carbazole-2,3-dicarboxylate (13e). Starting with 12e (100 mg) fol-

lowing general procedure C, 13e was isolated as yellow oil (98 mg,

1608 (s), 1562, 1527 (w), 1462, 1382, 1366, 1305 (m), 1267, 1228,

1206, 1161 (s), 1112, 1084, 1039, 847, 809, 780 (m), 609, 581 (w)

cm^ꢁ1. MS (EI, 70 eV): m/z (%)¼677 ([M]^þ, 100), 563 (21), 548 (14),

100%). ¹H NMR (300 MHz, CDCl₃):

d

¼0.81 (t, 3H, J¼6.9 Hz, CH₃),

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

5315

0.82 (t, 6H, J¼7.0 Hz, 2CH₃), 1.21e1.33 (m, 12H, 6CH₂), 1.30e1.41 (m,

6H, 3CH₂), 1.61e1.70 (m, 6H, 3CH₂), 3.81 (s, 3H, CH₃N), 4.10 (t, 2H,

J¼6.7 Hz, CH₂O), 4.21 (t, 2H, J¼7.0 Hz, CH₂O), 4.32 (t, 2H, J¼7.0 Hz,

CH₂O), 6.52 (d,1H, J¼16.2 Hz), 7.41 (d,1H, J¼8.1 Hz, ArH), 7.51 (s,1H,

ArH), 7.63 (s, 1H, ArH), 7.81 (d, 1H, J¼16.2 Hz), 8.01 (d, 1H, J¼8.1 Hz,

38.8 (CH, C-2), 60.4, 60.5, 60.5, 61.3 (CH₂O),108.6 (CH),109.8 (C),117.3

(CH), 118.0 (C), 119.6, 119.8 (CH), 126.4, 127.9, 128.8 (C), 130.8 (CH),

138.8 (C),142.5,142.6 (CH),142.7 (C),166.6,166.7,166.9,172.9 (CO). IR

(KBr):

n¼2989, 2934, 2903 (w), 1694, 1625, 1604 9 (s), 1528, 1477,

1464,1446,1392,1367 (m),1274,1220,1158 (s),1111,1092,1034, 973,

914, 855 (m), 777 (w), 727 (m), 660, 646, 612, 558 (w) cm^ꢁ1. GCeMS

(EI, 70 eV): m/z (%)¼523 (M^þ, 100), 478 (18), 450 (88), 404 (84), 375

(23), 332 (22), 303 (34), 275 (25), 231 (51), 217 (9). HRMS (EI, 70 eV):

calcd for C₂₉H₃₃NO₈(M^þ): 523.22062; found: 523.22073.

ArH), 8.41 (s, 1H, ArH). ¹³C NMR (75 MHz, CDCl₃):

d¼13.0 (3CH₃),

22.6 (4CH₂), 24.5 (3CH₂), 27.5, 27.6, 27.7 (CH₂), 28.4 (CH₃N), 30.5

(2CH₂), 63.8, 64.7, 65.1 (CH₂O), 108.0, 108.2, 117.4, 119.0, 120.3 (CH),

121.2 (C), 121.7 (CH), 122.1, 122.9, 130.8, 132.4, 141.2, 141.3 (C), 144.0

(CH), 166.1, 166.6, 168.1 (CO). IR (KBr):

n

¼2927 (w), 1708 (s), 1627,

1602, 1563, 1500, 1455, 1388, 1369, 1343, 1305 (m), 1259, 1224, 1163,

1108 (s), 1078, 1038, 979, 905, 845, 810, 781, 725, 663, 642, 609,

583,543 (w) cm^ꢁ1. (EI^þ, 70 eV): m/z (%)¼591 ([M]^þ, 100), 406 (26),

322 (05), 43 (08). HRMS: m/z calcd for C₃₆H₄₉NO₆[M]^þ: 591.35544;

found: 591.35593.

3.15.8. Dibutyl

6,7-bis((E)-3-butoxy-3-oxoprop-1-enyl)-9-methyl-

2,9-dihydro-1H-carbazole-2,3-dicarboxylate (15c). Product 15c was

prepared starting with 2c (446 mg, 1.0 mmol), n-butyl acrylate

(0.70 mL, 5.0 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %),

NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ^ꢀC for 48 h following

general procedure B, as a yellow highly viscous oil (450 mg, 71%). ¹H

3.15.5. (2E,2⁰E)-Diethyl 3,3⁰-(1-methyl-1H-indole-2,6-diyl)diacrylate or

(2E,2⁰E)-diethyl 3,3⁰-(1-methyl-1H-indole-3,6-diyl)diacrylate (14). Pro

duct 14 was isolated as a side product of 12b as a light brown oil. ¹H

NMR (300 MHz, CDCl₃):

d

¼0.9 (t, 3H, J¼7.2 Hz, CH₃), 0.9 (t, 3H,

J¼7.4 Hz, CH₃), 0.9 (t, 6H, J¼7.3 Hz, 2CH₃), 1.3e1.4 (m, 8H, 4CH₂),

1.6e1.7 (m, 8H, 4CH₂), 3.0 (dd, 1H_a, J¼8.5, 17.3, Hz, C-1), 3.6 (dd, 1H_b,

J¼2.0, 17.2 Hz, C-1),3.7 (s, 3H, CH₃N), 4.0 (dd, 1H, J¼2.0, 8.8 Hz, C-2),

4.1 (t, 4H, J¼6.7 Hz, 2CH₂O), 4.2 (t, 4H, J¼6.7 Hz, 2CH₂O), 6.2 (d, 1H,

J¼15.5 Hz, CH), 6.3 (d, 1H, J¼16.4 Hz, CH), 7.4 (s, 1H, ArH), 7.8 (s, 1H,

ArH), 7.8 (s, 1H, C-4), 8.0 (d, 1H, J¼16.4 Hz, H), 8.0 (d, 1H, J¼15.5 Hz,

NMR (250 MHz, CDCl₃):

d

¼1.19e1.31 (m, 6H, 2CH₃), 3.78 (s, 3H,

NCH₃), 4.16e4.26 (m, 4H, 2CH₂O), 6.41 (d,1H, J¼15.9 Hz, CH), 6.44 (d,

1H, J¼15.7 Hz, CH), 6.87 (s, 1H, ArH), 7.27 (dd, J¼1.2, 8.5, ArH), 7.3 (s,

1H, ArH), 7.50 (d, 1H, J¼8.5 Hz, ArH), 7.70 (d,1H, J¼15.4 Hz, ArH), 7.73

(d, 1H, J¼15.4 Hz, ArH). ¹³C NMR (62.9 MHz, CDCl₃):

d¼14.4, 30.1

CH). ¹³C NMR (62.9 MHz, CDCl₃):

d

¼13.6 (CH₃), 13.7 (2CH₃), 13.8

(NCH₃), 60.4, 60.7 (CH₂O), 102.7, 110.5, 116.6, 119.4, 119.9, 121.6 (CH),

128.1, 128.9 (C), 131.0 (CH), 136.0, 138.0 (C), 144.7 (CH), 165.8, 166.3

(CH₃), 18.9 (CH₂), 19.2 (2CH₂), 19.3 (CH₂), 23.8 (CH₂), 30.0 (CH₃N),

30.4 (CH₂), 30.8 (2CH₂), 30.9 (CH₂), 38.8 (CH, C-2), 64.4 (CH₂O), 64.5

(2CH₂O), 65.2 (CH₂O), 108.6 (CH), 109.9 (C), 117.4 (CH), 118.2 (C),

119.7, 119.9 (CH), 126.4, 128.0, 128.5 (C), 130.7 (CH), 138.8 (C), 142.6,

(CO). IR (KBr):

n

¼2978, 2929, 2852 (w), 1705, 1699, 1628, 1604 (s),

1464, 1362, 1302, 1284, 1261, 1242 (m), 1157, 1137, 1090, 1032, 975,

964 (s), 867 (m), 805 (s), 744, 700, 646, 600, 582 cm^ꢁ1. MS (EI, 70 eV):

m/z (%)¼327 (M^þ,100), 282 (15), 255 (04),180 (05). HRMS (EI, 70 eV):

calcd for C₂₃H₂₉NO₄[M]^þ: 327.14706; found: 327.14715.

142.7 (CH) 142.8 (C), 166.7, 166.8, 167.0, 172.9 (CO). IR (KBr):

n

¼2932

(w), 1698, 1624, 1604, 1528 (s), 1464 (m), 1700, 1622 (s), 1548, 1380,

1287, 1274, 1243, 1213 (m), 1168 (s), 1062, 1025, 965, 864 (m), 780,

738, 721, 549 (w) cm^ꢁ1. (EI, 70 eV): m/z (%)¼635 ([M]^þ, 12), 591 (2),

531 (7), 380 (24), 379 (100), 304 (5), 215 (20), 67 (12). HRMS: m/z

calcd for C₃₇H₄₉NO₈(M)^þ: 635.34527; found: 635.34556.

3.15.6. Dimethyl 6,7-bis((E)-3-methoxy-3-oxoprop-1-enyl)-9-

methyl-2,9-dihydro-1H-carbazole-2,3-dicarboxylate (15a). Product

15a was prepared starting with 2c (446 mg, 1.0 mmol), 2-

ethylhexyl acrylate (0.5 mL, 5.0 mmol), Pd(OAc)₂(11 mg,

5 mol %), SPhos (10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL)

at 120 ^ꢀC for 48 h following general procedure B, as a yellow

highly viscous oil (316 mg, 68%). ¹H NMR (300 MHz, CDCl₃):

3.15.9. Di(isobutyl) 6,7-bis((E)-3-isobutoxy-3-oxoprop-1-enyl)-9-

methyl-2,9-dihydro-1H-carbazole-2,3-dicarboxylate (15d). Compound

15d was synthesized starting with 2c (455 mg, 1.0 mmol) and, iso-

butyl acrylate (0.72 mL, 5.0 mmol) following general procedure B, as

a yellow highly viscous oil (455 mg, 72%). ¹H NMR (250 MHz, CDCl₃):

d

¼3.01e3.61 (m, 2H_{a b}, C-1), 3.52 (s, 3H, CH₃N), 3.62 (s, 3H, CH₃O),

/

3.71 (s, 6H, 2CH₃O), 3.81 (s, 3H, CH₃O), 4.01 (br d, 1H, J¼7.2 Hz C-

2), 6.42 (d, 1H, J¼15.6 Hz, CH), 6.43 (d, 1H, J¼15.6 Hz, CH), 7.32 (s,

1H, ArH), 7.71 (s, 1H, ArH), 7.82 (s, 1H, CH), 8.02 (d, 1H, J¼15.8 Hz,

CH), 8.03 (d, 1H, J¼15.7 Hz, CH). ¹³C NMR (62.9 MHz, CDCl₃):

d

¼0.70 (d, 6H, J¼6.9 Hz, 2CH₃), 0.90e1.00 (m, 18H, 6CH₃), 1.70e1.80

(m, 3H, CH), 1.90e2.00 (m,1H, CH), 3.00 (dd,1H_a, J¼8.6,17.2 Hz, H-1),

3.60 (dd,1H_b, J¼1.8,17.3 Hz, H-1), 3.60e3.70 (m, 5H, NCH₃and CH₂O),

3.90e4.00 (m, 6H, 3CH₂O), 4.00e4.10 (dd, 1H_a, J¼1.6, 8.4 Hz, H-2),

6.20 (d, 1H, J¼15.6 Hz, ArH), 6.30 (d, 1H, J¼15.6 Hz, ArH), 7.40 (s, 1H,

ArH), 7.70 (s, 1H, ArH), 7.80 (s, 1H, H-4), 8.10 (d, 2H, J¼15.6 Hz, ArH).

d

¼23.9 (CH₂), 30.0 (CH₃N), 38.6 (C(4)H), 51.6, 51.7, 51.8, 52.6

(CH₃O), 108.5 (CH), 109.7 (C), 117.1 (CH), 117.3 (C), 119.1, 119.2 (CH),

126.4, 127.8, 128.3 (C), 131.4 (CH), 138.8 (C), 142.6, 142.7 (CH), 142.9

¹³C NMR (75 MHz, CDCl₃):

d¼18.7 (CH₃), 18.8 (CH₃), 19.2 (4CH₃), 19.3

(C), 167.0, 167.1, 167.3, 173.4 (CO). IR (KBr):

n

¼2950, 2921, 2851 (w),

(2CH₃), 23.7 (CH₂), 27.6 (CH), 27.8 (2CH), 27.9 (CH), 30.0 (NCH₃), 38.7

(CH, C-2), 70.5, 70.6, 70.7, 71.2 (CH₂O), 108.6 (CH), 109.8 (C), 117.3

(CH), 118.2 (C), 119.6, 119.8 (CH), 126.4, 127.9, 128.3 (C), 130.5 (CH),

138.8 (C), 142.5,142.6 (CH),142.9 (C), 166.6, 166.7, 166.9,172.8 (CO). IR

1693, 1625, 1602, 1525, 1433, 1365 (s), 1310, 1271, 1228, 1189, 1162,

1088 (m), 1035, 972, 912, 919, 853, 802, 775, 725 (s) cm^ꢁ1. GCeMS

(EI, 70 eV): m/z (%)¼467 (M^þ, 75), 434 (38), 405 (100), 374 (59),

347 (26), 316 (15). HRMS: m/z calcd for C₂₅H₂₅N NaO₈[MþNa]^þ:

490.14724; found: 490.14693.

(KBr):

n

¼2958, 2932, 2873 (w), 1702, 1692 (s), 1623, 1605, 1528, 1483,

1468, 1393, 1375, 1342, 1287, 1271 (m), 1219, 1163 (s), 1084, 1035, 980

(m), 945, 908, 884, 863, 778, 729, 645, 613, 572 (w) cm^ꢁ1. GCeMS (EI,

70 eV): m/z (%)¼635 (M^þ, 100), 578 (27), 498 (55), 409 (43), 375 (32),

333 (51), 288 (16), 275 (33), 196 (22), 173(77). HRMS (EI, 70 eV): calcd

for C₃₇H₄₉NO₈(M^þ): 635.34582; found: 635.34571.

3.15.7. Diethyl

6,7-bis((E)-3-ethoxy-3-oxoprop-1-enyl)-9-methyl-

2,9-dihydro-1H-carbazole-2,3-dicarboxylate (15b). Compound 15b

was synthesized starting with 2c (446 mg, 1.0 mmol), following

general procedure B, as a yellow highly viscous oil (450 mg, 86%). ¹H

NMR (250 MHz, CDCl₃):

d

¼1.10 (t, 3H, J¼7.0 Hz, CH₃), 1.30 (t, 6H,

3.15.10. Di(tert-butyl) 6,7-bis((E)-3-tert-butoxy-3-oxoprop-1-enyl)-9-

methyl-2,9-dihydro-1H-carbazole-2,3-dicarboxylate (15e). Compound

15e was synthesized starting with 2c (446 mg, 1.0 mmol), following

general procedure B, as a yellow highly viscous oil (463 mg, 72%). ¹H

J¼7.1 Hz, 2CH₃), 1.30 (t, 3H, J¼7.0 Hz, CH₃), 3.00 (dd, 1H_a, J¼8.8,

17.1 Hz, H-1), 3.60 (dd, 1H_b, J¼2.3, 17.1 Hz, H-1), 3.70 (s, 3H, NCH₃),

3.90e4.00 (m, 2H, CH₂O), 4.10 (dd,1H_a, J¼2.6, 9.0 Hz, H-2), 4.20e4.30

(m, 6H, 3CH₂O), 6.20 (d, 1H, J¼15.7 Hz, ArH), 6.30 (d, 1H, J¼15.7 Hz,

ArH), 7.40 (s, 1H, ArH), 7.70 (s, 1H, ArH), 7.80 (s, 1H, H-4), 8.00 (d, 1H,

J¼15.8 Hz, ArH), 8.10 (d, 1H, J¼15.8 Hz, ArH). ¹³C NMR (62 MHz,

NMR (250 MHz, CDCl₃):

(s, 9H, 3CH₃), 3.00 (dd, 1H_a, J¼8.9, 17.2 Hz, H-1), 3.50 (dd, 1H_b, J¼2.2,

d

¼1.30 (s, 9H, 3CH₃), 1.50 (s, 18H, 6CH₃), 1.50

,

17.2 Hz, H-1), 3.70 (s, 3H, NCH₃), 3.90 (dd, 1H_a, J¼2.2, 8.6 Hz, H-2),

6.20 (d, 1H, J¼15.5 Hz, ArH), 6.30 (d, 1H, J¼15.5 Hz, ArH), 7.40 (s, 1H,

CDCl₃):

d¼14.0 (CH₃),14.3 (2CH₃),14.5 (CH₃), 23.8 (CH₂), 30.0 (NCH₃),

5316

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

ArH), 7.70 (s, 1H, ArH), 7.80 (s, 1H, H-4), 7.90 (d, 1H, J¼15.7 Hz, ArH),

DMF (5 mL) at 120 ^ꢀC for 48 h following general procedure B, as

a yellow highly viscous oil (636 mg, 74%). ¹H NMR (300 MHz, CDCl₃):

8.00 (d,1H, J¼15.7 Hz, ArH). ¹³C NMR (75 MHz, CDCl₃):

¼23.6 (CH₂),

d

27.9 (3CH₃), 28.1 (CH₃), 28.3 (6CH₃), 28.4 (2CH₃), 30.0 (CH₃CN), 39.5

(C(2)H), 80.1, 80.4, 80.5, 81.3 (C), 108.4 (CH), 109.7 (C), 117.2 (CH),

120.3 (C),121.3,121.6 (CH),126.4,127.9,128.4 (C),129.3(CH),138.7 (C),

141.8, 141.9(CH), 142.6 (C), 166.0, 166.1, 166.4, 172.1 (CO). IR (KBr):

d

¼0.8e0.9 (m, 24H, aliphatic), 0.9e1.2 (m, 12H, 6CH₂), 1.2e1.3 (m,

12H, 6CH₂), 0.8e0.9 (m, 8H, 2CH₂), 3.0 (dd, 1H_a, J¼8.6, 17.2 Hz, C-1),

3.6 (m, 1H_b, C-1), 3.7 (s, 3H, CH₃N), 3.9e4.1 (m, 3H, 1H_a, C-2/CH₂O),

4.1e4.2 (m, 6H, 3CH₂O), 6.3 (d, 1H, J¼15.6 Hz, CH), 6.3 (d, 1H,

J¼15.7 Hz, CH), 7.4 (s, 1H, ArH), 7.7 (s, 1H, ArH), 7.8 (s, 1H, C-4, CH), 8.1

n

¼2977, 2929 (w), 1713 (s), 1611, 1530, 1478, 1455, 1392, 1367, 1285,

1256, 1221 (m), 1152 (s), 1089, 979, 847, 794, 530 (w) cm^ꢁ1. MS (EI,

70 eV): m/z (%)¼635 (M^þ, 15), 634 (10), 577 (46), 562 (100), 259 (25),

225 (50), 181 (97), 63 (37). HRMS (EI, 70 eV): calcd for C₃₇H₄₉NO₈

(M^þ): 635.34582; found: 635.34535.

(d, 2H, J¼15.6 Hz, CH). ¹³C NMR (62.9 MHz, CDCl₃):

¼11.4, 12.1, 14.0,

d

14.3, 15.3, 15.3, 17.9, 19.5, 19.7 (CH₃), 17.0, 19.2 (CH), 19.9 (CH₂), 19.3

(CH), 22.6, 23.7, 23.8, 26.1, 26.2, 26.3, 26.4, 26.7, 26.8 (CH₂), 28.7

(CH₃N), 30.3, 30.5, 30.1, 33.0 (CH₂), 38.0 (CH), 63.1, 63.7, 64.8, 65.1

(CH₂O), 108.5 (CH), 109.9 (C), 117.3 (CH), 118.2 (C), 119.7, 119.9 (CH),

126.4, 128.0, 128.5 (C), 130.7 (CH), 138.8, 142.6 (C), 142.6 (CH), 166.7,

3.15.11. Dihexyl 6,7-bis((E)-3-(hexyloxy)-3-oxoprop-1-enyl)-9-

methyl-2,9-dihydro-1H-carbazole-2,3-dicarboxylate (15f). Product

15f was prepared starting with 2c (446 mg, 1.0 mmol), n-hexyl ac-

rylate (0.9 mL, 5.0 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos

(10 mol %), NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at 120 ^ꢀC for 48 h

following general procedure B, as a yellow highly viscous oil

166.8, 166.9, 173.0 (CO). IR (KBr):

n¼2953, 2926, 2870 (w), 1701, 1626

(m), 1605, 1551, 1527, 1465,1455, 1378 (w), 1272 (s), 1220 (m), 1160 (s),

1034, 974, 855, 777, 735, 700, 661, 642 (w) cm^ꢁ1. (EI^þ, 70 eV): m/z

(%)¼859 (M^þ, 32), 857 (11), 734 (09), 678 (11), 677 (26), 676 (25), 572

(10), 519 (12), 434 (12), 390 (12), 84 (39), 83 (24), 71 (22), 70 (34), 69

(65), 57 (64), 56 (59), 55 (62), 44 (87), 43 (100). HRMS [ESI^þ] (Car-

bazole): m/z calcd for C₅₃H₈₀NO₈(MþH): 858.58698; found:

658.58698.

(598 mg, 80%). ¹H NMR (300 MHz, CDCl₃):

d¼0.81e0.93 (m, 12H,

CH₃), 1.32e1.41 (m, 16H, 8CH₂), 1.61e1.72 (m, 16H, 8CH₂), 3.00 (dd,

1H_a, J¼8.5,17.1 Hz, C-1); 3.61 (dd,1H_b, J¼2.1,17.1 Hz, C-1), 3.82 (s, 3H,

CH₃N), 3.91 (dd, 1H_a, J¼1.7, 6.7 Hz, C-2), 4.12e4.22 (m, 8H, 4CH₂O),

6.31 (d, 2H, J¼16.0 Hz, CH), 7.30 (s,1H, ArH), 7.49 (s,1H, ArH), 8.01 (s,

1H, C-4), 8.02 (d, 2H, J¼16.0 Hz, CH). ¹³C NMR (62.9 MHz, CDCl₃):

3.15.14. Dimethyl 6,7-bis((E)-3-methoxy-3-oxoprop-1-enyl)-9-

methyl-9H-carbazole-2,3-dicarboxylate (16a). Compound 16a was

synthesized starting with 15a (100 mg, 0.22 mmol), following

general procedure C, as a yellow highly viscous oil (99 mg, 100%). ¹H

d

¼14.0 (CH₃), 22.5 (CH₂), 25.7(CH₂), 28.4 (CH₂), 28.7 (CH₂), 28.8, 29.7

(CH₂), 30.1 (CH₃N), 31.2 (CH₂), 31.5 (CH₂), 31.6 (CH₂), 33.3 (CH), 64.5,

64.8, 64.8, 65.4 (CH₂O),108.9 (CH),109.6,112.8 (C),120.0,120.4,120.5

(CH), 127.4, 128.1, 129.6 (C), 136.6 (CH), 138.6, 138.7 (C), 142.5, 142.6

NMR (300 MHz, CDCl₃):

d

¼3.54 (s, 3H, CH₃), 3.64 (s, 3H, CH₃), 3.74

(s, 6H, 2CH₃), 3.77 (s, 3H, CH₃), 6.3 (d, 1H, J¼15.6 Hz, CH), 6.4 (d, 1H

J¼16.3 Hz, CH), 7.4 (s, 1H, ArH), 7.5 (s, 1H, ArH), 8.0 (d, 1H, J¼15.6 Hz,

CH), 8.1 (d, 1H, J¼15.6 Hz, CH), 8.5 (s, 2H, ArH). ¹³C NMR (75.5 MHz,

(CH), 166.6, 166.8, 168.0, 172.8 (CO). IR (KBr):

n

¼2953, 2926, 2856

(w), 1701, 1622, 1605 (s), 1551, 1527, 1465, 1455, 1378, 1337 (w), 1242

(m),1159 (s), 973, 908, 849, 728, 674, 648, 605 (w) cm^ꢁ1. (EI^þ, 70 eV):

m/z (%)¼747 (M^þ, 10), 596 (11), 595 (31), 594 (37), 595 (100), 492

(20), 465 (16), 464 (33), 463 (68), 407 (07), 380 (30), 362 (35), 336

(13), 355 (18), 278 (13), 251 (13), 234 (23). HRMS: m/z calcd for

C₄₅H₆₅NO₈(M^þ): 747.47047; found: 747.46850.

CDCl₃):

d

¼29.6 (CH₃N), 52.5, 52.6, 52.8, 52.9 (CH₃O), 107.9, 109.4,

119.6, 120.2, 122.7, 122.9 (CH), 123.1, 123.8, 124.5, 125.5, 126.0, 126.9,

128.9, 133.7 (C), 142.0, 142.4 (CH), 166.7, 167.1, 167.8, 169.4 (CO). IR

(KBr):

n

¼3089 (w), 1652 (s), 1455, 1277 (m), 1097, 1060 (s), 912 (w),

845, 798, 699 (s) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼465 (M^þ, 53),

434 (31), 405 (100), 374 (83). HRMS: m/z calcd for C₂₅H₂₃NO₈(M^þ):

465.14181; found: 465.141506.

3.15.12. Bis(2-ethylhexyl) 6,7-bis((E)-3-(2-ethylhexyloxy)-3-

oxoprop-1-enyl)-9-methyl-2,9-dihydro-1H-carbazole-2,3-

dicarboxylate (15g). Product 15g was prepared starting with 2c

(446 mg, 1.0 mmol), 2-ethylhexyl acrylate (1.10 mL, 5.0 mmol),

Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %), NEt₃(1.10 mL,

8.0 mmol), DMF (5 mL) at 120 ^ꢀC for 48 h following general pro-

cedure B, as a yellow highly viscous oil (618 mg, 72%). ¹H NMR

3.15.15. Dibutyl 6,7-bis((E)-3-butoxy-3-oxoprop-1-enyl)-9-methyl-

9H-carbazole-2,3-dicarboxylate (16c). Compound 16c was synthe-

sized starting with 15c (100 mg, 0.16 mmol), following general

procedure C, as a yellow highly viscous oil (98 mg, 100%). ¹H NMR

(300 MHz, CDCl₃):

d

¼0.9 (t, 3H, J¼7.3 Hz, CH₃), 0.9 (t, 3H, J¼7.3 Hz,

(300 MHz, CDCl₃):

Aliphatic), 1.51e1.62 (m, 4H, CH-aliphatic), 3.02e3.61 (dd, 2H_{a b}, C-

d

¼0.82e0.93 (m, 24H, 8CH₃), 1.21e1.43 (m, 32H,

CH₃), 0.9 (t, 3H, J¼7.5 Hz, CH₃), 0.9 (t, 3H, J¼7.3 Hz, CH₃), 1.3e1.4 (m,

8H, 4CH₂), 1.6e1.7 (m, 8H, 4CH₂), 3.7 (s, 3H, CH₃N), 4.1 (t, 4H,

J¼6.7 Hz, 2CH₂O), 4.2 (t, 2H, J¼7.1 Hz, CH₂O), 4.3 (t, 2H, J¼6.9 Hz,

CH₂O), 6.3 (d, 1H, J¼15.9 Hz), 6.4 (d, 1H, J¼15.9 Hz), 7.4 (s, 1H, ArH),

7.4 (s, 1H, ArH), 8.0 (d, 1H, J¼15.2 Hz), 8.1 (d, 1H, J¼15.8 Hz), 8.1 (s,

/

1), 3.71 (s, 3H, CH₃N), 3.82 (dd, 1H_a, J¼3.2, 5.3 Hz, C-2), 4.12 (dd, 8H,

J¼2.4, 5.8 Hz, 4CH₂O), 6.32 (d, 1H, J¼15.7 Hz), 6.33 (d, 1H,

J¼15.7 Hz), 7.41 (s, 1H, ArH), 7.72 (s, 1H, ArH), 7.83 (s, 1H, C(4)), 8.01

(d, 1H, J¼15.7 Hz), 8.12 (d, 1H, J¼15.7 Hz). ¹³C NMR (62 MHz, CDCl₃):

1H, ArH), 8.3 (s, 1H, ArH). ¹³C NMR (75.5 MHz, CDCl₃):

d¼13.7, 13.7

d

¼10.9 (CH₃), 11.0 (CH₃), 14.1 (CH₃), 23.0 (CH₂), 23.9 (CH₂), 29.0

(CH₃), 19.2 (CH₂), 19.2 (CH₂), 19.3 (CH₂), 29.5 (CH₃N), 30.6 (CH₂),

30.7 (2CH₂), 30.8 (CH₂), 64.5, 64.6, 65.4, 65.8 (CH₂O), 107.7, 109.2,

119.8, 120.0, 121.8, 122.5 (CH), 122.5, 122.9, 123.6, 126.8, 132.4, 133.6

(C), 141.6, 142.0 (CH), 142.7 (C), 166.3, 166.7, 167.2, 168.9 (CO). IR

(CH₂), 29.7 (CH₂), 30.1 (CH₃N), 30.5 (CH₂), 31.2, 38.6, 38.7 (CH), 38.9

(CH-2), 38.9 (CH), 67.0, 67.1, 67.3, 67.5 (CH₂O), 108.6 (CH), 110.0 (C),

117.3 (CH), 118.0 (C), 119.7, 120.0 (CH), 126.4, 128.0, 128.5 (C), 130.5

(CH), 138.8 (C), 142.5, 142.6 (CH), 142.8 (C), 166.8, 166.9, 167.0, 173.0

(KBr):

n

¼2957, 2932, 2872 (w), 1705 (s), 1623, 1596, 1561, 1463 (m),

(CO). IR (KBr):

n

¼2928, 2925, 2858 (w), 1703 (s), 1631, 1605, 1528,

1387, 1341 (w), 1262, 1226, 1162, 1107 (s), 1080, 1063, 1021, 967 (m),

906, 856, 774, 737, 713, 659, 618, 594 (w) cm^ꢁ1. (EI^þ, 70 eV): m/z

(%)¼633 (M^þ, 24), 560 (09), 531 (69), 507 (100), 458 (29), 378 (41),

302 (28). HRMS (ESI^þ): m/z calcd for C₃₇H₄₈NO₈[MþH]^þ:

634.33744; found: 634.33799.

1460, 1380, 1265, 1220 (m), 1161 (s), 1113, 1085, 1031, 974 (m), 852,

773, 730, 695, 645, 609 (w) cm^ꢁ1, (EI, 70 eV): m/z (%)¼859 (M^þ, 12),

699 (10), 590 (11), 588 (11), 572 (11), 460 (5), 83 (20), 71 (22), 70

(11), 69 (16), 57 (100), 44 (93). HRMS: m/z calcd for C₅₃H₈₁NO₈

(M^þþ1): 859.596901; found: 859.59567.

3.15.16. Bis(2-ethylhexyl) 6,7-bis((E)-3-(2-ethylhexyloxy)-3-oxoprop-

1-enyl)-9-methyl-9H-carbazole-2,3-dicarboxylate (16g). Compound

16g was synthesized starting with 15g (100 mg, 0.12 mmol), fol-

lowing general procedure C, as a yellow highly viscous oil (99 mg,

3.15.13. Bis(6-methylheptyl) 9-methyl-6,7-bis((E)-3-(6-methy

lheptyloxy)-3-oxoprop-1-enyl)-2,9-dihydro-1H-carbazole-2,3-

dicarboxylate (15h). Product 15h was prepared starting with 2c

(446 mg, 1.0 mmol), 6-methylheptyl acrylate (1.0 mL, 5.0 mmol),

Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %), NEt₃(1.10 mL, 8.0 mmol),

100%). ¹H NMR (300 MHz, CDCl₃):

(m, 32H, CH-aliphatic), 1.6e1.7 (m, 4H, aliphatic), 3.9 (s, 3H, CH₃N),

d

¼0.8e0.9 (m, 24H, 8CH₃), 1.2e1.4

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

5317

4.1 (dd, 4H, J¼2.6, 5.7 Hz, 2CH₂O), 4.2 (dd, 4H, J¼2.6, 5.7 Hz, 2CH₂O),

(300 MHz, CDCl₃):

d

¼1.5 (s, 9H, 3CH₃), 1.5 (s, 9H, 3CH₃), 1.5 (s, 9H,

6.4 (d, 1H, J¼15.7 Hz, CH), 6.4 (d, 1H, J¼15.7 Hz, CH), 7.5 (s, 1H, ArH),

7.6 (s, 1H, ArH), 8.1 (d, 1H, J¼15.7 Hz, CH), 8.2 (d, 1H, J¼15.8 Hz, CH),

3CH₃), 1.5 (s, 9H, 3CH₃), 3.8 (s, 3H, CH₃N), 6.2 (d, 1H, J¼16.1 Hz, CH),

6.3 (d, 1H, J¼15.7 Hz, CH), 6.3 (d, 1H, J¼15.7 Hz, CH), 6.4 (d, 1H,

J¼16.0 Hz, CH), 7.4 (s, 1H, ArH), 7.7 (d, 1H, J¼16.0 Hz, CH), 7.8 (d, 1H,

J¼16.0 Hz, CH), 7.9 (d, 1H, J¼15.8 Hz, CH), 8.0 (d, 1H, J¼14.2 Hz, CH),

8.3 (s, 1H, ArH), 8.5 (s, 1H, ArH). ¹³C NMR (62.9 MHz, CDCl₃):

d¼10.9

(3CH₃), 11.0 (CH₃), 14.1 (4CH₃), 23.0 (2CH₂), 23.7 (2CH₂), 23.8 (2CH₂),

23.9 (2CH₂), 28.9 (2CH₂), 29.0 (2CH₂), 29.6 (CH₃N), 30.4 (2CH₂), 30.5

(2CH₂), 30.9, 38.5, 38.7, 38.8, (CH), 67.1, 67.3, 68.1, 68.5 (CH₂O), 107.8,

109.4, 120.1, 120.3, 122.0, 122.7 (CH), 122.9, 123.1, 123.8, 127.0, 132.7,

133.8 (C), 141.8, 142.2 (CH), 142.8, 142.9 (C), 166.5, 166.8, 167.4, 169.1

8.0 (s, 1H, ArH). ¹³C NMR (62.9 MHz, CDCl₃):

d¼28.1 (CH₃), 28.2

(CH₃), 28.3 (CH₃), 30.9 (CH₃CN), 80.4, 80.6, 80.7, 81.5 (CeO), 108.7

(CH), 114.1 (C), 119.3, 120.5, 122.6, 122.7 (CH), 126.6 (C), 127.7 (CH),

128.8 (C), 129.6 (CH), 131.0 (C), 134.9 (CH) 139.0, 139.3 (C), 141.5

(CO). IR (KBr):

n

¼2927(w), 1712, 1624, 1601, 1562, 1459, 1379, 1260,

(CH), 165.0, 165.7, 165.9, 166.9 (CO). IR (KBr):

n

¼2976, 2931 (w),

1229, 1165, 1108, 1081, 1015, 975, 858, 774, 726, 615 (s) cm^ꢁ1. GCeMS

(EI^þ, 70 eV): m/z (%)¼857 (M^þ, 23), 699 (23), 588 (27), 346 (18), 302

(29). HRMS: m/z calcd for C₅₃H₇₉NO₈(M^þ): 857.5806; found:

857.5803.

1694, 1621, 1548, 1475, 1455, 1390, 1365, 1289, 1254, 1217, 1140, 965,

846, 764 (s) cm^ꢁ1. EI^þ(70 eV): m/z (%)¼635 (M^þ, 15), 579 (04), 523

(07), 478 (17), 766 (20), 304 (28). HRMS: m/z calcd for C₃₇H₄₉NO₈

(M^þ): 635.34582; found: 635.34532.

3.15.17. (2E,2⁰E,2⁰⁰E,2⁰⁰⁰E)-Tetraethyl 3,3⁰,3⁰⁰,3⁰⁰⁰-(1-methyl-1H-indole-

2,3,5,6-tetrayl) tetraacrylate (17b). Product 17b was prepared

starting with 2c (446 mg, 1.0 mmol), ethyl acrylate (0.6 mL,

5.0 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %), NEt₃

(1.10 mL, 8.0 mmol), DMF (5 mL) at 90 ^ꢀC for 36 h following general

procedure A, as a yellow highly viscous oil (397 mg, 76%). ¹H NMR

3.15.20. (2E,2⁰E,2⁰⁰E,2⁰⁰⁰E)-Tetrakis(2-ethylhexyl) 3,3⁰,3⁰⁰,3⁰⁰⁰-(1-methyl-

1H-indole-2,3,5,6-tetrayl) tetraacrylate (17g). Product 17g was pre-

pared starting with 2c (446 mg, 1.0 mmol), 2-ethylhexyl acrylate

(1.10 mL, 5.0 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %),

NEt₃(1.10 mL, 8.0 mmol), DMF (5 mL) at 90 ^ꢀC for 36 h following

general procedure A, as a yellow highly viscous oil (645 mg, 75%). ¹H

(300 MHz, CDCl₃):

d

¼1.3 (t, 6H, J¼6.8 Hz, 2CH₃), 1.3 (t, 6H, J¼7.0 Hz,

NMR (300 MHz, CDCl₃):

d

¼0.81e0.92 (m, 24H, 8CH₃), 1.23e1.44 (m,

2CH₃), 3.8 (s, 3H, CH₃N), 4.2e4.3 (m, 8H, 4CH₂O), 6.2 (d, 1H,

J¼15.8 Hz, CH), 6.3 (d, 1H, J¼15.7 Hz, CH), 6.3 (d, 1H, J¼15.4 Hz, CH),

6.4 (d,1H, J¼16.0 Hz, CH), 7.4 (s,1H, ArH), 7.8 (d,1H, J¼16.0 Hz), 7.9 (d,

1H, J¼16.0 Hz), 8.0 (s, 1H, ArH), 8.0 (d, 1H, J¼15.8 Hz), 8.1 (d, 1H,

32H, CH₂-aliphatic), 1.52e1.61 (m, 4H, CH), 3.83 (s, 3H, CH₃N),

4.01e4.12 (m, 8H, 4CH₂O), 6.21 (d, 1H, J¼16.1 Hz), 6.32 (d, 1H,

J¼15.6 Hz), 6.33 (d,1H, J¼15.7 Hz), 6.41 (d,1H, J¼16.0 Hz), 7.52 (s,1H,

ArH), 7.74 (d,1H, J¼16.0 Hz), 7.81 (d,1H, J¼16.0 Hz), 8.01 (s,1H, ArH),

J¼15.8 Hz). ¹³C NMR (62.9 MHz, CDCl₃):

d

¼13.2 (CH₃), 13.3 (2CH₃),

8.02 (d, 2H, J¼16.0 Hz). ¹³C NMR (75.5 MHz, CDCl₃):

¼10.9 (CH₃),

d

13.4 (CH₃), 30.4 (CH₃N), 59.5, 59.6, 59.7, 60.2 (CH₂O), 107.9 (CH),

113.2 (C), 116.7, 119.4, 119.7, 120.1, 125.1, (CH), 125.7, 127.8 (C), 129.3

(CH), 130.0 (C), 134.7 (CH), 138.1, 138.4 (C), 141.2, 141.3 (CH), 164.7,

11.0 (3CH₃), 14.0 (4CH₃), 22.9 (4CH₂), 23.7 (CH₂), 23.8 (2CH₂), 23.9,

28.1, 28.9 (CH₂), 29.0 (2CH₂), 30.3 (CH₂), 30.4 (2CH₂), 30.5 (CH₂), 31.3

(CH₃N), 38.8 (CH), 38.9 (3CH), 66.9, 67.0, 67.1, 67.6 (CH₂O), 108.9

(CH), 114.1 (C), 117.8, 120.4, 120.7, 121.0, 125.9 (CH), 126.7, 128.8 (C),

130.4 (CH), 131.0 (C), 135.5 (CH), 139.0, 139.4 (C), 142.1, 142.2 (CH),

165.4,165.6,166.5 (CO). IR (KBr):

n

¼2979, 2930, 2872 (w),1704,1613

(s), 1463, 1445, 1367 (m), 1259, 1160, 1093, 1028, 974, 855 (s), 809,

785, 770, 727, 702, 607 (m) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼523

(M^þ,100), 477 (18), 452 (88), 402 (84), 375 (23), 350 (70). HRMS: m/z

calcd for C₂₉H₃₃NO₈(M^þ): 523.22062; found: 523.22073.

165.8, 166.4, 166.6, 167.5 (CO). IR (KBr):

n¼2957, 2927, 2872, 2858

(w),1706,1691,1624 (s),1600,1548,1460,1379,1283,1254,1215 (w),

1164 (s), 1029, 970, 864 (m), 769, 727, 695, 639, 595 (w) cm^ꢁ1. EI^þ

(70 eV): m/z (%)¼859 (M^þ, 46), 703 (11), 701 (14), 591 (13), 590 (32),

571 (11), 572 (28), 543 (15), 460 (14), 432 (21), 431 (13), 416 (10), 414

(13), 304 (19), 276 (19), 71 (31), 70 (20), 57 (100), 44 (19), 43 (44).

HRMS (ESI^þ): m/z calcd for C₅₃H₈₂NO₈[M^þþH]: 860.6035; found:

860.6029.

3.15.18. (2E,2⁰E,2⁰⁰E,2⁰⁰⁰E)-Tetrabutyl 3,3⁰,3⁰⁰,3⁰⁰⁰-(1-methyl-1H-indole-

2,3,5,6-tetrayl)tetraacrylate (17c). Product 17c was prepared start-

ing with 2c (446 mg, 1.0 mmol), n-butyl acrylate (0.70 mL,

5.0 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %), NEt₃

(1.10 mL, 8.0 mmol), DMF (5 mL) at 90 ^ꢀC for 36 h following general

procedure B, as a yellow highly viscous oil (450 mg, 71%). ¹H NMR

3.15.21. (2E,2⁰E)-Diethyl

late (18). By heating 17b in xylene side-product 18 was derived. ¹H

NMR (250 MHz, CDCl₃):

3,3⁰-(1-methyl-1H-indole-5,6-diyl)diacry

(300 MHz, CDCl₃):

d¼0.8e0.9 (m, 12H, 4CH₃), 1.3e1.5 (m, 8H, 4CH₂),

1.6e1.7 (m, 8H, 4CH₂), 3.7 (s, 3H, CH₃N), 4.1 (t, 4H, J¼6.9 Hz, 2CH₂O),

4.2 (t, 4H, J¼6.9 Hz, 2CH₂O), 6.2 (d, 1H, J¼16.4 Hz, CH), 6.2 (d, 1H,

J¼15.4 Hz, CH), 6.3 (d, 1H, J¼15.8 Hz, CH), 6.4 (d, 1H, J¼16.2 Hz, CH),

7.4 (s, 1H, ArH), 7.7 (d, 1H, J¼16.2 Hz, CH), 7.8 (d, 1H, J¼16.2 Hz, CH),

7.9 (s, 1H, ArH), 8.0 (d, 1H, J¼15.4 Hz, CH), 8.0 (d, 1H, J¼15.4 Hz, CH).

d¼1.3 (t, 3H, J¼7.1 Hz, CH₃), 1.3 (t, 3H,

J¼7.1 Hz, CH₃), 3.7 (s, 3H, CH₃N), 4.2 (q, 2H, J¼7.2 Hz, CH₂O), 4.2 (q,

2H, J¼7.2 Hz, CH₂O), 6.2 (d, 1H, J¼15.9 Hz, CH), 6.3 (d, 1H, J¼15.9 Hz,

CH), 6.4 (d, 1H, J¼3.0 Hz, ArH), 7.0 (d, 1H, J¼3.0 Hz, ArH), 7.5 (s, 1H,

ArH), 7.8 (s,1H, ArH), 8.1 (d,1H, J¼15.9 Hz, CH), 8.2 (d,1H, J¼15.9 Hz,

¹³C NMR (75.5 MHz, CDCl₃):

d¼13.7 (CH₃), 13.7 (2CH₃), 13.8 (CH₃),

CH). ¹³C NMR (75.5 MHz, CDCl₃):

d

¼14.4 (2CH₃), 33.0 (CH₃N), 60.4

19.1, 19.1, 19.2, 19.2, 30.6, 30.7, 30.8, 30.8 (CH₂), 31.4 (CH₃N), 64.4,

64.5, 64.5, 65.0 (CH₂O), 108.9 (CH), 114.1 (C), 117.6, 120.3, 120.6,

121.0, 125.9 (CH), 126.6, 128.6 (C), 130.3 (CH), 130.9 (C), 135.5 (CH),

139.0, 139.3, 142.0, 142.1 (C), 165.7, 166.3, 166.6, 167.4 (CO). IR (KBr):

(CH₂O), 60.5 (CH₂O), 102.0, 108.3, 119.1, 119.5, 120.5 (CH), 126.4,

128.4, 130.0 (C), 132.0 (CH), 137.5 (C), 143.2, 143.4 (CH), 166.8, 167.0

(CO). IR (KBr):

n

¼2925 (w), 1703, 1626, 1604, 1505, 1462, 1446, 1422,

1366, 1349, 1303, 1260, 1174, 1159, 1094, 1030, 974, 856, 761, 748,

718, 655, 590 (s) cm^ꢁ1. GCeMS (EI, 70 eV): m/z (%)¼327 ([M]^þ, 100),

298 (52), 277 (33). HRMS (EI): m/z calcd for C₁₉H₂₁NO₄[M^þ]:

327.14706; found: 327.147666.

n

¼2932 (w), 1699, 1622, 1548 (s), 1463 (m), 1416, 1379, (s), 1273 (m),

1243, 1212, 1168, 1062, 1025, 956, 864, 780 (s), 738 (m), 694, 647,

588 (s) cm^ꢁ1. (EI, 70 eV): m/z (%)¼635 (M^þ, 100), 591 (18), 562 (16),

534 (14), 509 (14), 507 (11), 478 (33), 460 (46), 431 (11), 360 (11),

334 (12), 304 (13), 260 (19), 231 (15), 57 (21). HRMS: m/z calcd for

C₃₇H₄₉NO₈(M^þ): 635.34527; found: 635.34554.

3.16. General procedure D for Sonogashira cross-coupling

reactions of 2a

3.15.19. (2E,2⁰E,2⁰⁰E,2⁰⁰⁰E)-tert-Butyl 3,3⁰,3⁰⁰,3⁰⁰⁰-(1-methyl-1H-indole-

2,3,5,6-tetrayl) tetraacrylate (17e). Product 17e was prepared

starting with 2c (446 mg, 1.0 mmol), tert-butyl acrylate (0.7 mL,

5.0 mmol), Pd(OAc)₂(11 mg, 5 mol %), SPhos (10 mol %), NEt₃

(1.10 mL, 8.0 mmol), DMF (5 mL) at 90 ^ꢀC for 36 h following general

procedure A, as a yellow highly viscous oil (559 mg, 88%). ¹H NMR

A mixture of Pd(OAc)₂(11 mg, 5 mol %), the ligand XPhos (L₂)

(48 mg,10 mol %) and 20 ml xylene was stirred at room temperature

for 30 min under an argon atmosphere. Then, CuI (19 mg, 10 mol %),

(ⁱPr)₂NH (5 ml), 1-methyl-2,3-dibromoindole (290 mg, 1 mmol) and

phenylacetylene (0.12 ml, 2.2 mmol) were added and the mixture

was stirred for 36 h at 120 ^ꢀC. The organic layer was washed with

5318

M. Hussain et al. / Tetrahedron 67 (2011) 5304e5318

Chem. 2001, 5, 507; (m) Lemster, T.; Pindur, U. Recent Res. Dev. Org. Bioorg. Chem.

2002, 5, 99; (n) Knolker, H.-J. Curr. Org. Synth. 2004, 1, 309.

water and extracted with CH₂Cl₂. The crude product was puriﬁed by

column chromatography (n-heptane/ethylacetate 10:1).

€

2. For some recent contributions, see: (a) Bedford, R. B.; Betham, M. J. Org. Chem.

2006, 71, 9403; (b) Lebold, T. P.; Kerr, M. A. Org. Lett. 2007, 9, 1883; (c) Wata-

nabe, T.; Ueda, S.; Inuki, S.; Oishi, S.; Fujii, N.; Ohno, H. Chem. Commun. 2007,

4516; (d) Jean, D. J., Jr.; Poon, S. F.; Schwarzbach, J. L. Org. Lett. 2007, 9, 4893; (e)

Liu, C.-Y.; Knochel, P. J. Org. Chem. 2007, 72, 7106; (f) Naffziger, M. R.; Ashburn,

B. O.; Perkins, J. R.; Carter, R. G. J. Org. Chem. 2007, 72, 9857.

3.16.1. 1-Methyl-2,3-bis(phenylethynyl)-1H-indole (19). Compound

19 was synthesized according to the general procedure D starting

with 2a (290 mg,1.0 mmol) as a brown, unstable semisolid (199 mg,

60%). ¹H NMR (CDCl₃, 250 MHz):

d

¼3.81 (s, 3H, CH₃), 7.12e7.34 (m,

9H, ArH), 7.52e7.57 (m, 4H, ArH), 7.70e7.74 (m, 1H, ArH). ¹³C NMR

(CDCl₃, 62.9 MHz):

€

3. (a) Forke, R.; Krahl, M. P.; Dabritz, F.; Jager, A.; Knolker, H.-J. Synlett 2008, 1870;

€

(b) Forke, R.; Krahl, M. P.; Krause, T.; Schlechtingen, G.; Knolker, H.-J. Synlett

2007, 268.

d

¼30.1 (CH₃), 78.9, 81.8, 93.5, 98.4 (C^C), 102.2

4. Ackermann, L.; Althammer, A. Angew. Chem., Int. Ed. 2007, 46, 1627.

5. Pindur, U. Heterocycles 2008, 27, 1253.

6. Kano, S.; Sugino, E.; Shibuya, S.; Hibino, S. J. Org. Chem. 1981, 46, 3856.

7. Pindur, U.; Adam, R. Helv. Chim. Acta 1990, 73, 827.

8. Voigt, K.; von Zezschwitz, P.; Rosauer, K.; Lansky, A.; Adams, A.; Reiser, O.; de

Meijere, A. Eur. J. Org. Chem. 1998, 1521 and references cited therein.

9. (a) Hussain, M.; Dang, T. T.; Langer, P. Synlett 2009, 1822; (b) Toguem, S.-M. T.;

Hussain, M.; Malik, I.; Villinger, A.; Langer, P. Tetrahedron Lett. 2009, 50, 4962;

(c) Hussain, M.; Hung, N. T.; Langer, P. Tetrahedron Lett. 2009, 50, 3929; (d)

Toguem, S.-M. T.; Langer, P. Synlett 2010, 1779.

(C), 108, 119.3, 119.9 (CH), 121.5 (C), 123.1 (CH), 123.2 (C), 124.7 (C),

126.6 (CH), 127.0 (C), 127.3, 127.5, 127.8, 130.3, 130.6 (CH), 135.7 (C).

IR (ATR, cm^ꢁ1):

n

¼3050 (w), 2962 (w), 2210 (w), 2195 (w), 1594 (w),

1569 (w), 1494 (w), 1477 (m), 1464 (m), 1439 (w), 1413 (w), 1372

(m), 1329 (m), 1259 (s), 1086 (s), 1067 (s), 1011 (s). MS (EI, 70 eV): m/

z (%)¼331 (M^þ, 100), 314 (4), 254 (4), 226 (1), 187 (1), 164 (3), 150

(2), 77 (1). HRMS (EI): calcd for C₂₅H₁₇N (M^þ) 331.13555, found

331.13528.

10. Tang, S.; Li, J.-H.; Xie, Y.-X.; Wang, N.-X. Synthesis 2007, 1535.

11. Ji, N.-Y.; Li, X.-M.; Cui, C.-M.; Wang, B.-G. Helv. Chim. Acta 2007, 90, 1731.

12. Ji, N.-Y.; Li, X.-M.; Cui, C.-M.; Wang, B.-G. Helv. Chim. Acta 2007, 90, 385.

€

References and notes

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€

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17. CCDC-823758 (5f), CCDC-823759 (6a), CCDC-823760(7) and CCDC-823758 (12c)

contain all crystallographic details of this publication, which are available free of

charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be ordered from the

following address: Cambridge Crystallographic Data Centre, 12 Union Road, GB-

Cambridge CB21EZ; Fax:(þ44)1223-336-033; or deposit@ccdc.cam.ac.uk).

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Article Doi

Synthesis of carbazoles and 1,2-dihydrocarbazoles by domino 'twofold Heck/6π-electrocyclization' reactions of di-, tri- and tetrabromoindoles

DOI: 10.1016/j.tet.2011.05.014

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