Hydroaminoalkylation/Buchwald-Hartwig Amination Sequences for the Synthesis of Novel Thieno- or Benzothieno-Annulated Tetrahydropyridines, Tetrahydroazasilines, and Tetrahydroazasilepines

European Journal of Organic Chemistry

Accepted Article

Title: Hydroaminoalkylation/Buchwald-Hartwig Amination Sequences

for the Synthesis of Novel Thieno- or Benzothieno-Annulated

Tetrahydropyridines, -azasilines, and -azasilepines

Authors: Michael Warsitz, Stefan H. Rohjans, and Sven Doye

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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202001523

Link to VoR: https://doi.org/10.1002/ejoc.202001523

01/2020

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Hydroaminoalkylation/Buchwald-Hartwig Amination Sequences

for the Synthesis of Novel Thieno- or Benzothieno-Annulated

Tetrahydropyridines, Tetrahydroazasilines, and

Tetrahydroazasilepines

Michael Warsitz, Stefan H. Rohjans, and Sven Doye*^[a]

[a]

M. Warsitz, Stefan H. Rohjans, Prof. Dr. S. Doye

Institut für Chemie, Universität Oldenburg

Carl-von-Ossietzky-Straße 9-11, 26129 Oldenburg (Germany)

E-mail: doye@uni-oldenburg.de

https://uol.de/oc-doye

Supporting information for this article is available on the WWW under http://_____.

Abstract: New two-step procedures that include an initial

hydroaminoalkylation reactions. While group 5 metal catalysts

selectively deliver the branched hydroaminoalkylation products,

ruthenium- and iridium-based catalysts give the linear isomers

exclusively, but they are limited to amine substrates that contain

metal-binding directing groups.

regioselective intermolecular hydroaminoalkylation of 2-allyl-, 2-

allyldimethylsilyl-

bromothiophenes or 3-bromobenzothiophenes with secondary

amines and subsequent intramolecular Buchwald-Hartwig

amination give direct access to structurally novel bicyclic

heterocycles including tetrahydrothienopyridines,

tetrahydrothienoazasilines, tetrahydrobenzothienoazasilines, and

tetrahydrobenzothienoazasilepines. The hydroaminoalkylation

or

2-dimethyl(vinyl)silyl-substituted

3-

a

reaction is catalyzed by a mono(aminopyridinato) titanium complex

which delivers the branched hydroaminoalkylation products or in the

Scheme 1. Intermolecular hydroaminoalkylation of alkenes.

In

comparison,

titanium-catalyzed

hydroaminoalkylation

case of vinylsilyl-substituted substrates, the use of

a

reactions offer the opportunity to control the regioselectivity of

the reaction by the structure of the ligands bonded to the metal

center of the catalyst. For example, hydroaminoalkylation

reactions catalyzed by the mono(formamidinato) titanium

complex I^[2c]or the mono(aminopyridinato) titanium complex II^[2d]

(Figure 1) favor the formation of the branched regioisomers,

while corresponding reactions performed in the presence of the

bis(aminopyridinato) titanium complexes III-V (Figure 1)

selectively convert styrenes or vinylsilanes into the linear

regioisomers.^[2b,2g,2k]However, in the case of alkyl-substituted

bis(aminopyridinato) titanium complex gives access to the linear

regioisomers. While in the latter case, the hydroaminoalkylation

products need to be purified prior to the palladium-catalyzed

amination step, all other two-step sequences can be run as a one-

pot procedure.

Introduction

alkenes,

hydroaminoalkylation products.

catalysts

III-V

still

deliver

the

branched

Bicyclic heterocycles include a wide structural diversity and

many of them are due to their various biological activities

pharmacologically important classes of chemical compounds.

Especially, nitrogen containing heterocycles are substantial for

drug design.^[1]Therefore new synthetic approaches for such

compound classes are of great interest in medicinal chemistry.

In recent years, our group developed a plethora of two-step

procedures for the synthesis of biologically relevant benzo-

annulated heterocycles such as 1,5-benzodiazepines,^[2e]1,5-

benzoazasilepines,^[2f]1,4-benzoazasilines,^[2g]benzazepines,

benzoxazepines,

benzothiazepines^[2h]

and

tetrahydroquinolines^[2k]. These two-step procedures combine an

initial titanium-catalyzed hydroaminoalkylation reaction^[3]of an

alkene and a subsequent intramolecular Buchwald-Hartwig

amination^[4]step. The catalytic hydroaminoalkylation of alkenes

(Scheme 1) is a highly atom-efficient reaction that allows the

direct addition of an α-C−H bond of a primary or secondary

amine across C−C double bonds.^[3]Corresponding reactions can

be performed in the presence of ruthenium,^[5]iridium,^[6]group 5

metal,^[7]zirconium,^[8]and titanium catalysts.^[2]The use of cationic

scandium-based catalysts enables the hydroaminoalkylation of

alkenes with tertiary amines.^[9]Depending on the choice of the

catalyst system, different regioselectivities are observed in the

Figure 1. Selected titanium catalysts for the hydroaminoalkylation of alkenes.

During attempts to expand the substrate scope of titanium-

catalyzed

hydroaminoalkylation

reactions

towards

heteroaromatic substrates we recently found that thiophene and

benzothiophene units are suitable building blocks for this

purpose. As

a consequence and in continuation of our

previously reported hydroaminoalkylation/Buchwald-Hartwig

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amination sequences (vide supra), we now describe new two-

step procedures for the synthesis of thieno- and benzothieno-

annulated heterocycles (Scheme 2). For that purpose, allyl-,

Delighted by these promising results and due to the well-

established fact that Buchwald-Hartwig reactions tolerate the

reagents used in titanium-catalyzed hydroaminoalkylation

reactions,^[2]we tested whether the hydroaminoalkylation of 2-

allylsilyl-

or

vinylsilyl-substituted

bromothiophenes

or

bromobenzothiophenes are employed as starting materials for

the initial hydroaminoalkylation reaction with N-methylanilines to

obtain the branched products or in the case of vinylsilyl-

substituted bromobenzothiophene, to also obtain the linear

allyl-3-bromothiophene (5) could be combined with

a

subsequent intramolecular Buchwald-Hartwig reaction into a

one-pot procedure (Scheme 3). For that purpose, 2-allyl-3-

bromothiophene (5) was heated to 160 °C with various N-

methylanilines in the presence of 10 mol% of catalyst II for 24 h.

After cooling the reaction mixture down to ambient temperature,

the reagents necessary for the Buchwald-Hartwig amination

were added. The resulting mixture was diluted with additional

toluene and then heated to 110 °C for further 24 h. In this

context, it should be noted that we performed the Buchwald-

Hartwig amination step under the same reaction conditions

which we already had employed successfully for several

hydroaminoalkylation/Buchwald-Hartwig sequences described in

our previous studies (2.5 mol% Pd₂(dba)₃, 7 mol% RuPhos, 1.5

equiv NaOtBu).^[2f-h]

products.

Depending

on

the

structure

of

the

hydroaminoalkylation products, subsequent intramolecular

Buchwald-Hartwig amination reactions then directly deliver novel

thieno-

or

benzothieno-annulated

tetrahydropyridines,

tetrahydroazasilines or tetrahydroazasilepines.

Table 1. Hydroaminoalkylation of various unsaturated thiophene derivatives

with N-methylaniline (1).^[a]

Scheme 2. Retrosynthetic analysis of 4,5,6,7-tetrahydrothienopyridines,

1,2,3,4-tetrahydrothienoazasilines,

1,2,3,4-tetrahydrobenzothienoazasilines,

and 2,3,4,5-tetrahydrobenzothienoazasilepines: 1) palladium-catalyzed

Buchwald-Hartwig amination; 2) titanium-catalyzed hydroaminoalkylation.

Results and Discussion

We started our investigations by reacting 2-allylthiophene (2)

with N-methylaniline (1) in toluene at 160 °C in the presence of

10 mol% of catalyst I (Table 1, entry 1). The desired branched

product 8a was obtained in excellent yield of 90 % and with

good regioselectivity of 92:8 in favor of the expected branched

isomer. In comparison, the corresponding reaction performed in

the presence of catalyst II delivered 8a with a slightly increased

yield of 93 % and with an enhanced regioselectivity of 99:1

(Table 1, entry 2). We also performed additional

hydroaminoalkylation reactions of the 2-allyldimethylsilyl- and 2-

dimethyl(vinyl)silyl-substituted thiophenes 3 and 4 under the

same conditions and again, in both cases, catalyst II gave better

results in comparison to catalyst I. Catalyst II delivered the

corresponding product 9a in excellent yield of 98 % and with a

regioselectivity as high as 99:1 in favor of the branched isomer

(Table 1, entry 4), whereas the corresponding product 10a was

obtained in lower yield of 89 % and with a decreased

regioselectivity of 96:4 (Table 1, entry 6). Because during these

initial studies, catalyst II turned out to be the best catalyst for the

regioselective hydroaminoalkylation of the thiophene substrates

2-4, we decided to run all further reactions that should deliver

branched products with this catalyst. With regard to the intended

two-step procedure we then carried out corresponding reactions

with the analogous brominated thiophenes 5-7 which offer the

Entry

X

Y

Ti-cat.

Yield [%]^[b]

Ratio

a/b^[c]

1

2

3

4

5

6

7

8

9

CH₂

H

I

90 (8a)

93 (8a)

89 (9a)

98 (9a)

83 (10a)

89 (10a)

84 (11a)

92 (12a)

83 (13a)

92:8

99:1

92:8

99:1

85:15

96:4

92:8

99:1

94:6

CH₂

H

II

I

SiMe₂CH₂

SiMe₂

H

II

I

H

SiMe₂

H

II

CH₂

Br

SiMe₂CH₂

SiMe₂

[a]

Reaction conditions: N-methylaniline (1, 2.0 mmol, 214 mg), alkene (2.2

[b]

mmol), Ti-catalyst (0.2 mmol, 10 mol%), toluene (1 mL), 160 °C, 24 h.

Isolated yield of the branched product. Product ratios were determined by

GC analysis prior to flash chromatography.

[c]

When 2-allyl-3-bromothiophene (5) and N-methylaniline (1) were

subjected

tetrahydrothienopyridine 20 was obtained in good yield of 83 %

(Scheme 3), which is in good agreement with the yield of 84 %

possibility of

a

subsequent Buchwald-Hartwig cyclization

to

the

one-pot

procedure,

the

desired

reaction. The desired branched products 11a-13a could be

isolated in excellent yields of 83-92 % (Table 1, entries 7-9).

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observed in the initial hydroaminoalkylation reaction (Table 1,

entry 7). To further investigate the scope of the one-pot

procedure, we reacted the meta- and para-methyl-substituted N-

methylanilines 14 and 15 with 5 and in both cases, the

corresponding products 21 and 22 could be isolated in good

yields of 83-84 %. Furthermore, a para-fluoro substituent was

also well tolerated and as a result, product 23 could be obtained

in 81 % yield. In contrast, the analogous reaction performed in

the presence of a para-chloro substituent delivered 24 only with

a significantly decreased yield of 54 %. Due to the fact that a

control experiment in which 5 was hydroaminoalkylated with 4-

chloro-N-methylaniline (17) in the presence of II led to the

corresponding branched product with 74 % yield, it is obvious

that side reactions during the Buchwald-Hartwig amination step

are responsible for the decreased yield of 24. Further results

presented in Scheme 3 show that the one-pot procedure also

tolerates para-methoxy and para-thiomethyl groups as can be

seen from the corresponding products 25 and 26 which were

isolated in good yields of 82 % and 79 %, respectively.

experimental section). In contrast, the corresponding

benzothiophen-annulated product 29 which was formed by

carrying

out

the

one-pot

procedure

with

allyl(3-

bromobenzo[b]thiophen-2-yl)dimethylsilane (27) could easily be

isolated after flash column chromatography on silica gel and in

this case, a yield of 73 % was obtained. The improved stability of

the benzothiophene derivative 29 with respect to silica gel led to

the decision to study the substrate scope of the one-pot process

using alkene 27. The corresponding results obtained with a

number of N-methylanilines are presented in Scheme 4. They

show that the meta- and para-methyl-substituted N-

methylanilines 14 and 15 could be converted to the

corresponding 7-membered rings 30 and 31 with slightly lower

yields of 62 % and 65 % when compared to the result obtained

with unsubstituted N-methylaniline (1). Reactions performed with

para-fluoro- and para-chloro-substituted N-methylanilines

delivered the corresponding products 32 and 33 in comparably

good yields of 64 % and 61 %, respectively. This finding is in

sharp contrast to the behavior of these N-methylanilines in

reactions performed with 2-allyl-3-bromothiophene (5, Scheme

3) in which the chloro-substituted product 24 could only be

obtained in a significantly lower yield. Further reactions showed

that para-methoxy and para-thiomethyl groups are also well

tolerated as the corresponding heterocycles 34 and 35 were

isolated in good yields of 67 % and 62 %, respectively.

Scheme 3. One-pot procedure for the synthesis of 4,5,6,7-

tetrahydrothienopyridines. Reaction conditions: 1) amine (2.0 mmol), 2-allyl-3-

bromothiophene (5, 447 mg, 2.2 mmol), II (155 mg, 0.2 mmol, 10 mol%),

toluene (1 mL), 160 °C, 24 h; 2) Pd₂(dba)₃(46 mg, 0.05 mmol, 2.5 mol%),

RuPhos (65 mg, 0.14 mmol, 7 mol%), NaOtBu (288 mg, 3.0 mmol), toluene (4

mL), 110 °C, 24 h. ^[a]Isolated yield.

Encouraged by the good results observed with alkene 5, we

tried to perform an analogous one-pot procedure with the

allyldimethylsilyl-substituted thiophene

6

to obtain the

corresponding 7-membered heterocycle (Scheme 4). Firstly, we

reacted 6 with N-methylaniline (1) and as expected, the desired

tetrahydrothienoazasilepine 28 was formed in an excellent yield

of 88 %. Unfortunately, product 28 was found to be difficult to

purify as it decomposes completely on silica gel. Therefore, in

order to minimize the decomposition, compound 28 was purified

by fast filtration through a pad of Al₂O₃(for further details see the

Scheme 4. One-pot procedure for the synthesis of 2,3,4,5-tetrahydrothieno- or

2,3,4,5-tetrahydrobenzothienoazasilepines. Reaction conditions: 1) amine (2.0

mmol), allyl(3-bromothiophen-2-yl)dimethylsilane (575 mg, 2.2 mmol) or

allyl(3-bromobenzo[b]thiophen-2-yl)dimethylsilane (685 mg, 2.2 mmol), II (155

mg, 0.2 mmol, 10 mol%), toluene (1 mL), 160 °C, 24 h; 2) Pd₂(dba)₃(46 mg,

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azasilepine derivatives 28-35 formed from the allylsilanes 6 and

27 (Scheme 4), these heterocycles do not possess any methyl

substituents at the 7-membered ring. Unfortunately, initial

experiments revealed that titanium complex III does not show

any catalytic activity in the hydroaminoalkylation of vinylsilane 36

with N-methylaniline (1). For that reason, we employed the

analogous complexes IV and V which have recently been

identified to be highly active hydroaminoalkylation catalysts.^[2e,9u]

Surprisingly, initial experiments with catalysts IV or V revealed

that the use of these titanium complexes obviously does not

allow to perform the hydroaminoalkylation and the subsequent

palladium-catalyzed Buchwald-Hartwig amination as a one-pot

procedure. Corresponding attempts always resulted in poor

conversion of the linear hydroaminoalkylation product in the

Buchwald-Hartwig amination and in addition, the formation of

large amounts of side-products complicated the purification of

the desired heterocyclic product. To overcome these problems,

we decided to run the Buchwald-Hartwig amination after

purification of the linear hydroaminoalkylation product by flash

column chromatography. To investigate the scope of the

resulting new two-step protocol, we reacted vinylsilane 36 with

various N-methylanilines and further secondary amines. As can

be seen from Table 2, entry 1, the hydroaminoalkylation reaction

of 36 with N-methylaniline (1) performed at 140 °C in the

presence of catalyst IV gave the expected linear regioisomer

46b in 50 % yield whereas the branched regioisomer was only

obtained in 11 % yield. Additionally, the reaction delivered an

unexpected third product (46c) in 19 % yield, which resulted

from a hydroaminoalkylation reaction of 36 with the initially

formed linear product 46b. It is worth mentioning that the

formation of similar dihydroaminoalkylation products has already

been reported in our previous studies.^{[2a,2i,2j,2k]}Corresponding

reactions performed with all other N-methylanilines presented in

Table 2 (entries 2-6) showed a comparable behavior with regard

to regioselectivity and the formation of dihydroaminoalkylation

products. Although the linear hydroaminoalkylation product was

always formed as the major regioisomer, its conversion into a

dihydroaminoalkylation product is responsible for the fact that

the desired compounds 47b-51b could only be isolated in

moderate yields (36-56 %). For example, the meta-substituted

hydroaminoalkylation product 47b was isolated in 49 % yield,

whereas the corresponding chlorinated product 48b could be

obtained in a slightly increased yield of 56 % (Table 2, entries 2

and 3). Further experiments showed that methoxy and

trifluoromethoxy substitution are also well tolerated and as a

result, the corresponding products 49b and 50b were obtained

in 52 % and 51 % yield, respectively (Table 2, entries 4 and 5).

In contrast, performing the corresponding reaction with the para-

(trifluoromethyl)thio-substituted N-methylaniline 40 delivered the

linear regioisomer 51b only with a disappointing yield of 36 %

(Table 2, entry 6). Due to the fact that in our previous studies,

catalysts IV and V had already proven to be highly active

catalysts for the α-C−H activation of methylene groups,^[2j,2k]we

then carried out additional hydroaminoalkylation reactions with

N-alkylanilines possessing alkyl groups larger than a methyl

group. During this study, it was found that hydroaminoalkylation

reations of 36 with N-benzylanilines (41-43) exclusively form the

corresponding linear products 52b-54b and as a consequence,

significantly increased yields of 78-93 % were obtained in these

cases (Table 2, entries 7-9). The enhanced regioselectivities can

easily be explained by the increased steric hindrance of the N-

0.05 mmol, 2.5 mol%), RuPhos (65 mg, 0.14 mmol, 7 mol%), NaOtBu (288 mg,

3.0 mmol), toluene (4 mL), 110 °C, 24 h. ^[a]Isolated yield.

Corresponding one-pot procedures were then carried out under

identical reaction conditions with the dimethyl(vinyl)silyl

substituted thiophene derivatives 7 and 36 and N-methylaniline

(1, Scheme 5). As observed with the allyldimethylsilyl-

substituted substrates 6 and 27 (Scheme 4), the thiophene-

annulated azasiline 37 could be isolated in better yield (79 %)

than the analogous benzothiophene-annulated product 38 (68 %,

Scheme 5). However, in agreement with the difficult isolation of

product 28 (Scheme 4), the purification of 37 was also

challenging due to decomposition on silica gel, whereas the

benzothiophene-annulated analogue 38 could easily be purified

through flash chromatography on silica gel. An additional

benzene unit annulated to the thiophene ring obviously results in

an increased stability of the silicon-containing heterocycles

presented in Schemes 4 and 5.

Scheme 5. One-pot procedure for the synthesis of

a

1,2,3,4-

tetrahydrothienoazasiline and 1,2,3,4-tetrahydrobenzothienoazasiline.

a

Reaction conditions: 1) N-methylaniline (1, 214 mg, 2.0 mmol), (3-

bromothiophen-2-yl)dimethyl(vinyl)silane (7, 544 mg, 2.2 mmol) or (3-

bromobenzo[b]thiophen-2-yl)dimethyl(vinyl)silane (36, 654 mg, 2.2 mmol), II

(155 mg, 0.2 mmol, 10 mol%), toluene (1 mL), 160 °C, 24 h; 2) Pd₂(dba)₃(46

mg, 0.05 mmol, 2.5 mol%), RuPhos (65 mg, 0.14 mmol, 7 mol%), NaOtBu

(288 mg, 3.0 mmol), toluene (4 mL), 110 °C, 24 h. ^[a]Isolated yield.

In this context, it must be mentioned that the

hydroaminoalkylation reactions of vinylsilanes 7 and 36 with N-

methylaniline (1, Scheme 5) which were the initial step of the

one-pot procedure for the synthesis of the azasilines 37 and 38

were performed in the presence of catalyst II and as a

consequence, the branched regioisomers were formed

selectively. Afterwards, intramolecular Buchwald-Hartwig

amination of these regioisomers gave access to the 6-

membered azasiline heterocycles. However, in previous

studies^[2g]of our group it was found that the bis(aminopyridinato)

titanium complex III represents a suitable catalyst for the

conversion of vinylsilanes into linear hydroaminoalkylation

products. This fact should offer a simple possibility to generate

7-membered heterocycles from vinylsilane 36 when complex III

is used as the catalyst for the initial hydroaminoalkylation step

because cyclization of the expected linear hydroaminoalkylation

products should directly give access to 7-membered

tetrahydrobenzothienoazasilepines (Table 2). In contrast to the

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benzyl substituents when compared to a methyl group and

consequently, it is not surprising that a corresponding reaction

with N-isobutylaniline (44) also delivered the desired linear

product 55b exclusively, but in this case, a slightly decreased

yield of only 68 % was obtained (Table 2, entry 10). In contrast,

employing 1,2,3,4-tetrahydroquinoline (45) as the amine

substrate gave the linear hydroaminoalkylation product 56b only

in moderate yield of 51 % and additionally, again small amounts

of the corresponding branched regioisomer 56a (4 %) and the

dihydroaminoalkylation product 56c (3 %) were isolated. Further

reactions performed with N-methylcyclohexylamine and N-

methylpropylamine as examples for dialkylamines showed no

formation of the corresponding hydroaminoalkylation products.

Finally, we turned our attention towards the cyclization of the

isolated linear hydroaminoalkylation products 46b-56b to obtain

the desired tetrahydrobenzothienoazasilepines (Table 2). For

that purpose, we performed intramolecular Buchwald-Hartwig

aminations of 46b-56b under the same conditions as described

before for the one-pot processes. The obtained results clearly

show that sterically less demanding substrates like the

unfunctionalized compound 46b as well as the meta-methyl- and

para-methoxy-substituted substrates 47b and 49b react

smoothly to the expected 7-membered heterocycles 57, 58 and

60 and as a consequence, these products could be isolated in

good yields of 76-82 % (Table 2, entries 1, 2, and 4). The chloro-

in good agreement with the modest yield obtained in the case of

24 (Scheme 3) which already showed the low tolerance for a

chloro-substituent.

The

para-(trifluoromethoxy)-substituted

substrate 50b delivered the corresponding product 61 in an

excellent yield of 93 % (Table 2, entry 5). In sharp contrast to the

latter result, para-(trifluoromethyl)thio substitution was not well

tolerated under this conditions and as a result, the desired

heterocycle 62 was only isolated in a disappointing yield of 26 %

(Table 2, entry 6). Interestingly, in this case, the unexpected

side-product 68 was obtained in 42 % yield. Obviously, at the

silicon center of substrate 51b, the bromobenzothiophene

moiety is substituted by a tert-butoxy group under the reaction

conditions of the Buchwald-Hartwig amination. Unfortunately, at

the moment, we do not have a plausible explanation for this

surprising behavior of compound 51b. Further Buchwald-Hartwig

aminations of the sterically more demanding benzyl-substituted

amines 52b-54b delivered the corresponding 2-substituted

tetrahydrobenzothienoazasilepines 63-65 in moderate yields of

54-61 % (Table 2, entries 7-9). We assume that the higher steric

hindrance caused by the α-substitution of the amines 52b-54b

are responsible for the decreased yields. This assumption is

clearly supported by the reaction of substrate 55b which

delivered the 2-isopropyl substituted heterocycle 66 in an

unsatisfactory yield of only 35 %, whereas the sterically less

hindered tetrahydroquinoline derivate 56b could be converted

into the corresponding product 67 with a significantly better yield

of 53 %.

substituted heterocycle 59 could only be isolated in

a

significantly lower yield of 45 % (Table 2, entry 3). This result is

Table 2. Two-step procedure for the synthesis of 2,3,4,5-tetrahydrobenzothienoazasilepines from (3-bromobenzo[b]thiophen-2-yl)dimethyl(vinyl)silane (36).^[a]

Entry

1

Amine

Ti-

cat.

Hydroaminoalkylation Product b

Yield b [%]^[a,b]

Ratio a/b/c^[c]

Buchwald-Hartwig

Amination Product

Yield [%]^[b,d]

IV

50

13:63:24

76

5

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2

IV

49

11:77:12

82

3

IV

56

52

13:74:13

45

78

4

V

11:62:27

5

IV

51

12:70:18

93

6

IV

36

12:80:8

26

7

8

IV

84

93

0:100:0

56

61

9

IV

78

0:100:0

54

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10

11

V

68

51

0:100:0

35

53

7:88:5

[a]

Reaction conditions: (1) amine (2.0 mmol), (3-bromobenzo[b]thiophen-2-yl)dimethyl(vinyl)silane (36, 654 mg, 2.2 mmol or 713 mg, 2.4 mmol), IV (154 mg, 0.2

mmol, 10 mol%) or V (221 mg, 0.2 mmol, 10 mol%), toluene (1 mL), 140 °C, 24 h. ^[b]Isolated Yield. ^[c]Calculated from the obtained isolated yields of a, b and c. ^[d]

Reaction conditions: hydroaminoalkylation product b (0.5 mmol), Pd₂(dba)₃(11 mg, 0.0125 mmol, 2.5 mol%), RuPhos (16 mg, 0.035 mmol, 7 mol%), NaOtBu (72

mg, 0.75 mmol), toluene (1.5 mL), 110 °C, 24 h.

titanium complexes I-V^[2c,2d,2j]were synthesized according to literature

procedures. All other chemicals were purchased from commercial

sources and were used without further purification. All products that have

Conclusion

already been reported in literature were identified by ¹H NMR

spectroscopy and ¹³C NMR spectroscopy; all analytical data was found to

be consistent with the literature. New substances were additionally

characterized by infrared spectroscopy (IR), mass spectroscopy (MS),

In summary, we have developed new two-step procedures for

the synthesis of structurally novel thieno- or benzothieno-

annulated

tetrahydropyridines,

tetrahydroazasilines,

and

high resolution mass spectrometry (HRMS), ²⁹Si NMR spectroscopy, and

¹⁹F NMR spectroscopy. The ratio of products was determined by GC

analysis prior to flash chromatography or was calculated from the

obtained isolated yields. NMR spectra were recorded on a Bruker

Avance DRX 500 or a Bruker Avance III, 500 MHz spectrometer. ¹H NMR

spectra are referenced to the signal of CDCl₃at δ = 7.26 ppm. ¹³C NMR

spectra are referenced to the signal of CDCl₃δ = 77.16 ppm. Infrared

spectra were recorded on a Bruker Tensor 27 or Bruker Vector 22

spectrometer. MS analyses were performed on a Thermo Scientific DFS

(EI, 70 eV), Waters Q-TOF Premier (ESI+, TOF) or Shimadzu GSMS-

QP2020 (EI, 70 eV). HRMS analyses were performed on a Thermo

Scientific DFS (EI, 70 eV) or Waters Q-TOF Premier (ESI+, TOF). GC

analyses were performed on a Shimadzu GC-2010 gas chromatograph

(column: FS-SE-54-CB-0.25, length = 30 m, inner diameter = 0.32 mm,

tetrahydroazasilepines. The procedures combine an initial

regioselective

allyldimethylsilyl-

bromothiophenes

hydroaminoalkylation

of

2-dimethyl(vinyl)silyl-substituted

3-bromobenzothiophenes with

2-allyl-,

2-

3-

a

or

subsequent intramolecular Buchwald-Hartwig amination. While

the 2-allyl- and 2-allyldimethylsilyl-substituted substrates are

selectively converted into the branched hydroaminoalkylation

products, the dimethylvinyl-substituted substrates offer the

possibility of a regiodivergent generation of the branched or the

linear hydroaminoalkylation products depending on the choice of

the titanium catalyst. As a result, in this case, either 6-

membered or 7-membered heterocycles can optionally be

generated by the Buchwald-Hartwig cyclization. The two-step

processes that use the mono(aminopyridinato) titanium catalyst

II for the initial hydroaminoalkylation step can be performed as

one-pot procedures, whereas the use of the bis(aminopyridinato)

film thickness

=

0.25 μm, (94 %-methyl)-(5 %-phenyl)-(1 %-

vinyl)polysiloxane) with a flame ionization detector.

Silylation or allylation of thiophene. General procedure A: Thiophene

(4.21 g, 50.0 mmol) was dissolved in dry THF (50 mL) under an argon

atmosphere. n-BuLi (2.5 M in hexanes, 20.0 mL, 50.0 mmol) was added

at 0 °C and the resulting mixture was stirred for 1 h at 0 °C. The

chlorosilane (50.0 mmol) or allyl bromide (6.05 g, 50.0 mmol) was added

at 0 °C. After stirring for 2 h at 25 °C, the mixture was quenched with

water (30 mL). Most of the organic solvent was removed under reduced

pressure and the residue was extracted with MTBE (3 × 10 mL). The

combined organic layers were washed with brine (10 mL), dried with

MgSO₄, filtered and concentrated under vacuum. The crude product was

purified by distillation.

titanium catalysts IV and

V

require that the linear

hydroaminoalkylation products are purified prior to the

Buchwald-Hartwig cyclization. Our future studies will focus on

the expansion of the reported hydroaminoalkylation/Buchwald-

Hartwig amination sequences to the incorporation of further

important heterocycles.

Experimental Section

2-Allylthiophene (2):^[12]General procedure A was used to synthesize 2

from thiophene (4.63 g, 50.0 mmol) and allyl bromide (6.05 g, 50.0 mmol).

After distillation (43 °C, 30 mbar), product 2 (4.41 g, 35.5 mmol, 71 %)

General: Unless otherwise noted, all reactions were performed under an

inert atmosphere of nitrogen in oven-dried Schlenk tubes equipped with

Teflon® stopcocks and magnetic stirring bars. Toluene was purified by

distillation from sodium wire and degassed. THF and diethyl ether were

purified by distillation from sodium wire. Petroleum ether (b.p. 40-60 °C,

PE), ethyl acetate and tert-butyl methyl ether (MTBE) used for flash

chromatography were distilled prior to use. All substrates were distilled or

recrystallized and degassed prior to use. For thin layer chromatography,

silica on TLC aluminium foils with fluorescent indicator 254 nm from

Fluka were used. For flash chromatography, silica gel from GRACE

Davison (particle size 0.037-0.063 mm) was used. The substances were

detected with UV light. N-methylanilines,^[10]N-isobutylaniline^[11]and

1

was obtained as a colorless liquid. H NMR (500 MHz, CDCl₃): δ = 3.58

(d, J = 6.6 Hz, 2 H), 5.10 (dd, J = 10.0, 1.4 Hz, 1 H), 5.16 (dd, J = 17.0,

1.6 Hz, 1 H), 6.00 (ddt, J = 16.8, 10.6, 6.7 Hz, 1 H), 6.81 (dd, J = 3.4, 1.1

Hz, 1 H), 6.94 (dd, J = 5.1, 3.4 Hz, 1 H), 7.15 (dd, J = 5.2, 1.2 Hz, 1 H)

ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = 34.2 (CH₂), 116.2

(CH₂), 123.6 (CH), 124.6 (CH), 126.8 (CH), 136.5 (CH), 142.8 (C) ppm.

IR (ATR, neat): λ⁻¹= 3079, 2979, 2906, 1639, 1428, 1284, 1036, 990,

916, 850, 821, 689 cm^‒1

.

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European Journal of Organic Chemistry

FULL PAPER

2-(Allyldimethylsilyl)thiophene (3):^[12]General procedure A was used

6.37 (dd, J = 20.1, 14.6 Hz, 1 H), 7.11 (d, J = 4.8 Hz, 1 H), 7.47 (d, J =

4.8 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ = –2.5 (CH₃),

117.7 (C), 131.1 (CH), 132.6 (CH), 132.8 (C), 133.7 (CH₂), 136.2 (CH)

ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −13.4 ppm. IR (ATR,

neat): λ⁻¹= 3051, 2958, 1479, 1396, 1331, 1250, 1135, 1084, 993, 855,

to synthesize

3

from thiophene (4.63 g, 50.0 mmol) and

allyl(chloro)dimethylsilane (6.73 g, 50.0 mmol). After distillation (34 °C,

1.6 × 10^–1mbar), product 3 (6.48 g, 35.5 mmol, 71 %) was obtained as a

colorless liquid. ¹H NMR (500 MHz, CDCl₃): δ =0.36 (s, 6 H), 1.81 (d, J =

8.0 Hz, 2 H), 4.88-4.95 (m, 2 H), 5.82 (ddt, J = 16.3, 9.8, 8.0 Hz, 1 H),

7.21 (dd, J = 4.6, 3.4 Hz, 1 H), 7.30 (d, J = 3.2 Hz, 1 H), 7.62 (d, J = 4.6

Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ = –2.3 (CH₃),

24.5 (CH₂), 113.8 (CH₂), 128.1 (CH), 130.6 (CH), 134.1 (CH), 134.5 (CH),

138.0 (C) ppm.

860, 834, 812, 776, 712, 656 cm^‒1

.

3-Bromo-2-(allyldimethylsilyl)benzo[b]thiophene

(27):

Diisopropylamine (5.06 g, 50.0 mmol) was dissolved in THF (50 mL) at

0 °C, n-BuLi (2.5 M in hexanes, 20.0 mL, 50.0 mmol) was added and the

resulting mixture was stirred for 1 h. 3-Bromobenzo[b]thiophene (10.65 g,

50.0 mmol) was added at 0 °C and the mixture was stirred for 1 h.

Allyl(chloro)dimethylsilane (6.73 g, 50.0 mmol) was added at 0 °C.

Afterwards the mixture was warmed to 25 °C and stirred for 2 h. Water

(30 mL) was added and most of the organic solvent was removed under

reduced pressure. The residue was extracted with MTBE (3 × 10 mL).

The combined organic layers were washed with brine (10 mL), dried with

MgSO₄, filtered and concentrated under vacuum. The crude product was

purified by flash chromatography (SiO₂, PE) to give product 27 (13.52 g,

2-(Vinyldimethylsilyl)thiophene (4): General procedure A was used to

synthesize

4

from thiophene (4.63 g, 50.0 mmol) and

chloro(dimethyl)vinylsilane (6.03 g, 50.0 mmol). After distillation (92 °C,

10 mbar), product 4 (6.46 g, 38.4 mmol, 77 %) was obtained as a

colorless liquid. ¹H NMR (500 MHz, CDCl₃): δ = 0.43 (s, 6 H), 5.82 (dd, J

= 20.3, 3.5 Hz, 1 H), 6.09 (dd, J = 14.5, 3.6 Hz, 1 H), 6.32 (dd, J = 20.3,

14.6 Hz, 1 H), 7.22 (dd, J = 4.7, 3.3 Hz, 1 H), 7.31 (d, J = 3.3 Hz, 1 H),

7.64 (d, J = 4.6 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ

= –1.7 (CH₃), 128.1 (CH), 130.9 (CH), 133.0 (CH₂), 134.7 (CH), 137.6

(CH), 137.8 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −14.3

ppm. GC/MS (EI, 70 eV): m/z (%) = 169 (4) [M+1]⁺, 168 (18) [M]⁺, 153

(100), 141 (10), 127 (23). HRMS (EI): calcd. (C₈H₁₂SSi) 168.0423, found

168.0426 [M]⁺. IR (ATR, neat): λ⁻¹= 3052, 2957, 1405, 1250, 1214,

1083, 1006, 990, 955, 853, 837, 809, 774, 703, 639 cm^‒1.

1

43.4 mmol, 87 %) as a colorless liquid. H NMR (500 MHz, CDCl₃): δ =

0.51 (s, 3 H), 0.51 (s, 3 H), 2.04 (d, J = 8.1 Hz, 2 H), 4.89-4.94 (m, 1 H),

4.95-5.00 (m, 1 H), 5.78-5.89 (m, 1 H), 7.38-7.42 (m, 1 H), 7.44-7.48 (m,

1 H), 7.83-7.89 (m, 2 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ

= –2.9 (CH₃), 22.9 (CH₂), 114.4 (CH₂), 115.0 (C), 122.1 (CH), 123.0 (CH),

124.8 (CH), 125.2 (CH), 133.5 (CH), 134.5 (C), 139.7 (C), 141.5 (C) ppm.

²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −4.7 ppm. GC/MS (EI, 70

eV): m/z (%) = 312 (8) [M+2]⁺, 311 (2) [M+1]⁺, 310 (7) [M]⁺, 271 (98), 269

(99), 231 (100), 189 (58), 147 (57), 115 (30). HRMS (EI): calcd.

(C₁₃H₁₅BrSSi) 309.9842, found 309.9835 [M]⁺. IR (ATR, neat): λ⁻¹= 3075,

2958, 2898, 1629, 1479, 1450, 1291, 1243, 1158, 1021, 990, 897, 881,

Silylation and allylation of 3-bromothiophene. General procedure B:

Diisopropylamine (5.06 g, 50.0 mmol) was dissolved in THF (50 mL) at

0 °C, n-BuLi (2.5 M in hexanes, 20.0 mL, 50.0 mmol) was added and the

resulting mixture was stirred for 1 h. 3-Bromothiophene (8.15 g, 50.0

mmol) was added at 0 °C and the mixture was stirred for 1 h. The

chlorosilane (65.0 mmol) or allyl bromide (7.86 g, 65.0 mmol) was added

at 0 °C. Afterwards, the mixture was warmed to 25 °C and stirred for 2 h.

Water (30 mL) was added and most of the organic solvent was removed

under reduced pressure. The residue was extracted with MTBE (3 × 10

mL). The combined organic layers were washed with brine (10 mL), dried

with MgSO₄, filtered and concentrated under vacuum. The crude product

was purified by distillation.

821, 803, 749, 726, 710, 655 cm^‒1

.

3-Bromo-2-(vinyldimethylsilyl)benzo[b]thiophene

(36):

Diisopropylamine (5.06 g, 50.0 mmol) was dissolved in THF (50 mL) at

0 °C, n-BuLi (2.5 M in hexanes, 20.0 mL, 50.0 mmol) was added and the

resulting mixture was stirred for 1 h. 3-Bromobenzo[b]thiophene (10.65 g,

50.0 mmol) was added at 0 °C and the mixture was stirred for 1 h.

Chloro(dimethyl)vinylsilane (6.03 g, 50.0 mmol) was added at 0 °C.

Afterwards the mixture was warmed to 25 °C and stirred for 2 h. Water

(30 mL) was added and most of the organic solvent was removed under

reduced pressure. The residue was extracted with MTBE (3 × 10 mL).

The combined organic layers were washed with brine (10 mL), dried with

MgSO₄, filtered and concentrated under vacuum. The crude product was

purified by flash chromatography (SiO₂, PE) to give product 36 (12.57 g,

42.3 mmol, 85 %) as a colorless liquid. R_f= 0.53 (SiO₂, PE). ¹H NMR

(500 MHz, CDCl₃): δ = 0.58 (s, 6 H), 5.91 (dd, J = 20.3, 3.3 Hz, 1 H), 6.16

(dd, J = 14.6, 3.4 Hz, 1 H), 6.45 (dd, J = 20.3, 14.6 Hz, 1 H), 7.39 (t, J =

7.5 Hz, 1 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.82-7.88 (m, 2 H) ppm. ¹³C{¹H}

NMR (125 MHz, JMOD, CDCl₃): δ = ‒2.4 (CH₃), 115.3 (C), 122.3 (CH),

123.1 (CH), 125.0 (CH), 125.4 (CH), 134.3 (CH₂), 134.6 (C), 135.9 (CH),

140.0 (C), 141.8 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ =

−12.4 ppm. GC/MS (EI, 70 eV): m/z (%) = 296 [M]⁺, 281 (19) [M − CH₃]⁺,

255 (8), 217 (56) [M − Br]⁺, 201 (100), 189 (13), 175 (18), 160 (14), 147

(27), 141 (13), 127 (10), 115 (42), 101 (12), 89 (13). HRMS (EI): calcd.

(C₁₂H₁₃BrSSi) 295.9685, found 295.9689 [M]⁺. IR (ATR, neat): λ⁻¹= 3078,

2958, 1629, 1479, 1395, 1331, 1250, 1159, 1136, 1084, 991, 897, 861,

3-Bromo-2-allylthiophene (5):^[13]General procedure B was used to

synthesize 5 from 3-bromothiophene (8.15 g, 50.0 mmol) and allyl

bromide (7.86 g, 65.0 mmol). After distillation (108 °C, 10 mbar), product

1

5 (5.94 g, 29.3 mmol, 59 %) was obtained as a colorless liquid. H NMR

(500 MHz, CDCl₃): δ = 3.55 (dt, J = 6.5, 1.5 Hz, 2 H), 5.15 (dq, J = 10.1,

1.4 Hz, 1 H), 5.17 (dq, J = 16.9, 1.5 Hz, 1 H), 5.96 (ddt, J = 16.7, 10.0,

6.5 Hz, 1 H), 6.95 (d, J = 5.3 Hz, 1 H), 7.15 (d, J = 5.4 Hz, 1 H) ppm.

¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ = 33.4 (CH₂), 108.9 (C), 116.9

(CH₂), 123.6 (CH), 130.0 (CH), 134.7 (CH), 137.1 (C) ppm.

3-Bromo-2-(allyldimethylsilyl)thiophene (6): General procedure B was

used to synthesize alkene 6 from 3-bromothiophene (8.15 g, 50.0 mmol)

and allyl(chloro)dimethylsilane (8.75 g, 65.0 mmol). After distillation

(96 °C, 3.4 × 10^–2mbar), product 6 (8.41 g, 32.2 mmol, 64 %) was

obtained as a colorless liquid. ¹H NMR (500 MHz, CDCl₃): δ = 0.41 (s, 6

H), 1.94 (d, J = 8.1 Hz, 2 H), 4.86-4.95 (m, 2 H), 5.73-5.83 (m, 1 H), 7.10

(d, J = 4.8 Hz, 1 H), 7.44 (d, J = 4.8 Hz, 1 H) ppm. ¹³C{¹H} NMR (125

MHz, DEPT, CDCl₃): δ = –2.9 (CH₃), 23.0 (CH₂), 114.1 (CH₂), 117.5 (C),

131.0 (CH), 132.5 (CH), 132.7 (C), 133.7 (CH) ppm. ²⁹Si{¹H} NMR (99

MHz, INEPT, CDCl₃): δ = −5.8 ppm. IR (ATR, neat): λ⁻¹= 3052, 2957,

1481, 1450, 1404, 1291, 1243, 1005, 990, 955, 880, 838, 809, 779, 750,

821, 757, 712, 663, 644 cm^‒1

.

Hydroaminoalkylation of alkenes with secondary amines. General

procedure C: An oven-dried Schlenk tube equipped with a Teflon®

stopcock and a magnetic stirring bar was transferred into a nitrogen-filled

glovebox and charged with the catalyst (0.20 mmol, 10 mol%), amine

(2.00 mmol), alkene (2.20 mmol), and toluene (1 mL). The tube was

sealed, removed from the glovebox, and placed in an aluminium heating

block. The reaction mixture was heated to the appropriate temperature

(140 °C or 160 °C) for 24 h. After the reaction mixture had been cooled to

room temperature, it was diluted with CH₂Cl₂(50 mL) and Celite^®was

726, 701, 624 cm^‒1

.

3-Bromo-2-(vinyldimethylsilyl)thiophene (7): General procedure

B

was used to synthesize alkene 7 from 3-bromothiophene (8.15 g, 50.0

mmol) and chloro(dimethyl)vinylsilane (7.84 g, 65.0 mmol). After

distillation (50 °C, 3.4 × 10^–2mbar), product 7 (8.53 g, 34.5 mmol, 69 %)

was obtained as a colorless liquid. ¹H NMR (500 MHz, CDCl₃): δ = 0.50

(s, 6 H), 5.83 (dd, J = 20.2, 3.6 Hz, 1 H), 6.10 (dd, J = 14.6, 3.6 Hz, 1 H),

8

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European Journal of Organic Chemistry

FULL PAPER

added. Then the solvents were removed under reduced pressure and the

residue was purified by flash chromatography (SiO₂).

flash chromatography (SiO₂, PE/EtOAc, 40:1), 11a (520 mg, 1.68 mmol,

84 %) was obtained as a slightly yellow oil. R_f= 0.30 (SiO₂, PE/EtOAc,

40:1). ¹H NMR (500 MHz, CDCl₃): δ = 1.06 (d, J = 6.7 Hz, 3 H), 2.12-2.23

(m, 1 H), 2.73 (dd, J = 14.7, 7.7 Hz, 1 H), 2.96 (dd, J = 14.8, 6.4 Hz, 1 H),

3.00 (dd, J = 12.6, 7.0 Hz, 1 H), 3.16 (dd, J = 12.6, 6.1 Hz, 1 H), 3.93 (br.

s, NH), 6.59-6.63 (m, 2 H), 6.69- 6.74 (m, 1 H), 6.94 (d, J = 5.4 Hz, 1 H),

7.16 (d, J = 5.3 Hz, 1 H), 7.16-7.21 (m, 2 H) ppm. ¹³C{¹H} NMR (125 MHz,

JMOD, CDCl₃): δ = 17.9 (CH₃), 34.0 (CH₂), 34.9 (CH), 49.6 (CH₂), 109.7

(C), 112.8 (CH), 117.3 (CH), 123.5 (CH), 129.2 (CH), 129.9 (CH), 137.4

(C), 148.1 (C) ppm. GC/MS (EI, 70 eV): m/z (%) = 311 (9) [M+2]⁺, 310 (1)

[M+1]⁺, 309 (9) [M]⁺, 230 (8), 106 (100). HRMS (EI): calcd. (C₁₄H₁₆NBrS)

309.0181, found 309.0175 [M]⁺. IR (ATR, neat): λ⁻¹= 3418, 3085, 3051,

3020, 2957, 2925, 2869, 2842, 1601, 1504, 1471, 1457, 1432, 1319,

N-(2-Methyl-3-(thiophen-2-yl)propyl)aniline (8a): General procedure C

was used to synthesize 8a from 2-allylthiophene (2, 273 mg, 2.20 mmol)

and N-methylaniline (1, 214 mg, 2.00 mmol) with catalyst II (155 mg, 0.02

mmol, 10 mol%) at 160 °C. After purification by flash chromatography

(SiO₂, PE/EtOAc, 30:1), 8a (430 mg, 1.86 mmol, 93 %) was obtained as

a slightly yellow oil. R_f= 0.26 (SiO₂, PE/EtOAc, 30:1). ¹H NMR (500 MHz,

CDCl₃): δ = 1.04 (d, J = 6.7 Hz, 3 H), 2.06-2.17 (m, 1 H), 2.77 (dd, J =

14.7, 7.5 Hz, 1 H), 2.96 (dd, J = 14.7, 6.3 Hz, 1 H), 2.98 (dd, J = 12.6, 7.0

Hz, 1 H), 3.14 (dd, J = 12.6, 6.1 Hz, 1 H), 4.38 (br. s, NH), 6.62 (d, J =

7.9 Hz, 2 H), 6.72 (t, J = 7.3 Hz, 1 H), 6.80 (dd, J = 3.5, 1.1 Hz, 1 H), 6.94

(dd, J = 5.1, 3.4 Hz, 1 H), 7.14 (dd, J = 5.2, 1.2 Hz, 1 H), 7.15-7.20 (m, 2

H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = 18.0 (CH₃), 35.1

(CH₂), 35.4 (CH), 49.5 (CH₂), 112.7 (CH), 117.1 (CH), 123.4 (CH), 125.3

(CH), 126.7 (CH), 129.2 (CH), 142.9 (C), 148.3 (C) ppm. GC/MS (EI, 70

eV): m/z (%) = 232 (5) [M+1]⁺, 231 (22) [M]⁺, 106 (100), 97 (9), 91 (2), 77

(12). HRMS (EI): calcd. (C₁₄H₁₇NS) 231.1076, found 231.1078 [M]⁺. IR

(ATR, neat): λ⁻¹= 3422, 3047, 2956, 2925, 1603, 1507, 1473, 1435,

1321, 1260, 1181, 852, 814, 749, 691 cm^‒1).

1258, 1179, 1153, 1085, 1069, 894, 852, 747, 690 cm^‒1

.

N-(3-((3-Bromothiophen-2-yl)dimethylsilyl)-2-methylpropyl)aniline

(12a): General procedure C was used to synthesize 12a from 3-bromo-2-

(allyldimethylsilyl)thiophene (575 mg, 2.20 mmol) and N-methylaniline (1,

214 mg, 2.00 mmol) with catalyst II (155 mg, 0.02 mmol, 10 mol%) at

160 °C. After purification by flash chromatography (SiO₂, PE/MTBE,

40:1), 12a (677 mg, 1.84 mmol, 92 %) was obtained as a yellow oil. R_f=

1

0.23 (SiO₂, PE/MTBE, 40:1). H NMR (500 MHz, CDCl₃): δ = 0.45 (s, 3

H), 0.45 (s, 3 H), 0.87 (dd, J = 14.8, 9.0 Hz, 1 H), 0.99 (d, J = 6.6 Hz, 3

H), 1.21 (dd, J = 14.8, 4.6 Hz, 1 H), 1.89-2.00 (m, 1 H), 2.89 (dd, J = 12.3,

7.2 Hz, 1 H), 3.01 (dd, J = 12.3, 6.1 Hz, 1 H), 3.75 (br. s, NH), 6.53-6.57

(m, 2 H), 6.66-6.70 (m, 1 H), 7.13 (d, J = 4.8 Hz, 1 H), 7.13-7.18 (m, 2 H),

7.48 (d, J = 4.8 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ

= –1.6 (CH₃), –1.3 (CH₃), 20.9 (CH₃), 21.4 (CH₂), 29.5 (CH), 52.9 (CH₂),

112.6 (CH), 116.9 (CH), 117.5 (C), 129.2 (CH), 131.0 (CH), 132.6 (CH),

133.6 (C), 148.3 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ =

−4.4 ppm. GC/MS (ESI+, 70 eV): m/z (%) = 370 (91) [M+2+H]⁺, 369 (22)

[M+1+H]⁺, 368 (91) [M+H]⁺, 333 (6), 206 (100), 146 (10), 119 (6). HRMS

(EI): calcd. (C₁₆H₂₃NBrSSi) 368.0498, found 368.0499 [M]⁺. IR (ATR,

neat): λ⁻¹= 3022, 2959, 2869, 1602, 1505, 1478, 1396, 1329, 1250, 1179,

1135, 1084, 990, 860, 820, 791, 747, 715, 690, 656 cm^‒1.

N-(3-(Dimethyl(thiophen-2-yl)silyl)-2-methylpropyl)aniline

(9a):

General procedure was used to synthesize 9a from 2-

C

(allyldimethylsilyl)thiophene (3, 401 mg, 2.20 mmol) and N-methylaniline

(1, 214 mg, 2.00 mmol) with catalyst II (155 mg, 0.02 mmol, 10 mol%) at

160 °C. After purification by flash chromatography (SiO₂, PE/MTBE,

40:1), 9a (565 mg, 1.95 mmol, 98 %) was obtained as a slightly yellow oil.

R_f= 0.50 (SiO₂, PE/MTBE, 40:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.36 (s,

6 H), 0.74 (dd, J = 14.8, 9.0 Hz, 1 H), 0.99 (d, J = 6.6 Hz, 3 H), 1.04 (dd,

J = 14.9, 4.5 Hz, 1 H), 1.89-2.00 (m, 1 H), 2.88 (dd, J = 12.2, 7.2 Hz, 1 H),

2.99 (dd, J = 12.2, 6.1 Hz, 1 H), 4.33 (br. s, NH), 6.55-6.61 (m, 2 H),

6.67- 6.73 (m, 1 H), 7.13-7.18 (m, 2 H), 7.19-7.22 (m, 1 H), 7.27-7.29 (m,

1 H), 7.60-7.63 (m, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ

= –1.0 (CH₃), –0.7 (CH₃), 21.0 (CH₃), 22.8 (CH₂), 29.5 (CH), 53.0 (CH₂),

112.7 (CH), 117.0 (CH), 128.2 (CH), 129.2 (CH), 130.6 (CH), 134.3 (CH),

138.9 (C), 148.3 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ =

−6.0 ppm. GC/MS (EI, 70 eV): m/z (%) = 290 (5) [M+1]⁺, 289 (23) [M]⁺,

141 (30), 106 (100), 77 (6). HRMS (EI): calcd. (C₁₆H₂₃NSSi) 289.1315,

found 289.1305 [M]⁺. IR (ATR, neat): λ⁻¹= 3417, 3050, 2959, 2901, 2178,

1602, 1505, 1471, 1406, 1377, 1322, 1250, 1213, 1179, 1083, 989, 818,

N-(2-((3-Bromothiophen-2-yl)dimethylsilyl)propyl)aniline

(13a):

General procedure C was used to synthesize 13a from 3-bromo-2-

(vinyldimethylsilyl)thiophene (7, 544 mg, 2.20 mmol) and N-methylaniline

(1, 214 mg, 2.00 mmol) with catalyst II (155 mg, 0.02 mmol, 10 mol%) at

160 °C. After purification by flash chromatography (SiO₂, PE/MTBE,

40:1), 13a (588 mg, 1.66 mmol, 83 %) was obtained as a slightly yellow

oil. R_f= 0.31 (SiO₂, PE/MTBE, 40:1). ¹H NMR (500 MHz, CDCl₃): δ =

0.45 (s, 3 H), 0.45 (s, 3 H), 1.09 (d, J = 7.4 Hz, 3 H), 1.64 (dqd, J = 9.5,

7.4, 5.2 Hz, 1 H), 3.01 (dd, J = 12.2, 9.5 Hz, 1 H), 3.29 (dd, J = 12.3, 5.2

Hz, 1 H), 3.67 (br. s, NH), 6.51-6.54 (m, 2 H), 6.65-6.70 (m, 1 H), 7.12-

7.17 (m, 3 H), 7.50 (d, J = 4.8 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz,

JMOD, CDCl₃): δ = –4.0 (CH₃), –3.5 (CH₃), 13.1 (CH₃), 19.9 (CH), 46.8

(CH₂), 113.0 (CH), 117.3 (CH), 117.9 (C), 129.3 (CH), 131.5 (CH), 132.6

(C), 132.9 (CH), 148.4 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃):

δ = −1.7 ppm. GC/MS (EI, 70 eV): m/z (%) = 355 (19) [M+2]⁺, 354 (4)

[M+1]⁺, 353 (17) [M]⁺, 221 (25), 219 (23), 106 (100) HRMS (EI): calcd.

792, 746, 706 cm^‒1

.

N-(2-(Dimethyl(thiophen-2-yl)silyl)propyl)aniline

procedure was used to synthesize

(10a):

10a

General

from 2-

C

(vinyldimethylsilyl)thiophene (4, 370 mg, 2.20 mmol) and N-methylaniline

(1, 214 mg, 2.00 mmol) with catalyst II (155 mg, 0.02 mmol, 10 mol%) at

160 °C. After purification by flash chromatography (SiO₂, PE/MTBE,

40:1), 10a (489 mg, 1.78 mmol, 89 %) was obtained as a yellow oil. R_f=

1

0.28 (SiO₂, PE/MTBE, 40:1). H NMR (500 MHz, CDCl₃): δ = 0.36 (s, 3

H), 0.37 (s, 3 H), 1.11 (d, J = 7.3 Hz, 3 H), 1.26-1.35 (m, 1 H), 3.00 (dd, J

= 12.2, 9.5 Hz, 1 H), 3.29 (dd, J = 12.3, 4.8 Hz, 1 H), 4.74 (br. s, NH),

6.56-6.63 (m, 2 H), 6.70-6.76 (m, 1 H), 7.16 (dd, J = 8.6, 7.3 Hz, 2 H),

7.22 (dd, J = 4.6, 3.4 Hz, 1 H), 7.29 (dd, J = 3.3, 1.1 Hz, 1 H), 7.64 (dd, J

= 4.7, 0.8 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = –

3.8 (CH₃), –3.1 (CH₃), 13.0 (CH₃), 20.8 (CH), 46.7 (CH₂), 112.8 (CH),

117.2 (CH), 128.2 (CH), 129.1 (CH), 130.9 (CH), 134.9 (CH), 136.9 (C),

148.1 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −3.1 ppm.

GC/MS (EI, 70 eV): m/z (%) = 276 (3) [M+1]⁺, 275 (13) [M]⁺, 217 (12),

191 (15), 141 (34), 106 (100), 77 (7). HRMS (EI): calcd. (C₁₅H₂₁NSSi)

275.1158, found 275.1162 [M]⁺. IR (ATR, neat): λ⁻¹= 3057, 2954, 2863,

1603, 1507, 1407, 1321, 1252, 1215, 1181, 1085, 993, 854, 831, 808,

(C₁₅H₂₀NBrSSi) 353.0264, found 353.0266 [M]⁺. IR (ATR, neat): λ⁻¹

=

3410, 3051, 2952, 2866, 1601, 1504, 1478, 1429, 1395, 1330, 1251,

1179, 1135, 1083, 990, 860, 835, 808, 772, 746, 715, 690, 638 cm^‒1.

One-pot procedure for the hydroaminoalkylation/Buchwald-Hartwig

amination sequence. General procedure D: An oven-dried Schlenk

tube equipped with a Teflon® stopcock and a magnetic stirring bar was

transferred into a nitrogen-filled glovebox and charged with catalyst II

(155 mg, 0.02 mmol, 10 mol%), alkene (2.20 mmol), amine (2.00 mmol),

and toluene (1 mL). After heating the mixture to 160 °C for 24 h, the

mixture was cooled to room temperature and transferred into a nitrogen-

filled glovebox, again. Pd₂(dba)₃(46 mg, 0.05 mmol, 2.5 mol%), RuPhos

(66 mg, 0.14 mmol, 7 mol%), NaOtBu (288 mg, 3.00 mmol), and toluene

(4 mL) were added. After heating the mixture to 110 °C for 24 h, the

mixture was cooled to room temperature and MTBE (40 mL) was added.

774, 748, 709, 692 cm^‒1

.

N-(3-(3-Bromothiophen-2-yl)-2-methylpropyl)aniline (11a): General

procedure C was used to synthesize 11a from 3-bromo-2-allylthiophene

(5, 447 mg, 2.20 mmol) and N-methylaniline (1, 214 mg, 2.00 mmol) with

catalyst II (155 mg, 0.02 mmol, 10 mol%) at 160 °C. After purification by

9

10.1002/ejoc.202001523

European Journal of Organic Chemistry

FULL PAPER

The suspension was filtered through Celite to remove solids and the

crude product was purified by flash chromatography (SiO₂).

JMOD, CDCl₃): δ = 18.6 (CH₃), 27.8 (CH), 31.1 (CH₂), 58.1 (CH₂), 115.5

(d, J = 22 Hz, CH), 115.7 (C), 119.9 (CH), 121.2 (CH), 123.1 (d, J = 8 Hz,

CH), 140.6 (C), 145.3 (C), 158.4 (d, J = 241 Hz, C) ppm. ¹⁹F NMR (470

MHz, CDCl₃): δ = −120.8 ppm. GC/MS (EI, 70 eV): m/z (%) = 248 (16)

[M+1]⁺, 247 (100) [M]⁺, 204 (42), 95 (9). HRMS (EI): calcd. (C₁₄H₁₄NFS)

247.0825, found 247.0824 [M]⁺. IR (ATR, neat): λ⁻¹= 3049, 2955, 2912,

2870, 2839, 1558, 1503, 1456, 1423, 1395, 1381, 1346, 1301, 1245,

6-Methyl-4-phenyl-4,5,6,7-tetrahydrothieno[3,2-b]pyridine

(20):

General procedure D was used to synthesize 20 from 3-bromo-2-

allylthiophene (5, 447 mg, 2.20 mmol) and N-methylaniline (1, 214 mg,

2.00 mmol). After purification by flash chromatography (SiO₂, PE/MTBE,

80:1), 20 (381 mg, 1.66 mmol, 83 %) was obtained as a slightly yellow oil.

R_f= 0.44 (SiO₂, PE/MTBE, 80:1). ¹H NMR (500 MHz, CDCl₃): δ = 1.08 (d,

J = 5.8 Hz, 3 H), 2.18-2.29 (m, 1 H), 2.47 (dd, J = 15.8, 9.5 Hz, 1 H), 2.92

(dd, J = 16.1, 5.3 Hz, 1 H), 3.27 (t, J = 10.6 Hz, 1 H), 3.63- 3.70 (m, 1 H),

6.79 (d, J = 4.5 Hz, 1 H), 6.95-7.02 (m, 2 H), 7.14 (d, J = 7.2 Hz, 2 H),

7.29 (t, J = 6.9 Hz, 2 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ

= 18.6 (CH₃), 27.9 (CH), 31.2 (CH₂), 57.3 (CH₂), 116.5 (C), 120.2 (CH),

120.9 (CH), 120.9 (CH), 121.6 (CH), 129.0 (CH), 140.2 (C), 148.9 (C)

ppm. GC/MS (EI, 70 eV): m/z (%) = 230 (23) [M+1]⁺, 229 (100) [M]⁺, 186

(55), 77 (15). HRMS (EI): calcd. (C₁₄H₁₅NS) 229.0920, found 229.0915

[M]⁺. IR (ATR, neat): λ⁻¹= 3061, 3036, 2956, 2912, 2871, 2839, 1597,

1558, 1495, 1458, 1401, 1382, 1347, 1303, 1251, 1188, 1156, 1127, 849,

1216, 1186, 1155, 1125, 830, 765, 706, 630 cm^‒1

.

4-(4-Chlorophenyl)-6-methyl-4,5,6,7-tetrahydrothieno[3,2-b]pyridine

(24): General procedure D was used to synthesize 24 from 3-bromo-2-

allylthiophene (5, 447 mg, 2.20 mmol) and 4-chloro-N-methylaniline (17,

283 mg, 2.00 mmol). After purification by flash chromatography (SiO₂,

PE/MTBE, 80:1), 24 (286 mg, 1.08 mmol, 54 %) was obtained as a

1

slightly yellow oil. R_f= 0.42 (SiO₂, PE/MTBE, 80:1). H NMR (500 MHz,

CDCl₃): δ = 1.06 (d, J = 6.7 Hz, 3 H), 2.16-2.27 (m, 1 H), 2.45 (dd, J =

16.2, 9.5 Hz, 1 H), 2.91 (dd, J = 16.2, 5.6 Hz, 1 H), 3.24 (dd, J = 12.0, 9.8

Hz, 1H), 3.60 (ddd, J = 12.1, 3.2, 1.4 Hz, 1 H), 6.73 (d, J = 5.5 Hz, 1 H),

7.00 (d, J = 5.5 Hz, 1 H), 7.04-7.08 (m, 2 H), 7.21-7.25 (m, 2 H) ppm.

¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ = 18.6 (CH₃), 27.9 (CH), 31.1

(CH₂), 57.4 (CH₂), 117.5 (C), 120.0 (CH), 121.3 (CH), 121.9 (CH), 126.4

(C), 129.0 (CH), 139.6 (C), 147.4 (C) ppm. GC/MS (EI, 70 eV): m/z (%) =

265 (65) [M+2]⁺, 264 (35) [M+1]⁺, 263 (100) [M]⁺, 186 (51). HRMS (EI):

767, 751, 698, 636 cm^‒1

.

6-Methyl-4-(m-tolyl)-4,5,6,7-tetrahydrothieno[3,2-b]pyridine

(21):

General procedure D was used to synthesize 21 from 3-bromo-2-

allylthiophene (5, 447 mg, 2.20 mmol) and N,3-dimethylaniline (14, 242

mg, 2.00 mmol). After purification by flash chromatography (SiO₂,

PE/MTBE, 80:1), 21 (411 mg, 1.69 mmol, 84 %) was obtained as a

calcd. (C₁₄H₁₄NClS) 263.0530, found 263.0526 [M]⁺. IR (ATR, neat): λ⁻¹

=

3038, 2957, 2913, 2871, 2840, 1593, 1558, 1489, 1457, 1421, 1393,

1383, 1349, 1303, 1249, 1129, 1092, 1008, 827, 708, 690, 628 cm^‒1.

1

slightly yellow oil. R_f= 0.45 (SiO₂, PE/MTBE, 80:1). H NMR (500 MHz,

CDCl₃): δ = 1.07 (d, J = 6.7 Hz, 3 H), 2.17-2.28 (m, 1 H), 2.33 (s, 3 H),

2.46 (dd, J = 16.1, 9.5 Hz, 1 H), 2.91 (dd, J = 16.1, 5.6 Hz, 1 H), 3.26 (dd,

J = 12.0, 9.8 Hz, 1 H), 3.61-3.67 (m, 1 H), 6.78 (d, J = 5.4 Hz, 1 H), 6.79-

6.83 (m, 1 H), 6.93-7.00 (m, 3 H), 7.18 (t, J = 7.7 Hz, 1 H) ppm. ¹³C{¹H}

NMR (125 MHz, JMOD, CDCl₃): δ = 18.6 (CH₃), 21.5 (CH₃), 27.9 (CH),

31.3 (CH₂), 57.3 (CH₂), 116.4 (C), 118.0 (CH), 120.4 (CH), 120.9 (CH),

121.6 (CH), 122.5 (CH), 128.8 (CH), 138.8 (C), 140.4 (C), 148.9 (C)

ppm. GC/MS (EI, 70 eV): m/z (%) = 244 (14) [M+1]⁺, 243 (100) [M]⁺, 200

(17), 91 (11). HRMS (EI): calcd. (C₁₅H₁₇NS) 243.1076, found 243.1080

[M]⁺. IR (ATR, neat): λ⁻¹= 3034, 2953, 2912, 2869, 2838, 1601, 1582,

4-(4-Methoxyphenyl)-6-methyl-4,5,6,7-tetrahydrothieno[3,2-

b]pyridine (25): General procedure D was used to synthesize 25 from 3-

bromo-2-allylthiophene (5, 447 mg, 2.20 mmol) and 4-methoxy-N-

methylaniline (18, 274 mg, 2.00 mmol). After purification by flash

chromatography (SiO₂, PE/MTBE, 80:1), 25 (427 mg, 1.65 mmol, 82 %)

was obtained as a slightly yellow oil. R_f= 0.31 (SiO₂, PE/MTBE, 80:1). ¹H

NMR (500 MHz, CDCl₃): δ = 1.10 (d, J = 6.5 Hz, 3 H), 2.22-2.33 (m, 1 H),

2.49 (dd, J = 16.0, 9.6 Hz, 1 H), 2.92 (dd, J = 16.0, 5.4 Hz, 1 H), 3.23 (t, J

= 10.9 Hz, 1 H), 3.52- 3.57 (m, 1 H), 3.84 (s, 3 H), 6.63 (d, J = 5.3 Hz, 1

H), 6.89 (d, J = 8.3 Hz, 2 H), 6.98 (d, J = 5.3 Hz, 1 H), 7.13 (d, J = 8.1 Hz,

2 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = 18.7 (CH₃), 27.7

(CH), 31.2 (CH₂), 55.5 (CH₃), 58.4 (CH₂), 114.3 (CH), 115.0 (C), 120.0

(CH), 120.9 (CH), 123.7 (CH), 141.5 (C), 142.7 (C), 155.4 (C) ppm.

GC/MS (EI, 70 eV): m/z (%) = 260 (32) [M+1]⁺, 259 (100) [M]⁺, 244 (41),

202 (29). HRMS (EI): calcd. (C₁₅H₁₇ONS) 259.1025, found 259.1023 [M]⁺.

IR (ATR, neat): λ⁻¹= 3101, 3037, 2995, 2952, 2907, 2869, 2833, 1558,

1505, 1457, 1439, 1397, 1287, 1237, 1179, 1126, 1035, 828, 706, 630

1557, 1488, 1454, 1396, 1345, 1301, 1247, 1125, 778, 701, 636 cm^‒1

.

6-Methyl-4-(p-tolyl)-4,5,6,7-tetrahydrothieno[3,2-b]pyridine (22):

General procedure D was used to synthesize 22 from 3-bromo-2-

allylthiophene (5, 447 mg, 2.20 mmol) and N,4-dimethylaniline (15, 242

mg, 2.00 mmol). After purification by flash chromatography (SiO₂,

PE/MTBE, 80:1), 22 (404 mg, 1.66 mmol, 83 %) was obtained as a

cm^‒1

.

1

slightly yellow oil. R_f= 0.57 (SiO₂, PE/MTBE, 80:1). H NMR (500 MHz,

CDCl₃): δ = 1.07 (d, J = 6.7 Hz, 3 H), 2.17-2.28 (m, 1 H), 2.32 (s, 3 H),

2.45 (dd, J = 16.1, 9.5 Hz, 1 H), 2.90 (dd, J = 16.3, 5.3 Hz, 1 H), 3.24 (dd,

J = 12.0, 9.9 Hz, 1 H), 3.60 (ddd, J = 12.0, 3.1, 1.3 Hz, 1 H), 6.72 (d, J =

5.4 Hz, 1 H), 6.97 (d, J = 5.3 Hz, 1 H), 7.03-7.07 (m, 2 H), 7.09-7.12 (m,

2 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = 18.6 (CH₃), 20.7

(CH₃), 27.8 (CH), 31.2 (CH₂), 57.8 (CH₂), 116.0 (C), 120.3 (CH), 120.9

(CH), 121.4 (CH), 129.6 (CH), 131.5 (C), 140.7 (C), 146.6 (C) ppm.

GC/MS (EI, 70 eV): m/z (%) = 244 (16) [M+1]⁺, 243 (100) [M]⁺, 200 (23),

91 (12). HRMS (EI): calcd. (C₁₅H₁₇NS) 243.1076, found 243.1075 [M]⁺.

IR (ATR, neat): λ⁻¹= 3025, 2953, 2914, 2868, 2838, 1611, 1557, 1509,

1455, 1419, 1395, 1380, 1344, 1299, 1249, 1127, 816, 706, 661, 630

6-Methyl-4-(4-(methylthio)phenyl)-4,5,6,7-tetrahydrothieno[3,2-

b]pyridine (26): General procedure D was used to synthesize 26 from 3-

bromo-2-allylthiophene (5, 447 mg, 2.20 mmol) and N-methyl-4-

(methylthio)aniline (19, 306 mg, 2.00 mmol). After purification by flash

chromatography (SiO₂, PE/MTBE, 80:1), 26 (410 mg, 1.58 mmol, 79 %)

was obtained as a slightly yellow oil. R_f= 0.39 (SiO₂, PE/MTBE, 80:1). ¹H

NMR (500 MHz, CDCl₃): δ = 1.06 (d, J = 6.7 Hz, 3 H), 2.15-2.26 (m, 1 H),

2.45 (dd, J = 16.1, 9.4 Hz, 1 H), 2.47 (s, 3 H), 2.90 (dd, J = 16.1, 5.6 Hz,

1 H), 3.24 (dd, J = 12.0, 9.7 Hz, 1 H), 3.58-3.63 (m, 1 H), 6.75 (d, J = 5.4

Hz, 1 H), 6.98 (d, J = 5.4 Hz, 1 H), 7.04-7.09 (m, 2 H), 7.21-7.25 (m, 2 H)

ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = 17.4 (CH₃), 18.6 (CH₃),

27.9 (CH), 31.2 (CH₂), 57.3 (CH₂), 116.7 (C), 120.1 (CH), 121.1 (CH),

121.4 (CH), 129.0 (CH), 129.9 (C), 140.0 (C), 146.9 (C) ppm. GC/MS (EI,

70 eV): m/z (%) = 276 (67) [M+1]⁺, 275 (100) [M]⁺, 260 (40), 186 (44).

HRMS (EI): calcd. (C₁₅H₁₇NS₂) 275.0797, found 275.0797 [M]⁺. IR (ATR,

neat): λ⁻¹= 3027, 2953, 2915, 2868, 2836, 1591, 1554, 1490, 1454, 1436,

1416, 1391, 1380, 1345, 1300, 1246, 1185, 1127, 846, 822, 706, 683,

cm^‒1

.

4-(4-Fluorophenyl)-6-methyl-4,5,6,7-tetrahydrothieno[3,2-b]pyridine

(23): General procedure D was used to synthesize 23 from 3-bromo-2-

allylthiophene (5, 447 mg, 2.20 mmol) and 4-fluoro-N-methylaniline (16,

250 mg, 2.00 mmol). After purification by flash chromatography (SiO₂,

PE/MTBE, 80:1), 23 (403 mg, 1.63 mmol, 81 %) was obtained as a

655, 625 cm^‒1

.

1

slightly yellow oil. R_f= 0.42 (SiO₂, PE/MTBE, 80:1). H NMR (500 MHz,

CDCl₃): δ = 1.07 (d, J = 6.7 Hz, 3 H), 2.17-2.28 (m, 1 H), 2.46 (dd, J =

16.1, 9.5 Hz, 1 H), 2.90 (d, J = 16.1, 5.5 Hz, 1 H), 3.22 (dd, J = 11.9, 9.9

Hz, 1 H), 3.54 (dd, J = 12.0, 3.2, 1.4 Hz, 1 H), 6.64 (d, J = 5.4 Hz, 1 H),

6.95-7.01 (m, 3 H), 7.06-7.12 (m, 2 H) ppm. ¹³C{¹H} NMR (125 MHz,

6,8,8-Trimethyl-4-phenyl-5,6,7,8-tetrahydro-4H-thieno[3,2-

b][1,4]azasilepine (28): An oven-dried Schlenk tube equipped with a

Teflon® stopcock and a magnetic stirring bar was transferred into a

10

10.1002/ejoc.202001523

European Journal of Organic Chemistry

FULL PAPER

nitrogen-filled glovebox and charged with catalyst II (155 mg, 0.02 mmol,

10 mol%), 3-bromo-2-(allyldimethylsilyl)thiophene (6, 575 mg, 2.20

mmol), N-methylaniline (1, 214 mg, 2.00 mmol), and toluene (1 mL). After

heating the mixture to 160 °C for 24 h, the mixture was cooled to room

temperature and was transferred into a nitrogen-filled glovebox, again.

Pd₂(dba)₃(46 mg, 0.05 mmol, 2.5 mol%), RuPhos (66 mg, 0.14 mmol, 7

mol%), NaOtBu (288 mg, 3.00 mmol), and toluene (4 mL) were added.

After heating the mixture to 110 °C for 24 h, the mixture was cooled to

room temperature and PE (40 mL) was added. The suspension was

filtered through a pad of Celite to remove solids. The solvent was

removed under reduced pressure. PE (100 mL) was added to the residue.

The solution was heated to reflux, then cooled to 0 °C and filtered

through a pad of Al₂O₃(activated, neutral). The solvent was removed

under reduced pressure and 28 (507 mg, 1.76 mmol, 88 %) was obtained

as a dark yellow oil. Due to the high instability of this compound in

solution, rapid decomposition processes which result in visible impurities

in the NMR spectra were observed. ¹H NMR (500 MHz, CDCl₃): δ = 0.04

(s, 3 H), 0.35 (s, 3 H), 0.60 (dd, J = 14.4, 10.8 Hz, 1 H), 0.94 (ddd, J =

14.1, 3.5, 1.4 Hz, 1 H), 1.08 (d, J = 6.8 Hz, 3 H), 2.23-2.33 (m, 1 H), 3.02

(dd, J = 14.9, 10.3 Hz, 1 H), 3.96 (ddd, J = 14.8, 2.4, 1.5 Hz, 1 H), 6.65-

6.69 (m, 2 H), 6.70-6.75 (m, 1 H), 7.01 (d, J = 4.7 Hz, 1 H), 7.17-7.21 (m,

2 H), 7.50 (d, J = 4.7 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT,

CDCl₃): δ = –1.9 (CH₃), –1.6 (CH₃), 23.5 (CH₃), 23.8 (CH₂), 29.6 (CH),

58.4 (CH₂), 113.4 (CH), 117.0 (CH), 127.1 (CH), 129.0 (CH), 129.9 (C),

130.1 (CH), 147.2 (C), 154.2 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT,

CDCl₃): δ = −7.3 ppm. GC/MS (EI, 70 eV): m/z (%) = 288 (16) [M+1]⁺,

287 (84) [M]⁺, 232 (100), 230 (39). HRMS (EI): calcd. (C₁₆H₂₁NSSi)

287.1158, found 287.1158 [M]⁺. IR (ATR, neat): λ⁻¹= 3087, 3058, 3029,

2951, 2923, 2897, 2866, 1595, 1496, 1450, 1405, 1386, 1253, 1170,

1085, 1028, 992, 843, 792, 743, 687 cm^‒1.

7.39 (m, 1 H), 7.83-7.86 (m, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD,

CDCl₃): δ = –2.3 (CH₃), –2.2 (CH₃), 21.9 (CH₃), 23.6 (CH₃), 23.6 (CH₂),

29.4 (CH), 57.9 (CH₂), 113.2 (CH), 116.5 (CH), 117.9 (CH), 122.3 (CH),

123.0 (CH), 123.8 (CH), 124.4 (CH), 128.8 (CH), 134.0 (C), 136.2 (C),

138.6 (C), 142.8 (C), 146.7 (C), 148.1 (C) ppm. ²⁹Si{¹H} NMR (99 MHz,

INEPT, CDCl₃): δ = −6.3 ppm. GC/MS (EI, 70 eV): m/z (%) = 352 (3)

[M+1]⁺, 351 (12) [M]⁺, 304 (26), 244 (25), 215 (26), 193 (25), 75 (100).

HRMS (EI): calcd. (C₂₁H₂₅NSSi) 351.1471, found 351.1466 [M]⁺. IR (ATR,

neat): λ⁻¹= 3057, 3026, 2953, 2923, 2900, 2866, 1601, 1491, 1451, 1363,

1252, 1186, 1045, 836, 825, 791, 764, 733, 697 cm^‒1

.

3,5,5-Trimethyl-1-(p-tolyl)-2,3,4,5-tetrahydro-1H-

benzo[4,5]thieno[3,2-b][1,4]azasilepine (31): General procedure D was

used to synthesize 31 from 3-bromo-2-

(allyldimethylsilyl)benzo[b]thiophene (27, 685 mg, 2.20 mmol) and N,4-

dimethylaniline (15, 242 mg, 2.00 mmol). After purification by flash

chromatography (SiO₂, PE/MTBE, 80:1), 31 (458 mg, 1.30 mmol, 65 %)

was obtained as colorless crystals. Slow cooling of a hot, saturated

solution of 31 in n-hexane gave crystals suitable for X-ray analysis.^[14]

Due to the high instability of this compound in solution, rapid

decomposition processes which result in visible impurities in the NMR

spectra were observed. Mp.: 106-108 °C. R_f= 0.51 (SiO₂, PE/MTBE,

1

80:1). H NMR (500 MHz, CDCl₃): δ = 0.10 (s, 3 H), 0.43 (s, 3 H), 0.63

(dd, J = 14.4, 11.2 Hz, 1 H), 0.98 (ddd, J = 14.4, 3.5, 1.5 Hz, 1 H), 1.12 (d,

J = 6.8 Hz, 3 H), 2.27 (s, 3 H), 2.34-2.44 (m, 1 H), 3.02 (dd, J = 14.9,

10.5 Hz, 1 H), 4.12-4.17 (m, 1 H), 6.45-6.55 (br. s, 2 H), 6.99 (d, J = 8.3

Hz, 2 H), 7.22-7.26 (m, 1 H), 7.30-7.35 (m, 1 H), 7.38-7.41 (m, 1 H),

7.85-7.88 (m, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = –

2.3 (CH₃), –2.0 (CH₃), 20.3 (CH₃), 22.6 (CH₃), 23.6 (CH₂), 29.4 (CH),

58.1 (CH₂), 113.4 (CH), 122.3 (CH), 123.0 (CH), 123.7 (CH), 124.4 (CH),

126.0 (C), 129.6 (CH), 133.6 (C), 136.2 (C), 142.8 (C), 144.4 (C), 148.2

(C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −6.3 ppm. GC/MS

(EI, 70 eV): m/z (%) = 352 (21) [M+1]⁺, 351 (63) [M]⁺, 296 (100). HRMS

(EI): calcd. (C₂₁H₂₅NSSi) 351.1471, found 351.1468 [M]⁺. IR (ATR, neat):

λ⁻¹= 3064, 3027, 2958, 2924, 2883, 1613, 1498, 1450, 1368, 1321, 1248,

1121, 1071, 1027, 971, 919, 846, 816, 803, 790, 767, 736, 712, 626 cm^‒1.

3,5,5-Trimethyl-1-phenyl-2,3,4,5-tetrahydro-1H-benzo[4,5]thieno[3,2-

b][1,4]azasilepine (29): General procedure D was used to synthesize 29

from 3-bromo-2-(allyldimethylsilyl)benzo[b]thiophene (27, 685 mg, 2.20

mmol) and N-methylaniline (1, 214 mg, 2.00 mmol). After purification by

flash chromatography (SiO₂, PE/MTBE, 80:1), 29 (493 mg, 1.46 mmol,

73 %) was obtained as a dark yellow oil. Due to the high instability of this

compound in solution, rapid decomposition processes which result in

visible impurities in the NMR spectra were observed. R_f= 0.51 (SiO₂,

PE/MTBE, 80:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.07 (s, 3 H), 0.40 (s, 3

H), 0.62 (dd, J = 14.4, 11.4 Hz, 1 H), 0.97 (ddd, J = 14.4, 3.4, 1.7 Hz, 1

H), 1.11 (d, J = 6.8 Hz, 3 H), 2.34-2.45 (m, 1 H), 3.00 (dd, J = 14.9, 10.6

Hz, 1 H), 4.11-4.16 (m, 1 H), 6.50-6.60 (m, 2 H), 6.72 (t, J = 7.3 Hz, 1 H),

7.13-7.19 (m, 2 H), 7.21-7.26 (m, 1 H), 7.30-7.35 (m, 1 H), 7.36-7.40 (m,

1 H), 7.84-7.87 (m, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ

= –2.4 (CH₃), –2.2 (CH₃), 23.6 (CH₃), 23.7 (CH₂), 29.3 (CH), 57.8 (CH₂),

113.4 (CH), 116.9 (CH), 122.2 (CH), 123.0 (CH), 123.8 (CH), 124.4 (CH),

129.0 (CH), 134.2 (C), 136.1 (C), 142.8 (C), 146.6 (C), 147.9 (C) ppm.

²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −6.2 ppm. GC/MS (EI, 70

eV): m/z (%) = 338 (32) [M+1]⁺, 337 (100) [M]⁺, 282 (91), 186 (37), 184

(42). HRMS (EI): calcd. (C₂₀H₂₃NSSi) 337.1315, found 337.1312 [M]⁺. IR

(ATR, neat): λ⁻¹= 3060, 3038, 2950, 2924, 2896, 2865, 1595, 1496,

1450, 1373, 1250, 1195, 1030, 847, 815, 792, 763, 744, 733, 720, 691,

1-(4-Fluorophenyl)-3,5,5-trimethyl-2,3,4,5-tetrahydro-1H-

benzo[4,5]thieno[3,2-b][1,4]azasilepine (32): General procedure D was

used

to

synthesize

32

from

3-bromo-2-

(allyldimethylsilyl)benzo[b]thiophene (27, 685 mg, 2.20 mmol) and 4-

fluoro-N-methylaniline (16, 250 mg, 2.00 mmol). After purification by flash

chromatography (SiO₂, PE/MTBE, 80:1), 32 (454 mg, 1.28 mmol, 64 %)

was obtained as a dark yellow oil. Due to the high instability of this

compound in solution, rapid decomposition processes which result in

visible impurities in the NMR spectra were observed. R_f= 0.51 (SiO₂,

PE/MTBE, 80:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.08 (s, 3 H), 0.41 (s, 3

H), 0.62 (dd, J = 14.4, 11.3 Hz, 1 H), 0.97 (ddd, J = 14.4, 3.5, 1.6 Hz, 1

H), 1.10 (d, J = 6.9 Hz, 3 H), 2.30-2.40 (m, 1 H), 3.02 (dd, J = 14.9, 10.5

Hz, 1 H), 4.05-4.11 (m, 1 H), 6.44-6.52 (br. s, 2 H), 6.87 (t, J = 8.5 Hz, 2

H), 7.22-7.27 (m, 1 H), 7.30-7.36 (m, 2 H), 7.84-7.87 (m, 1 H) ppm.

¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = –2.3 (CH₃), –2.1 (CH₃), 22.6

(CH₂), 23.6 (CH₃), 29.3 (CH), 58.3 (CH₂), 114.0 (CH), 115.5 (d, J = 22 Hz,

CH), 122.1 (CH), 123.1 (CH), 123.9 (CH), 124.5 (CH), 134.1 (C), 136.0

(C), 142.9 (C), 143.1 (C), 147.8 (C), 155.5 (d, J = 235 Hz, C) ppm.

²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −6.3 ppm. ¹⁹F NMR (470

MHz, CDCl₃): δ = −128.9 ppm. GC/MS (EI, 70 eV): m/z (%) = 356 (30)

[M+1]⁺, 355 (100) [M]⁺, 313 (22), 300 (78), 113 (14). HRMS (EI): calcd.

635 cm^‒1

.

3,5,5-Trimethyl-1-(m-tolyl)-2,3,4,5-tetrahydro-1H-

benzo[4,5]thieno[3,2-b][1,4]azasilepine (30): General procedure D was

used

to

synthesize

30

from

3-bromo-2-

(allyldimethylsilyl)benzo[b]thiophene (27, 685 mg, 2.20 mmol) and N,3-

dimethylaniline (14, 242 mg, 2.00 mmol). After purification by flash

chromatography (SiO₂, PE/MTBE, 80:1), 30 (434 mg, 1.23 mmol, 62 %)

was obtained as a dark yellow oil. Due to the high instability of this

compound in solution, rapid decomposition processes which result in

visible impurities in the NMR spectra were observed. R_f= 0.55 (SiO₂,

PE/MTBE, 80:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.08 (s, 3 H), 0.39 (s, 3

H), 0.60 (dd, J = 14.4, 11.3 Hz, 1 H), 0.96 (ddd, J = 14.3, 3.4, 1.6 Hz, 1

H), 1.10 (d, J = 6.8 Hz, 3 H), 2.25 (s, 3 H), 2.32-2.42 (m, 1 H), 2.97 (dd, J

= 14.9, 10.6 Hz, 1 H), 4.09-4.14 (m, 1 H), 6.25-6.45 (br. s, 2 H), 6.53-6.56

(m, 1 H), 7.02-7.07 (m, 1 H), 7.21-7.25 (m, 1 H), 7.29-7.34 (m, 1 H), 7.35-

(C₂₀H₂₂NFSSi) 355.1221, found 355.1222 [M]⁺. IR (ATR, neat): λ⁻¹

3055, 2951, 2866, 1500, 1451, 1372, 1322, 1251, 1224, 1194, 1159,

1028, 847, 814, 790, 767, 752, 735, 646 cm^‒1

=

.

1-(4-Chlorophenyl)-3,5,5-trimethyl-2,3,4,5-tetrahydro-1H-

benzo[4,5]thieno[3,2-b][1,4]azasilepine (33): General procedure D was

used

to

synthesize

33

from

3-bromo-2-

(allyldimethylsilyl)benzo[b]thiophene (27, 685 mg, 2.20 mmol) and 4-

chloro-N-methylaniline (17, 283 mg, 2.00 mmol). After purification by

flash chromatography (SiO₂, PE/MTBE, 80:1), 33 (456 mg, 1.23 mmol,

11

10.1002/ejoc.202001523

European Journal of Organic Chemistry

FULL PAPER

61 %) was obtained as a dark yellow oil. R_f= 0.51 (SiO₂, PE/MTBE, 80:1).

¹H NMR (500 MHz, CDCl₃): δ = 0.08 (s, 3 H), 0.42 (s, 3 H), 0.63 (dd, J =

14.4, 11.5 Hz, 1 H), 0.99 (ddd, J = 14.4, 3.3, 1.6 Hz, 1 H), 1.12 (d, J = 6.8

Hz, 3 H), 2.32-2.42 (m, 1 H), 3.01 (dd, J = 15.0, 10.6 Hz, 1 H), 4.08 (d, J

= 14.9 Hz, 1 H), 6.38-6.58 (br. s, 2 H), 7.08-7.14 (m, 2 H), 7.24-7.28 (m,

1 H), 7.32-7.38 (m, 2 H), 7.87 (d, J = 8.0 Hz, 1 H) ppm. ¹³C{¹H} NMR

(125 MHz, JMOD, CDCl₃): δ = –2.5 (CH₃), –2.2 (CH₃), 23.6 (CH₃), 23.6

(CH₂), 29.3 (CH), 58.0 (CH₂), 114.4 (CH), 121.7 (C), 122.0 (CH), 123.1

(CH), 123.9 (CH), 124.6 (CH), 128.9 (CH), 134.6 (C), 135.8 (C), 142.8

(C), 145.3 (C), 147.3 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ

= −6.2 ppm. GC/MS (EI, 70 eV): m/z (%) = 373 (46) [M+2]⁺, 372 (33)

[M+1]⁺, 371 (100) [M]⁺, 318 (37), 316 (87), 113 (91), 59 (43). HRMS (EI):

calcd. (C₂₀H₂₂NClSSi) 371.0925, found 371.0921 [M]⁺. IR (ATR, neat):

λ⁻¹= 3064, 2950, 2896, 2866, 1593, 1489, 1372, 1323, 1250, 1194, 1184,

160 °C for 24 h, the mixture was cooled to room temperature and was

transferred into a nitrogen-filled glovebox, again. Pd₂(dba)₃(46 mg, 0.05

mmol, 2.5 mol%), RuPhos (66 mg, 0.14 mmol, 7 mol%), NaOtBu (288

mg, 3.00 mmol), and toluene (4 mL) were added. After heating the

mixture to 110 °C for 24 h, the mixture was cooled to room temperature

and PE (40 mL) was added. The suspension was filtered through a pad

of Celite to remove solids. The solvent was removed under reduced

pressure. PE (100 mL) was added to the residue, the solution was

heated to reflux, then cooled to 0 °C and filtered through a pad of Al₂O₃

(activated, neutral). The solvent was removed under reduced pressure

and 37 (433 mg, 1.58 mmol, 79 %) was obtained as a dark yellow oil.

Due to the high instability of this compound in solution, rapid

decomposition processes which result in visible impurities in the NMR

spectra were observed. ¹H NMR (500 MHz, CDCl₃): δ = 0.29 (s, 3 H),

0.32 (s, 3 H), 1.04 (d, J = 7.5 Hz, 3 H), 1.15-1.25 (m, 1 H), 3.66 (dd, J =

12.9, 9.4 Hz, 1 H), 3.84 (dd, J = 12.9, 3.3 Hz, 1 H), 6.74 (d, J = 4.9 Hz, 1

H), 7.01-7.06 (m, 1 H), 7.15-7.19 (m, 2 H), 7.28-7.31 (m, 2 H), 7.38 (d, J

= 4.9 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ = –3.4

(CH₃), –1.0 (CH₃), 12.7 (CH₃), 17.1 (CH), 58.1 (CH₂), 109.8 (C), 121.7

(CH), 122.5 (CH), 122.9 (CH), 129.0 (CH), 129.8 (CH), 149.8 (C), 154.8

(C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −9.9 ppm. GC/MS

(EI, 70 eV): m/z (%) = 274 (15) [M+1]⁺, 273 (81) [M]⁺, 231 (100), 216 (31).

HRMS (EI): calcd. (C₁₅H₁₉NSSi) 273.1002, found 273.1005 [M]⁺. IR (ATR,

neat): λ⁻¹= 3082, 3058, 3030, 2948, 2926, 2900, 2865, 1594, 1515, 1494,

1455, 1408, 1387, 1344, 1247, 1179, 1114, 1095, 1032, 993, 845, 833,

1028, 847, 811, 792, 766, 733, 670, 643 cm^‒1

.

1-(4-Methoxyphenyl)-3,5,5-trimethyl-2,3,4,5-tetrahydro-1H-

benzo[4,5]thieno[3,2-b][1,4]azasilepine (34): General procedure D was

used

to

synthesize

34

from

3-bromo-2-

(allyldimethylsilyl)benzo[b]thiophene (27, 685 mg, 2.20 mmol) and 4-

methoxy-N-methylaniline (18, 274 mg, 2.00 mmol). After purification by

flash chromatography (SiO₂, PE/MTBE, 80:1), 34 (492 mg, 1.34 mmol,

67 %) was obtained as a dark yellow oil. R_f= 0.12 (SiO₂, PE/MTBE, 80:1).

¹H NMR (500 MHz, CDCl₃): δ = 0.10 (s, 3 H), 0.41 (s, 3 H), 0.62 (dd, J =

14.4, 10.9 Hz, 1 H), 0.97 (ddd, J = 14.3, 3.5, 1.3 Hz, 1 H), 1.09 (d, J = 6.8

Hz, 3 H), 2.29-2.39 (m, 1 H), 3.03 (dd, J = 14.9, 10.5 Hz, 1 H), 3.75 (s, 3

H), 4.08-4.13 (m, 1 H), 6.53 (d, J = 8.5 Hz, 2 H), 6.76 (d, J = 9.0 Hz, 2 H),

7.19-7.23 (m, 1 H), 7.28-7.33 (m, 1 H), 7.33-7.36 (m, 1 H), 7.82-7.85 (m,

1 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = –2.1 (CH₃), –1.9

(CH₃), 23.4 (CH₂), 23.5 (CH₃), 29.4 (CH), 55.5 (CH₃), 58.5 (CH₂), 114.6

(CH), 114.7 (CH), 122.4 (CH), 123.0 (CH), 123.7 (CH), 124.4 (CH), 132.9

(C), 136.3 (C), 140.9 (C), 142.8 (C), 148.4 (C), 151.6 (C) ppm. ²⁹Si{¹H}

NMR (99 MHz, INEPT, CDCl₃): δ = 7.3 ppm. GC/MS (EI, 70 eV): m/z (%)

= 367 (3) [M]⁺, 268 (100), 240 (27), 133 (14). HRMS (EI): calcd.

800, 771, 726, 696, 660 cm^‒1

.

3,4,4-Trimethyl-1-phenyl-1,2,3,4-tetrahydrobenzo[4,5]thieno[3,2-

b][1,4]azasiline (38): General procedure D was used to synthesize 38

from 3-bromo-2-(vinyldimethylsilyl)benzo[b]thiophene (36, 654 mg, 2.20

mmol) and N-methylaniline (1, 214 mg, 2.00 mmol). After purification by

flash chromatography (SiO₂, PE/MTBE, 80:1), 38 (442 mg, 1.37 mmol,

68 %) was obtained as a dark yellow oil. Due to the high instability of this

compound in solution, rapid decomposition processes which result in

visible impurities in the NMR spectra were observed. R_f= 0.43 (SiO₂,

PE/MTBE, 80:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.34 (s, 3 H), 0.36 (s, 3

H), 1.03 (d, J = 7.5 Hz, 3 H), 1.31-1.42 (m, 1 H), 3.73 (dd, J = 13.7, 11.4

Hz, 1 H), 4.07 (dd, J = 13.7, 3.7 Hz, 1 H), 6.94-7.00 (m, 3 H), 7.11-7.14

(m, 2 H), 7.21-7.28 (m, 3 H), 7.81-7.84 (m, 1 H) ppm. ¹³C{¹H} NMR (125

MHz, DEPT, CDCl₃): δ = –4.1 (CH₃), –1.8 (CH₃), 12.8 (CH₃), 15.9 (CH),

59.6 (CH₂), 120.9 (C), 121.3 (CH), 121.5 (CH), 122.6 (CH), 123.2 (CH),

123.5 (CH), 124.5 (CH), 128.9 (CH), 135.0 (C), 142.7 (C), 148.6 (C),

149.0 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −7.7 ppm.

GC/MS (EI, 70 eV): m/z (%) = 324 (3) [M+1]⁺, 323 (14) [M]⁺, 264 (30),

207 (32), 193 (100), 191 (58), 162 (95). HRMS (EI): calcd. (C₁₉H₂₁NSSi)

323.1158, found 323.1161 [M]⁺. IR (ATR, neat): λ⁻¹= 3058, 3034, 2953,

2925, 2902, 2865, 1594, 1492, 1454, 1345, 1248, 1188, 1164, 1051,

(C₂₁H₂₅ONSSi) 367.1421, found 367.1426 [M]⁺. IR (ATR, neat): λ⁻¹

=

3060, 2952, 2901, 2869, 2832, 1504, 1461, 1352, 1287, 1236, 1180,

1162, 1035, 827, 793, 758, 750, 735, 703 cm^‒1.

3,5,5-Trimethyl-1-(4-(methylthio)phenyl)-2,3,4,5-tetrahydro-1H-

benzo[4,5]thieno[3,2-b][1,4]azasilepine (35): General procedure D was

used

to

synthesize

35

from

3-bromo-2-

(allyldimethylsilyl)benzo[b]thiophene (27, 685 mg, 2.20 mmol) and N-

methyl-4-(methylthio)aniline (19, 306 mg, 2.00 mmol). After purification

by flash chromatography (SiO₂, PE/MTBE, 80:1), 35 (474 mg, 1.24 mmol,

62 %) was obtained as a dark yellow oil. Due to the high instability of this

compound in solution, rapid decomposition processes which result in

visible impurities in the NMR spectra were observed. R_f= 0.35 (SiO₂,

PE/MTBE, 80:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.06 (s, 3 H), 0.40 (s, 3

H), 0.61 (dd, J = 14.4, 11.4 Hz, 1 H), 0.96 (ddd, J = 14.4, 3.4, 1.6 Hz, 1

H), 1.10 (d, J = 6.8 Hz, 3 H), 2.29-2.42 (m, 1 H), 2.42 (s, 3 H), 2.99 (dd, J

= 14.9, 10.6 Hz, 1 H), 4.06-4.12 (m, 1 H), 6.44-6.56 (br. s, 2 H), 7.12-7.19

(m, 2 H), 7.22-7.26 (m, 1 H), 7.31-7.35 (m, 1 H), 7.35-7.38 (m, 1 H), 7.83-

7.87 (m, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = –2.4

(CH₃), –2.2 (CH₃), 18.5 (CH₃), 23.6 (CH₃), 23.7 (CH₂), 29.4 (CH), 58.0

(CH₂), 114.1 (CH), 122.1 (CH), 123.1 (CH), 123.9 (CH), 123.9 (C), 124.5

(CH), 130.6 (CH), 134.3 (C), 136.0 (C), 142.8 (C), 145.4 (C), 147.5 (C)

ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −6.7 ppm. GC/MS (EI,

70 eV): m/z (%) = 384 (31) [M+1]⁺, 383 (100) [M]⁺, 328 (75), 113 (12).

HRMS (EI): calcd. (C₂₁H₂₅NS₂Si) 383.1192, found 383.1186 [M]⁺. IR

(ATR, neat): λ⁻¹= 3064, 3027, 2953, 2924, 2883, 1591, 1554, 1490,

1022, 976, 938, 851, 831, 799, 764, 747, 733, 692 cm^‒1

.

N-(2-((3-Bromobenzo[b]thiophen-2-yl)dimethylsilyl)propyl)aniline

(46a),

N-(3-((3-bromobenzo[b]thiophen-2-

(46b), and N-(1,5-bis((3-

yl)dimethylsilyl)propyl)aniline

bromobenzo[b]thiophen-2-yl)dimethylsilyl)pentan-3-yl)aniline (46c):

General procedure C was used to synthesize 46b from N-methylaniline

(1,

214

mg,

2.00

mmol)

and

3-bromo-2-

(vinyldimethylsilyl)benzo[b]thiophene (36, 713 mg, 2.40 mmol) with

titanium catalyst IV (154 mg, 0.20 mmol, 10 mol%) at 140 °C. After

purification by flash chromatography (SiO₂, PE/EtOAc, 30:1), 46a (85 mg,

0.21 mmol, 11 %), 46b (401 mg, 0.99 mmol, 50 %), and 46c (271 mg,

0.39 mmol, 19 %) were obtained as slightly yellow oils. 46a: R_f= 0.30

(SiO₂, PE/EtOAc, 30:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.54 (s, 6 H),

1.15 (d, J = 7.4 Hz, 3 H), 1.76 (dqd, J = 9.4, 7.4, 5.4 Hz, 1 H), 3.08 (dd, J

= 12.3, 9.6 Hz, 1 H), 3.35 (dd, J = 12.4, 5.2 Hz, 1 H), 6.55 (d, J = 7.9 Hz,

2 H), 6.69 (t, J = 7.3 Hz, 1 H), 7.11-7.16 (m, 2 H), 7.41 (t, J = 7.0 Hz, 1 H),

7.47 (t, J = 7.5 Hz, 1 H), 7.84-7.90 (m, 2 H) ppm. ¹³C{¹H} NMR (125 MHz,

JMOD, CDCl₃): δ = ‒4.0 (CH₃), ‒3.6 (CH₃), 13.1 (CH), 19.8 (CH), 47.1

(CH₂), 113.3 (CH), 115.4 (C), 117.7 (CH), 122.3 (CH), 123.2 (CH), 125.1

(CH), 125.5 (CH), 129.3 (CH), 134.2 (C), 139.9 (C), 141.7 (C), 147.8 (C)

ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −0.5 ppm. GC/MS (EI,

1250, 1184, 1028, 847, 826, 792, 760, 733, 670 cm^‒1

.

3,4,4-Trimethyl-1-phenyl-1,2,3,4-tetrahydrothieno[3,2-b][1,4]azasiline

(37): An oven-dried Schlenk tube equipped with a Teflon® stopcock and

a magnetic stirring bar was transferred into a nitrogen-filled glovebox and

charged with catalyst II (155 mg, 0.02 mmol, 10 mol%), 3-bromo-2-

(vinyldimethylsilyl)thiophene (7, 544 mg, 2.20 mmol), N-methylaniline (1,

214 mg, 2.00 mmol), and toluene (1 mL). After heating the mixture to

12

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European Journal of Organic Chemistry

FULL PAPER

70 eV): m/z (%) = 403 (4) [M]⁺, 324 (7) [M − Br]⁺, 282 (15), 269 (6) [M −

1093, 1072, 1021, 989, 939, 910, 880, 836, 806, 766, 751, 726, 711, 690,

649, 591, 504 cm^‒1. 47b: R_f= 0.17 (SiO₂, PE/EtOAc, 50:1). ¹H NMR (500

MHz, CDCl₃): δ = 0.53 (s, 6 H), 1.08-1.15 (m, 2 H), 1.68-1.76 (m, 2 H),

2.29 (s, 3 H), 3.15 (t, J = 7.1 Hz, 2 H), 6.40-6.45 (m, 2 H), 6.54 (d, J = 7.4

Hz, 1 H), 7.07 (t, J = 7.6 Hz, 1 H), 7.42 (t, J = 7.4 Hz, 1 H), 7.48 (t, J = 7.5

Hz, 1 H), 7.85-7.92 (m, 2 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD,

CDCl₃): δ = ‒2.3 (CH₃), 12.9 (CH₂), 21.7 (CH₃), 24.1 (CH₂), 47.1 (CH₂),

110.0 (CH), 113.6 (CH), 115.1 (C), 118.2 (CH), 122.3 (CH), 123.1 (CH),

125.0 (CH), 125.4 (CH), 129.2 (CH), 135.0 (C), 139.0 (C), 139.9 (C),

141.6 (C), 148.4 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ =

−2.3 ppm. GC/MS (EI, 70 eV): m/z (%) = 417 (4) [M]⁺, 402 (1) [M − CH₃]⁺,

231 (9), 204 (16), 147 (11), 120 (100) [M − C₁₂H₁₄BrSSi]⁺, 91 (14) [M −

C₁₃H₁₇BrNSSi]⁺. HRMS (ESI, +): calcd. (C₂₀H₂₅BrNSSi) 418.0660, found

418.0663 [M+H]⁺. IR (ATR, neat): λ⁻¹= 3409, 3047, 3017, 2952, 2919,

2860, 1604, 1589, 1509, 1482, 1450, 1420, 1410, 1327, 1303, 1290,

1273, 1250, 1243, 1180, 1164, 1100, 1070, 1020, 989, 880, 839, 824,

804, 767, 751, 726, 711, 690, 641, 591, 503 cm^‒1. 47c: R_f= 0.30 (SiO₂,

PE/EtOAc, 50:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.48 (s, 6 H), 0.49 (s, 6

H), 0.98 (ddd, J = 14.5, 12.8, 5.0 Hz, 2 H), 1.11 (ddd, J = 14.6, 12.6, 4.4

Hz, 2 H), 1.52-1.61 (m, 2 H), 1.62-1.71 (m, 2 H), 2.27 (s, 3 H), 3.32 (quint,

J = 5.8 Hz, 1 H), 6.36-6.42 (m, 2 H), 6.49 (d, J = 7.3 Hz, 1 H), 7.02 (t, J =

7.7 Hz, 1 H), 7.39-7.43 (m, 2 H), 7.45-7.49 (m, 2 H), 7.83-7.90 (m, 4 H)

ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = ‒2.4 (CH₃), ‒2.3 (CH₃),

11.1 (CH₂), 21.8 (CH₃), 27.9 (CH₂), 57.3 (CH), 110.2 (CH), 113.9 (CH),

115.0 (C), 117.7 (CH), 122.2 (CH), 123.1 (CH), 124.9 (CH), 125.3 (CH),

129.2 (CH), 135.0 (C), 139.0 (C), 139.9 (C), 141.6 (C), 148.0 (C) ppm.

²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −1.9 ppm. GC/MS (EI, 70

eV): m/z (%) = 715 (2) [M]⁺, 416 (13) [M − C₁₂H₁₄BrSSi]⁺, 204 (100), 189

(19), 164 (15), 147 (26), 115 (16), 73 (11). HRMS (ESI, +): calcd.

(C₃₂H₃₈Br₂NS₂Si₂) 714.0351, found 714.0419 [M+H]⁺. IR (ATR, neat): λ⁻¹

= 3409, 3053, 2953, 2920, 1603, 1587, 1509, 1482, 1450, 1420, 1409,

1323, 1304, 1290, 1249, 1242, 1182, 1163, 1070, 1020, 989, 939, 881,

C₉H₁₂N]⁺, 191 (14), 176 (6), 147 (12), 115 (11), 106 (100) [M

−

C₁₂H₁₄BrSSi]⁺, 77 (11) [M

−

C₁₃H₁₇BrNSSi]⁺. HRMS (EI): calcd.

(C₁₉H₂₂BrNSSi) 403.0420, found 403.0423 [M]⁺. IR (ATR, neat): λ⁻¹

=

3415, 3052, 3019, 2953, 2900, 2864, 1602, 1556, 1504, 1479, 1450,

1420, 1377, 1319, 1290, 1250, 1243, 1179, 1160, 1154, 1132, 1092,

1070, 1021, 989, 940, 879, 836, 806, 779, 746, 726, 710, 690, 649, 591,

503 cm^‒1. 46b: R_f= 0.27 (SiO₂, PE/EtOAc, 30:1). ¹H NMR (500 MHz,

CDCl₃): δ = 0.49 (s, 6 H), 1.06-1.11 (m, 2 H), 1.67-1.75 (m, 2 H), 3.14 (t,

J = 7.1 Hz, 2 H), 6.63 (d, J = 7.8 Hz, 2 H), 6.71 (t, J = 7.3 Hz, 1 H), 7.15 (t,

J = 7.9 Hz, 2 H), 7.40 (t, J = 7.2 Hz, 1 H), 7.46 (t, J = 7.5 Hz, 1 H), 7.85 (t,

J = 7.1 Hz, 2 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = ‒2.3

(CH₃), 12.9 (CH₂), 23.8 (CH₂), 47.5 (CH₂), 113.5 (CH), 115.1 (C), 118.0

(CH), 122.3 (CH), 123.1 (CH), 125.0 (CH), 125.4 (CH), 129.4 (CH), 134.9

(C), 139.9 (C), 141.6 (C), 147.6 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT,

CDCl₃): δ = −2.3 ppm. GC/MS (EI, 70 eV): m/z (%) = 403 (4) [M]⁺, 323 (5),

269 (2) [M − C₉H₁₂N]⁺, 231 (9), 190 (22), 175 (4), 163 (4), 147 (9), 132

(5), 115 (9), 106 (100) [M − C₁₂H₁₄BrSSi]⁺, 77 (13) [M − C₁₃H₁₇BrNSSi]⁺.

HRMS (EI): calcd. (C₁₉H₂₂BrNSSi) 403.0420, found 403.0420 [M]⁺. IR

(ATR, neat): λ⁻¹= 3410, 3052, 3019, 2952, 2923, 2863, 1602, 1504,

1480, 1450, 1429, 1420, 1409, 1367, 1320, 1290, 1250, 1243, 1179,

1160, 1154, 1096, 1070, 1020, 989, 880, 830, 804, 746, 727, 711, 690,

641, 617, 591, 503 cm^‒1. 46c: R_f= 0.35 (SiO₂, PE/EtOAc, 30:1). ¹H NMR

(500 MHz, CDCl₃): δ = 0.48 (d, J = 4.2 Hz, 12 H), 0.98 (ddd, J = 14.5,

12.8, 5.0 Hz, 2 H), 1.10 (ddd, J = 14.5, 12.6, 4.4 Hz, 2 H), 1.52-1.61 (m, 2

H), 1.63-1.72 (m, 2 H), 3.32 (quint, J = 5.8 Hz, 1 H), 6.57 (d, J = 6.5 Hz, 2

H), 6.66 (t, J = 7.2 Hz, 1 H), 7.09-7.14 (m, 2 H), 7.39-7.43 (m, 2 H), 7.45-

7.49 (m, 2 H), 7.85 (t, J = 8.4 Hz, 4 H) ppm. ¹³C{¹H} NMR (125 MHz,

JMOD, CDCl₃): δ = ‒2.3 (CH₃), 11.1 (CH₂), 27.8 (CH₂), 57.3 (CH), 113.2

(CH), 115.0 (C), 116.7 (CH), 122.3 (CH), 123.1 (CH), 124.9 (CH), 125.3

(CH), 129.3 (CH), 135.0 (C), 139.9 (C), 141.6 (C), 148.0 (C) ppm.

²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −2.0 ppm. GC/MS (EI, 70

eV): m/z (%) = 699 (1) [M]⁺, 402 (14) [M − C₁₂H₁₄BrSSi]⁺, 269 (4) [M −

C₂₁H₂₅BrNSSi]⁺, 190 (100), 175 (5), 147 (17), 115 (11), 77 (2) [M −

C₂₅H₃₀Br₂NS₂Si₂]⁺. HRMS (EI): calcd. (C₃₁H₃₅Br₂NS₂Si₂) 699.0111, found

699.0101 [M]⁺. IR (ATR, neat): λ⁻¹= 3409, 3053, 3019, 2953, 2923, 1600,

1554, 1503, 1482, 1450, 1429, 1420, 1410, 1356, 1320, 1290, 1249,

1242, 1180, 1160, 1132, 1070, 1020, 989, 906, 880, 840, 809, 779, 746,

840, 809, 779, 750, 726, 710, 690, 641, 591, 503 cm^‒1

.

N-(2-((3-Bromobenzo[b]thiophen-2-yl)dimethylsilyl)propyl)-4-

chloroaniline (48a), N-(3-((3-bromobenzo[b]thiophen-2-

yl)dimethylsilyl)propyl)-4-chloroaniline (48b), and N-(1,5-bis((3-

bromobenzo[b]thiophen-2-yl)dimethylsilyl)pentan-3-yl)-4-

726, 710, 690, 646, 619, 591, 503 cm^‒1

.

chloroaniline (48c): General procedure C was used to synthesize 48b

from 4-chloro-N-methylaniline (17, 283 mg, 2.00 mmol) and 3-bromo-2-

(vinyldimethylsilyl)benzo[b]thiophene (36, 713 mg, 2.40 mmol) with

titanium catalyst IV (154 mg, 0.20 mmol, 10 mol%) at 140 °C. After flash

chromatography (SiO₂, PE/EtOAc, 50:1), 48a (84 mg, 0.19 mmol, 10 %),

48b (490 mg, 1.12 mmol, 56 %), and 48c (143 mg, 0.19 mmol, 10 %)

were obtained as slightly yellow oils. 48a: R_f= 0.22 (SiO₂, PE/EtOAc,

50:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.54 (s, 3 H), 0.55 (s, 3 H), 1.14 (d,

J = 7.4 Hz, 3 H), 1.71-1.80 (m, 1 H), 3.05 (dd, J = 12.4, 9.3 Hz, 1 H), 3.30

(dd, J = 12.4, 5.6 Hz, 1 H), 6.39 (d, J = 8.8 Hz, 2 H), 7.05 (d, J = 8.8 Hz,

2 H), 7.42 (t, J = 7.9 Hz, 1 H), 7.48 (t, J = 7.3 Hz, 1 H), 7.84-7.90 (m, 2 H)

ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = ‒4.2 (CH₃), ‒3.5 (CH₃),

13.1 (CH₃), 19.8 (CH), 46.9 (CH₂), 113.9 (CH), 115.4 (C), 121.8 (C),

122.3 (CH), 123.2 (CH), 125.1 (CH), 125.5 (CH), 129.0 (CH), 134.2 (C),

139.9 (C), 141.7 (C), 146.7 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT,

CDCl₃): δ = −0.6 ppm. GC/MS (EI, 70 eV): m/z (%) = 437 (7) [M]⁺, 358 (4)

[M − Br]⁺, 316 (15), 300 (4), 281 (5), 269 (20) [M − C₉H₁₁ClN]⁺, 231 (9),

225 (12), 210 (7), 189 (25), 183 (9), 175 (13), 147 (33), 140 (100) [M −

C₁₂H₁₄BrSSi]⁺, 115 (28), 105 (9), 77 (9). HRMS (ESI, +): calcd.

(C₁₉H₂₂BrClNSSi) 438.0114, found 438.0114 [M+H]⁺. IR (ATR, neat): λ⁻¹

= 3420, 3054, 3023, 2953, 2900, 2866, 1599, 1497, 1479, 1450, 1420,

1400, 1377, 1313, 1290, 1250, 1243, 1193, 1176, 1160, 1133, 1117,

1093, 1070, 1020, 989, 879, 836, 809, 779, 751, 726, 710, 693, 671, 591,

501 cm^‒1. 48b: R_f= 0.14 (SiO₂, PE/EtOAc, 50:1). ¹H NMR (500 MHz,

CDCl₃): δ = 0.50 (s, 6 H), 1.06-1.11 (m, 2 H), 1.65-1.72 (m, 2 H), 3.08 (t,

J = 7.1 Hz, 2 H), 6.47 (d, J = 8.8 Hz, 2 H), 7.07 (d, J = 8.8 Hz, 2 H), 7.40

(t, J = 7.6 Hz, 1 H), 7.46 (t, J = 7.5 Hz, 1 H), 7.83-7.88 (m, 2 H) ppm.

¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = ‒2.3 (CH₃), 12.8 (CH₂), 23.8

(CH₂), 47.1 (CH₂), 114.0 (CH), 115.1 (C), 121.9 (C), 122.3 (CH), 123.1

(CH), 125.1 (CH), 125.4 (CH), 129.1 (CH), 134.8 (C), 139.9 (C), 141.6

(C), 146.8 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −2.3 ppm.

N-(2-((3-Bromobenzo[b]thiophen-2-yl)dimethylsilyl)propyl)-3-

methylaniline (47a), N-(3-((3-bromobenzo[b]thiophen-2-

yl)dimethylsilyl)propyl)-3-methylaniline (47b), and N-(1,5-bis((3-

bromobenzo[b]thiophen-2-yl)dimethylsilyl)pentan-3-yl)-3-

methylaniline (47c): General procedure C was used to synthesize 47b

from N,3-dimethylaniline (14, 242 mg, 2.00 mmol) and 3-bromo-2-

(vinyldimethylsilyl)benzo[b]thiophene (36, 713 mg, 2.40 mmol) with

titanium catalyst IV (154 mg, 0.20 mmol, 10 mol%) at 140 °C. After flash

chromatography (SiO₂, PE/EtOAc, 50:1), 47b (411 mg, 0.98 mmol, 49 %)

and 47c (104 mg, 0.15 mmol, 7 %) were obtained as slightly yellow oils.

In addition, a third fraction that contained 47a and some impurities was

also isolated. This mixture was subjected to bulb-to-bulb distillation

(240 °C, 1 × 10^-3mbar) to obtain 47a (60 mg, 0.14 mmol, 7 %) as a

slightly yellow oil. 47a: R_f= 0.28 (SiO₂, PE/EtOAc, 50:1). ¹H NMR (500

MHz, CDCl₃): δ = 0.57 (s, 6 H), 1.16 (d, J = 7.4 Hz, 3 H), 1.79 (dqd, J =

9.2, 7.4, 5.5 Hz, 1 H), 2.25 (s, 3 H), 3.08 (dd, J = 12.4, 9.5 Hz, 1 H), 3.37

(dd, J = 12.4, 5.3 Hz, 1 H), 6.32-6.39 (m, 2 H), 6.53 (d, J = 7.4 Hz, 1 H),

7.05 (t, J = 7.7 Hz, 1 H), 7.42-7.46 (m, 1 H), 7.50 (t, J = 7.2 Hz, 1 H), 7.89

(dd, J = 13.8, 8.0 Hz, 2 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃):

δ = ‒4.0 (CH₃), ‒3.6 (CH₃), 13.1 (CH₃), 19.9 (CH), 21.7 (CH₃), 46.7 (CH₂),

110.1 (CH), 113.7 (CH), 115.3 (C), 118.2 (CH), 122.2 (CH), 123.2 (CH),

125.0 (CH), 125.4 (CH), 129.1 (CH), 134.4 (C), 139.0 (C), 139.9 (C),

141.7 (C), 148.3 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ =

−0.5 ppm. GC/MS (EI, 70 eV): m/z (%) = 417 (3) [M]⁺, 338 (5) [M − Br]⁺,

296 (11), 189 (10), 147 (18), 120 (100) [M − C₁₂H₁₄BrSSi]⁺, 115 (14), 91

(14) [M − C₁₃H₁₇BrNSSi]⁺, 77 (8), 65 (7). HRMS (ESI, +): calcd.

(C₂₀H₂₅BrNSSi) 418.0660, found 418.0656 [M+H]⁺. IR (ATR, neat): λ⁻¹

=

3413, 3047, 3014, 2953, 2923, 2902, 2864, 1604, 1589, 1507, 1479,

1450, 1420, 1376, 1320, 1304, 1290, 1250, 1243, 1179, 1166, 1132,

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GC/MS (EI, 70 eV): m/z (%) = 437 (6) [M]⁺, 422 (2) [M − CH₃]⁺, 358 (3)

[M − Br]⁺, 269 (5) [M − C₉H₁₁ClN]⁺, 231 (17), 224 (31), 189 (14), 175 (8),

147 (21), 140 (100) [M − C₁₂H₁₄BrSSi]⁺, 115 (21), 105 (10), 77 (10).

HRMS (EI): calcd. (C₁₉H₂₁BrClNSSi) 437.0030, found 437.0025 [M]⁺. IR

(ATR, neat): λ⁻¹= 3413, 3054, 2952, 2924, 2860, 1599, 1497, 1482,

1450, 1420, 1400, 1319, 1290, 1243, 1176, 1162, 1119, 1093, 1083,

1070, 1020, 989, 880, 839, 811, 779, 751, 726, 711, 671, 640, 626, 591,

503 cm^‒1. 48c: R_f= 0.25 (SiO₂, PE/EtOAc, 50:1). ¹H NMR (500 MHz,

CDCl₃): δ = 0.44 (s, 6 H), 0.44 (s, 6H), 0.93 (ddd, J = 14.5, 12.6, 5.2 Hz,

2 H), 1.02 (ddd, J = 14.6, 12.2, 4.5 Hz, 2 H), 1.44-1.54 (m, 2 H), 1.57-

1.66 (m, 2 H), 3.20 (quint, J = 5.8 Hz, 1 H), 3.44 (br. s, 1 H), 6.38 (d, J =

7.6 Hz, 2 H), 6.93-6.97 (m, 2 H), 7.37-7.41 (m, 2 H), 7.42-7.47 (m, 2 H),

7.80-7.84 (m, 4 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ =

‒2.4 (CH₃), 11.0 (CH₂), 27.7 (CH₂), 57.3 (CH), 114.1 (CH), 115.0 (C),

121.1 (C), 122.2 (CH), 123.1 (CH), 125.0 (CH), 125.3 (CH), 129.0 (CH),

134.8 (C), 139.8 (C), 141.6 (C), 146.5 (C) ppm. ²⁹Si{¹H} NMR (99 MHz,

INEPT, CDCl₃): δ = −2.0 ppm. GC/MS (EI, 70 eV): m/z (%) = 733 (9) [M]⁺,

718 (<1) [M − CH₃]⁺, 522 (2) [M − C₈H₄BrS]⁺, 436 (49) [M − C₁₂H₁₄BrSSi]⁺,

269 (19) [M − C₂₁H₂₄BrClNSSi]⁺, 224 (100), 189 (39), 184 (18), 175 (12),

147 (54), 115 (24), 59 (11). HRMS (ESI, +): calcd. (C₃₁H₃₅Br₂ClNS₂Si₂)

733.9805, found 733.9800 [M+H]⁺. IR (ATR, neat): λ⁻¹= 3413, 3054,

3022, 2953, 2924, 2877, 2857, 1599, 1496, 1482, 1450, 1420, 1400,

1317, 1290, 1242, 1177, 1160, 1093, 1070, 1020, 989, 906, 880, 840,

0.98-1.16 (m, 4 H), 1.55-1.74 (m, 4 H), 3.27 (br. s, 1 H), 3.76 (s, 3 H),

6.48-6.59 (m, 2 H), 6.73 (d, J = 8.6 Hz, 2 H), 7.40-7.44 (m, 2 H), 7.46-

7.50 (m, 2 H), 7.85-7.91 (m, 4 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD,

CDCl₃): δ = ‒2.4 (CH₃), 11.0 (CH₂), 27.6 (CH₂), 55.8 (CH₃), 58.1 (CH),

114.6 (CH), 115.0 (C), 115.0 (CH), 122.2 (CH), 123.0 (CH), 124.9 (CH),

125.2 (CH), 135.0 (C), 139.8 (C), 141.6 (C), 142.1 (C), 151.7 (C) ppm.

²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −1.9 ppm. GC/MS (EI, 70

eV): m/z (%) = 729 (22) [M]⁺, 714 (1) [M − CH₃]⁺, 518 (2) [M − C₈H₄BrS]⁺,

432 (54) [M − C₁₂H₁₄BrSSi]⁺, 269 (15) [M − C₂₂H₂₇BrNOSSi]⁺, 220 (100),

189 (33), 180 (21), 162 (18), 147 (49), 115 (20), 59 (7). HRMS (ESI, +):

calcd. (C₃₂H₃₈Br₂NOS₂Si₂) 730.0300, found 730.0305 [M+H]⁺. IR (ATR,

neat): λ⁻¹= 3392, 3054, 2950, 2926, 2829, 1616, 1590, 1554, 1509, 1482,

1450, 1442, 1420, 1407, 1354, 1320, 1290, 1242, 1232, 1179, 1160,

1130, 1107, 1070, 1039, 1020, 989, 939, 906, 880, 840, 813, 780, 750,

737, 726, 710, 669, 646, 591, 503 cm^‒1

.

N-(2-((3-Bromobenzo[b]thiophen-2-yl)dimethylsilyl)propyl)-4-

(trifluoromethoxy)aniline (50a), N-(3-((3-bromobenzo[b]thiophen-2-

yl)dimethylsilyl)propyl)-4-(trifluoromethoxy)aniline (50b), and N-(1,5-

bis((3-bromobenzo[b]thiophen-2-yl)dimethylsilyl)pentan-3-yl)-4-

(trifluoromethoxy)aniline (50c): General procedure C was used to

synthesize 50b from N-methyl-4-(trifluoromethoxy)aniline (39, 382 mg,

2.00 mmol) and 3-bromo-2-(vinyldimethylsilyl)benzo[b]thiophene (36, 713

mg, 2.40 mmol) with titanium catalyst IV (154 mg, 0.20 mmol, 10 mol%)

at 140 °C. After flash chromatography (SiO₂, PE/EtOAc, 50:1), 50a (87

mg, 0.18 mmol, 9 %), 50b (501 mg, 1.03 mmol, 51 %), and 50c (207 mg,

0.26 mmol, 13 %) were obtained as slightly yellow oils. 50a: R_f= 0.22

(SiO₂, PE/EtOAc, 50:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.54 (s, 3 H),

0.55 (s, 3 H), 1.15 (d, J = 7.4 Hz, 3 H), 1.77 (dqd, J = 9.2, 7.4, 5.7 Hz, 1

H), 3.07 (dd, J = 12.4, 9.3 Hz, 1 H), 3.31 (dd, J = 12.4, 5.6 Hz, 1 H), 6.42

(d, J = 9.0 Hz, 2 H), 6.96 (d, J = 8.9 Hz, 2 H), 7.40-7.44 (m, 1 H), 7.46-

7.50 (m, 1 H), 7.84-7.90 (m, 2 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT,

CDCl₃): δ = ‒4.2 (CH₃), ‒3.5 (CH₃), 13.1 (CH₃), 19.8 (CH), 47.1 (CH₂),

113.2 (CH), 115.5 (C), 120.9 (q, J = 255 Hz, C), 122.3 (CH), 122.4 (CH),

123.3 (CH), 125.2 (CH), 125.6 (CH), 134.2 (C), 139.9 (C), 140.5 (C),

141.7 (C), 146.9 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ =

−0.7 ppm. ¹⁹F NMR (470 MHz, CDCl₃): δ = −58.4 ppm. GC/MS (EI, 70

eV): m/z (%) = 487 (5) [M]⁺, 408 (4) [M − Br]⁺, 366 (16), 275 (12), 269

(12) [M − C₁₀H₁₁F₃NO]⁺, 233 (8), 217 (6), 190 (100) [M − C₁₂H₁₄BrSSi]⁺,

175 (8), 147 (18), 115 (16). HRMS (ESI, +): calcd. (C₂₀H₂₂BrF₃NOSSi)

488.0327, found 488.0321 [M+H]⁺. IR (ATR, neat): λ⁻¹= 3423, 3057,

2956, 2903, 2869, 1612, 1513, 1479, 1450, 1420, 1407, 1379, 1322,

1290, 1243, 1220, 1199, 1154, 1112, 1072, 1021, 1010, 989, 916, 880,

810, 779, 750, 736, 726, 710, 667, 646, 591, 501 cm^‒1

.

N-(2-((3-Bromobenzo[b]thiophen-2-yl)dimethylsilyl)propyl)-4-

methoxyaniline (49a), N-(3-((3-bromobenzo[b]thiophen-2-

yl)dimethylsilyl)propyl)-4-methoxyaniline (49b), and N-(1,5-bis((3-

bromobenzo[b]thiophen-2-yl)dimethylsilyl)pentan-3-yl)-4-

methoxyaniline (49c): General procedure C was used to synthesize 49b

from 4-methoxy-N-methylaniline (18, 274 mg, 2.00 mmol) and 3-bromo-

2-(vinyldimethylsilyl)benzo[b]thiophene (36, 713 mg, 2.40 mmol) with

titanium catalyst V (221 mg, 0.20 mmol, 10 mol%) at 140 °C. After flash

chromatography (SiO₂, PE/EtOAc, 15:1), 49a (82 mg, 0.19 mmol, 9 %),

49b (450 mg, 1.04 mmol, 52 %), and 49c (337 mg, 0.46 mmol, 23 %)

were obtained as slightly yellow oils. 49a: R_f= 0.20 (SiO₂, PE/EtOAc,

15:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.55 (s, 6 H), 1.15 (d, J = 7.4 Hz, 3

H), 1.71-1.80 (m, 1 H), 3.05 (dd, J = 12.2, 9.4 Hz, 1 H), 3.32 (dd, J = 12.2,

5.3 Hz, 1 H), 3.75 (s, 3 H), 6.50 (d, J = 8.9 Hz, 2 H), 6.75 (d, J = 8.9 Hz, 2

H), 7.40-7.44 (m, 1 H), 7.46-7.50 (m, 1 H), 7.84-7.91 (m, 2 H) ppm.

¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = ‒4.0 (CH₃), ‒3.6 (CH₃), 13.1

(CH₃), 19.9 (CH), 47.7 (CH₂), 55.9 (CH₃), 114.3 (CH), 115.0 (CH), 115.3

(C), 122.2 (CH), 123.2 (CH), 125.0 (CH), 125.4 (CH), 134.4 (C), 139.9

(C), 141.7 (C), 142.4 (C), 152.1 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT,

CDCl₃): δ = −0.5 ppm. GC/MS (EI, 70 eV): m/z (%) = 433 (12) [M]⁺, 418

(1) [M − CH₃]⁺, 354 (1) [M − Br]⁺, 312 (7), 296 (3), 269 (9) [M −

C₁₀H₁₄NO]⁺, 189 (13), 175 (8), 147 (17), 136 (100) [M − C₁₂H₁₄BrSSi]⁺,

123 (9), 115 (15). HRMS (ESI, +): calcd. (C₂₀H₂₅BrNOSSi) 434.0610,

found 434.0606 [M+H]⁺. IR (ATR, neat): λ⁻¹= 3400, 3056, 2990, 2950,

2900, 2866, 2829, 1617, 1590, 1509, 1479, 1464, 1450, 1420, 1406,

1377, 1320, 1307, 1290, 1242, 1232, 1179, 1160, 1132, 1109, 1070,

1037, 1021, 987, 879, 836, 813, 779, 751, 727, 710, 686, 636, 609, 591,

504 cm^‒1. 49b: R_f= 0.15 (SiO₂, PE/EtOAc, 15:1). ¹H NMR (500 MHz,

CDCl₃): δ = 0.54 (s, 6 H), 1.09-1.15 (m, 2 H), 1.68-1.76 (m, 2 H), 3.11 (t,

J = 7.1 Hz, 2 H), 3.31 (br. s, 1 H), 3.77 (s, 3 H), 6.58 (d, J = 8.9 Hz, 2 H),

6.79 (d, J = 8.9 Hz, 2 H), 7.42 (t, J = 7.5 Hz, 1 H), 7.48 (t, J = 7.6 Hz, 1 H),

7.85-7.91 (m, 2 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ =

‒2.3 (CH₃), 12.9 (CH₂), 24.0 (CH₂), 48.0 (CH₂), 55.9 (CH₃), 114.2 (CH),

115.0 (CH), 115.0 (C), 122.2 (CH), 123.1 (CH), 125.0 (CH), 125.3 (CH),

134.9 (C), 139.8 (C), 141.6 (C), 142.6 (C), 152.1 (C) ppm. ²⁹Si{¹H} NMR

(99 MHz, INEPT, CDCl₃): δ = −2.3 ppm. GC/MS (EI, 70 eV): m/z (%) =

433 (10) [M]⁺, 418 (1) [M − CH₃]⁺, 354 (1) [M − Br]⁺, 231 (8), 220 (10),

206 (5), 189 (6), 175 (4), 162 (5), 147 (10), 136 (100) [M − C₁₂H₁₄BrSSi]⁺,

115 (8). HRMS (EI): calcd. (C₂₀H₂₄BrNOSSi) 433.0526, found 433.0524

[M]⁺. IR (ATR, neat): λ⁻¹= 3386, 3054, 2949, 2927, 2860, 2829, 1617,

1590, 1510, 1480, 1464, 1450, 1442, 1420, 1407, 1366, 1320, 1290,

1241, 1232, 1179, 1162, 1112, 1087, 1070, 1037, 1020, 989, 880, 840,

814, 751, 727, 710, 667, 643, 636, 591, 519, 503 cm^‒1. 49c: R_f= 0.27

(SiO₂, PE/EtOAc, 15:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.51 (s, 12 H),

829, 807, 780, 751, 727, 711, 687, 669, 647, 606, 593, 521, 504 cm^‒1

.

50b: R_f= 0.18 (SiO₂, PE/EtOAc, 50:1). ¹H NMR (500 MHz, CDCl₃): δ =

0.51 (s, 6 H), 1.07-1.12 (m, 2 H), 1.66-1.74 (m, 2 H), 3.10 (t, J = 7.1 Hz, 2

H), 6.50 (d, J = 9.0 Hz, 2 H), 6.99 (d, J = 8.2 Hz, 2 H), 7.39-7.43 (m, 1 H),

7.44-7.49 (m, 1 H), 7.83-7.88 (m, 2 H) ppm. ¹³C{¹H} NMR (125 MHz,

DEPT, CDCl₃): δ = ‒2.3 (CH₃), 12.9 (CH₂), 23.9 (CH₂), 47.2 (CH₂), 113.1

(CH), 115.2 (C), 120.9 (q, J = 255 Hz, C), 122.3 (CH), 122.4 (CH), 123.2

(CH), 125.1 (CH), 125.5 (CH), 134.8 (C), 139.9 (C), 140.5 (C), 141.6 (C),

147.0 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −2.3 ppm. ¹⁹

F

NMR (470 MHz, CDCl₃): δ = −58.4 ppm. GC/MS (EI, 70 eV): m/z (%) =

487 (5) [M]⁺, 407 (5), 274 (30), 260 (6), 231 (12), 190 (100) [M −

C₁₂H₁₄BrSSi]⁺, 147 (14), 115 (13). HRMS (EI): calcd. (C₂₀H₂₁BrF₃NOSSi)

487.0243, found 487.0239 [M]⁺. IR (ATR, neat): λ⁻¹= 3417, 3057, 2954,

2926, 2866, 1612, 1514, 1482, 1450, 1410, 1322, 1290, 1243, 1220,

1199, 1153, 1113, 1070, 1021, 1010, 989, 916, 880, 827, 814, 780, 751,

727, 711, 669, 641, 613, 591, 514, 503 cm^‒1. 50c: R_f= 0.23 (SiO₂,

PE/EtOAc, 50:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.51 (s, 6 H), 0.51 (s, 6

H), 1.00 (ddd, J = 14.5, 12.4, 5.2 Hz, 2 H), 1.10 (ddd, J = 14.6, 12.3, 4.5

Hz, 2 H), 1.53-1.62 (m, 2 H), 1.65-1.74 (m, 2 H), 3.28 (quint, J = 5.8 Hz, 1

H), 6.46 (d, J = 8.8 Hz, 2 H), 6.94 (d, J = 8.3 Hz, 2 H), 7.41-7.45 (m, 2 H),

7.47-7.51 (m, 2 H), 7.84-7.90 (m, 4 H) ppm. ¹³C{¹H} NMR (125 MHz,

DEPT, CDCl₃): δ = ‒2.4 (CH₃), 11.1 (CH₂), 27.8 (CH₂), 57.5 (CH), 113.2

(CH), 115.1 (C), 120.9 (q, J = 255 Hz, C), 122.2 (CH), 122.4 (CH), 123.1

(CH), 125.0 (CH), 125.4 (CH), 134.8 (C), 139.9 (C), 140.0 (C), 141.6 (C),

146.7 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −2.0 ppm. ¹⁹

NMR (470 MHz, CDCl₃): δ = −58.2 ppm. GC/MS (EI, 70 eV): m/z (%) =

F

14

10.1002/ejoc.202001523

European Journal of Organic Chemistry

FULL PAPER

783 (1) [M]⁺, 486 (8) [M − C₁₂H₁₄BrSSi]⁺, 274 (100), 234 (11), 189 (15),

161 (2) [M − C₂₅H₃₀Br₂NS₂Si₂]⁺, 147 (18), 115 (12). HRMS (ESI, +): calcd.

(C₃₂H₃₅Br₂F₃NOS₂Si₂) 784.0017, found 784.0022 [M+H]⁺. IR (ATR, neat):

λ⁻¹= 3417, 3056, 2954, 2926, 1610, 1512, 1482, 1450, 1409, 1322, 1290,

1243, 1220, 1199, 1156, 1110, 1070, 1020, 1009, 989, 939, 914, 904,

937, 906, 880, 840, 814, 779, 750, 726, 711, 667, 643, 591, 564, 517,

503 cm^‒1

.

N-(3-((3-Bromobenzo[b]thiophen-2-yl)dimethylsilyl)-1-

phenylpropyl)aniline (52b): General procedure

C

was used to

880, 840, 811, 779, 751, 726, 711, 669, 641, 614, 591, 503 cm^‒1

.

synthesize 52b from N-benzylaniline (41, 367 mg, 2.00 mmol) and 3-

bromo-2-(vinyldimethylsilyl)benzo[b]thiophene (36, 654 mg, 2.20 mmol)

with titanium catalyst IV (154 mg, 0.20 mmol, 10 mol%) at 140 °C. After

flash chromatography (SiO₂, PE/EtOAc, 30:1), the obtained crude

product was purified by bulb-to-bulb distillation (240 °C, 1 × 10^-3mbar) to

give 52b (808 mg, 1.68 mmol, 84 %) as a yellow oil. R_f= 0.28 (SiO₂,

PE/EtOAc, 30:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.47 (s, 6 H), 0.96-1.05

(m, 1 H), 1.14-1.22 (m, 1 H), 1.84-1.95 (m, 2 H), 4.28 (t, J = 6.6 Hz, 1 H),

6.53 (d, J = 7.5 Hz, 2 H), 6.65 (t, J = 7.2 Hz, 1 H), 7.05-7.09 (m, 2 H),

7.20-7.25 (m, 1 H), 7.28-7.34 (m, 4 H), 7.41 (ddd, J = 8.2, 7.1, 1.1 Hz, 1

H), 7.47 (ddd, J = 8.0, 7.1, 0.9 Hz, 1 H), 7.85 (t, J = 7.4 Hz, 2 H) ppm.

¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ = ‒2.4 (CH₃), ‒2.3 (CH₃), 12.1

(CH₂), 32.8 (CH₂), 60.8 (CH), 113.7 (CH), 115.2 (C), 117.6 (CH), 122.3

(CH), 123.2 (CH), 125.0 (CH), 125.4 (CH), 126.8 (CH), 127.1 (CH), 128.7

(CH), 129.2 (CH), 134.7 (C), 139.9 (C), 141.7 (C), 143.5 (C), 147.5 (C)

ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −2.1 ppm. GC/MS (EI,

70 eV): m/z (%) = 479 (1) [M]⁺, 182 (100) [M − C₁₂H₁₄BrSSi]⁺, 147 (6),

115 (6), 104 (10), 77 (12) [M − C₁₉H₂₁BrNSSi]⁺. HRMS (ESI, +): calcd.

N-(2-((3-Bromobenzo[b]thiophen-2-yl)dimethylsilyl)propyl)-4-

((trifluoromethyl)thio)aniline (51a), N-(3-((3-bromobenzo[b]thiophen-

2-yl)dimethylsilyl)propyl)-4-((trifluoromethyl)thio)aniline (51b), and

N-(1,5-bis((3-bromobenzo[b]thiophen-2-yl)dimethylsilyl)pentan-3-yl)-

4-((trifluoromethyl)thio)aniline (51c): General procedure C was used to

synthesize 51b from N-methyl-4-((trifluoromethyl)thio)aniline (40, 414 mg,

2.00 mmol) and 3-bromo-2-(vinyldimethylsilyl)benzo[b]thiophene (36, 713

mg, 2.40 mmol) with titanium catalyst IV (154 mg, 0.20 mmol, 10 mol%)

at 140 °C. After flash chromatography (SiO₂, PE/EtOAc, 30:1), 51a (55

mg, 0.11 mmol, 5 %), 51b (368 mg, 0.73 mmol, 36 %), and 51c (66 mg,

0.08 mmol, 4 %) were obtained as slightly yellow oils. In addition, a third

fraction that contained a mixture of 51a and 51b (55 mg, 11a/11b =

15:85) was also isolated. 51a: R_f= 0.28 (SiO₂, PE/EtOAc, 30:1). ¹H NMR

(500 MHz, CDCl₃): δ = 0.53 (s, 3 H), 0.54 (s, 3 H), 1.14 (d, J = 7.4 Hz, 3

H), 1.72-1.81 (m, 1 H), 3.09 (dd, J = 12.6, 9.3 Hz, 1 H), 3.32 (dd, J = 12.6,

5.7 Hz, 1 H), 3.98 (br. s, 1 H), 6.41 (d, J = 8.7 Hz, 2 H), 7.33 (d, J = 8.6

Hz, 2 H), 7.40-7.45 (m, 1 H), 7.46-7.50 (m, 1 H), 7.86 (t, J = 7.4 Hz, 2 H)

ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = ‒4.3 (CH₃), ‒3.5 (CH₃),

13.1 (CH₃), 19.8 (CH), 46.3 (CH₂), 109.3 (C), 113.1 (CH), 115.6 (C),

122.3 (CH), 123.3 (CH), 125.2 (CH), 125.6 (CH), 129.9 (q, J = 308 Hz, C),

133.9 (C), 138.2 (CH), 139.9 (C), 141.7 (C), 150.3 (C) ppm. ²⁹Si{¹H}

NMR (99 MHz, INEPT, CDCl₃): δ = −0.7 ppm. ¹⁹F NMR (470 MHz,

CDCl₃): δ = −44.6 ppm. GC/MS (EI, 70 eV): m/z (%) = 503 (8) [M]⁺, 424

(4) [M − Br]⁺, 382 (17), 291 (15), 269 (23) [M − C₁₀H₁₁F₃NS]⁺, 249 (9),

231 (10), 206 (100) [M − C₁₂H₁₄BrSSi]⁺, 189 (30), 175 (15), 164 (10), 147

(38), 137 (25), 115 (34). HRMS (ESI, +): calcd. (C₂₀H₂₂BrF₃NS₂Si)

504.0098, found 504.0093 [M+H]⁺. IR (ATR, neat): λ⁻¹= 3423, 3057,

3022, 2954, 2902, 2869, 1594, 1506, 1477, 1450, 1406, 1324, 1292,

1253, 1243, 1184, 1147, 1109, 1090, 1072, 1021, 989, 880, 836, 814,

806, 779, 751, 727, 711, 689, 593, 561, 517, 503 cm^‒1. 51b: R_f= 0.27

(SiO₂, PE/EtOAc, 30:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.51 (s, 6 H),

1.07-1.12 (m, 2 H), 1.67-1.74 (m, 2 H), 3.13 (t, J = 7.1 Hz, 2 H), 4.02 (br.

s, 1 H), 6.51 (d, J = 8.8 Hz, 2 H), 7.37 (d, J = 8.7 Hz, 2 H), 7.39-7.43 (m,

1 H), 7.44-7.49 (m, 1 H), 7.83-7.87 (m, 2 H) ppm. ¹³C{¹H} NMR (125 MHz,

DEPT, CDCl₃): δ = ‒2.3 (CH₃), 12.9 (CH₂), 23.8 (CH₂), 46.4 (CH₂), 109.4

(C), 113.1 (CH), 115.2 (C), 122.3 (CH), 123.2 (CH), 125.1 (CH), 125.5

(CH), 129.9 (q, J = 308 Hz, C), 134.7 (C), 138.3 (CH), 139.9 (C), 141.6

(C), 150.4 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −2.3 ppm.

¹⁹F NMR (470 MHz, CDCl₃): δ = −44.6 ppm. GC/MS (EI, 70 eV): m/z (%)

= 503 (8) [M]⁺, 488 (4) [M − CH₃]⁺, 423 (6), 290 (41), 231 (21), 222 (14),

206 (100) [M − C₁₂H₁₄BrSSi]⁺, 189 (19), 175 (9), 162 (8), 147 (27), 137

(36), 115 (23), 105 (8). HRMS (ESI, +): calcd. (C₂₀H₂₂BrF₃NS₂Si)

504.0098, found 504.0093 [M+H]⁺. IR (ATR, neat): λ⁻¹= 3419, 3056,

3022, 2953, 2926, 2863, 1596, 1507, 1477, 1450, 1407, 1327, 1292,

1252, 1243, 1184, 1147, 1109, 1090, 1072, 1020, 989, 939, 880, 839,

816, 779, 751, 727, 711, 591, 563, 517, 503 cm^‒1. 51c: R_f= 0.35 (SiO₂,

PE/EtOAc, 30:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.45 (s, 6 H), 0.45 (s, 6

H), 0.94 (ddd, J = 14.5, 12.6, 5.2 Hz, 2 H), 0.99-1.08 (m, 2 H), 1.46-1.55

(m, 2 H), 1.59-1.69 (m, 2 H), 3.27 (quint, J = 5.7 Hz, 1 H), 3.77 (br. s, 1

H), 6.42 (d, J = 8.6 Hz, 2 H), 7.25 (d, J = 8.3 Hz, 2 H), 7.38-7.42 (m, 2 H),

7.43-7.48 (m, 2 H), 7.82 (d, J = 8.3 Hz, 4 H) ppm. ¹³C{¹H} NMR (125 MHz,

JMOD, CDCl₃): δ = ‒2.4 (CH₃), 11.1 (CH₂), 27.9 (CH₂), 57.0 (CH), 108.7

(C), 113.2 (CH), 115.1 (C), 122.3 (CH), 123.1 (CH), 125.0 (CH), 125.4

(CH), 129.9 (q, J = 308 Hz, C), 134.7 (C), 138.3 (CH), 139.8 (C), 141.6

(C), 150.1 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −2.0 ppm.

¹⁹F NMR (470 MHz, CDCl₃): δ = −44.6 ppm. GC/MS (EI, 70 eV): m/z (%)

= 803 (2) [M]⁺, 502 (7) [M − C₁₂H₁₄BrSSi]⁺, 290 (100), 250 (11), 221 (16),

207 (21), 189 (24), 175 (9), 147 (33), 115 (20), 73 (25). HRMS (ESI, +):

calcd. (C₃₂H₃₅Br₂F₃NS₃Si₂) 799.9789, found 799.9787 [M+H]⁺. IR (ATR,

neat): λ⁻¹= 3415, 3056, 2953, 2926, 2877, 2856, 1594, 1504, 1482, 1450,

1407, 1327, 1290, 1250, 1243, 1186, 1147, 1112, 1089, 1070, 1020, 989,

(C₂₅H₂₇BrNSSi) 480.0817, found 480.0818 [M+H]⁺. IR (ATR, neat): λ⁻¹

=

3413, 3082, 3053, 3023, 2953, 2906, 2850, 1600, 1502, 1482, 1450,

1426, 1357, 1290, 1243, 1206, 1179, 1097, 1070, 1020, 989, 936, 900,

880, 839, 814, 746, 727, 711, 699, 690, 591, 544, 503 cm^‒1

.

N-(3-((3-Bromobenzo[b]thiophen-2-yl)dimethylsilyl)-1-(4-

fluorophenyl)propyl)aniline (53b): General procedure C was used to

synthesize 53b from N-(4-fluorobenzyl)aniline (42, 402 mg, 2.00 mmol)

and 3-bromo-2-(vinyldimethylsilyl)benzo[b]thiophene (36, 654 mg, 2.20

mmol) with titanium catalyst IV (154 mg, 0.20 mmol, 10 mol%) at 140 °C.

After flash chromatography (SiO₂, PE/EtOAc, 50:1), the obtained crude

product was purified by bulb-to-bulb distillation (250 °C, 1 × 10^-3mbar) to

give 53b (890 mg, 1.79 mmol, 89 %) as a yellow oil. R_f= 0.23 (SiO₂,

PE/EtOAc, 50:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.48 (s, 3 H), 0.48 (s, 3

H), 0.96-1.04 (m, 1 H), 1.12-1.20 (m, 1 H), 1.79-1.92 (m, 2 H), 4.26 (t, J =

6.6 Hz, 1 H), 6.51 (d, J = 7.9 Hz, 2 H), 6.67 (t, J = 7.3 Hz, 1 H), 6.97-7.02

(m, 2 H), 7.06-7.11 (m, 2 H), 7.25-7.31 (m, 2 H), 7.42 (t, J = 7.6 Hz, 1 H),

7.48 (t, J = 7.5 Hz, 1 H), 7.87 (t, J = 7.3 Hz, 2 H) ppm. ¹³C{¹H} NMR (125

MHz, JMOD, CDCl₃): δ = ‒2.4 (CH₃), ‒2.4 (CH₃), 11.9 (CH₂), 33.0 (CH₂),

60.2 (CH), 113.6 (CH), 115.2 (C), 115.5 (d, J = 21 Hz, CH), 117.6 (CH),

122.3 (CH), 123.2 (CH), 125.1 (CH), 125.5 (CH), 128.2 (d, J = 8 Hz, CH),

129.2 (CH), 134.5 (C), 139.3 (C), 139.9 (C), 141.6 (C), 147.2 (C), 161.9

(d, J = 245 Hz, C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −2.1

ppm. ¹⁹F NMR (470 MHz, CDCl₃): δ = −116.0 ppm. GC/MS (EI, 70 eV):

m/z (%) = 497 (1) [M]⁺, 269 (2) [M − C₁₅H₁₅FN]⁺, 200 (100) [M −

C₁₂H₁₄BrSSi]⁺, 147 (6), 115 (6), 104 (8), 77 (11) [M − C₁₉H₂₀BrFNSSi]⁺.

HRMS (EI): calcd. (C₂₅H₂₅BrFNSSi) 497.0639, found 497.0632 [M]⁺. IR

(ATR, neat): λ⁻¹= 3416, 3052, 3020, 2953, 2906, 2850, 1600, 1556,

1503, 1482, 1450, 1427, 1316, 1290, 1250, 1243, 1219, 1179, 1154,

1132, 1089, 1070, 1020, 1013, 990, 901, 880, 860, 831, 811, 787, 746,

727, 711, 690, 636, 620, 591, 541, 503 cm^‒1

.

N-(3-((3-Bromobenzo[b]thiophen-2-yl)dimethylsilyl)-1-(4-

(trifluoromethyl)phenyl)propyl)aniline (54b): General procedure

C

was used to synthesize 54b from N-(4-(trifluoromethyl)benzyl)aniline (43,

503 mg, 2.00 mmol) and 3-bromo-2-(vinyldimethylsilyl)benzo[b]thiophene

(36, 654 mg, 2.20 mmol) with titanium catalyst IV (154 mg, 0.20 mmol, 10

mol%) at 140 °C. After flash chromatography (SiO₂, PE/EtOAc, 50:1),

54b (855 mg, 1.56 mmol, 78 %) was obtained as a yellow oil. R_f= 0.22

(SiO₂, PE/EtOAc, 50:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.49 (s, 3 H),

0.50 (s, 3 H), 0.98-1.08 (m, 1 H), 1.14-1.23 (m, 1 H), 1.88 (q, J = 7.5 Hz,

2 H), 4.34 (t, J = 6.5 Hz, 1 H), 6.49 (d, J = 7.9 Hz, 2 H), 6.68 (t, J = 7.2 Hz,

1 H), 7.09 (t, J = 7.5 Hz, 2 H), 7.40-7.46 (m, 3 H), 7.49 (t, J = 7.5 Hz, 1 H),

7.57 (d, J = 8.0 Hz, 2 H), 7.87 (t, J = 7.1 Hz, 2 H) ppm. ¹³C{¹H} NMR (125

MHz, JMOD, CDCl₃): δ = ‒2.4 (CH₃), ‒2.4 (CH₃), 11.9 (CH₂), 32.9 (CH₂),

15

10.1002/ejoc.202001523

European Journal of Organic Chemistry

FULL PAPER

60.4 (CH), 113.5 (CH), 115.2 (C), 117.9 (CH), 122.3 (CH), 123.2 (CH),

124.4 (q, J = 272 Hz, C), 125.1 (CH), 125.5 (CH), 125.7 (q, J = 4 Hz, CH),

127.0 (CH), 129.3 (CH), 129.4 (q, J = 29 Hz, C), 134.3 (C), 139.8 (C),

141.6 (C), 146.9 (C), 148.0 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT,

CDCl₃): δ = −2.1 ppm. ¹⁹F NMR (470 MHz, CDCl₃): δ = −62.4 ppm.

GC/MS (EI, 70 eV): m/z (%) = 547 (1) [M]⁺, 250 (100) [M − C₁₂H₁₄BrSSi]⁺,

189 (4), 147 (6), 115 (5), 104 (5), 77 (10) [M − C₂₀H₂₀BrF₃NSSi]⁺. HRMS

(EI): calcd. (C₂₆H₂₅BrF₃NSSi) 547.0607, found 547.0608 [M]⁺. IR (ATR,

neat): λ⁻¹= 3415, 3053, 3020, 2953, 2910, 2852, 1619, 1602, 1503, 1482,

1450, 1427, 1417, 1323, 1290, 1250, 1243, 1209, 1162, 1119, 1107,

1066, 1016, 990, 934, 901, 880, 839, 816, 780, 747, 727, 711, 690, 601,

0.54 (s, 6 H), 1.08-1.14 (m, 2 H), 1.56-1.69 (m, 3 H), 1.99-2.05 (m, 1 H),

2.71-2.86 (m, 2 H), 3.23 (dtd, J = 9.3, 6.3, 3.0 Hz, 1 H), 6.50 (d, J = 7.8

Hz, 1 H), 6.63 (t, J = 7.3 Hz, 1 H), 6.94-7.01 (m, 2 H), 7.40-7.44 (m, 1 H),

7.46-7.50 (m, 1 H), 7.85-7.91 (m, 2 H) ppm. ¹³C{¹H} NMR (125 MHz,

JMOD, CDCl₃): δ = ‒2.4 (CH₃), ‒2.4 (CH₃), 11.2 (CH₂), 26.4 (CH₂), 27.5

(CH₂), 30.7 (CH₂), 54.0 (CH), 114.3 (CH), 115.1 (C), 117.2 (CH), 121.6

(C), 122.3 (CH), 123.1 (CH), 125.0 (CH), 125.4 (CH), 126.8 (CH), 129.3

(CH), 134.8 (C), 139.9 (C), 141.6 (C), 144.5 (C) ppm. ²⁹Si{¹H} NMR (99

MHz, INEPT, CDCl₃): δ = −1.9 ppm. GC/MS (EI, 70 eV): m/z (%) = 429

(1) [M]⁺, 349 (9), 216 (7), 189 (6), 158 (8), 147 (6), 132 (100) [M −

C₁₂H₁₄BrSSi]⁺, 117 (9). HRMS (EI): calcd. (C₂₁H₂₄BrNSSi) 429.0577,

found 429.0575 [M]⁺. IR (ATR, neat): λ⁻¹= 3403, 3053, 3014, 2919, 2842,

1606, 1584, 1554, 1502, 1480, 1450, 1433, 1420, 1412, 1353, 1307,

1290, 1274, 1250, 1243, 1182, 1160, 1154, 1132, 1119, 1104, 1070,

1036, 1020, 989, 926, 903, 880, 840, 819, 780, 741, 726, 710, 671, 639,

591, 561, 536, 503 cm^‒1. 56c: R_f= 0.22 (SiO₂, PE/EtOAc, 40:1). ¹H NMR

(500 MHz, CDCl₃): δ = 0.45 (s, 12 H), 0.83-0.99 (m, 4 H), 1.49-1.59 (m, 4

H), 1.74 (t, J = 6.6 Hz, 2 H), 2.68 (t, J = 6.6 Hz, 2 H), 6.47 (br. s, 1 H),

6.57 (t, J = 7.3 Hz, 1 H), 6.89-6.97 (m, 2 H), 7.36-7.40 (m, 2 H), 7.41-7.46

(m, 2 H), 7.78-7.84 (m, 4 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD,

CDCl₃): δ = ‒2.4 (CH₃), 8.4 (CH₂), 23.6 (CH₂), 29.4 (CH₂), 31.2 (CH₂),

54.7 (C), 114.5 (CH), 115.0 (C), 116.6 (CH), 120.8 (C), 122.3 (CH), 123.1

(CH), 124.9 (CH), 125.3 (CH), 126.8 (CH), 129.3 (CH), 134.9 (C), 139.8

(C), 141.6 (C), 143.9 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ

= −1.5 ppm. GC/MS (EI, 70 eV): m/z (%) = 725 (4) [M]⁺, 710 (1) [M −

CH₃]⁺, 646 (1) [M − Br]⁺, 428 (100) [M − C₁₂H₁₄BrSSi]⁺, 269 (10) [M −

C₂₃H₂₇BrNSSi]⁺, 216 (98), 189 (24), 158 (45), 147 (34), 130 (11), 115

(15), 59 (7). HRMS (ESI, +): calcd. (C₃₃H₃₈Br₂NS₂Si₂) 726.0351, found

726.0349 [M+H]⁺. IR (ATR, neat): λ⁻¹= 3400, 3053, 3014, 2924, 2852,

1727, 1606, 1586, 1556, 1479, 1450, 1420, 1346, 1313, 1290, 1250,

1243, 1213, 1182, 1160, 1124, 1109, 1070, 1037, 1020, 989, 907, 880,

591, 503 cm^‒1

.

N-(1-((3-Bromobenzo[b]thiophen-2-yl)dimethylsilyl)-4-methylpentan-

3-yl)aniline (55b): General procedure C was used to synthesize 55b

from N-isobutylaniline (44, 298 mg, 2.00 mmol) and 3-bromo-2-

(vinyldimethylsilyl)benzo[b]thiophene (36, 654 mg, 2.20 mmol) with

titanium catalyst V (221 mg, 0.20 mmol, 10 mol%) at 140 °C. After flash

chromatography (SiO₂, PE/EtOAc, 60:1), a mixture of N-isobutylaniline

(44) and crude 55b was obtained. Subsequent purification by bulb-to-

bulb distillation (234 °C, 1 × 10^-3mbar) gave 55b (605 mg, 1.35 mmol,

68 %) as a yellow oil. R_f= 0.23 (SiO₂, PE/EtOAc, 60:1). ¹H NMR (500

MHz, CDCl₃): δ = 0.48 (s, 3 H), 0.48 (s, 3 H), 0.91 (d, J = 6.8 Hz, 3 H),

0.94 (d, J = 6.9 Hz, 3 H), 0.99 (ddd, J = 14.7, 12.5, 5.0 Hz, 1 H), 1.18

(ddd, J = 14.7, 12.4, 4.3 Hz, 1 H), 1.41-1.50 (m, 1 H), 1.65-1.74 (m, 1 H),

1.87-1.98 (m, 1 H), 3.19 (dt, J = 7.8, 4.7 Hz, 1 H), 3.45 (br. s, 1 H), 6.57

(d, J = 7.8 Hz, 2 H), 6.63 (t, J = 7.3 Hz, 1 H), 7.11-7.16 (m, 2 H), 7.39-

7.43 (m, 1 H), 7.45-7.49 (m, 1 H), 7.86 (t, J = 7.9 Hz, 2 H) ppm. ¹³C{¹H}

NMR (125 MHz, DEPT, CDCl₃): δ = ‒2.3 (CH₃), 11.8 (CH₂), 18.4 (CH₃),

19.0 (CH₃), 25.7 (CH₂), 31.0 (CH), 60.7 (CH), 113.0 (CH), 115.0 (C),

116.5 (CH), 122.3 (CH), 123.1 (CH), 125.0 (CH), 125.3 (CH), 129.4 (CH),

135.1 (C), 139.9 (C), 141.7 (C), 148.8 (C) ppm. ²⁹Si{¹H} NMR (99 MHz,

INEPT, CDCl₃): δ = −2.1 ppm. GC/MS (EI, 70 eV): m/z (%) = 445 (3) [M]⁺,

402 (11) [M − C₃H₇]⁺, 269 (3) [M − C₁₂H₁₈N]⁺, 190 (100), 175 (6), 148 (95)

[M − C₁₂H₁₄BrSSi]⁺, 132 (15), 115 (15), 106 (7), 93 (6), 77 (10) [M −

C₁₆H₂₃BrNSSi]⁺. HRMS (ESI, +): calcd. (C₂₂H₂₉BrNSSi) 446.0973, found

446.0969 [M+H]⁺. IR (ATR, neat): λ⁻¹= 3410, 3053, 3019, 2956, 2929,

2870, 1599, 1503, 1482, 1450, 1429, 1410, 1386, 1367, 1320, 1290,

1249, 1243, 1179, 1162, 1132, 1099, 1070, 1036, 1020, 989, 880, 840,

840, 807, 780, 750, 726, 710, 640, 591, 541, 503 cm^‒1

.

Buchwald-Hartwig amination. General procedure E: An oven dried

Schlenk tube equipped with a Teflon® stopcock and a magnetic stirring

bar was transferred into a nitrogen-filled glovebox and charged with the

amine (0.50 mmol), Pd₂(dba)₃(11 mg, 0.0125 mmol), RuPhos (16 mg,

0.035 mmol), NaOtBu (72 mg, 0.75 mmol), and toluene (1.5 mL). The

tube was sealed, removed from the glovebox and placed in an aluminium

heating block. The reaction mixture was heated to 110 °C for 24 h. After

cooling down the reaction mixture, it was diluted by addition of CH₂Cl₂

(50 mL), Celite was added and the solvents were removed under

reduced pressure. The residue was purified by flash chromatography

(SiO₂).

814, 779, 744, 727, 711, 690, 640, 591, 503 cm^‒1

.

2-(1-((3-Bromobenzo[b]thiophen-2-yl)dimethylsilyl)ethyl)-1,2,3,4-

tetrahydroquinoline (56a), 2-(2-((3-bromobenzo[b]thiophen-2-

yl)dimethylsilyl)ethyl)-1,2,3,4-tetrahydroquinoline (56b), and 2,2-

bis(2-((3-bromobenzo[b]thiophen-2-yl)dimethylsilyl)ethyl)-1,2,3,4-

tetrahydroquinoline (56c): General procedure

C

was used to

5,5-Dimethyl-1-phenyl-2,3,4,5-tetrahydro-1H-benzo[4,5]thieno[3,2-

b][1,4]azasilepine (57): General procedure E was used to synthesize 57

from 46b (202 mg, 0.50 mmol). After purification by flash

chromatography (SiO₂, PE/EtOAc, 40:1), 57 (123 mg, 0.38 mmol, 76 %)

was obtained as a slightly yellow oil. R_f= 0.55 (SiO₂, PE/EtOAc, 40:1). ¹H

NMR (500 MHz, CDCl₃): δ = 0.28 (s, 6 H), 0.86-89 (m, 2 H), 2.08-2.15 (m,

2 H), 3.85-3.91 (m, 2 H), 6.63 (d, J = 8.0 Hz, 2 H), 6.74 (t, J = 7.3 Hz, 1

H), 7.15-7.20 (m, 2 H), 7.21-7.25 (m, 1 H), 7.30-7.34 (m, 1 H), 7.38 (d, J

= 8.0 Hz, 1 H), 7.85 (d, J = 8.1 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz,

JMOD, CDCl₃): δ = ‒2.1 (CH₃), 13.7 (CH₂), 22.9 (CH₂), 51.7 (CH₂), 114.0

(CH), 117.3 (CH), 122.6 (CH), 123.1 (CH), 123.9 (CH), 124.6 (CH), 129.1

(CH), 133.6 (C), 136.3 (C), 143.0 (C), 146.5 (C), 148.5 (C) ppm. ²⁹Si{¹H}

NMR (99 MHz, INEPT, CDCl₃): δ = −3.9 ppm. GC/MS (EI, 70 eV): m/z

(%) = 323 (99) [M]⁺, 308 (21) [M − CH₃]⁺, 294 (14), 282 (100), 266 (13),

249 (14), 236 (7), 218 (8), 202 (15), 188 (5), 174 (9), 151 (11), 133 (8),

115 (12), 99 (11), 77 (22) [M − C₁₃H₁₆NSSi]⁺, 59 (16). HRMS (EI): calcd.

(C₁₉H₂₁NSSi) 323.1158, found 323.1151 [M]⁺. IR (ATR, neat): λ⁻¹= 3060,

3039, 2950, 2920, 2874, 1594, 1577, 1559, 1519, 1496, 1462, 1450,

1427, 1404, 1372, 1362, 1336, 1316, 1293, 1249, 1193, 1156, 1143,

1124, 1084, 1073, 1051, 1031, 1020, 999, 990, 957, 946, 909, 846, 833,

synthesize 56b from 1,2,3,4-tetrahydroquinoline (45, 266 mg, 2.00 mmol)

and 3-bromo-2-(vinyldimethylsilyl)benzo[b]thiophene (36, 654 mg, 2.20

mmol) with titanium catalyst IV (154 mg, 0.20 mmol, 10 mol%) at 140 °C.

After flash chromatography (SiO₂, PE/EtOAc, 40:1), 56a (20 mg, 0.04

mmol, 2 %), 56b (423 mg, 0.98 mmol, 49 %), and 56c (22 mg, 0.03 mmol,

2 %) were obtained as yellow oils. 56a: R_f= 0.23 (SiO₂, PE/EtOAc, 40:1).

¹H NMR (500 MHz, CDCl₃): δ = 0.57 (s, 3 H), 0.60 (s, 3 H), 1.15 (d, J =

7.6 Hz, 3 H), 1.65-1.72 (m, 1 H), 1.78-1.92 (m, 2 H), 2.68-2.83 (m, 2 H),

3.47-3.53 (m, 1 H), 6.33 (d, J = 7.8 Hz, 1 H), 6.57 (t, J = 7.2 Hz, 1 H),

6.88-6.94 (m, 2 H), 7.41 (t, J = 8.0 Hz, 1 H), 7.47 (t, J = 7.5 Hz, 1 H),

7.83-7.90 (m, 2 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ =

‒2.3 (CH₃), ‒2.1 (CH₃), 10.7 (CH₃), 25.6 (CH), 27.1 (CH₂), 27.6 (CH₂),

54.2 (CH), 114.3 (CH), 115.2 (C), 117.1 (CH), 121.4 (C), 122.3 (CH),

123.2 (CH), 125.1 (CH), 125.5 (CH), 126.8 (CH), 129.2 (CH), 135.1 (C),

139.9 (C), 141.7 (C), 144.8 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT,

CDCl₃): δ = −1.1 ppm. GC/MS (EI, 70 eV): m/z (%) = 429 (2) [M]⁺, 350 (2)

[M − Br]⁺, 269 (1) [M − C₁₁H₁₄N]⁺, 216 (6),147 (7), 132 (100) [M −

C₁₂H₁₄BrSSi]⁺, 115 (8). HRMS (ESI, +): calcd. (C₂₁H₂₅BrNSSi) 430.0660,

found 430.0652 [M+H]⁺. IR (ATR, neat): λ⁻¹= 3412, 3053, 3016, 2952,

2924, 2869, 2842, 1729, 1604, 1586, 1502, 1480, 1450, 1434, 1377,

1342, 1309, 1290, 1274, 1250, 1243, 1197, 1160, 1114, 1072, 1021, 987,

814, 779, 763, 744, 731, 719, 690, 643, 600, 593, 549, 529, 514 cm^‒1

.

936, 880, 836, 807, 779, 727, 711, 690, 656, 593, 540, 530, 504 cm^‒1

56b: R_f= 0.20 (SiO₂, PE/EtOAc, 40:1). ¹H NMR (500 MHz, CDCl₃): δ =

.

16

10.1002/ejoc.202001523

European Journal of Organic Chemistry

FULL PAPER

5,5-Dimethyl-1-(m-tolyl)-2,3,4,5-tetrahydro-1H-benzo[4,5]thieno[3,2-

b][1,4]azasilepine (58): General procedure E was used to synthesize 58

from 47b (209 mg, 0.50 mmol). After purification by flash

chromatography (SiO₂, PE/EtOAc, 60:1), 58 (138 mg, 0.41 mmol, 82 %)

was obtained as a colorless oil. R_f= 0.35 (SiO₂, PE/EtOAc, 60:1). ¹H

NMR (500 MHz, CDCl₃): δ = 0.34 (s, 6 H), 0.90-0.94 (m, 2 H), 2.12-2.19

(m, 2 H), 2.31 (s, 3 H), 3.91 (br. s, 2 H), 6.46 (d, J = 8.1 Hz, 1 H), 6.57 (s,

1 H), 6.62 (d, J = 7.3 Hz, 1 H), 7.06-7.12 (m, 1 H), 7.24-7.29 (m, 1 H),

7.33-7.38 (m, 1 H), 7.41-7.46 (m, 1 H), 7.88 (d, J = 8.1 Hz, 1 H) ppm.

¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ = ‒2.1 (CH₃), 13.6 (CH₂), 22.0

(CH₃), 23.0 (CH₂), 51.8 (CH₂), 111.7 (CH), 114.5 (CH), 118.4 (CH), 122.7

(CH), 123.0 (CH), 123.8 (CH), 124.6 (CH), 129.0 (CH), 133.3 (C), 136.4

(C), 138.7 (C), 142.9 (C), 146.6 (C), 148.7 (C) ppm. ²⁹Si{¹H} NMR (99

MHz, INEPT, CDCl₃): δ = −4.0 ppm. GC/MS (EI, 70 eV): m/z (%) = 337

(100) [M]⁺, 322 (18) [M − CH₃]⁺, 308 (14), 296 (81), 280 (12), 263 (15),

236 (9), 218 (11), 202 (16), 188 (13), 175 (10), 151 (11), 115 (16), 91

(22) [M − C₁₃H₁₆NSSi]⁺, 59 (22). HRMS (ESI, +): calcd. (C₂₀H₂₄NSSi)

338.1399, found 338.1389 [M+H]⁺. IR (ATR, neat): λ⁻¹= 3099, 3056,

3032, 2952, 2872, 1602, 1582, 1563, 1519, 1490, 1462, 1430, 1356,

1287, 1252, 1209, 1186, 1173, 1152, 1043, 1017, 990, 981, 907, 837,

2.19 (m, 2 H), 3.88 (br. s, 2 H), 6.61 (d, J = 8.7 Hz, 2 H), 7.06 (d, J = 8.6

Hz, 2 H), 7.29 (ddd, J = 8.0, 7.0, 1.0 Hz, 1 H), 7.37 (ddd, J = 8.1, 7.0, 1.3

Hz, 1 H), 7.41 (dt, J = 7.9, 0.9 Hz, 1 H), 7.89 (dt, J = 8.1, 0.8 Hz, 1 H)

ppm. ¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ = ‒2.3 (CH₃), 13.7 (CH₂),

22.8 (CH₂), 52.0 (CH₂), 114.2 (CH), 120.9 (q, J = 255 Hz, C), 122.2 (CH),

122.3 (CH), 123.2 (CH), 124.1 (CH), 124.8 (CH), 134.4 (C), 136.0 (C),

140.6 (C), 143.1 (C), 145.4 (C), 147.9 (C) ppm. ²⁹Si{¹H} NMR (99 MHz,

INEPT, CDCl₃): δ = −3.8 ppm. ¹⁹F NMR (470 MHz, CDCl₃): δ = −58.2

ppm. GC/MS (EI, 70 eV): m/z (%) = 407 (100) [M]⁺, 392 (20) [M − CH₃]⁺,

366 (64), 322 (5) [M − CF₃O]⁺, 223 (10), 202 (11), 99 (18), 69 (14) [M −

C₁₉H₂₀NOSSi]⁺. HRMS (EI): calcd. (C₂₀H₂₀F₃NOSSi) 407.0981, found

407.0970 [M]⁺. IR (ATR, neat): λ⁻¹= 3057, 2953, 2874, 1610, 1563, 1506,

1457, 1434, 1374, 1362, 1324, 1244, 1220, 1204, 1154, 1126, 1061,

1024, 981, 959, 917, 831, 804, 779, 761, 733, 714, 670, 613, 594, 549,

530, 511, 503 cm^‒1

.

5,5-Dimethyl-1-(4-((trifluoromethyl)thio)phenyl)-2,3,4,5-tetrahydro-

1H-benzo[4,5]thieno[3,2-b][1,4]azasilepine (62) and N-(3-(tert-

butoxydimethylsilyl)propyl)-4-((trifluoromethyl)thio)aniline

(68):

General procedure E was used to synthesize 62 from 51b (252 mg, 0.50

mmol). After purification by flash chromatography (SiO₂, PE/EtOAc, 50:1),

62 (54 mg, 0.13 mmol, 26 %) was obtained as a colorless oil. In addition,

68 (76 mg, 0.21 mmol, 42 %) was obtained as a yellow oil. 62: R_f= 0.45

(SiO₂, PE/EtOAc, 50:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.24 (s, 6 H),

0.86-0.89 (m, 2 H), 2.12 (br. s, 2 H), 3.84 (br. s, 2 H), 6.56 (br. s, 2 H),

7.24-7.29 (m, 1 H), 7.32-7.43 (m, 4 H), 7.86 (d, J = 7.8 Hz, 1 H) ppm.

¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = ‒2.5 (CH₃), 13.8 (CH₂), 22.9

(CH₂), 51.7 (CH₂), 109.9 (C), 114.1 (CH), 122.1 (CH), 123.3 (CH), 124.3

(CH), 124.9 (CH), 129.9 (q, J = 309 Hz, C), 135.3 (C), 135.8 (C), 138.0

(CH), 143.1 (C), 147.1 (C), 148.8 (C) ppm. ²⁹Si{¹H} NMR (99 MHz,

INEPT, CDCl₃): δ = −3.7 ppm. ¹⁹F NMR (470 MHz, CDCl₃): δ = −44.3

ppm. GC/MS (EI, 70 eV): m/z (%) = 423 (100) [M]⁺, 408 (15) [M − CH₃]⁺,

404 (3) [M − F]⁺, 382 (41), 354 (15) [M − CF₃]⁺, 281 (18), 222 (22), 177

794, 781, 760, 729, 706, 691, 649 cm^‒1

.

1-(4-Chlorophenyl)-5,5-dimethyl-2,3,4,5-tetrahydro-1H-

benzo[4,5]thieno[3,2-b][1,4]azasilepine (59): General procedure E was

used to synthesize 59 from 48b (219 mg, 0.50 mmol). After purification

by flash chromatography (SiO₂, PE/EtOAc, 50:1), 59 (80 mg, 0.22 mmol,

45 %) was obtained as a colorless oil. R_f= 0.28 (SiO₂, PE/EtOAc, 50:1).

¹H NMR (500 MHz, CDCl₃): δ = 0.27 (s, 6 H), 0.85-0.89 (m, 2 H), 2.06-

2.11 (m, 2 H), 3.83 (br. s, 2 H), 6.53 (d, J = 8.7 Hz, 2 H), 7.10 (d, J = 9.2

Hz, 2 H), 7.22-7.26 (m, 1 H), 7.30-7.36 (m, 2 H), 7.85 (dt, J = 7.8, 0.9 Hz,

1 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ = ‒2.2 (CH₃), 13.7

(CH₂), 22.8 (CH₂), 51.9 (CH₂), 115.0 (CH), 122.2 (C), 122.4 (CH), 123.2

(CH), 124.1 (CH), 124.8 (CH), 129.1 (CH), 134.2 (C), 136.0 (C), 143.1

(C), 145.2 (C), 147.9 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ

= −3.9 ppm. GC/MS (EI, 70 eV): m/z (%) = 357 (100) [M]⁺, 342 (20) [M −

CH₃]⁺, 316 (77), 281 (23), 202 (16), 179 (12), 151 (11), 115 (12), 99 (21),

75 (12), 59 (16). HRMS (EI): calcd. (C₁₉H₂₀ClNSSi) 357.0769, found

357.0767 [M]⁺. IR (ATR, neat): λ⁻¹= 3099, 3070, 3042, 2952, 2872, 1593,

1563, 1519, 1490, 1463, 1432, 1412, 1359, 1333, 1296, 1276, 1252,

1200, 1183, 1153, 1127, 1096, 1043, 1020, 981, 939, 907, 837, 811, 793,

(7) [M − C₁₃H₁₆NSSi]⁺, 115 (10), 99 (22), 77 (13), 69 (15) [M

−

C₁₉H₂₀NS₂Si]⁺, 59 (19). HRMS (EI): calcd. (C₂₀H₂₀F₃NS₂Si) 423.0753,

found 423.0750 [M]⁺. IR (ATR, neat): λ⁻¹= 3064, 2952, 2922, 2876, 2856,

1589, 1556, 1496, 1457, 1430, 1376, 1360, 1324, 1306, 1287, 1252,

1193, 1146, 1109, 1090, 1074, 1023, 999, 959, 907, 849, 833, 816, 779,

764, 731, 670, 629, 594, 566, 547, 520, 513, 504 cm^‒1. 68: R_f= 0.20

(SiO₂, PE/EtOAc, 50:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.14 (s, 6 H),

0.58-0.64 (m, 2 H), 1.26 (s, 9 H), 1.63-1.71 (m, 2 H), 3.13 (t, J = 7.1 Hz, 2

H), 6.56 (d, J = 8.6 Hz, 2 H), 7.41 (d, J = 8.6 Hz, 2 H) ppm. ¹³C{¹H} NMR

(125 MHz, JMOD, CDCl₃): δ = 1.2 (CH₃), 16.0 (CH₂), 23.4 (CH₂), 32.2

(CH₃), 46.4 (CH₂), 72.5 (C), 109.1 (C), 113.0 (CH), 129.9 (q, J = 308 Hz,

C), 138.4 (CH), 150.7 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ

= 7.6 ppm. ¹⁹F NMR (470 MHz, CDCl₃): δ = −44.7 ppm. GC/MS (EI, 70

eV): m/z (%) = 365 (22) [M]⁺, 350 (1) [M − CH₃]⁺, 309 (13), 292 (34) [M −

C₄H₉O]⁺, 276 (5), 250 (5), 222 (9), 206 (93) [M − C₈H₁₉OSi]⁺, 164 (8), 149

(5), 137 (21), 105 (14), 75 (100), 57 (29) [M − C₁₂H₁₇F₃NOSSi]⁺. HRMS

(ESI, +): calcd. (C₁₆H₂₇F₃NOSSi) 366.1535, found 366.1529 [M+H]⁺. IR

(ATR, neat): λ⁻¹= 3430, 2974, 2930, 2874, 1597, 1509, 1474, 1462,

1409, 1389, 1364, 1329, 1296, 1252, 1197, 1184, 1149, 1112, 1092,

1044, 1020, 891, 836, 817, 789, 771, 753, 704, 680, 563, 519 cm^‒1.

760, 731, 709, 661, 649, 631, 577, 547, 510 cm^‒1

.

1-(4-Methoxyphenyl)-5,5-dimethyl-2,3,4,5-tetrahydro-1H-

benzo[4,5]thieno[3,2-b][1,4]azasilepine (60): General procedure E was

used to synthesize 60 from 49b (217 mg, 0.50 mmol). After purification

by flash chromatography (SiO₂, PE/EtOAc, 50:1), 60 (138 mg, 0.39 mmol,

78 %) was obtained as a colorless oil. R_f= 0.23 (SiO₂, PE/EtOAc, 50:1).

¹H NMR (500 MHz, CDCl₃): δ = 0.32 (s, 6 H), 0.89 (t, J = 6.6 Hz, 2 H),

2.06-2.11 (m, 2 H), 3.77 (s, 3 H), 3.87-3.92 (m, 2 H), 6.64 (d, J = 8.8 Hz,

2 H), 6.79 (d, J = 8.8 Hz, 2 H), 7.22 (t, J = 7.5 Hz, 1 H), 7.31 (t, J = 7.5 Hz,

1 H), 7.36 (d, J = 8.0 Hz, 1 H), 7.84 (d, J = 8.1 Hz, 1 H) ppm. ¹³C{¹H}

NMR (125 MHz, DEPT, CDCl₃): δ = ‒1.8 (CH₃), 13.5 (CH₂), 22.9 (CH₂),

52.5 (CH₂), 55.7 (CH₃), 114.7 (CH), 115.7 (CH), 122.8 (CH), 123.0 (CH),

123.7 (CH), 124.5 (CH), 131.8 (C), 136.4 (C), 140.7 (C), 142.9 (C), 149.1

(C), 152.0 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −4.2 ppm.

GC/MS (EI, 70 eV): m/z (%) = 353 (100) [M]⁺, 338 (23) [M − CH₃]⁺, 312

(39), 281 (14), 252 (31), 59 (20). HRMS (EI): calcd. (C₂₀H₂₃NOSSi)

353.1264, found 353.1264 [M]⁺. IR (ATR, neat): λ⁻¹= 3102, 3059, 2996,

2950, 2870, 2832, 1563, 1504, 1463, 1440, 1432, 1354, 1286, 1237,

1194, 1179, 1152, 1036, 981, 909, 831, 816, 794, 759, 731, 700, 649,

5,5-Dimethyl-1,2-diphenyl-2,3,4,5-tetrahydro-1H-

benzo[4,5]thieno[3,2-b][1,4]azasilepine (63): General procedure E was

used to synthesize 63 from 52b (240 mg, 0.50 mmol). After purification

by flash chromatography (SiO₂, PE/EtOAc, 30:1), 63 (112 mg, 0.28 mmol,

56 %) was obtained as a slightly yellow oil. Due to the high instability of

this compound in solution, rapid decomposition processes which result in

visible impurities in the NMR spectra were observed. R_f= 0.52 (SiO₂,

PE/EtOAc, 30:1). ¹H NMR (500 MHz, CDCl₃): δ = 0.30 (s, 3 H), 0.47 (s, 3

H), 0.89-0.97 (m, 1 H), 1.05-1.13 (m, 1 H), 2.05-2.51 (m, 2 H), 5.06 (br. s,

1 H), 6.61-6.71 (m, 2 H), 6.74 (t, J = 7.3 Hz, 1 H), 7.06-7.15 (m, 4 H),

7.18-7.46 (m, 6 H), 7.89 (d, J = 8.1 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz,

JMOD, CDCl₃): δ = ‒1.3 (CH₃), ‒0.4 (CH₃), 11.3 (CH₂), 32.1 (CH₂), 66.0

(CH), 115.0 (CH), 118.1 (CH), 123.0 (CH), 123.7 (CH), 123.8 (CH), 124.5

(CH), 127.0 (CH), 127.2 (CH), 128.6 (CH), 128.9 (CH), 134.9 (C), 137.1

(C), 141.8 (C), 143.0 (C), 144.4 (C), 149.4 (C) ppm. ²⁹Si{¹H} NMR (99

574 cm^‒1

.

5,5-Dimethyl-1-(4-(trifluoromethoxy)phenyl)-2,3,4,5-tetrahydro-1H-

benzo[4,5]thieno[3,2-b][1,4]azasilepine (61): General procedure E was

used to synthesize 61 from 50b (244 mg, 0.50 mmol). After purification

by flash chromatography (SiO₂, PE/EtOAc, 50:1), 61 (189 mg, 0.46 mmol,

93 %) was obtained as a colorless oil. R_f= 0.47 (SiO₂, PE/EtOAc, 50:1).

¹H NMR (500 MHz, CDCl₃): δ = 0.32 (s, 6 H), 0.91-0.93 (m, 2 H), 2.11-

17

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FULL PAPER

MHz, INEPT, CDCl₃): δ = −2.5 ppm. GC/MS (EI, 70 eV): m/z (%) = 399

(74) [M]⁺, 384 (22) [M − CH₃]⁺, 371 (25), 322 (6) [M − C₆H₅]⁺, 356 (4), 308

(11), 294 (20), 282 (100), 266 (39), 251 (23), 234 (10). HRMS (EI): calcd.

(C₂₅H₂₅NSSi) 399.1471, found 399.1465 [M]⁺. IR (ATR, neat): λ⁻¹= 3062,

3026, 2953, 2926, 2887, 2246, 1593, 1559, 1493, 1452, 1426, 1407,

1379, 1346, 1302, 1289, 1250, 1206, 1174, 1143, 1124, 1086, 1067,

1036, 1020, 990, 959, 906, 844, 807, 794, 780, 764, 757, 727, 693, 647,

1 H), 7.86 (d, J = 8.0 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD,

CDCl₃): δ = ‒2.1 (CH₃), ‒1.0 (CH₃), 9.1 (CH₂), 19.5 (CH₃), 22.1 (CH₃),

24.2 (CH₂), 30.0 (CH), 64.8 (CH), 114.6 (CH), 117.4 (CH), 123.0 (CH),

123.2 (CH), 123.9 (CH), 124.4 (CH), 129.0 (CH), 135.1 (C), 138.0 (C),

142.7 (C), 142.8 (C), 149.1 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT,

CDCl₃): δ = −21.9 ppm. GC/MS (EI, 70 eV): m/z (%) = 365 (26) [M]⁺, 322

(100) [M − C₃H₇]⁺, 294 (11), 282 (9), 266 (11), 251 (8), 191 (12), 77 (9)

619, 614, 603, 593, 566, 547, 527, 509 cm^‒1

.

[M −

C₁₆H₂₂NSSi]⁺, 59 (13). HRMS (ESI, +): calcd. (C₂₂H₂₈NSSi)

366.1712, found 366.1704 [M+H]⁺. IR (ATR, neat): λ⁻¹= 3060, 3024,

2954, 2926, 2870, 1593, 1559, 1514, 1494, 1454, 1427, 1409, 1387,

1349, 1304, 1289, 1270, 1250, 1179, 1160, 1149, 1119, 1086, 1066,

1036, 1024, 991, 973, 907, 854, 837, 807, 784, 777, 764, 730, 690, 644,

2-(4-Fluorophenyl)-5,5-dimethyl-1-phenyl-2,3,4,5-tetrahydro-1H-

benzo[4,5]thieno[3,2-b][1,4]azasilepine (64): General procedure E was

used to synthesize 64 from 53b (249 mg, 0.50 mmol). After purification

by flash chromatography (SiO₂, PE/EtOAc, 30:1), 64 (127 mg, 0.30 mmol,

61 %) was obtained as a slightly yellow oil. R_f= 0.55 (SiO₂, PE/EtOAc,

603, 506 cm^‒1

.

1

30:1). H NMR (500 MHz, CDCl₃): δ = 0.31 (s, 3 H), 0.49 (s, 3 H), 0.91-

9,9-Dimethyl-5,6,6a,7,8,9-

0.98 (m, 1 H), 1.07-1.15 (m, 1 H), 2.28 (br. s, 2 H), 5.07 (br. s, 1 H), 6.69

(br. s, 2 H), 6.77 (t, J = 7.3 Hz, 1 H), 6.95 (br. s, 2 H), 7.07-7.20 (m, 3 H),

7.21-7.51 (m, 3 H), 7.91 (d, J = 8.1 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz,

JMOD, CDCl₃): δ = ‒1.3 (CH₃), ‒0.4 (CH₃), 11.2 (CH₂), 32.1 (CH₂), 64.9

(CH), 114.7 (CH), 115.3 (d, J = 21 Hz, CH), 118.2 (CH), 123.0 (CH),

123.4 (CH), 123.9 (CH), 124.6 (CH), 128.8 (CH), 128.9 (CH), 135.1 (C),

137.0 (C), 140.1 (C), 141.5 (C), 143.1 (C), 149.1 (C), 161.8 (d, J = 245

Hz, C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ = −21.9 ppm. ¹⁹F

NMR (470 MHz, CDCl₃): δ = −115.6 ppm. GC/MS (EI, 70 eV): m/z (%) =

417 (63) [M]⁺, 402 (11) [M − CH₃]⁺, 389 (24), 340 (4) [M − C₆H₅]⁺, 322 (3)

[M − C₆H₄F]⁺, 282 (100), 266 (33), 251 (21), 135 (17), 77 (16) [M −

C₁₉H₁₉FNSSi]⁺. HRMS (EI): calcd. (C₂₅H₂₄FNSSi) 417.1377, found

417.1371 [M]⁺. IR (ATR, neat): λ⁻¹= 3060, 3037, 2952, 2924, 2886, 2244,

1593, 1559, 1507, 1492, 1452, 1407, 1377, 1347, 1320, 1302, 1287,

1250, 1222, 1206, 1174, 1157, 1143, 1123, 1094, 1084, 1069, 1036,

1020, 1014, 1001, 990, 959, 907, 854, 831, 810, 777, 766, 730, 691, 644,

hexahydrobenzo[4',5']thieno[3',2':2,3][1,4]azasilepino[1,7-

a]quinoline (67): General procedure E was used to synthesize 67 from

56b (215 mg, 0.50 mmol). After purification by flash chromatography

(SiO₂, PE/EtOAc, 50:1), 67 (93 mg, 0.27 mmol, 53 %) was obtained as a

colorless oil which solidified upon standing. R_f= 0.35 (SiO₂, PE/EtOAc,

1

50:1). H NMR (500 MHz, CDCl₃): δ = 0.18 (s, 3 H), 0.47 (s, 3 H), 0.89

(ddd, J = 14.6, 11.8, 4.7 Hz, 1 H), 1.00 (ddd, J = 14.5, 6.1, 3.7 Hz, 1 H),

1.85-1.92 (m, 1 H), 1.96-2.03 (m, 1 H), 2.12-2.20 (m, 1 H), 2.21-2.30 (m,

1 H), 2.89-2.97 (m, 1 H), 3.04-3.14 (m, 1 H), 3.58-3.64 (m, 1 H), 6.17 (dd,

J = 8.2, 1.0 Hz, 1 H), 6.70 (td, J = 7.3, 1.1 Hz, 1 H), 6.88 (t, J = 7.7 Hz, 1

H), 7.14 (d, J = 7.4 Hz, 1 H), 7.24 (ddd, J = 8.0, 7.0, 1.0 Hz, 1 H), 7.34

(ddd, J = 8.1, 7.0, 1.2 Hz, 1 H), 7.42 (dt, J = 8.0, 0.9 Hz, 1 H), 7.87 (dt, J

= 8.1, 0.8 Hz, 1 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ = ‒2.5

(CH₃), ‒2.2 (CH₃), 13.8 (CH₂), 23.6 (CH₂), 28.6 (CH₂), 29.5 (CH₂), 59.9

(CH), 115.4 (CH), 117.1 (CH), 120.8 (C), 122.6 (CH), 123.2 (CH), 123.8

(CH), 124.5 (CH), 126.8 (CH), 129.3 (CH), 133.8 (C), 136.0 (C), 142.5

(C), 143.2 (C), 147.9 (C) ppm. ²⁹Si{¹H} NMR (99 MHz, INEPT, CDCl₃): δ

= −4.3 ppm. GC/MS (EI, 70 eV): m/z (%) = 349 (100) [M]⁺, 334 (22) [M −

CH₃]⁺, 321 (18), 216 (12), 205 (26), 117 (10), 59 (12). HRMS (EI): calcd.

(C₂₁H₂₃NSSi) 349.1320, found 349.1312 [M]⁺. IR (ATR, neat): λ⁻¹= 3062,

3034, 2936, 2913, 2894, 2874, 2847, 1602, 1576, 1559, 1493, 1453,

1427, 1382, 1359, 1350, 1336, 1302, 1283, 1262, 1253, 1214, 1207,

1194, 1170, 1134, 1123, 1112, 1079, 1057, 1039, 1019, 999, 944, 930,

921, 894, 883, 850, 844, 834, 813, 799, 780, 766, 746, 733, 717, 710,

634, 603, 579, 561, 547, 530, 509 cm^‒1

.

5,5-Dimethyl-1-phenyl-2-(4-(trifluoromethyl)phenyl)-2,3,4,5-

tetrahydro-1H-benzo[4,5]thieno[3,2-b][1,4]azasilepine (65): General

procedure E was used to synthesize 65 from 54b (274 mg, 0.50 mmol).

After purification by flash chromatography (SiO₂, PE/EtOAc, 50:1), the

obtained crude product was purified by bulb-to-bulb distillation (220 °C, 3

× 10^-3mbar) to give 65 (126 mg, 0.27 mmol, 54 %) as a yellow oil. R_f=

694, 680, 651, 633, 599, 593, 544, 531, 516 cm^‒1

.

1

0.38 (SiO₂, PE/EtOAc, 50:1). H NMR (500 MHz, CDCl₃): δ = 0.32 (s, 3

H), 0.49 (s, 3 H), 0.93-1.00 (m, 1 H), 1.09-1.17 (m, 1 H), 2.30 (br. s, 2 H),

5.11 (br. s, 1 H), 6.66 (br. s, 2 H), 6.78 (t, J = 7.3 Hz, 1 H), 6.90-7.23 (m,

4 H), 7.34 (t, J = 7.6 Hz, 1 H), 7.38-7.66 (m, 4 H), 7.92 (d, J = 8.1 Hz, 1

H) ppm. ¹³C{¹H} NMR (125 MHz, JMOD, CDCl₃): δ = ‒1.4 (CH₃), ‒0.4

(CH₃), 11.3 (CH₂), 31.9 (CH₂), 66.0 (CH), 115.0 (CH), 118.6 (CH), 123.1

(CH), 123.4 (CH), 124.0 (CH), 124.3 (q, J = 272 Hz, C), 124.7 (CH),

125.6 (q, J = 3 Hz, CH), 127.5 (CH), 129.0 (CH), 129.3 (q, J = 32 Hz, C),

135.0 (C), 137.0 (C), 141.9 (C), 143.1 (C), 148.5 (C) ppm. ²⁹Si{¹H} NMR

(99 MHz, INEPT, CDCl₃): δ = −21.9 ppm. ¹⁹F NMR (470 MHz, CDCl₃): δ

= −62.3 ppm. GC/MS (EI, 70 eV): m/z (%) = 467 (100) [M]⁺, 452 (55) [M −

CH₃]⁺, 439 (29), 424 (12), 390 (5) [M − C₆H₅]⁺, 362 (14), 334 (14), 322 (4)

[M − C₇H₄F₃]⁺, 308 (13), 294 (20), 282 (84), 266 (41), 251 (28), 115 (19),

Acknowledgements

We thank the Research Training Group "Chemical Bond

Activation" (GRK 2226) funded by the Deutsche

Forschungsgemeinschaft for financial support of this project as

well as Jessica Reimer for experimental assistance.

Keywords: Amination • Amines • Hydroaminoalkylation •

Palladium • Titanium

77 (38) [M

−

C₂₀H₁₉F₃NSSi]⁺. HRMS (EI): calcd. (C₂₆H₂₄F₃NSSi)

467.1345, found 467.1337 [M]⁺. IR (ATR, neat): λ⁻¹= 3062, 3039, 2953,

2926, 2887, 2863, 1617, 1593, 1559, 1493, 1452, 1412, 1379, 1347,

1323, 1302, 1287, 1250, 1210, 1189, 1163, 1122, 1109, 1084, 1067,

1036, 1016, 991, 954, 907, 850, 836, 807, 797, 780, 764, 746, 731, 691,

670, 657,650, 633, 601, 524, 511 cm^‒1.

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¹H NMR (500 MHz, CDCl₃): δ = 0.08 (s, 3 H), 0.43 (s, 3 H), 0.65-0.74 (m,

1 H), 0.83-1.08 (m, 7 H), 1.78-1.99 (m, 2 H), 2.08-2.15 (m, 1 H), 3.99 (br.

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18

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10.1002/ejoc.202001523

European Journal of Organic Chemistry

FULL PAPER

Entry for the Table of Contents

Hydroaminoalkylation reactions of 2-allyl-, 2-allyldimethylsilyl- or 2-dimethyl(vinyl)silyl-substituted 3-bromothiophenes or 3-

bromobenzothiophenes with secondary amines deliver the branched or the linear addition products with high regioselectivity. A

combination of this reaction with a subsequent intramolecular Buchwald-Hartwig amination results in several one-pot processes that

give direct access to structurally novel thiophene- or benzothiophene-annulated 6- and 7-membered heterocycles.

Key Topic: Heterocycles

20

Article Doi

Hydroaminoalkylation/Buchwald-Hartwig Amination Sequences for the Synthesis of Novel Thieno- or Benzothieno-Annulated Tetrahydropyridines, Tetrahydroazasilines, and Tetrahydroazasilepines

DOI: 10.1002/ejoc.202001523

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Article abstract of DOI:10.1002/ejoc.202001523

Full text of DOI:10.1002/ejoc.202001523

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