Catalyst-free Friedel-Crafts reaction of 1-(N-acylamino)alkyltriarylphosphonium salts with electron-rich arenes

Accepted Manuscript

Catalyst-free Friedel-Crafts reaction of 1-(N-acylamino)alkyltriarylphosphonium salts

with electron-rich arenes

Jakub Adamek, Anna Węgrzyk, Monika Krawczyk, Karol Erfurt

PII:

S0040-4020(18)30326-0

10.1016/j.tet.2018.03.053

TET 29393

DOI:

Reference:

To appear in: Tetrahedron

Received Date: 8 February 2018

Revised Date: 23 March 2018

Accepted Date: 25 March 2018

Please cite this article as: Adamek J, Węgrzyk A, Krawczyk M, Erfurt K, Catalyst-free Friedel-Crafts

reaction of 1-(N-acylamino)alkyltriarylphosphonium salts with electron-rich arenes, Tetrahedron (2018),

doi: 10.1016/j.tet.2018.03.053.

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ACCEPTED MANUSCRIPT

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Catalyst-free Friedel-Crafts reaction of 1-(N-

acylamino)alkyltriarylphosphonium salts

with electron-rich arenes

Leave this area blank for abstract info.

Jakub Adamek*, Anna Węgrzyk, Monika Krawczyk, Karol Erfurt

Silesian University of Technology, 44-100 Gliwice, Poland

O

R²

15 examples

up to 84% yield

R¹

N

Ar

1. ArH, r.t.

2. base

H

R²

O

R²

PR₃HBF₄

R¹

N

PAr¹₃BF₄

H₂N

COOH

R²

H

amino acids

16 examples

ArH, ∆

Ar¹₃P

up to 92% yield

BF₄

Ar

1

ACCEPTED MANUSCRIPT

Tetrahedron

journal homepage: www.elsevier.com

Catalyst-free Friedel-Crafts reaction of 1-(N-acylamino)alkyltriarylphosphonium salts

with electron-rich arenes

Jakub Adamek^a,b,, Anna Węgrzyk^a,b, Monika Krawczyk^a,b, Karol Erfurt^c

^aDepartment of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland

^bBiotechnology Centre of Silesian University of Technology, B. Krzywoustego 8, 44-100 Gliwice, Poland

^cDepartment of Chemical Organic Technology and Petrochemistry, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland

ARTICLE INFO

ABSTRACT

Article history:

Received

Received in revised form

Accepted

Friedel-Crafts reaction of 1-(N-acylamino)alkyltriarylphosphonium salts with arenes or

heteroarenes without the need for any catalyst provided access to a wide range of biologically

interesting N-(1-arylalkyl)amides or 1-arylalkylphosphonium salts which can be of great interest

in the chemistry of ylides and phosphonium ionic liquids. Depending on reaction conditions and

substrate structure, the reaction can be conducted selectively with high yields toward each of the

above-mentioned products. Mechanistic aspects of the above transformations were also

considered.

Available online

Keywords:

Friedel-Crafts-reaction

α-Amidoalkylation

α-Amidoalkylating reagents

Phosphonium salts

Arenes

.

Amides

1. Introduction

of N-acyliminium cations 2 in α-amidoalkylation reactions

(Scheme 1).^9-13

Phosphonium salts are commonly used in chemistry as phase

transfer catalysts or solvents (phosphonium ionic liquids),^1-4but

most of all as reagents in many reactions, especially as ylide

precursors in the Wittig reaction, which is of great importance

in the synthesis of biologically active substances.^5-8

One of the most important transformations, from the organic

synthesis point of view, are reactions of carbon-carbon bond

formation. The α-amidoalkylations of aromatics or

heteroaromatics are examples with great potential of the

synthetic methods available for C-C bond formation, which

have developed and improved for a number of years.^14-24

α-Amidoalkylation of arenes was first performed by Einhorn at

the beginning of the 20th century. The Einhorn method was

based on Brønsted-acid-catalyst aromatic electrophilic

alkylation

(the

Friedel-Crafts-type

reaction)

using

(N-hydroxymethyl)amide as the alkylating reagent.²⁵Over the

past few decades, variations of this methodology include the

use of a variety of catalysts and extension of the structure of

α-amidoalkylating agents have been developed.^20,26-31In 1991

Katritzky described α-amidoalkylation of active aromatic

compounds with N-[1-(benzotriazol-1-yl)alkyl]amides in the

presence of aluminum chloride (the classical course of the

reaction, Scheme 2/a).²⁰More recently, 1-(N-acylamino)alkyl

sulfones were used as effective α-amidoalkylating agents in the

Friedel-Crafts reaction. However, in the case of α-amido

sulfones, the products differ depending upon reaction

conditions and substrate structures. Petrini showed that

N-[1-(phenylsulfonyl)alkyl]oxazolidin-2-ones in the presence

of TiCl₄at −78°C react smoothly with aromatic compounds to

Scheme 1. 1-(N-acylamino)alkylphosphonium salts as an

α-amidoalkylating agent.

The specific types of phosphonium salts which have

interesting chemical properties are 1-(N-acylamino)alkyl-

phosphonium salts 1. Individual structural features, including

the presence of an acylamino group in the direct neighborhood

of a positively charged phosphonium moiety, make the

1-(N-acylamino)alkylphosphonium salts 1 effective precursors

———

Corresponding author. Tel.: +48 032-237-1081; fax: +48 032-237-2094; e-mail: jakub.adamek@polsl.pl

2

Tetrahedron

ACCEPTED MANUSCRIPT

give the expected adducts in good yields (the classical course of

the reaction, Scheme 2/b).²⁶On the other hand, at higher

temperature and in the presence of an acidic catalyst (Lewis

acid, amberlyst-15, montmorillonite K10) unusual reaction

The use of different aromatics or heteroaromatics affected the

reaction conditions. For comparison, reactions of

1-(N-pivaloylamino)ethyltriphenylphosphonium

tetrafluoro-

borate 1a with 1,3,5-trimethoxybenzene, 1,3-dimethoxy-

products have been obtained (the non-classical course of the benzene and indole occur at 80°C, 100°C and 80°C,

reaction, Scheme 2/c).^27-30Although the course of the α-

respectively, but reactions with less active anisole or thiophene

amidoalkylation of aromatics has been the subject of many require much higher temperatures: 150°C or even 180°C in the

studies, the literature gives no information on factors, excluding

the influence of temperature and the substrate structures,

deciding on the classical or non-classical direction of the

reaction.

case of the latter (entries 7, 2, 15, 1 and 16, Table 1).

Scheme 3. Reaction of 1-(N-pivaloylamino)ethyltriphenyl-

phosphonium tetrafluoroborate 1a with 1,3,5-trimethoxy-

benzene.

However, in each example, the main reaction products were

1-arylalkylphosphonium salts 4 - products of the non-classical

course of the reaction. Attempts to perform the reaction with

non-activated or deactivated arenes such as toluene, benzene or

chlorobenzene failed.

Recently, we have demonstrated that C_α-P⁺bond strength

can be reduced by replacing the triphenylphosphonium moiety

by more electron-withdrawing tris[(p-trifluoromethyl)phenyl]-

phosphonium or tris(m-chlorophenyl)phosphonium groups.³¹

Such a reduction makes the generation of N-acyliminium

cations easier, which facilitates the reaction with aromatics and

allows it to be carried out under milder conditions.

Scheme 2. α-Amidoalkylation of electron-rich arenes and

heteroarenes – various synthetic routes.

In this paper, we present attempts to conduct the α-amido-

alkylation reaction of aromatics or heteroaromatics using

1-(N-acylamino)alkylphosphonium salts — a new class of

effective α-amidoalkylating agents recently introduced into

organic chemistry.^9-13The course of the reaction was

investigated, its plausible mechanism was proposed, but above

all the criteria to control the direction of a reaction either in the

classical or non-classical manner were evaluated.

2. Results and discussion

Although 1-(N-acylamino)alkylphosphonium salts are very

reactive α-amidoalkylating reagents, the possibility of their

α-amidoalkylation of aromatics or heteroaromatics has not been

investigated so far. Therefore, we studied whether such

reactions can be performed.

The reactivity of phosphonium salts toward aromatic

systems was conducted based on

1-(N-pivaloylamino)ethyltriphenylphosphonium

a

reaction of

tetrafluoro-

borate 1a with 1,3,5-trimethoxybenzene. The progress of the

reaction was monitored based on NMR spectroscopy.

Surprisingly, the analysis of NMR spectra of the reaction

mixture indicated that the amidoalkylation product 3g was not

formed at all. The main reaction product was another

phosphonium salt: 1-(2,4,6-trimethoxyphenyl)ethyltriphenyl-

phosphonium tetrafluoroborate 4f (see Scheme 3). Other

triphenylphosphonium salts 1 react with 1,3,5-trimethoxy-

benzene in a similar way (entries 10, 11, 13 and 14, Table 1).

Figure 1. Concentration of the substrate, and classical and non-

classical products as a function of time for the reaction of

1-(N-pivaloylamino)ethyltris(m-chlorophenyl)phosphonium

tetrafluoroborate 1f with 1,3,5-trimethoxybenzene at 26°C.

3

ACCEPTED MANUSCRIPT

To

this

end,

we

synthesized

and

tested

The concentration of the classical product 3g quickly reaches

1-(N-acylamino)alkylphosphonium salts

1

derived from its maximum and then recedes, while the concentration of the

tris(m-chlorophenyl)phosphine or tris[p-(trifluoromethyl)-

phenyl]phosphine. First, we performed the reaction of

1-(N-pivaloylamino)ethyltris(m-chlorophenyl)phosphonium

tetrafluoroborate 1f with 1,3,5-dimethoxybenzene. The

progress of the reaction was monitored by NMR spectroscopy.

As we expected, the reaction occurs in milder conditions, even

at room temperature. This time, both possible compounds 3g

non-classical product 4g at the beginning of the reaction is low

and then rapidly grows. The induction period, which is

characteristic for the formation of the final product in the

consecutive-type reaction, is very clearly visible. Furthermore,

it can be seen that the reaction rate constant k₁for the formation

of the classical product 3g is higher than the reaction rate

constant k₂for the transformation of the classical product to the

and 4g were detected in the reaction mixture. Changes in the non-classical product 4g. A favorable ratio of the rate constants

concentration of substrate 1f, classical 3g and non-classical

product 4g as a function of time were measured and these are

shown in Figure 1.

k₁/k₂seems to be crucial for the possibility of separating the

classical reaction product.

Table 1. Synthesis of 1-arylalkylphosphonium salts 4.

O

R²

25-50^oC

+ (Het)ArH

R¹

N

H

PAr¹₃BF₄

(Het)Ar

1

4

Molar ratio of

1 : (Het)ArH

Entry

1

R¹

R²

Ar¹

Ph

(Het)ArH

T, °C

150

100

25

Time, h

4

Yield, %

55

a

1a

1b

1c

1d

1e

1a

1f

t-Bu

Me

Ph

anisole

-

2

4a

4b

4c

4d

4e

4f

2

t-Bu

Bn

1,3-dimethoxybenzene

1,3,5-trimethoxybenzene

indole

1 : 2

1 : 15

1 : 2

1 : 15

1 : 5

1 : 2

3

70

3

4

83

4

BnO

t-Bu

Bn

2

75

5

Bn

2

92

6

i-Bu

Me

p-C₆H₄CF₃

10 min

32

7

Ph

80

1

85

8

Me

m-C₆H₄Cl

80

1

4g

4h

4f

66

9

1g

1b

1c

1h

1i

Me

p-C₆H₄CF₃

80

1

49

10

11

12

13

14

15

16

Me

Ph

80

1

91

BnO

t-Bu

Ph

80

1

4i

78

Bn

p-C₆H₄CF₃

25

10 min

4j

64

CH₂Ot-Bu

CH₂PhOBn

Me

Ph

80

5

2

1

2

4k

4l

91

1j

80

85

1a

80

4m

4n

87

a

Me

thiophene

-

180

40

^aArenes were used as solvent (2 cm³/0.2 mmol of 1).

A plausible mechanism, which explains described kinetic 5 generated from 1-(N-acylamino)alkylphosphonium salt 1

facts, is shown in Scheme 4. In the first step, there is a typical

reacts smoothly with activated arene (Friedel-Crafts type

electrophilic aromatic substitution S_EAr. N-Acyliminium cation

reaction). In the next step, the protonation of amide 3 occurs,

4

Tetrahedron

ACCEPTED MANUSCRIPT

which initiates its transformation to 1-arylalkylphosphonium

salt 4. Because of the electron donating character of the applied

arenes, resonance-stabilized 1-arylalkylcarbenium cation 6 can

form during this reaction. A similar mechanism for the Friedel–

Crafts reactions of activated arenes and heteroarenes with α-

amido sulfones was proposed by Petrini³⁰and a few years later

by Kadam.²⁷

According to the proposed mechanism, the reaction may be

quenched at the N-(1-arylalkyl)amides formation step by

addition of a base at the right reaction moment. This makes the

protonation of obtained N-(1-arylalkyl)amides 3 impossible and

stops further transformations. We have checked this hypothesis

(ethyldiisopropylamine) when the highest concentration of

N-(1-arylalkyl)amide 3 was observed. This protocol allowed us

to obtain

a number of N-(1-arylalkyl)amides 3 from

1-(N-acylamino)alkyltris(m-chlorophenyl)- or 1-(N-acylamino)-

alkyltris[(p-trifluoromethyl)phenyl]phosphonium salts 1f-g and

1k-n with either good or very good yields (see Table 2).

Reactions with electron-rich arenes occur in a short time (as

little as 3 minutes, entry 11, Table 2) at room temperature. Only

in the case of thiophene was it necessary to raise the

temperature to 50°C. Attempts to carry out the reaction with

less activated or deactivated arenes such as anisole, toluene or

chlorobenzene failed.

adding

to

the

reaction

mixture

Hünig’s

base

O

R²

BF₄

O

R²OMe

OMe

R¹

N

H

O

R²

R¹

N

S_EAr

OMe

R¹

N

PAr¹₃BF₄

+

MeO

H

+

HBF₄

- PAr¹

H

3

MeO

OMe

O

R²

1

3

R¹

N

H

5

R²OMe

BF₄

R²OMe

OH R²OMe

MeO

OMe

O

PAr¹

H

BF₄

OMe

3

Ar¹₃P

MeO

R¹

N

R¹

N

H

MeO

H

R²

MeO

OMe

3

4

MeO

6

Scheme 4. α-Amidoalkylation of electron-rich arenes and heteroarenes by 1-(N-acylamino)alkylphosphonium salts 1 – a plausible

mechanism.

The reactivity of phosphonium salts

1

with other conducted at 80°C and the addition of 1,3,5-trimethoxybenzene

was preserved to keep the conditions typical for the synthesis of

1-arylalkylphosphonium salts from 1-(N-acylamino)-

alkylphosphonium salts 1 described above (see Table 1). As we

expected, 1-(2,4,6-trimethoxyphenyl)ethyltriphenyl-

NH-protective groups has also been investigated. Carbamate

derivatives, such as 1-(N-benzyloxycarbonylamino)alkyltris-

[(p-trifluoromethyl)phenyl]phosphonium salts 1e and 1h, react

smoothly with 1,3-dimethoxybenzene or 1,3,5-trimethoxy-

4

benzene at room temperature, but after 10 min only the non- phosphonium tetrafluoroborate 4f was obtained as only one

classical products (salts 4e and 4j) were obtained. Reducing the reaction product with the yield of 97%.

reaction temperature to 0°C did not give the desired effects

(entry 9, Table 2). Still, 1-arylalkyltris[(p-trifluoromethyl)-

phenyl]phosphonium tetrafluoroborate 4e was the main

reaction product. In our previous study, we also described the

reaction of 1-imidoalkylphosphonium salts with arenes.³¹The

use of imide derivatives requires harsher reaction conditions,

especially high temperature and long reaction time, but gives

only classical products. The ease of non-classical product

formation can be related to the ease of protonation of classical

products, which are formed in the first step of the reaction.

Protonation of carbamates is much easier than protonation of

amides and imides.³²

The development of an effective method for the synthesis of

N-(1-arylalkyl)amides 3 allowed us to obtain further evidence,

which will verify the consecutive character of the reactions of

1-(N-acylamino)alkylphosphonium salts 1 with arenes. In the

last experiment, we studied if 1-arylalkyltriarylphosphonium

salts 4 (the non-classical product) can be obtained from

Scheme 5. Synthesis of 1-(2,4,6-trimethoxyphenyl)-

ethyltriphenylphosphonium tetrafluoroborate 4f from

N-[1-(2,4,6-trimethoxyphenyl)ethyl]pivalamid 3g.

3. Conclusion

We have developed a convenient method for carbon-

carbon bond formation based on the catalyst-free Friedel-Crafts

reaction of 1-(N-acylamino)alkyltriarylphosphonium salts with

electron-rich arenes. In combination with

a previously

described method for preparation of 1-(N-acylamino)-

alkyltriarylphosphonium salts from amino acids derivatives, the

present protocol provides easy access to a wide range of

N-(1-arylalkyl)amides or 1-arylalkylphosphonium salts. The

analysis of reaction kinetics allowed us to define the factors

N-(1-arylalkyl)amides

3 (the classical product) and the

corresponding triarylphosphonium tetrafluoroborates. The

reaction of N-[1-(2,4,6-trimethoxyphenyl)ethyl]pivalamid 3g

with triphenylphosphonium tetrafluoroborate (Scheme 5) was

5

ACCEPTED MANUSCRIPT

that affect the course of the transformation and propose a

plausible reaction mechanism.

much more reactive 1-(N-acylamino)alkylphosphonium salts 1

derived from triarylphosphines with electron-withdrawing

Reactions of 1-(N-acylamino)alkyltriphenylphosphonium substituents, reactions with arenes occur under milder

salts with arenes need to be carried out at an elevated

temperature (80-180°C). In these conditions,

1-arylalkylphosphonium salts (the non-classical reaction

course) are formed as the main reaction products. In the case of

conditions (room temperature, short reaction time). Because of

the favorable ratio of the rate constants, we are able to interrupt

the reaction at the stage of N-(1-arylalkyl)amides formation.

Table 2. Synthesis of N-(1-arylalkyl)amides 3.

Molar ratio of

1 : (Het)ArH

Time,

min

Yield,

%

Entry

1

R¹

R²

Ar¹

(Het)ArH

T, °C

25

0

3

a

1f

t-Bu

Bn

Me

Ph

m-C₆H₄Cl

p-C₆H₄CF₃

m-C₆H₄Cl

p-C₆H₄CF₃

m-C₆H₄Cl

p-C₆H₄CF₃

m-C₆H₄Cl

p-C₆H₄CF₃

m-C₆H₄Cl

p-C₆H₄CF₃

anisole

-

120

40

25

5

3a

3b

3c

3d

3e

3f

0

a

2

1g

1f

anisole

-

0

3

1,3-dimethoxybenzene

1,3,5-trimethoxybenzene

indole

1 : 15

67

84

72

76

77

0

4

1g

1k

1l

5

6

i-Pr

i-Bu

Me

Ph

10

5

7

1m

1e

1f

Bn

8

BnO

t-Bu

Bn

9

3f

traces

83

77

73

80

82

76

0

10

11

12

13

14

15

16

17

18

19

20

25

50

3g

3h

3i

1g

1k

1n

1l

3

5

Me

i-Pr

i-Bu

Bn

20

10

5

Bn

3j

1m

1h

1g

1f

Bn

3k

3l

BnO

t-Bu

Bn

10

30

45

30

Me

i-Pr

3m

3n

3o

68

51

32

53

a

thiophene

-

a

thiophene

-

a

1l

thiophene

-

^aArenes were used as solvent (2 cm³/0.2 mmol of 1).

6

Tetrahedron

ACCEPTED MANUSCRIPT

The type of NH-protective group is of great importance

To a solution of 1-(N-acylamino)alkyltriarylphosphonium salt

for the course of the considered transformations. The use of

phosphonium salts with a carbamate NH-protective group makes

the obtaining of 1-arylalkylphosphonium salts easier. In turn, an

imide NH-protective group favors the classical course of the

reaction and the formation of N-(1-arylalkyl)imides. This is

related to the ease of the protonation of the aforementioned

NH-protective group — a crucial step for the subsequent reaction

yielding 1-arylalkylphosphonium salts.

1 (0.2 mmol) in DCM (2 cm³), an aromatic compound (3.0

mmol) was added. The reaction mixture was stirred at room

temperature for the time given in Table 2. Then, (i-Pr)₂EtN (34.2

µl, 25.8 mg, 0.2 mmol) was added and stirring was continued for

15 min. The solvent was evaporated under reduced pressure and

the product was extracted from the residue with toluene (50°C, 3

× 3 cm³). Next, the toluene was evaporated and the pure

N-(1-arylalkyl)amide 3 was isolated by column chromatography

[toluene/ethyl acetate; 2:1, v/v].

4. Experimental section

4.1. General

4.3.1. N-[1-(2,4-dimethoxyphenyl)ethyl]pivalamid (3b). White

1

crystals (22.3 mg, 84% yield), mp 126.5-128.0^oC. H NMR (400

MHz, CDCl₃) δ 7.10 (d, J = 8.3 Hz, 1H), 6.63 (d, J = 6.8 Hz,

1H), 6.48 (d, J = 2.2 Hz, 1H), 6.43 (dd, J₁= 8.3 Hz, J₂= 2.3 Hz,

1H), 5.13 (dq, J₁= 14.2 Hz, J₂= 7.0 Hz, 1H), 3.86 (s, 3H), 3.79

(s, 3H), 1.40 (d, J = 6.9 Hz, 3H), 1.17 (s, 9H) ppm; ¹³C NMR

(100 MHz, CDCl₃) δ 177.0, 160.0, 158.1, 128.7, 123.8, 104.1,

99.4, 55.4, 55.3, 47.2, 38.6, 27.5, 21.7 ppm; IR (ATR) 3388

(ν_N-H), 2961 (ν_C-H), 1640 (ν_C=O), 1522 (ν_C=C), 1506 (δ_N-H), 1206

(ν_C-O-CAr) cm^-1; HRMS (ESI-TOF) calcd for C₁₅H₂₃NO₃Na [M +

Na]⁺288.1576 found 288.1580.

Melting points were determined in capillaries and were

uncorrected. IR-spectra were measured on an FT-IR

spectrophotometer (ATR method). H, ¹³C NMR were recorded

1

at operating frequencies of 400 and 100 MHz, respectively, using

TMS as the resonance shift standard. ³¹P NMR spectra were

recorded at operating frequencies of 161.9 MHz without the

resonance shift standard, with respect to H₃PO₄as zero ppm. All

chemical shifts (δ) are reported in ppm and coupling constants (J)

in Hz. High resolution mass spectrometry (HR-MS) analyses

were performed on a Waters Xevo G2 Q-TOF mass spectrometer

equipped with an ESI source operating in positive ion mode. The

accurate mass and composition of the molecular ion adducts was

calculated using the MassLynx software incorporated within the

instrument.

4.3.2. N-[1-(2,4-dimethoxyphenyl)phenylmethyl]pivalamid (3c).

White crystals (23.5 mg, 72% yield), mp 139.5-141.0^oC. ¹H

NMR (400 MHz, CDCl₃) δ 7.26-7.15 (m, 6H), 6.97 (d, J = 8.5

Hz, 1H), 6.49 (s, 1H), 6.47 (dd, J₁= 9.4 Hz, J₂= 3.7 Hz, 1H),

6.29 (d, J = 8.6 Hz, 1H), 3.80 (s, 3H), 3.73 (s, 3H), 1.23 (s, 9H)

ppm; ¹³C NMR (100 MHz, CDCl₃) δ 177.2, 160.4, 158.3, 142.4,

130.2, 128.2, 126.6, 126.5, 121.8, 104.3, 99.6, 55.4, 55.4, 53.8,

38.7, 27.6 ppm; IR (ATR) 3310 (ν_N-H), 2970 (ν_C-H), 1637 (ν_C=O),

1520 (ν_C=C), 1506 (δ_N-H), 1207 (ν_C-O-CAr) cm^-1; HRMS (ESI-TOF)

calcd for C₂₀H₂₅NO₃Na [M + Na]⁺350.1732 found 350.1736.

4.2. Substrate synthesis

The synthesis of 1-(N-acylamino)alkyltriarylphosphonium salts 1

was carried out according to a previously described two-steps

procedure:⁹

4.3.3.

N-[1-(2,4-dimethoxyphenyl)-2-methylpropyl]phenyl-

acetamid (3d). White crystals (24.9 mg, 76% yield), mp 99.0-

Electrochemical decarboxylative α-methoxylation of N-acyl-α-

amino acids

1

100.5^oC. H NMR (400 MHz, CDCl₃) δ 7.36-7.23 (m, 5H), 6.97

(d, J = 8.1 Hz, 1H), 6.54 (d, J = 9.6 Hz, 1H), 6.37 (dd, J₁= 8.2

Hz, J₂= 2.4 Hz, 1H), 6.34 (d, J = 2.3 Hz, 1H), 4.65 (t, J = 9.5 Hz,

1H), 3.76 (s, 3H), 3.62 (d, J = 16.3 Hz, 1H), 3.53 (d, J = 16.3 Hz,

1H), 3.47 (s, 3H), 1.93-1.89 (m, 1H), 0.87 (d, J = 6.7 Hz, 3H),

0.66 (d, J = 6.8 Hz, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ

169.7, 159.8, 157.8, 135.2, 130.6, 129.7, 128.8, 127.1, 121.3,

103.6, 98.9, 58.5, 55.2, 54.7, 44.0, 32.5, 20.1, 19.5 ppm; IR

(ATR) 3254 (ν_N-H), 2955 (ν_C-H), 1632 (ν_C=O), 1552 (δ_N-H), 1508

(ν_C=C), 1205 (ν_C-O-CAr) cm^-1; HRMS (ESI-TOF) calcd for

C₂₀H₂₅NO₃Na [M + Na]⁺350.1732 found 350.1733.

The electrolysis was conducted in an undivided glass

electrolyzer (85 cm³) equipped with a thermostatic jacket, a

magnetic stirrer, a concentrically arranged, cylindrical Pt mesh

anode (47 cm²) and cathode (44 cm²). To the thus prepared

electrolyzer, N-acyl-α-amino acid (3.0 mmol), SiO₂-Pip (200 mg,

0.22 mmol) and methanol (30 cm³) were added. The

electrochemical decarboxylative α-methoxylation was executed

while stirring, at a constant current of 0.15 A, at 10°C until a

3.75 F/mol charge had passed. Then, SiO₂-Pip was filtered off,

and the methanol was evaporated under reduced pressure to

obtain N-(1-methoxyalkyl)amide, which was used in the next

reaction without further purification.

4.3.4. N-[1-(2,4-dimethoxyphenyl)-3-methylbutyl]phenylacetamid

(3e). White crystals (27.5 mg, 77% yield), mp 131.0-132.0^oC. ¹H

NMR (400 MHz, CDCl₃) δ 7.35-7.21 (m, 5H), 7.02 (d, J = 7.9

Hz, 1H), 6.38-6.36 (m, 3H), 5.06 (dt, J₁= 9.3 Hz, J₂= 7.7 Hz,

1H), 3.76 (s, 3H), 3.58 (d, J = 16.2 Hz, 1H), 3.52 (s, 3H), 3.52 (d,

J = 16.0 Hz, 1H), 1.52-1.48 (m, 2H), 1.38-1.31 (m, 1H), 0.88 (d,

J = 6.6 Hz, 3H), 0.85 (d, J = 6.6 Hz, 3H) ppm; ¹³C NMR (100

MHz, CDCl₃) δ 169.5, 159.9, 158.1, 135.2, 129.7, 129.5, 128.8,

127.1, 122.4, 103.7, 99.1, 55.3, 54.9, 50.5, 44.5, 44.0, 25.2, 22.7,

22.5 ppm; IR (ATR) 3312 (ν_N-H), 2956 (ν_C-H), 1636 (ν_C=O), 1538

(δ_N-H), 1505 (ν_C=C), 1154 (ν_C-O-CAr) cm^-1; HRMS (ESI-TOF) calcd

for C₂₁H₂₇NO₃Na [M + Na]⁺364.1889 found 364.1887.

Transformation of N-(1-methoxyalkyl)amides to 1-(N-acyl-

amino)alkyltriarylphosphonium salts 1

To a solution of triarylphosphine (1 mmol) in DCM (2 cm³), a

tetrafluoroboric acid diethyl ether complex (HBF₄·Et₂O, 136 µl,

161.9 mg, 1 mmol) was added at 0°C. The reaction mixture was

stirred for

2

h

at room temperature. Thereafter,

N-(1-methoxyalkyl)amide (1 mmol) was added and stirring was

continued for 15 min. Evaporation of the solvent yielded the

crude 1-(N-acylamino)alkyltriarylphosphonium salt 1, which was

used in the next reaction without further purification.

4.3.5. N-[1-(2,4,6-trimethoxyphenyl)ethyl]pivalamid (3g). White

1

crystals (24.5 mg, 83% yield), mp 108.0-109.0^oC. H NMR (400

4.3. Reactions of 1-(N-acylamino)alkyltriarylphosphonium

MHz, CDCl₃) δ 7.23 (d, J = 8.6 Hz, 1H), 6.14 (s, 2H), 5.70 (dq,

J₁= 9.3 Hz, J₂= 6.9 Hz, 1H), 3.84 (s, 6H), 3.80 (s, 3H), 1.31 (d,

J = 6.9 Hz, 3H), 1.16 (s, 9H) ppm; ¹³C NMR (100 MHz, CDCl₃)

δ 176.7, 160.0, 158.3, 112.1, 91.1, 55.8, 55.3, 40.3, 38.6, 27.5,

21.1 ppm; IR (ATR) 3459 (ν_N-H), 2971 (ν_C-H), 1648 (ν_C=O), 1593

salts 1 with electron-rich arenes:

Transformation of 1-(N-acylamino)alkyltriarylphosphonium salts

1 to N-(1-arylalkyl)amides 3

7

(ν_C=C), 1498 (δ_N-H), 1127 (ν_C-O-CAr) cm^-1; HRMS (ESI-TOF) calcd

3342 (ν_N-H), 2964 (ν_C-H), 1637 (ν_C=O), 1514 (δ_N-H) cm^-1; HRMS

ACCEPTED MANUSCRIPT

for C₁₆H₂₅NO₄Na [M + Na]⁺318.1681 found 318.1681.

(ESI-TOF) calcd for C₁₁H₁₇NOSNa [M + Na]⁺234.0929 found

234.0931.

4.3.6.

N-[1-(2,4,6-trimethoxyphenyl)phenylmethyl]pivalamid

(3h). White crystals (26.1 mg, 73% yield), mp 128.0-129.0^oC. ¹H

NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 9.5 Hz, 1H), 7.20-7.17

(m, 5H), 6.89 (d, J = 9.5 Hz, 1H), 6.17 (s, 2H), 3.82 (s, 3H), 3.79

(s, 6H), 1.23 (s, 9H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ 177.0,

160.6, 158.7, 143.1, 128.0, 126.2, 126.2, 110.4, 91.3, 55.9, 55.3,

46.8, 38.8, 27.6 ppm; IR (ATR) 3453 (ν_N-H), 2959 (ν_C-H), 1652

(ν_C=O), 1594 (ν_C=C), 1507 (δ_N-H), 1120 (ν_C-O-CAr) cm^-1; HRMS

(ESI-TOF) calcd for C₂₁H₂₇NO₄Na [M + Na]⁺380.1838 found

380.1839.

4.3.12. N-[1-(2-thienyl)-2-methylpropyl]phenylacetamid (3o).

1

White crystals (14.5 mg, 53% yield), mp 85.0-87.0^oC. H NMR

(400 MHz, CDCl₃) δ 7.40-7.22 (m, 5H), 7.14 (dd, J₁= 5.1 Hz, J₂

= 1.1 Hz, 1H), 6.90 (dd, J₁= 5.1 Hz, J₂= 3.5 Hz, 1H), 6.80-6.76

(m, 1H), 5.70 (d, J = 8.8 Hz, 1H), 5.11 (dd, J₁= 9.2 Hz, J₂= 6.7

Hz, 1H), 3.63 (d, J = 16.0 Hz, 1H), 3.57 (d, J = 16.0 Hz, 1H),

2.06-1.93 (m, 1H), 0.85 (d, J = 6.7 Hz, 3H), 0.78 (d, J = 6.8 Hz,

3H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ 170.1, 145.2, 134.8,

129.4, 129.0, 127.4, 126.6, 124.3, 123.7, 54.4, 43.8, 34.0, 19.5,

17.8 ppm; IR (ATR) 3253 (ν_N-H), 2958 (ν_C-H), 1639 (ν_C=O), 1541

(δ_N-H) cm^-1; HRMS (ESI-TOF) calcd for C₁₆H₁₉NOSNa [M +

Na]⁺296.1085 found 296.1084.

4.3.7. N-[1-(2,4,6-trimethoxyphenyl)ethyl]phenylacetamid (3i).

White crystals (26.3 mg, 80% yield), mp 117.5-119.0^oC. ¹H

NMR (400 MHz, CDCl₃) δ 7.35-7.24 (m, 5H), 6.91 (d, J = 9.3

Hz, 1H), 6.04 (s, 2H), 5.72 (dq, J₁= 9.5 Hz, J₂= 6.9 Hz, 1H),

3.76 (s, 3H), 3.60 (d, J = 16.4 Hz, 1H), 3.60 (s, 6H), 3.53 (d, J =

16.4 Hz, 1H), 1.24 (d, J = 6.9 Hz, 3H) ppm; ¹³C NMR (100 MHz,

CDCl₃) δ 169.4, 160.0, 158.1, 135.3, 129.8, 128.7, 127.0, 111.2,

90.7, 55.4, 55.2, 44.1, 40.4, 21.0 ppm; IR (ATR) 3355 (ν_N-H),

Transformation of 1-(N-acylamino)alkyltriarylphosphonium salts

1 to 1-arylalkylphosphonium salts 4

To a solution of 1-(N-acylamino)alkyltriarylphosphonium salt

1 (0.25 mmol) in DCM (2 cm³), an aromatic compound (0.5

mmol) was added. The solvent was evaporated under reduced

pressure and the residue was heated under the conditions

(temperature, time) given in Table 1. The crude product was

washed with toluene (50°C, 3 × 1 cm³) and recrystallized using

CH₂Cl₂/Et₂O (1:2, v/v) or CH₃CN/Et₂O (1:2, v/v) yielding, in

most cases, 1-arylalkylphosphonium salts 4 as colorless crystals.

2931 (ν_C-H), 1647 (ν_C=O), 1585 (ν_C=C), 1534 (δ_N-H), 1137 (ν_C-O-CAr

)

cm^-1; HRMS (ESI-TOF) calcd for C₁₉H₂₃NO₄Na [M + Na]⁺

352.1525 found 352.1525.

4.3.8.

N-[1-(2,4,6-trimethoxyphenyl)-2-methylpropyl]phenyl-

acetamid (3j). White crystals (29.3 mg, 82% yield), mp 100.0-

1

101.0^oC. H NMR (400 MHz, CDCl₃) δ 7.37-7.22 (m, 5H), 6.75

4.3.13.

1-(4-methoxyphenyl)ethyltriphenylphosphonium

1

(d, J = 10.1 Hz, 1H), 6.04 (s, 2H), 5.33 (t, J = 9.9 Hz, 1H), 3.77

(s, 3H), 3.63 (d, J = 16.4 Hz, 1H), 3.58 (br s, 6H), 3.52 (d, J =

16.4 Hz, 1H), 1.94-1.78 (m, 1H), 0.89 (d, J = 6.7 Hz, 3H), 0.67

(d, J = 6.8 Hz, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ 169.6,

159.9, 158.5, 135.4, 129.8, 128.7, 126.9, 110.1, 90.7, 55.3, 55.2,

50.2, 44.1, 33.0, 19.6, 19.5 ppm; IR (ATR) 3413 (ν_N-H), 2953

(ν_C-H), 1659 (ν_C=O), 1587 (ν_C=C), 1515 (δ_N-H), 1137 (ν_C-O-CAr) cm^-1;

HRMS (ESI-TOF) calcd for C₂₁H₂₇NO₄Na [M + Na]⁺380.1838

found 380.1837.

tetrafluoroborate (4a). Resin (21.9 mg, 55% yield). H NMR

(400 MHz, CDCl₃) δ 7.81-7.76 (m, 3H), 7.68-7.57 (m, 12H),

6.90-6.84 (m, 2H), 6.74-6.70 (m, 2H), 5.25 (dq, J₁= 14.4 Hz, J₂

= 7.3 Hz, 1H), 3.76 (s, 3H), 1.80 (dd, J₁= 18.9 Hz, J₂= 7.3 Hz,

3H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ 160.0 (d, J = 3.0 Hz),

135.0 (d, J = 3.0 Hz), 134.4 (d, J = 9.0 Hz), 131.3 (d, J = 5.8 Hz),

130.2 (d, J = 12.1 Hz), 124.4 (d, J = 5.6 Hz), 117.4 (d, J = 82.3

Hz), 114.4 (d, J = 2.4 Hz), 55.3, 35.2 (d, J = 43.5 Hz), 17.2 (d, J

= 0.7 Hz) ppm; ³¹P NMR (161.9 MHz, CDCl₃) δ 25.9 ppm; IR

(ATR) 2935 (ν_C-H), 1609 (ν_C=C), 1513 (ν_C=C), 1254 (ν_C-O-CAr), 1051

(ν_C-P) cm^-1; HRMS (ESI-TOF) calcd for C₂₇H₂₆OP [M⁺] 397.1721

found 397.1732. The major p-isomer was isolated by column

chromatography (DCM : acetonitrile; 3:1, v/v). An o-isomer is

also formed during the reaction. Molar ratio of para to ortho

isomer is 3.4:1. Attempts to isolate o-isomer by column

chromatography (DCM : acetonitrile; 3:1, v/v) or crystallization

failed.

4.3.9.

N-[1-(2,4,6-trimethoxyphenyl)-3-methylbutyl]phenyl-

acetamid (3k). White crystals (28.3 mg, 76% yield), mp 79.5-

1

81.0^oC. H NMR (400 MHz, CDCl₃) δ 7.35-7.21 (m, 5H), 6.67

(d, J = 9.8 Hz, 1H), 6.04 (s, 2H), 5.70 (dt, J₁= 9.8 Hz, J₂= 7.4

Hz, 1H), 3.77 (s, 3H), 3.59 (br s, 6H), 3.58 (d, J = 16.3 Hz, 1H),

3.51 (d, J = 16.3 Hz, 1H), 1.54-1.46 (m, 1H), 1.43-1.30 (m, 2H),

0.90 (d, J = 6.4 Hz, 3H), 0.85 (d, J = 6.3 Hz, 3H) ppm; ¹³C NMR

(100 MHz, CDCl₃) δ 169.3, 160.0, 158.4, 135.5, 129.8, 128.7,

126.9, 111.0, 90.8, 55.5, 55.2, 44.6, 44.1, 42.9, 25.4, 22.8, 22.8

ppm; IR (ATR) 3402 (ν_N-H), 2950 (ν_C-H), 1661 (ν_C=O), 1589 (ν_C=C),

1497 (δ_N-H), 1136 (ν_C-O-CAr) cm^-1; HRMS (ESI-TOF) calcd for

C₂₂H₂₉NO₄Na [M + Na]⁺394.1994 found 394.1996.

4.3.14.

1-(2,4-dimethoxyphenyl)ethyltriphenylphosphonium

tetrafluoroborate (4b). White crystals (35.5 mg, 83% yield), mp

151.0-153.0^oC. ¹H NMR (400 MHz, CDCl₃) δ 7.87-7.79 (m, 3H),

7.72-7.64 (m, 6H), 7.53-7.44 (m, 6H), 6.61 (dd, J₁= 8.5 Hz, J₂=

2.4 Hz, 1H), 6.40-6.34 (m, 2H), 5.21 (dq, J₁= 14.8 Hz, J₂= 7.4

Hz, 1H), 3.81 (s, 3H), 3.41 (s, 3H), 1.82 (dd, J₁= 18.5 Hz, J₂=

7.4 Hz, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ 161.8 (d, J =

3.0 Hz), 158.1 (d, J = 5.6 Hz), 135.2 (d, J = 3.0 Hz), 134.2 (d, J =

8.9 Hz), 130.2 (d, J = 12.1 Hz), 130.1 (d, J = 5.0 Hz), 117.3 (d, J

= 82.4 Hz), 112.6 (d, J = 5.4 Hz), 105.5 (d, J = 2.6 Hz), 98.6 (d, J

= 2.5 Hz), 55.6, 55.2, 29.7 (d, J = 45.7 Hz), 16.5 ppm; ³¹P NMR

(161.9 MHz, CDCl₃) δ 24.2 ppm; IR (ATR) 3193 (ν_CAr-H), 2961

(ν_C-H), 1650 (ν_C=C), 1613 (ν_C=C), 1214 (ν_C-O-CAr), 1026 (ν_C-P) cm^-1;

HRMS (ESI-TOF) calcd for C₂₈H₂₈O₂P [M⁺] 427.1827 found

427.1830.

4.3.10. N-[1-(1H-indol-3-yl)ethyl]pivalamid (3m). White crystals

1

(16.6 mg, 68% yield), mp 170.0-172.0^oC. H NMR (400 MHz,

CDCl₃) δ 8.31 (s, 1H), 7.61 (d, J = 7.9 Hz, 1H), 7.38 (dt, J₁= 8.2

Hz, J₂= 0.8 Hz, 1H), 7.23-7.19 (m, 1H), 7.13-7.09 (m, 2H), 5.81

(d, J = 7.1 Hz, 1H), 5.49-5.42 (m, 1H), 1.62 (d, J = 6.7 Hz, 3H),

1.19 (s, 9H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ 177.5, 136.7,

126.1, 122.4, 121.2, 119.8, 119.4, 118.4, 111.3, 41.9, 38.7, 27.6,

20.4 ppm; IR (ATR) 3270 (ν_N-H), 2971 (ν_C-H), 1614 (ν_C=O), 1533

(δ_N-H) cm^-1; HRMS (ESI-TOF) calcd for C₁₅H₂₀N₂ONa [M + Na]⁺

267.1473 found 267.1476.

4.3.11. N-[1-(2-thienyl)ethyl]pivalamid (3n). Orange crystals

1

(10.8 mg, 51% yield), mp 60.0-62.0^oC. H NMR (400 MHz,

4.3.15.

1-(2,4-dimethoxyphenyl)phenylmethyltriphenyl-

CDCl₃) δ 7.20-7.19 (m, 1H), 6.96-6.94 (m, 2H), 5.85 (d, J = 4.1

Hz, 1H), 5.39 (dq, J₁= 13.8 Hz, J₂= 6.8 Hz, 1H), 1.57 (d, J = 6.8

Hz, 3H), 1.21 (s, 9H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ 177.2,

147.6, 126.8, 124.2, 123.6, 44.4, 38.6, 27.4, 22.0 ppm; IR (ATR)

phosphonium tetrafluoroborate (4c). White crystals (36.8 mg,

1

75% yield), mp 199.5-200.5^oC. H NMR (400 MHz, CDCl₃) δ

7.89-7.76 (m, 3H), 7.67-7.59 (m, 6H), 7.50-7.41 (m, 6H), 7.33-

7.26 (m, 1H), 7.26-7.20 (m, 2H), 7.14-7.08 (m, 2H), 7.00-6.96

8

Tetrahedron

ACCEPTED MANUSCRIPT

(m, 1H), 6.52 (d, J = 18.2 Hz, 1H), 6.45-6.43 (m, 2H), 3.80 (s,

= 2.9 Hz), 159.2, 136.3 (d, J = 15.8 Hz), 135.5 (d, J = 2.9 Hz),

3H), 3.62 (s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ 161.8 (d, J

= 2.2 Hz), 157.7 (d, J = 6.7 Hz), 135.1 (d, J = 3.0 Hz), 134.5 (d, J

= 9.0 Hz), 132.5 (d, J = 3.1 Hz), 131.6 (d, J = 6.2 Hz), 130.4 (d, J

= 6.2 Hz), 130.1 (d, J = 12.2 Hz), 129.2 (d, J = 1.9 Hz), 129.0 (d,

J = 2.7 Hz), 118.4 (d, J = 82.2 Hz), 112.8 (d, J = 3.5 Hz), 105.5

(d, J = 1.5 Hz), 99.1 (d, J = 1.5 Hz), 55.6, 55.5, 41.9 (d, J = 45.6

Hz) ppm; ³¹P NMR (161.9 MHz, CDCl₃) δ 22.0 ppm; IR (ATR)

3059 (ν_CAr-H), 1611 (ν_C=C), 1583 (ν_C=C), 1504 (ν_C=C), 1438 (ν_C=C),

1214 (ν_C-O-CAr), 1036 (ν_C-P) cm^-1; HRMS (ESI-TOF) calcd for

C₃₃H₃₀O₂P [M⁺] 489.1983 found 489.1985.

132.9 (d, J = 10.1 Hz), 132.7 (d, J = 8.8 Hz), 132.2 (d, J = 13.3

Hz), 119.8 (d, J = 81.3 Hz), 99.9 (d, J = 5.4 Hz), 91.1, 55.7, 55.4,

29.7 (d, J = 43.7 Hz), 14.5 ppm; ³¹P NMR (161.9 MHz, CDCl₃) δ

22.8 ppm; IR (ATR) 3088 (ν_CAr-H), 2947 (ν_C-H), 1589 (ν_C=C), 1467

(ν_C=C), 1127 (ν_C-O-CAr), 1051 (ν_C-P) cm^-1; HRMS (ESI-TOF) calcd

for C₂₉H₂₇Cl₃O₃P [M⁺] 559.0763 found 559.0765.

4.3.20. 1-(2,4,6-trimethoxyphenyl)ethyltris[(4-trifluoromethyl)-

phenyl]phosphonium tetrafluoroborate (4h).³¹White crystals

(32.4 mg, 49% yield), mp 166.5-168.0^oC. H NMR (400 MHz,

1

CDCl₃) δ 7.96-7.92 (m, 6H), 7.76-7.70 (m, 6H), 6.00 (s, 2H),

5.60-5.40 (m, 1H), 3.82 (s, 3H), 3.35 (br s, 6H), 1.94 (dd, J₁=

14.4 Hz, J₂= 8.1 Hz, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ

162.9 (d, J = 3.1 Hz), 159.3, 136.8 (qd, J₁= 33.6 Hz, J₂= 3.0

Hz), 135.0 (d, J = 10.0 Hz), 127.0 (dq, J₁= 12.3 Hz, J₂= 3.8 Hz),

122.8 (q, J = 274.8 Hz), 122.1 (d, J = 81.6 Hz), 99.8 (d, J = 5.3

Hz), 91.0 (d, J = 2.3 Hz), 55.6, 55.2, 29.4 (d, J = 43.6 Hz), 14.4

ppm; ³¹P NMR (161.9 MHz, CDCl₃) δ 23.3 ppm; IR (ATR) 2944

(ν_C-H), 1608 (ν_C=C), 1591 (ν_C=C), 1321 (ν_C-F), 1127 (ν_C-O-CAr), 1062

(ν_C-P) cm^-1; HRMS (ESI-TOF) calcd for C₃₂H₂₇F₉O₃P [M⁺]

661.1554 found 661.1555.

4.3.16.

1-(2,4-dimethoxyphenyl)-2-phenylethyltriphenyl-

phosphonium tetrafluoroborate (4d). White crystals (46.4 mg,

92% yield), mp 174.0-176.0^oC. ¹H NMR (400 MHz,

CDCl₃/CD₃CN) δ 7.96-7.88 (m, 3H), 7.79-7.70 (m, 6H), 7.59-

7.48 (m, 6H), 7.20-7.13 (m, 3H), 6.92 (dd, J₁= 6.9 Hz, J₂= 2.1

Hz, 2H), 6.66 (dd, J₁= 8.6 Hz, J₂= 2.1 Hz, 1H), 6.39 (dd, J₁=

8.5 Hz, J₂= 2.1 Hz, 1H), 6.30 (d, J = 1.7 Hz, 1H), 5.25-5.18 (m,

1H), 3.79 (s, 3H), 3.56-3.39 (m, 2H), 3.25 (s, 3H) ppm; ¹³C NMR

(100 MHz, CDCl₃/CD₃CN) δ 161.1 (d, J = 3.0 Hz), 158.1 (d, J =

5.8 Hz), 135.5, 135.4, 134.8 (d, J = 3.0 Hz), 133.4 (d, J = 9.1

Hz), 129.7 (d, J = 12.1 Hz), 127.9, 127.6, 126.6, 116.5 (d, J =

82.6 Hz), 109.3 (d, J = 5.0 Hz), 105.1 (d, J = 2.4 Hz), 98.2 (d, J =

2.2 Hz), 54.7, 54.7, 36.0 (d, J = 44.2 Hz), 35.4 ppm; ³¹P NMR

(161.9 MHz, CDCl₃/CD₃CN) δ 23.1 ppm; IR (ATR) 2942 (ν_C-H),

1606 (ν_C=C), 1586 (ν_C=C), 1507 (ν_C=C), 1438 (ν_C=C), 1210 (ν_C-O-CAr),

1051 (ν_C-P) cm^-1; HRMS (ESI-TOF) calcd for C₃₄H₃₂O₂P [M⁺]

503.2140 found 503.2142.

4.3.21.

1-(2,4,6-trimethoxyphenyl)phenylmethyltriphenyl-

phosphonium tetrafluoroborate (4i). White crystals (40.6 mg,

1

78% yield), mp 224.0-225.5^oC. H NMR (400 MHz, CDCl₃) δ

7.81-7.73 (m, 3H), 7.63-7.56 (m, 6H), 7.39-7.31 (m, 6H), 7.30-

7.26 (m, 1H), 7.23-7.15 (m, 2H), 7.04-6.97 (m, 2H), 6.60 (d, J =

19.0 Hz, 1H), 6.14 (s, 2H), 3.85 (s, 3H), 3.50 (s, 6H) ppm; ¹³C

NMR (100 MHz, CDCl₃) δ 162.8 (d, J = 1.6 Hz), 158.5 (d, J =

5.8 Hz), 134.7 (d, J = 3.0 Hz), 134.1 (d, J = 8.8 Hz), 132.0 (d, J =

3.1 Hz), 130.0 (d, J = 5.1 Hz), 129.9 (d, J = 12.1 Hz), 128.9 (d, J

= 2.5 Hz), 128.8 (d, J = 3.1 Hz), 120.0 (d, J = 83.0 Hz), 101.7 (d,

J = 3.9 Hz), 91.2, 55.8, 55.5, 41.3 (d, J = 47.1 Hz) ppm; ³¹P

NMR (161.9 MHz, CDCl₃) δ 24.1 ppm; IR (ATR) 2904 (ν_C-H),

4.3.17. 1-(2,4-dimethoxyphenyl)-3-methylbutyltris[(4-trifluoro-

methyl)phenyl]phosphonium tetrafluoroborate (4e). White

crystals (21.6 mg, 32% yield), decomposition - 180.0^oC. ¹H NMR

(400 MHz, CD₃CN) δ 8.08-7.91 (m, 6H), 7.78-7.65 (m, 6H), 6.71

(dd, J₁= 8.5 Hz, J₂= 2.3 Hz, 1H), 6.50-6.42 (m, 2H), 5.25-5.17

(m, 1H), 3.80 (s, 3H), 3.40 (s, 3H), 2.37-2.24 (m, 1H), 1.97-1.94

(m,1H), 1.48-1.35 (m, 1H), 0.95 (d, J = 6.6 Hz, 3H), 0.83 (d, J =

6.7 Hz, 3H) ppm; ¹³C NMR (100 MHz, CD₃CN) δ 162.3 (d, J =

3.3 Hz), 158.9 (d, J = 6.1 Hz), 135.9 (qd, J₁= 33.3 Hz, J₂= 3.2

Hz), 135.7 (d, J = 9.8 Hz), 130.7-130.5 (m), 126.9 (dq, J₁= 12.4

Hz, J₂= 3.7 Hz), 123.3 (qd, J₁= 271.2 Hz, J₂= 1.2 Hz), 121.3 (d,

J₁= 82.2 Hz), 109.3 (d, J = 5.7 Hz), 106.2 (d, J = 2.7 Hz), 98.7

(d, J = 2.7 Hz), 55.3, 55.0, 37.4, 33.9 (d, J = 46.3 Hz), 26.1 (d, J

= 14.1 Hz), 22.3, 19.8 ppm; ³¹P NMR (161.9 MHz, CD₃CN) δ

23.9 ppm; IR (ATR) 2961 (ν_C-H), 1610 (ν_C=C), 1508 (ν_C=C), 1319

(ν_C-F), 1127 (ν_C-O-CAr), 1061 (ν_C-P) cm^-1; HRMS (ESI-TOF) calcd

for C₃₄H₃₁O₂F₉P [M⁺] 637.1918 found 637.1915.

1608 (ν_C=C), 1590 (ν_C=C), 1439 (ν_C=C), 1149 (ν_C-O-CAr), 1049 (ν_C-P

)

cm^-1; HRMS (ESI-TOF) calcd for C₃₄H₃₂O₃P [M⁺] 519.2089

found 519.2090.

4.3.22. 2-phenyl-1-(2,4,6-trimethoxyphenyl)ethyltris[(4-trifluoro-

methyl)phenyl]phosphonium tetrafluoroborate (4j). White

1

crystals (47.2 mg, 64% yield), mp 192.5-194.5^oC. H NMR (400

MHz, CD₃CN) δ 8.01-7.98 (m, 6H), 7.79-7.74 (m, 6H), 7.20-7.13

(m, 3H), 7.08-7.04 (m, 2H), 6.08 (d, J = 1.9 Hz, 1H), 5.91 (s,

1H), 5.53 (ddd, J₁= 17.0 Hz, J₂= 12.2, J₃= 3.5 Hz, 1H), 3.95

(ddd, J₁= 12.8 Hz, J₂= 12.7, J₃= 5.9 Hz, 1H), 3.75 (s, 3H), 3.46-

3.40 (m, 1H), 3.26 (s, 3H), 3.22 (s, 3H) ppm; ¹³C NMR (100

MHz, CD₃CN) δ 164.1 (d, J = 2.8 Hz), 160.9 (d, J = 3.8 Hz),

160.5 (d, J = 6.6 Hz), 138.3, 138.1, 136.7 (qd, J₁= 33.1 Hz, J₂=

3.2 Hz), 136.6 (d, J = 9.9 Hz), 135.1, 129.7, 129.4, 128.1, 127.8

(dq, J₁= 12.6 Hz, J₂= 3.8 Hz), 124.3 (q, J = 272.6 Hz), 123.2 (d,

J = 81.4 Hz), 98.5 (d, J = 5.2 Hz), 92.4 (d, J = 2.5 Hz), 91.8 (d, J

= 1.6 Hz), 56.7, 56.4, 55.5, 37.2 (d, J = 40.8 Hz), 33.9 ppm; ³¹P

NMR (161.9 MHz, CD₃CN) δ 22.3 ppm; IR (ATR) 3108 (ν_CAr-H),

1603 (ν_C=C), 1320 (ν_C-F), 1112 (ν_C-O-CAr), 1061 (ν_C-P) cm^-1; HRMS

(ESI-TOF) calcd for C₃₈H₃₁O₃F₉P [M⁺] 737.1867 found

737.1866.

4.3.18.

1-(2,4,6-trimethoxyphenyl)ethyltriphenylphosphonium

tetrafluoroborate (4f). White crystals (41.7 mg, 91% yield), mp

205.0-207.0^oC. ¹H NMR (400 MHz, CDCl₃) δ 7.88-7.77 (m, 3H),

7.71-7.62 (m, 6H), 7.48-7.37 (m, 6H), 6.03 (s, 2H), 5.25 (dq, J₁=

14.7 Hz, J₂= 7.3 Hz, 1H), 3.84 (s, 3H), 3.31 (br s, 6H), 1.91 (dd,

J₁= 18.2 Hz, J₂= 7.3 Hz, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃)

δ 162.5 (d, J = 2.8 Hz), 159.4, 134.8 (d, J = 3.0 Hz), 134.0 (d, J =

8.9 Hz), 130.0 (d, J = 12.0 Hz), 118.6 (d, J = 82.4 Hz), 101.0 (d,

J = 5.2 Hz), 90.9 (d, J = 2.2 Hz), 55.7, 55.3, 29.5 (d, J = 46.7

Hz), 14.4 ppm; ³¹P NMR (161.9 MHz, CDCl₃) δ 22.5 ppm; IR

(ATR) 3067 (ν_CAr-H), 2944 (ν_C-H), 1589 (ν_C=C), 1437 (ν_C=C), 1133

4.3.23. 2-tert-butoxy-1-(2,4,6-trimethoxyphenyl)ethyltriphenyl-

phosphonium tetrafluoroborate (4k). White crystals (48.2 mg,

(ν_C-O-CAr), 1046 (ν_C-P

)

cm^-1; HRMS (ESI-TOF) calcd for

1

91% yield), mp 184.5-185.5^oC. H NMR (400 MHz, CD₃CN) δ

C₂₉H₃₀O₃P [M⁺] 457.1933 found 457.1942.

7.83-7.72 (m, 3H), 7.65-7.50 (m, 12H), 6.04 (br s, 2H), 5.51

(ddd, J₁= 15.2 Hz, J₂= 10.3 Hz, J₃= 5.0 Hz, 1H), 4.36 (dd, J₁=

19.6 Hz, J₂= 10.0 Hz, 1H), 3.75 (ddd, J₁= 33.2 Hz, J₂= 9.2 Hz,

J₃= 5.3 Hz, 1H), 3.74 (s, 3H), 3.53 (br s, 6H), 0.86 (s, 9H) ppm;

¹³C NMR (100 MHz, CD₃CN) δ 163.6 (d, J = 2.7 Hz), 160.0 (d, J

= 5.5 Hz), 135.4 (d, J = 9.4 Hz), 135.2 (d, J = 3.1 Hz), 130.4 (d, J

= 12.3 Hz), 121.0 (d, J = 83.6 Hz), 101.0 (d, J = 5.2 Hz), 92.0 (d,

4.3.19.

1-(2,4,6-trimethoxyphenyl)ethyltris(3-chlorophenyl)-

phosphonium tetrafluoroborate (4g). Resin (37.0 mg, 66% yield).

¹H NMR (400 MHz, CDCl₃) δ 7.86-7.71 (m, 6H), 7.60-7.41 (m,

3H), 7.29-7.18 (m, 3H), 6.06 (s, 2H), 5.32 (dq, J₁= 14.6 Hz, J₂=

7.3 Hz, 1H), 3.84 (s, 3H), 3.43 (br s, 6H), 1.93 (dd, J₁= 19.0 Hz,

J₂= 7.3 Hz, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ 162.9 (d, J

9

J = 1.9 Hz), 75.2, 60.4 (d, J = 3.1 Hz), 56.5, 56.3, 38.4 (d, J =

To

a

solution

of

N-[1-(2,4,6-trimethoxyphenyl)-

ACCEPTED MANUSCRIPT

46.9 Hz), 27.1 ppm; ³¹P NMR (161.9 MHz, CD₃CN) δ 37.5 ppm;

IR (ATR) 2957 (ν_C-H), 1608 (ν_C=C), 1591 (ν_C=C), 1438 (ν_C=C), 1111

ethyl]pivalamid 3g (5.0 mg, 0.0169 mmol) in DCM (1 cm³),

triphenylphosphonium tetrafluoroborate (5.9 mg, 0.0169 mmol)

and 1,3,5-trimethoxybenzene (2.8 mg, 0.0169 mmol) were added.

The solvent was evaporated under reduced pressure and the

residue was kept under a heat source at 80°C. The progress of the

reaction was monitored based on NMR spectroscopy. The yield

was estimated by ¹H NMR with the use of

dimethyldiphenylsilane as the internal standard.

(ν_C-O-CAr), 1062 (ν_C-P

)

cm^-1; HRMS (ESI-TOF) calcd for

C₃₃H₃₈O₄P [M⁺] 529.2508 found 529.2508.

4.3.24. 2-[4-(benzyloxy)phenyl]-1-(2,4,6-trimethoxyphenyl)ethyl-

triphenylphosphonium tetrafluoroborate (4l). Resin (54.4 mg,

1

85% yield). H NMR (400 MHz, CDCl₃) δ 7.86-7.78 (m, 3H),

7.73-7.63 (m, 6H), 7.49-7.40 (m, 6H), 7.39-7.26 (m, 5H), 6.82-

6.71 (m, 4H), 6.05 (d, J = 1.7 Hz, 1H), 5.84 (br s, 1H), 5.29 (ddd,

J₁= 16.8 Hz, J₂= 11.5 Hz, J₃= 2.9 Hz, 1H), 4.96 (s, 2H), 3.86-

3.73 (m, 1H), 3.79 (s, 3H), 3.30-3.19 (m, 1H), 3.25 (s, 3H), 3.19

(s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ 162.6 (d, J = 2.7

Hz), 159.7 (d, J = 3.7 Hz), 159.5 (d, J = 6.6 Hz), 157.7, 136.9,

135.0 (d, J = 3.0 Hz), 134.0 (d, J = 9.0 Hz), 130.1 (d, J = 12.1

Hz), 129.5, 129.4, 128.5, 127.9, 127.4, 118.6 (d, J = 82.3 Hz),

114.8, 98.9 (d, J = 4.9 Hz), 91.1 (d, J = 1.8 Hz), 90.9 (d, J = 2.3

Hz), 69.9, 56.0, 55.6, 54.7, 36.8 (d, J = 43.0 Hz), 33.0 ppm; ³¹P

NMR (161.9 MHz, CDCl₃) δ 21.9 ppm; IR (ATR) 2939 (ν_C-H),

1589 (ν_C=C), 1438 (ν_C=C), 1104 (ν_C-O-CAr), 1050 (ν_C-P) cm^-1; HRMS

(ESI-TOF) calcd for C₄₂H₄₀O₄P [M⁺] 639.2664 found 639.2668.

Acknowledgments

The financial support of the National Science Centre, Poland

(NCN) Grant No. 2015/19/D/ST5/00733 is gratefully

acknowledged.

Special dedication to Professor Roman Mazurkiewicz in

gratitude for inspiration and all the help.

References and notes

4.3.25.

1-(1H-indol-3-yl)ethyltriphenylphosphonium

1

1.

2.

3.

Werner, T. Adv. Synth. Catal. 2009, 351, 1469-1481.

He, R.; Ding, C.; Marouka, K. Angew. Chem. 2009, 48, 4559-4561.

Bradaric, C. J.; Downard, A.; Kennedy, C.; Robertson, A. J.; Zhou, Y.

Green Chem. 2003, 5, 143-152.

Plechkova, N. V.; Seddon, K. R. Chem. Soc. Rev. 2008, 37, 123-150.

Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863–927.

Johnson, A. W. in Ylides and imines of phosphorus, A Wiley-

Interscience Publication, New York, 1993, pp. 221-300.

Kolodiazhnyi, O. I. in Phosphorus Ylides, Wiley, Weinheim, 1999, pp.

359-539.

Selva, M.; Perosa, A.; Noè, M. in Organophosphorous Chemistry,

Tebby, J. C.; Loakes, D.; Allen, D. W. editors; the Royal Society of

Chemistry, Cambridge, 2016, pp. 132-169.

Mazurkiewicz, R.; Adamek, J.; Październiok-Holewa, A.; Zielińska,

K.; Simka, W.; Gajos, A.; Szymura, K. J. Org. Chem. 2012, 77, 1952-

1960.

tetrafluoroborate (4m). Resin (35.4 mg, 87% yield). H NMR

(400 MHz, CDCl₃) δ 9.50 (s, 1H), 7.73-7.70 (m, 3H), 7.59-7.50

(m, 6H), 7.50-7.41 (m, 7H), 7.03-6.99 (m, 1H), 6.86-6.73 (m,

2H), 6.63 (t, J = 3.0 Hz, 1H), 5.05 (dq, J₁= 14.9 Hz, J₂= 7.5 Hz,

1H), 1.75 (dd, J₁= 18.5 Hz, J₂= 7.3 Hz, 3H) ppm; ¹³C NMR

(100 MHz, CDCl₃) δ 135.9, 135.0 (d, J = 2.9 Hz), 134.3 (d, J =

8.8 Hz), 130.2 (d, J = 11.9 Hz), 126.4 (d, J = 6.6 Hz), 126.1 (d, J

= 4.1 Hz), 122.3, 119.8, 117.9, 117.6 (d, J = 81.9 Hz), 112.6,

105.4 (d, J = 6.0 Hz), 29.7 (d, J = 45.8 Hz), 17.6 ppm; ³¹P NMR

(161.9 MHz, CDCl₃) δ 23.1 ppm; IR (ATR) 3394 (ν_N-H), 3059

(ν_CAr-H), 1588 (ν_C=C), 1438 (ν_C=C), 1051 (ν_C-P) cm^-1; HRMS (ESI-

TOF) calcd for C₂₈H₂₅NP [M⁺] 406.1725 found 406.1721.

4.

5

6.

7.

8.

9.

4.3.26. 1-(2-thienyl)ethyltriphenylphosphonium tetrafluoroborate

(4n). White crystals (15.0 mg, 40% yield), mp 181.5-183.5^oC. ¹H

NMR (400 MHz, CDCl₃) δ 7.82-7.77 (m, 3H), 7.71-7.62 (m,

12H), 7.21-7.19 (m, 1H), 6.94-6.92 (m, 1H), 6.90-6.87 (m, 1H),

5.73 (dq, J₁= 14.2 Hz, J₂= 7.1 Hz, 1H), 1.85 (dd, J₁= 18.2 Hz,

J₂= 7.2 Hz, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃) δ 135.1 (d, J

= 3.0 Hz), 135.0 (d, J = 6.9 Hz), 134.3 (d, J = 9.1 Hz), 130.6 (d, J

= 8.0 Hz), 130.3 (d, J = 12.3 Hz), 127.3 (d, J = 3.1 Hz), 126.9 (d,

J = 3.9 Hz), 117.1 (d, J = 83.0 Hz), 32.3 (d, J = 47.2 Hz), 18.7

ppm; ³¹P NMR (161.9 MHz, CDCl₃) δ 26.0 ppm; IR (ATR) 3102

(ν_CAr-H), 2941 (ν_C-H), 1485 (ν_C=C), 1440 (ν_C=C), 1051 (ν_C-P) cm^-1;

HRMS (ESI-TOF) calcd for C₂₄H₂₂PS [M⁺] 373.1180 found

373.1183.

10. Adamek, J.; Mazurkiewicz, R.; Październiok-Holewa, A.; Grymel, M.;

Kuźnik, A.; Zielińska, K. J. Org. Chem. 2014, 79, 2765-2770.

11. Adamek, J.; Mazurkiewicz, R.; Październiok-Holewa, A.; Kuźnik, A.;

Grymel, M.; Zielińska, K.; Simka, W. Tetrahedron 2014, 70, 5725-

5729.

12. Adamek, J.; Październiok-Holewa, A.; Zielińska, K.; Mazurkiewicz, R.

Phosphorus, Sulfur Silicon Relat. Elem. 2013, 188, 967-980.

13. Październiok-Holewa, A.; Adamek, J.; Mazurkiewicz, R.; Zielińska, K.

Phosphorus, Sulfur Silicon Relat. Elem. 2013, 188, 205-212.

14. Saidi, M. R.; Nazari, M. Monatsh. Chem. 2004, 135, 309-312.

15. Kleinman, E. F. in Comprehensive Organic Synthesis; Trost, B. M.

editor; Pergamon Press, New York, 1991. Vol. 2. Chapter 4.1.

16. Mazurkiewicz, R.; Październiok-Holewa, A.; Adamek, J.; Zielińska, K.

Adv. Heterocycl. Chem. 2014, 111, 43-94.

Reaction

of

1-(N-pivaloylamino)ethyltris(m-chlorophenyl)-

17. a) Zaug, H. E. Synthesis 1970, 49-73; b) Zaug, H. E. Synthesis 1984,

85-110; c) Zaug, H. E. Synthesis 1984, 181-212.

18. Katritzky, A. R.; Manju, K.; Singh, S. K.; Meher, N. K. Tetrahedron

2005, 61, 2555-2581.

phosphonium tetrafluoroborate 1f with 1,3,5-trimethoxybenzene

– Measurement of changes in concentrations of the substrate,

and classical and non-classical products by NMR.

To

a solution of 1-(N-pivaloylamino)ethyltris(m-chloro-

19. Katritzky, A. R.; Lan, X.; Yang, J. Z.; Denisko, O. V. Chem. Rev.

1998, 98, 409-548.

20. Katritzky, A. R.; Pernak, J.; Fan, W.-Q. Synthesis 1991, 868-870.

21. Petrini, M. Chem. Rev. 2005, 105, 3949-3977.

22. Schneider, A. E.; Manolikakes, G. J. Org. Chem. 2015, 80, 6193-6212.

23. Aranzamendi, E.; Arrasate, S.; Sotomayor, N.; Gonzalez-Diaz, H.;

Lete, E. ChemistryOpen 2016, 5, 540-549.

24. a) Speckamp, W. N.; Hiemstra, H. Tetrahedron 1985, 41, 4367-4416.

b) Hiemstra, H.; Speckamp, W. N. in Comprehensive Organic

Synthesis, Throst, B. M.; Flemming, I. editors; Pergamon, Oxford,

1991, vol. 2, pp. 1047-1082. c) Hiemstra, H.; Speckamp, W. N. The

Alkaloids 1988, 32, 271-339.

phenyl)phosphonium tetrafluoroborate 1f (23.2 mg, 0.04 mmol)

in CDCl₃(0.65 cm³), 1,3,5-trimethoxybenzene (100.2 mg, 0.6

mmol) was added. Dimethyldiphenylsilane (5 mg) was used as

the internal standard. The reaction mixture was placed directly

into the NMR-tube. Changes in the concentrations of the

substrate, and classical and non-classical products were

monitored by ¹H NMR spectroscopy.

4.4. Transfomation of N-[1-(2,4,6-trimethoxyphenyl)-

ethyl]pivalamid 3g to 1-(2,4,6-trimethoxyphenyl)ethyl-

triphenylphosphonium tetrafluoroborate 4f.

10

Tetrahedron

ACCEPTED MANUSCRIPT

25.

Sohupp, G.; Spröngerts, E.; Szelinski, B.; Gottler, M. Ann. Chem.

1905, 343, 207-305.

Einhorn, A.; Bisohkopff, E.; Ladisch, C.; Mauermayer, T.;

26. Mecozzi, T.; Petrini, M.; Profeta, R. Tetrahedron: Asymmetry 2003,

14, 1171-1178.

27. Kadam, S. T.; Thirupathi, P.; Kim, S. S. Tetrahedron 2009, 65, 10383-

10389.

28. Thirupathi, P.; Kim, S. S. Eur. J. Org. Chem. 2010, 1798–1808.

29. Thirupathi, P.; Kim, S. S. J. Org. Chem. 2009, 74, 7755–7761.

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4093-4096.

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Org. Chem. 2017, 13, 1446-1455.

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6464-6467.

Supplementary Material

1

Supporting information includes H, ¹³C and ³¹P NMR spectra

of all new compounds 3-4. Supplementary data associated with

this article can be found in the online version.

ACCEPTED MANUSCRIPT

Table 1. Synthesis of 1-arylalkylphosphonium salts 4.

O

R²

25-50^oC

+ (Het)ArH

R¹

N

H

PAr¹₃BF₄

(Het)Ar

1

4

Molar ratio of

1 : (Het)ArH

Entry

1

R¹

t-Bu

R²

Ar¹

Ph

(Het)ArH

T, °C

150

100

25

Time, h

4

Yield, %

55

a

1a

1b

1c

1d

1e

1a

1f

Me

Ph

anisole

-

2

4a

4b

4c

4d

4e

4f

2

t-Bu

Bn

1,3-dimethoxybenzene

1,3,5-trimethoxybenzene

indole

1 : 2

1 : 15

1 : 2

1 : 15

1 : 5

1 : 2

3

70

3

4

83

4

BnO

t-Bu

Bn

2

75

5

Bn

2

92

6

i-Bu

Me

p-C₆H₄CF₃

10 min

32

7

Ph

80

1

85

8

Me

m-C₆H₄Cl

80

1

4g

4h

4f

66

9

1g

1b

1c

1h

1i

Me

p-C₆H₄CF₃

80

1

49

10

11

12

13

14

15

16

Me

Ph

80

1

91

BnO

t-Bu

Ph

80

1

4i

78

Bn

p-C₆H₄CF₃

25

10 min

4j

64

CH₂Ot-Bu

CH₂PhOBn

Me

Ph

80

5

2

1

2

4k

4l

91

1j

80

85

1a

80

4m

4n

87

a

Me

thiophene

-

180

40

^aArenes were used as solvent (2 cm³/0.2 mmol of 1).

ACCEPTED MANUSCRIPT

Table 2. Synthesis of N-(1-arylalkyl)amides 3.

Molar ratio of

1 : (Het)ArH

Time,

min

Yield,

%

Entry

1

R¹

R²

Ar¹

(Het)ArH

T, °C

25

0

3

a

1f

t-Bu

Bn

Me

Ph

m-C₆H₄Cl

p-C₆H₄CF₃

m-C₆H₄Cl

p-C₆H₄CF₃

m-C₆H₄Cl

p-C₆H₄CF₃

m-C₆H₄Cl

p-C₆H₄CF₃

m-C₆H₄Cl

p-C₆H₄CF₃

anisole

-

120

40

25

5

3a

3b

3c

3d

3e

3f

0

a

2

1g

1f

anisole

-

0

3

1,3-dimethoxybenzene

1,3,5-trimethoxybenzene

indole

1 : 15

67

84

72

76

77

0

4

1g

1k

1l

5

6

i-Pr

i-Bu

Me

Ph

10

5

7

1m

1e

1f

Bn

8

BnO

t-Bu

Bn

9

3f

traces

83

77

73

80

82

76

0

10

11

12

13

14

15

16

17

18

19

20

25

50

3g

3h

3i

1g

1k

1n

1l

3

5

Me

i-Pr

i-Bu

Bn

20

10

5

Bn

3j

1m

1h

1g

1f

Bn

3k

3l

BnO

t-Bu

Bn

10

30

45

30

Me

i-Pr

3m

3n

3o

68

51

32

53

a

thiophene

-

a

thiophene

-

a

1l

thiophene

-

^aArenes were used as solvent (2 cm³/0.2 mmol of 1).

Article Doi

Catalyst-free Friedel-Crafts reaction of 1-(N-acylamino)alkyltriarylphosphonium salts with electron-rich arenes

DOI: 10.1016/j.tet.2018.03.053

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