Development of decarboxylative coupling processes for the synthesis of azomethines and ketones

FULL PAPER

DOI: 10.1002/ejoc.201101103

Development of Decarboxylative Coupling Processes for the Synthesis of

Azomethines and Ketones

Florence Collet,^[a]Bingrui Song,^[a]Felix Rudolphi,^[a]and Lukas J. Gooßen*^[a]

Keywords: Azomethines / Cross-coupling / Decarboxylation / Ketones / Multicomponent reactions

A bimetallic catalyst system has been developed that allows

the synthesis of azomethines by a one-pot three-component

decarboxylative coupling, starting from simple, nontoxic pre-

cursors, i.e. potassium α-oxo carboxylates, aryl halides and

primary amines. In the presence of 15 mol-% copper/phen-

anthroline and 1 mol-% Pd/dppf, a wide range of valuable

imines is conveniently accessible in high yields at 100 °C, an

unprecedentedly low temperature for redox-neutral de-

carboxylative cross-coupling reactions. Hydrogenation of the

azomethine products leads to secondary amines. Alterna-

tively, they can be hydrolyzed in situ to aryl ketones. The

resulting ketone synthesis via azomethine intermediates is

also of interest as it gives higher yields at much lower tem-

peratures than the direct decarboxylative coupling of α-oxo

carboxylates with aryl halides.

Azomethines can also be used as substrates for aza-

Diels–Alder, Mannich and aza-Morita–Baylis–Hillman

(aza-MBH) reactions.^[4e,5,6]Their hydrolysis leads to the

formation of ketones.^[7]Moreover, imino groups can serve

as directing groups in C–H activation reactions.^[8]In ad-

dition, azomethines are used as ligands, e.g. in Fe-based

olefin polymerization catalysts.^[9]A direct, yet modular ac-

cess to this class of intermediates based on readily available

reagents, in which all three substituents could be indepen-

dently varied, is thus of high interest.

As depicted in Scheme 2, various methods for the synthe-

sis of azomethines have been reported. Traditionally, they

are prepared by the condensation of a carbonyl function-

ality with a primary amine (Scheme 2, pathway I),^[10]the

addition of organometallic reagents to nitriles (II),^[11]or the

arylation of nitriles under Friedel–Crafts conditions

(III).^[12]Examples of modern transition-metal-catalyzed

syntheses include the hydroamination of alkynes catalyzed

by Ru, Rh, Au or Ti (IV),^[13]the ruthenium-catalyzed oxi-

Introduction

Azomethines are valuable intermediates in organic syn-

thesis. As illustrated in Scheme 1, a wide range of amines^[1]

and other nitrogen-containing molecules^[2]can be synthe-

sized from azomethines. The reduction of imines is one of

the most widely used strategies for the preparation of

amines.^[3]α-Branched amines (e.g. allylic, propargylic,

α-alkylated and arylated amines) can be obtained by ad-

dition of organometallic nucleophiles such as organo-

lithium, -copper, -zinc or -magnesium reagents to the imine

moiety.^[4]

Scheme 1. Products accessible from imine synthons.

[a] Fachbereich Chemie, Technische Universität Kaiserslautern

Erwin-Schrödinger-Straße 54, 67663 Kaiserslautern, Germany

Fax: +49-631-205-3921

E-mail: goossen@chemie.uni-kl.de

Supporting information for this article is available on the

WWW under http://dx.doi.org/10.1002/ejoc.201101103.

Scheme 2. Synthetic entries to azomethines.

6486

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Decarboxylative Coupling for the Synthesis of Azomethines and Ketones

dative coupling of aldimines and boronates (V),^[14]the pal- carboxylate salts and primary amines, this would represent

ladium-catalyzed addition of arenes or boronic acids to a highly modular one-pot azomethine synthesis by starting

nitriles (II or III)^[15]and the dehydrogenative coupling of from three independently variable, broadly available and

alcohols and amines.^[16]However, none of these syntheses easy-to-handle components. In a preliminary communica-

is fully modular as the products result from combinations tion, we have demonstrated the validity of the concept of

of only two reagents. The benefit of multicomponent reac- the one-pot three-component decarboxylative azomethine

tions is that they allow the generation of greater molecular synthesis from potassium α-oxo carboxylates, aryl halides

diversity in a single step.^[17]However, to the best of our and primary amines.^[35]Herein, we present a detailed report

knowledge, the Pd-catalyzed cross-coupling of aryl halides, of the catalyst development as well as the scope and limita-

isonitriles and organometallic reagents is the only known tions of the methodology. Moreover, we describe further

synthesis that allows an independent variation of all three investigations leading to a new one-pot protocol for the

substituents of the azomethine (Scheme 2, VI).^[18]Unfortu- synthesis of ketones by decarboxylative coupling with in

nately, the low availability, toxicity and bad odour of iso- situ hydrolysis of the imines.

nitriles limit the practical utility of this synthetic strategy.

In the most widely used azomethine synthesis, the con-

Mechanistic Considerations

densation of amines with ketones, two of the three compo-

nents of the final product, originate from the ketone build-

ing block. Ketones are usually assembled by Friedel–Crafts

acylation of arenes (VII),^[19]coupling of organometallic

species with carboxylic acid derivatives, e.g. Weinreb amides

(VIII)^[20]or acid chlorides (IX),^[21]or carboxylic acids acti-

vated in situ with anhydrides^[22]or coupling reagents.^[23]

Further synthetic entries to ketones include the coupling of

acyl anion equivalents (X), e.g. cyanohydrins, acetals, di-

thianes or hydrazones, with carbon electrophiles, as well as

the insertion of C–C multiple bonds into aldehyde C–H

bonds.^[24–26]

In the context of our work on decarboxylative cross-cou-

pling reactions, we have recently communicated an alterna-

tive synthesis for aryl ketones, which involves the generation

of acyl nucleophiles by the decarboxylation of α-oxo carb-

oxylates with a copper catalyst and their in situ coupling

with aryl halides with a palladium cocatalyst (Scheme 3,

top).^[27]The key advantage of this and related decarbox-

ylative couplings,^[28]which have successfully been used in

the synthesis of biaryls,^[29,30]vinyl arenes,^[31]allyl deriva-

tives,^[32]esters^[33]and aryl ketones,^[27,34]is that they draw

on easily available carboxylic acid derivatives rather than

sensitive organometallic reagents as sources of carbon nu-

cleophiles.

The mechanistic basis for our desired decarboxylative

azomethine synthesis is outlined in Scheme 4. We reasoned

that upon mixing α-oxo carboxylate 1 with primary amine

2, at least a fraction of the molecules might condense via

the hemiaminal to α-imino carboxylate 5. Once inside the

coordination sphere of the copper catalyst, either of these

carboxylates should lose CO₂more readily than the α-oxo

carboxylate due to the higher stability of imidoyl over acyl

anions.^[36,37]At a reaction temperature well below that re-

quired for the decarboxylation of copper α-oxo carboxyl-

ates, the α-imino carboxylate complex b should already ex-

trude CO₂, which results in the selective formation of the

imidoylcopper complex c. In the transmetallation step, the

imidoyl residue should be transferred to the arylpalladium

halide e, regenerating the initial copper halide species a. The

arylpalladium species e arises from the oxidative addition

of aryl halide 3 to the second catalyst component, the low-

valent palladium(0) species d. The desired azomethine

product 4 would be liberated from complex f by reductive

elimination, regenerating the original palladium species d

and closing the catalytic cycle.

Scheme 3. Decarboxylative synthesis of ketones and azomethines.

Scheme 4. Mechanistic outline of the targeted imine/ketone synthe-

sis.

We envisioned that a mechanistically related decarbox-

ylative cross-coupling between α-iminocarboxylates and

The Pd/Cu-catalyzed decarboxylative coupling of α-oxo

aryl halides should also be possible (Scheme 3, bottom). If carboxylates with aryl bromides requires very forcing condi-

α-iminocarboxylates could be generated directly from α-oxo tions, i.e. 170 °C for 16 h.^[27,38]If the above decarboxylative

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F. Collet, B. Song, F. Rudolphi, L. J. Gooßen

FULL PAPER

synthesis of azomethines indeed proceeded at substantially Table 1. Optimization of the reaction conditions.^[a]

reduced temperatures, it would be useful also for the syn-

thesis of aryl ketones 6. Rather than decarboxylatively cou-

pling α-oxo carboxylates 1 themselves, they could be con-

verted in situ into more reactive α-imino carboxylates 5 by

using an inexpensive amine 2, then react to the azomethines

4, and finally be hydrolyzed to the ketones 6 (Scheme 4,

dotted arrow). Overall, the role of the amine would be that

Entry Ligand

Additive

Yield [%]^[b]

of a recyclable “organocatalyst” that would help to reduce

the activation barrier of the decarboxylation step.^[29j,39]

1

2

3

4

5

6

P(o-Tol)₃

dppf

–

5

Mg(OTf)₂

3 Å MS

Mg(OTf)₂

Mg(OTf)₂, 3 Å MS

62

27

40

68

85

Results and Discussion

Decarboxylative Coupling of α-Imino Carboxylates and

Aryl Bromides

[a] Reaction conditions: 1.2 mmol 5a, 1.0 mmol 3a, 15 mol-%

CuBr, 15 mol-% 1,10-phenanthroline, 1 mol-% Pd(F₆-acac)₂,

0.5 mol-% dppf or 1 mol-% P(oTol)₃, 5 mol-% Mg(OTf)₂when ap-

plicable, 200 mg 3 Å molecular sieves (MS), 2 mL NMP, 130 °C,

16 h. dppf = 1,1Ј-bis(diphenylphosphanyl)ferrocene. [b] Yields de-

termined by GC analysis by using n-tetradecane as the internal

standard.

The first step towards the desired azomethine synthesis

was to study the decarboxylative coupling of preformed α-

imino carboxylates with aryl halides. We attempted to syn-

thesize α-imino carboxylate salts by stirring α-oxo carbox-

ylic acids with amines in methanol and, once the reaction

was complete, deprotonated the resulting α-imino acids

with potassium tert-butoxide. However, the condensation

step did not go to completion for aliphatic amines, and

most of the products did not crystallize. In contrast, 2-{[4-

(dimethylamino)phenyl]imino}-2-phenylacetate (5a) was di-

rectly obtained in high yields and crystalline form. Thus,

we chose the reaction of 5a with 4-bromotoluene (3a) as a

model for optimizing the decarboxylative cross-coupling

step. The starting conditions consisted of the solvent and

catalyst system optimized for the decarboxylative ketone

synthesis, i.e. 1 mol-% Pd(F₆-acac)₂, 2 mol-% P(o-Tol)₃,

15 mol-% CuBr and 15 mol-% 1,10-phenanthroline.^[27]Af-

ter stirring of the reaction mixture at 170 °C in N-methyl-

pyrrolidinone (NMP)/quinoline for 16 h, the desired azo-

methine 4aaa was isolated in almost quantitative yield as a

mixture of stereoisomers. Encouraged by this finding, we

lowered the reaction temperature to 130 °C and studied the

reaction systematically (Table 1). Control experiments con-

firmed that, at this low reaction temperature, the decarbox-

ylative coupling between α-oxo carboxylates and aryl ha-

lides does not proceed. In contrast, the azomethine product

4aaa was formed in detectable amounts at this temperature

(Entry 1).

Table 2. Scope of the imine synthesis from preformed α-imino carb-

oxylate 5a.^[a]Ar = aryl, heteroaryl.

The addition of Lewis acids, in particular Mg(OTf)₂, was

found to strongly facilitate the reaction (Entry 2). This find-

ing can be rationalized by the coordination of the Lewis

acid to the nitrogen atom of the imino carboxylate, thereby

reducing the electron density in the α-position to the carb-

oxylate group and enhancing the decarboxylation rate. The

beneficial effect of molecular sieves (Entry 3) can be attrib-

uted to their Lewis acidity, but may also result from their

ability to remove trace amounts of water from the reaction

mixture, thereby precluding hydrolysis of the starting mate-

rial. Among the ligands tested, bis(diphenylphosphanyl)fer-

rocene (dppf) gave the best results (Entries 4 and 5). In

combination with Mg(OTf)₂and molecular sieves as addi-

[a] Reaction conditions: 1.2 mmol 5a, 1.0 mmol aryl bromide 3,

15 mol-% CuBr, 15 mol-% 1,10-phenanthroline, 1 mol-% Pd(F₆-

acac)₂, 1 mol-% dppf, 5 mol-% Mg(OTf)₂, 200 mg 3 Å molecular

sieves, 2 mL NMP, 130 °C, 16 h. PDP = 4-(dimethylamino)phenyl.

[b] Isolated yields. [c] Yield determined by GC analysis by using n-

tives, the azomethine product 4aaa was formed in 85% yield tetradecane as the internal standard.

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Decarboxylative Coupling for the Synthesis of Azomethines and Ketones

(Entry 6). The only side reaction observed was protode- Table 3. Evaluation of primary amines in the three-component cou-

pling.^[a]R²= aryl, alkyl.

carboxylation of imino carboxylate 5a, which led to the ald-

imine. Control experiments revealed that, under the above

reaction conditions, this aldimine does not react with aryl

bromide 3a with formation of azomethine 4aaa, which con-

firms that the product is indeed formed by decarboxylative

coupling rather than protodecarboxylation followed by a

Heck-type reaction.

We next examined the scope of this optimized protocol

with regard to the electrophilic coupling partner by treating

imino carboxylate 5a with various aryl bromides

3

(Table 2). In all cases, the azomethines 4 were obtained in

moderate to good yields. Both electron-rich (3a–f) and elec-

tron-poor (3g–j) aryl bromides were successfully coupled,

and many functional groups were tolerated including

amino, keto, cyano, ester and trifluoromethyl residues. Un-

der the mild reaction conditions, 1-bromo-4-chlorobenzene

(3l) reacted exclusively at the bromine atom leaving the

chlorine intact. The successful conversion of 3-bromopyr-

idine (3m) demonstrates that nitrogen heterocycles are also

compatible with this reaction. Only for the sterically

crowded aryl bromide 3n was an unsatisfactory yield ob-

tained.

[a] Reaction conditions: 0.6 mmol 1a, 0.6 mmol amine 2, 0.5 mmol

3a, 15 mol-% CuBr, 15 mol-% 1,10-phenanthroline, 1 mol-% Pd(F₆-

acac)₂, 1 mol-% dppf, 5 mol-% Mg(OTf)₂, 100 mg 3 Å molecular

sieves, 1 mL NMP, 130 °C, 16 h. [b] Isolated yields.

Based on these findings, we decreased the reaction tem-

perature to 100 °C, shortened the reaction time to 6 h, and

reoptimized the catalyst system using 2b as the amine com-

ponent. Several parameters were evaluated, including dif-

ferent combinations of palladium cross-coupling catalysts

with copper decarboxylation cocatalysts. Selected results fo-

cusing on solvents and additives are listed in Table 4. More

data can be found in the corresponding communication,^[35]

and the complete data for screening are included in the Sup-

porting Information.

Development of a One-Pot Azomethine Synthesis

With optimized conditions for the decarboxylative cross-

coupling in hand, we focused on the development of a one-

pot protocol for the synthesis of azomethines from α-oxo

carboxylates 1, amines 2 and aryl halides 3 without prior

isolation of α-imino carboxylates 5. The key challenge was

that the condensation step would have to proceed under

nonacidic conditions. This implies that the amine has to

react with a carbonyl atom adjacent to a negatively charged

carboxylate group. An NMR experiment revealed that

when heating potassium 2-oxo-2-phenylacetate (1a), cyclo-

hexylamine (2b) and molecular sieves in methanol for sev-

eral hours, appreciable amounts (80%) of the imino carb-

oxylate 5b were formed, but still 20% of 1a remained pres-

ent (see Supporting Information). This confirmed that the

condensation step was rather slow. For a successful one-

pot azomethine synthesis, the water released in the imine

condensation step would have to be continuously trapped,

and the reaction would have to be performed at a tempera-

ture too low for decarboxylation of the α-oxo carboxylate

salts present in the reaction mixture. This way, it should be

possible to avoid the competing protodecarboxylation and

the formation of aryl ketones. Indeed, when we heated a

mixture of 1a, 4-(dimethylamino)aniline (2a) and 4-bromo-

toluene (3a) in the presence of molecular sieves and the pre-

viously optimized catalyst system to 130 °C for 16 h, the

desired azomethine product 4aaa was isolated in 60% yield.

We next evaluated whether the reaction would also work

with the amines whose α-imino carboxylates we had been

unable to isolate, and found that they gave even better re-

Table 4. Optimization of the one-pot three-component imine syn-

thesis.^[a]

Entry Solvent

Lewis acid

Additive Yield [%]^[b]

1

2

3

4

5

6

7

NMP

quinoline

DMF^[c]

DMPU^[d]

NMP

Mg(OTf)₂

–

Mg(OTf)₂

–

3 Å MS

–

3 Å MS

75

81

25

93

43

5

92^[e]

[a] Reaction conditions: 1.2 mmol 1a, 1.2 mmol 2b, 1.0 mmol 3a,

15 mol-% CuBr, 15 mol-% 1,10-phenanthroline, 1 mol-% Pd(F₆-

acac)₂, 1 mol-% dppf, 5 mol-% Lewis acid, 200 mg 3 Å molecular

sieves, 2 mL of NMP, 100 °C, 6 h. [b] Yields determined by GC

analysis using n-tetradecane as the internal standard. [c] DMF =

N,N-dimethylformamide. [d] DMPU = 1,3-dimethyl-3,4,5,6-tetra-

hydro-2(1H)-pyrimidinone. [e] 16 h.

Control experiments revealed that the presence of both a

sults (Table 3). For 2b, the corresponding azomethine, 4aba, copper and a palladium catalyst is essential for this reac-

was formed in almost quantitative yield. tion. The choice of the palladium source had only a limited

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F. Collet, B. Song, F. Rudolphi, L. J. Gooßen

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influence on the reaction outcome. We chose Pd(F₆-acac)₂to remain with NMP and extend the reaction time to 16 h,

on the basis that it is easy to handle and not hygroscopic. which also gave excellent conversion (Entry 7).

Among the phosphane ligands tested, dppf remained the

most effective. The combination of CuBr with 1,10-phen- the optimized conditions [1 mol-% Pd(F₆-acac)₂, 1 mol-%

anthroline was the optimal decarboxylation catalyst. dppf, 15 mol-% CuBr, 15 mol-% 1,10-phenanthroline, 3 Å

We next explored the scope of the one-pot reaction under

As can be seen from the selected results in Table 4, 4aba molecular sieves, NMP, 100 °C, 16 h]. As can be seen in

was obtained in 75% yield from 1a, 2b and 3a after stirring Table 5, various aryl bromides 3 were successfully coupled

in NMP at 100 °C for 16 h by using a catalyst system con- with potassium α-aryl- or α-alkyl-α-oxoacetates 1 and pri-

sisting of 1 mol-% Pd(F₆-acac)₂, 1 mol-% dppf, 15 mol-% mary amines 2. Electron-rich (3a–e) and electron-deficient

CuBr, 15 mol-% 1,10-phenanthroline, 5 mol-% Mg(OTf)₂substrates bearing cyano (3h), ester (3i), trifluoromethyl (3j)

and 200 mg 3 Å molecular sieves. The presence of molecu- or nitro (3r) groups gave similarly high yields. Heteroaryl

lar sieves was crucial for achieving high yields, but for this bromides such as 3-bromopyridine (3m) and 3-bromothio-

substrate combination, Lewis acids were not required phene (3t) also gave good results. When starting from 4-

(Table 4, Entries 1–3). The evaluation of solvents revealed bromobenzaldehyde (3q), the aldehyde group reacted with

that the reaction proceeds particularly fast in quinoline (En- the amine to the corresponding imine. Thus, 2.2 equiv. of

tries 2, 4–6). However, due to the difficulty of separating the primary amine were employed, and the corresponding

the azomethine product from this basic amine, we decided imine 4abq was isolated. The use of the electron-rich, steri-

Table 5. Substrate scope of the one-pot three-component imine synthesis.^[a]R¹= aryl, heteroaryl, alkyl; R²= aryl, alkyl; R³= heteroaryl.

[a] Reaction conditions: 1.2 mmol α-oxo carboxylate 1, 1.2 mmol primary amine 2, 1.0 mmol aryl bromide 3, 15 mol-% CuBr, 15 mol-%

1,10-phenanthroline, 1 mol-% Pd(F₆-acac)₂, 1 mol-% dppf, 200 mg 3 Å molecular sieves, 2 mL NMP, 100 °C, 16 h. [b] Isolated yields. [c]

From 4-chlorotoluene. [d] 2.2 equiv. of amine. [e] 36 h. [f] 130 °C. [g] Yield determined by GC analysis using n-tetradecane as the internal

standard.

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Decarboxylative Coupling for the Synthesis of Azomethines and Ketones

cally demanding phosphane 2-(dicyclohexylphosphanyl)- 80 °C) was less effective, and deaminated product was ob-

2Ј,4Ј,6Ј-triisopropylbiphenyl instead of dppf allowed us to tained predominantly with palladium catalysts.

extend the reaction from aryl bromides to aryl chlorides.

This is exemplified by the synthesis of 4aba from 4-chloro-

toluene.

Application of the Decarboxylative α-Imino Carboxylate

Coupling to the Synthesis of Aryl Ketones

Variation of the α-oxo carboxylate substrate 1 showed

that α-aryl α-oxo carboxylates with electron-rich (1b,c,h) or

electron-poor ring substituents (1d,e) as well as heteroar-

enecarboxylates (1f,g) were all smoothly converted. For the

aliphatic α-oxo carboxylate 1i, longer reaction times were

required. The synthesis of enolizable azomethines is also

possible (4jba), but their isolation in pure form through dis-

tillation proved troublesome. For such compounds, a dif-

ferent workup procedure has to be developed, or they have

to be used without further purification.

The amine component is also variable (2a–i). For both

linear and branched aliphatic amines, good yields were ob-

tained. In order to convert electron-rich anilines (2a,d,h,i),

the reaction temperatures had to be increased to 130 °C.

The performance limit of the current system is reached with

the electron-deficient aniline 2j. For even less electron-rich

anilines, no conversion was observed, which may be due to

their low reactivity in imine condensation reactions.

As the synthesis of azomethines was found to proceed in

such high yields at temperatures well below those required

for the synthesis of ketones by decarboxylative coupling of

α-oxo carboxylates 1, we decided to develop a one-pot syn-

thesis of ketones by intermediate formation of azomethines

(Scheme 5). In this process, the α-oxo carboxylate salts 1

would need to be converted into α-imino carboxylates 5,

which would have to be coupled under decarboxylation

with aryl halides 3, and the resulting azomethines 4 would

have to be hydrolyzed to ketones 6. By lowering the de-

carboxylation barrier with added amine, the reaction tem-

peratures might be dramatically reduced, thus minimizing

thermal degradation of sensitive substrates.

Reduction of the Azomethine into the Corresponding Amine

Scheme 5. Synthesis of ketones via azomethines.

Considering that the reduction of azomethines to sec-

ondary amines is an important synthetic application, we in-

vestigated this reaction using 4aba, a typical example of the

products accessible by our new synthetic method. We tested

various reaction conditions (Table 6) and found that the

highest yields of amine 7a were obtained when the azome-

thine is treated either with a 3:1 mixture of sodium borohy-

dride and aluminium chloride (Entry 4), or with lithium al-

uminium hydride (Entry 5) in tetrahydrofuran (THF).

As the basic azomethines 4 would no longer need to be

separated from the reaction medium, it should now be pos-

sible to use quinoline as the solvent (Table 4, Entry 4). In

addition to its beneficial effect on the reaction rate, it can

easily be removed along with the amine mediator in an

acidic workup. We used 2b as the amine mediator as it is

inexpensive, and the corresponding α-imino carboxylates

have been proven to be particularly reactive towards de-

carboxylation. After stirring a mixture of 1a, 2b and 3a in

the presence of molecular sieves and the previously opti-

mized catalyst system [1 mol-% Pd(F₆-acac)₂, 1 mol-%

dppf, 15 mol-% CuBr, 15 mol-% 1,10-phenanthroline, 3 Å

molecular sieves] in quinoline at 100 °C for 10 h, GC analy-

sis revealed that the azomethine intermediate 4aba had

formed in quantitative yield. The reaction mixture was al-

lowed to cool slightly, a mixture of 2 m HCl and THF (1:1,

3 mL) was added and the reaction mixture was stirred at

80 °C for 1 h to completely hydrolyze the azomethine inter-

mediate. After acidic workup, ketone 6a was isolated in

97% overall yield.

Table 6. Optimization of the reduction step.^[a]

Entry Reducing agent

Solvent

T [°C]

Yield [%]^[b]

1

2

3

4

5

6

7

LiAlH₄

LiAlH₄/AlCl₃

NaBH₄

NaBH₄/AlCl₃

LiAlH₄

H₂/Pt/C

THF

EtOH

40

60

80

0

66

4

97

100

44

0^[c]

Having thus identified an effective protocol for the syn-

thesis of ketones, we next investigated its scope. As can be

seen from the examples in Table 7, a wide range of diversely

substituted aryl ketones were accessible in good to excellent

yields. The reaction works equally well for aryl bromides

bearing electron-donating and -withdrawing groups. In all

cases, better conversions were achieved by using the new

H₂/Pd/C

[a] Reaction conditions: 1 mmol 4aba, 2 mL solvent, 16 h. [b]

Yields determined by GC analysis using n-tetradecane as the in-

ternal standard. [c] The deaminated product was obtained in 91%

yield.

Due to the steric hindrance and low polarity of the C=N amine-mediated protocol than the previously reported di-

bond in the ketimine group, a reaction temperature of 60 °C rect decarboxylative coupling of α-oxo carboxylate salts.^[27]

is required. Hydrogenation in the presence of a hetero- The mild reaction conditions even allowed the synthesis of

geneous platinum catalyst (10 bar H₂, 5 mol-% Pt/C, EtOH, 4-nitrobenzophenone (6e) in 65% yield, which was obtained

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F. Collet, B. Song, F. Rudolphi, L. J. Gooßen

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Table 7. Substrate scope of the one-pot ketone synthesis.^[a]R¹= aryl, heteroaryl, alkyl, Ar = aryl, heteroaryl, vinyl.

[a] Reaction conditions: 1.2 mmol α-oxo carboxylate 1, 1.2 mmol primary amine 2, 1.0 mmol aryl bromide 3, 15 mol-% CuBr, 15 mol-%

1,10-phenanthroline, 1 mol-% Pd(F₆-acac)₂, 1 mol-% dppf, 200 mg 3 Å molecular sieves, 2 mL quinoline, 100 °C, 10 h; quenching with

3 mL 2 m HCl/THF (1:1), 80 °C, 1 h. [b] Isolated yields. [c] 36 h. [d] Yield determined by GC analysis by using n-tetradecane as the

internal standard.

only in traces by using the previous protocol.^[27]The advan-

tages of the new protocol are visible for heterocyclic deriva-

Conclusions

tives: in the coupling of both 3-bromothiophene and 3-bro-

We have developed a highly modular, one-pot three-com-

mopyridine, the corresponding aryl ketones 6h and 6i were ponent protocol for the synthesis of diversely substituted

isolated in 97 and 91% yield rather than 50 and 57%, azomethines by decarboxylative coupling, starting from

respectively. Moreover, the new protocol allows the de- simple potassium α-oxo carboxylates, primary amines and

carboxylative coupling of vinyl halides, as demonstrated by various aryl halides. This new procedure, which is mediated

the synthesis of 6j.

by a bimetallic copper/palladium catalyst, shows a remark-

The reaction is also broadly applicable to α-oxo carb- able substrate scope and excellent functional-group toler-

oxylate substrates. α-Aryl α-oxo carboxylates with electron- ance. All three substituents in the azomethine products can

rich and electron-poor substituents were smoothly con- be individually varied. A wide range of valuable imines is

verted, and even heterocyclic derivatives gave good yields. thus accessible in high yields at 100 °C, an unprecedentedly

The conversion of aliphatic α-oxo carboxylates was also low temperature for decarboxylative cross-couplings. In

possible, but requires longer reaction times. Even the enoliz- combination with in situ hydrolysis of the azomethines, the

able ketone 6p was obtained in 85% yield after 36 h. The new reaction can also be used for the synthesis of ketones

limit of the current catalyst system was reached with the from α-oxo carboxylate salts and aryl halides in the pres-

sterically crowded substrate 2-oxo-2-(2,4,6-trimethylphen- ence of cyclohexylamine. In this process, the inexpensive

yl)acetate.

amine mediator serves to reduce the reaction temperature

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Eur. J. Org. Chem. 2011, 6486–6501

Decarboxylative Coupling for the Synthesis of Azomethines and Ketones

0.01 mmol), 1,10-phenanthroline (27.0 mg, 0.15 mmol), 1,1Ј-bis(di-

of the decarboxylation step by intermediate imine conden-

sation. The concept of lowering the temperature of decar-

boxylative couplings of α-oxo carboxylates by performing

them in the presence of amines should also open new op-

portunities for related decarboxylation transformations of

α-oxo carboxylates, e.g. 1,2- and 1,4-additions, allylations

or arylations with C–H activation.

phenylphosphanyl)ferrocene (5.7 mg, 0.01 mmol), magnesium tri-

fluoromethane sulfonate (16.1 mg, 0.05 mmol) and activated

ground 3 Å molecular sieves (200 mg). The reaction vessel was

evacuated and flushed with nitrogen three times. A solution of the

appropriate aryl halide 3 (1.00 mmol) and n-tetradecane (50 μL) in

NMP (2 mL) was added by syringe. The resulting mixture was

stirred at 130 °C for 16 h, diluted with saturated sodium hydrogen-

carbonate solution (20 mL) and extracted repeatedly with ethyl

acetate (20 mL portions). The combined organic layers were

washed with saturated sodium hydrogencarbonate solution, water

and brine, dried with MgSO₄, filtered, and the volatiles were re-

moved in vacuo. The residue was purified by column chromatog-

raphy (SiO₂; hexane/ethyl acetate gradient) to yield the correspond-

ing azomethine 4.

Experimental Section

General Methods: Reactions were performed in oven-dried glass-

ware containing a teflon-coated stirrer bar and dry septum under

nitrogen unless otherwise specified. All reactions were monitored

by GC using n-tetradecane as an internal standard. Response fac-

tors of the products with regard to n-tetradecane were obtained

experimentally by analyzing known quantities of the substances.

GC analyses were carried out by using an HP-5 capillary column

(phenyl methyl siloxane 30ϫ320ϫ0.25 m, 100/2.3–30–300/3) and

a time program beginning with 2 min at 60 °C followed by 30 °C/

min ramp to 300 °C, then 3 min at this temperature. For products

with higher retention times, the final temperature period was ex-

tended to 16 min. Column chromatography was performed by

using an automated chromatography system with prepacked SiO₂

columns (12 g). NMR spectra were obtained with 400 or 600 FT

NMR instruments by using CDCl₃as solvent, with proton and

carbon resonances at 400/600 MHz and 101/151 MHz, respectively,

unless otherwise stated. Chemical shifts (δ) are reported in parts

per million (ppm). Mass spectrometric data were acquired with a

GC–MS ion trap spectrometer. HRMS data were acquired with a

GC–MS-TOF spectrometer by using EI ionization. Potassium 2-

oxo-2-phenylacetate, potassium 2-(4-cyanophenyl)-2-oxoacetate,

potassium 2-(2-furyl)-2-oxoacetate and potassium trimethyl-

pyruvate were obtained by reaction of the commercially available

carboxylic acids with potassium tert-butoxide in 2-propanol. Potas-

sium 2-(2,5-dimethylphenyl)-2-oxoacetate and potassium 2-(4-

methoxyphenyl)-2-oxoacetate were obtained by Friedel–Crafts

acylation of the corresponding commercially available arenes with

ethyl oxalyl chloride in CH₂Cl₂, followed by ester hydrolysis with

potassium hydroxide in 2-propanol. NMP and quinoline were dis-

tilled with 3 Å molecular sieves prior to use. Copper salts were

dried in vacuo at 60 °C prior to use. Molecular sieves were ground

and dried in vacuo at 250 °C prior to use. Potassium salts were

dried in vacuo at room temperature for 2 h prior to use. Liquid

amines were distilled and dried with 3 Å molecular sieves prior to

use. All other compounds are commercially available and were used

without further purification.

N,N-Dimethyl-NЈ-[(phenyl)(4-tolyl)methylene]-p-phenylenediamine

(4aaa): Compound 4aaa was synthesized according to the general

procedure described above from 5a (368 mg, 1.20 mmol) and 4-

bromotoluene (3a) (171 mg, 122 μL, 1.00 mmol). After purification

by column chromatography (hexane/ethyl acetate, 90:10), 4aaa

(290 mg, 85%) was obtained as an orange solid (m.p. 99 °C). The

spectroscopic data were identical to those reported in the litera-

ture.^[35]

N-[(4-Methoxyphenyl)(phenyl)methylene]-NЈ,NЈ-dimethyl-p-phen-

ylenediamine (4aab): Compound 4aab was synthesized according to

the general procedure described above from 5a (368 mg,

1.20 mmol) and 2-bromoanisole (3b) (187 mg, 126 μL, 1.00 mmol).

After purification by column chromatography (hexane/ethyl acet-

ate, 80:20), 4aab (270 mg, 82%) was obtained as an orange solid

(m.p. = 119 °C). ¹H NMR [400 MHz, CDCl₃, two sets of signals

for (E) and (Z) isomers, ratio approx. 1.7:1]: δ = 7.66–7.78 (m, 2

H), 7.36–7.49 (m, 1 H), 7.26–7.48 (m, 2 H), 7.08–7.23 (m, 2 H),

6.80–6.97 (m, 2 H), 6.66–6.78 (m, 2 H), 6.53–6.65 (m, 2 H), 3.83

and 3.87 (s, 3 H), 2.88 and 2.91 (2 s, 6 H) ppm. ¹³C NMR

[101 MHz, CDCl₃, two sets of signals for (E) and (Z) isomers]: δ

= 165.6 and 165.9, 161.3, 159.4, 147.1 and 147.2, 141.0 and 141.2,

137.3, 133.2, 131.4, 130.6, 130.0, 129.6, 129.21, 129.15, 128.1,

128.0, 123.0 and 123.1, 113.4, 112.7 and 112.8, 55.1 and 55.3,

40.9 ppm. C₂₂H₂₂N₂O (330.43): calcd. C 79.97, H 6.71, N 8.48;

found C 79.88, H 6.82, N 8.64. MS (70 eV): m/z (%) = 332 (31),

331 (100), 330 (15) [M]⁺, 254 (38), 208 (13), 77 (19), 40 (14). IR

(KBr): ν = 1653 (m), 1607 (s), 1559 (s), 1507 (vs), 1437 (m), 1260

˜

(s), 1228 (s), 1166 (s), 1064 (m), 1030 (s), 816 (vs), 702 (s), 670 (s),

662 (m), 540 (m) cm^–1.

N,N-Dimethyl-NЈ-[(4-methylsulfanylphenyl)(phenyl)methylene]-p-

phenylenediamine (4aac): Compound 4aac was synthesized accord-

ing to the general procedure described above from 5a (368 mg,

1.20 mmol) and 2-bromothioanisole (3c) (203 mg, 1.00 mmol). Af-

ter purification by column chromatography (hexane/ethyl acetate,

85:15), 4aac (220 mg, 64%) was obtained as an orange solid (m.p.

110 °C). ¹H NMR [400 MHz, CDCl₃, two sets of signals for (E)

and (Z) isomers]: δ = 7.64–7.69 and 7.69–7.75 (2 m, 2 H), 7.26–

7.36 and 7.37–7.47 (2 m, 3 H), 7.08–7.13 and 7.23–7.26 (2 m, 2 H),

7.14–7.21 (m, 2 H), 6.68–6.76 (m, 2 H), 6.54–6.63 (m, 2 H), 2.89

and 2.91 (2 s, 6 H), 2.50 and 2.52 (2 s, 3 H) ppm. ¹³C NMR

[101 MHz, CDCl₃, two sets of signals for (E) and (Z) isomers]: δ

= 165.2 and 165.5, 147.3, 141.4, 140.9, 140.7, 140.6, 139.1, 137.15,

137.11, 133.45, 130.2, 130.1, 129.5, 129.3, 129.1, 128.2, 128.10,

128.05, 125.3, 123.3, 123.1, 112.6 and 112.8, 40.8, 15.1 and

15.3 ppm. C₂₂H₂₂N₂S (346.49): calcd. C 76.26, H 6.40, N 8.08, S

Potassium

2-{[4-(Dimethylamino)phenyl]imino}-2-phenylacetate

(5a): A mixture of 2-oxo-2-phenylacetic acid (751 mg, 5 mmol) and

N,N-dimethyl-p-phenylenediamine (613 mg, 4.5 mmol) in methanol

(20 mL) was stirred at 25 °C for 16 h. The mixture was filtered, and

the solid collected washed with diethyl ether (5 mL) to yield an

orange solid (1178 mg), which was suspended in diethyl ether

(20 mL) and stirred with potassium tert-butoxide (493 mg,

4.39 mmol) at 25 °C for 1 h. The mixture was filtered, washed with

diethyl ether (5 mL) and dried to give 5a as a yellow solid (1.29 g,

4.22 mmol, 94%). The spectroscopic data were identical to those

reported in the literature.^[35]

General Procedure for the Decarboxylative Coupling of 5a and Aryl

Bromides 3a–n: An oven-dried 20 mL vessel was charged with 5a

(368 mg, 1.20 mmol), copper(I) bromide (21.5 mg, 0.15 mmol), 9.25; found C 76.09, H 6.24, N 8.15, S 9.18. MS (70 eV): m/z (%)

palladium(II) 1,1,1,3,3,3-hexafluoroacetylacetonate

(5.2 mg, = 347 (33), 346 (100) [M]⁺, 345 (11), 269 (23), 223 (12), 135 (19),

Eur. J. Org. Chem. 2011, 6486–6501

www.eurjoc.org

6493

F. Collet, B. Song, F. Rudolphi, L. J. Gooßen

FULL PAPER

77 (17). IR (KBr): ν = 1605 (s), 1549 (m), 1507 (vs), 1441 (m), 1338

N-[(4-acetylphenyl)(phenyl)methylene]-NЈ,NЈ-dimethyl-p-phenyl-

enediamine (4aag): Compound 4aag was synthesized according to

the general procedure described above from 5a (368 mg,

1.20 mmol) and 1-bromo-4-chlorobenzene (3g) (199 mg,

1.00 mmol). After purification by column chromatography (hex-

ane/ethyl acetate, 80:20), 4aag (195 mg, 57%) was obtained as a

reddish brown solid (m.p. 111 °C). ¹H NMR [400 MHz, CDCl₃,

two sets of signals for (E) and (Z) isomers, ratio approx. 1.1:1]: δ

= 7.89–7.99 (m, 2 H), 7.67–7.74 and 7.80–7.85 (2 m, 2 H), 7.27–

7.47 (m, 4 H), 7.15–7.19 (m, 1 H), 6.66–7.76 (m, 2 H), 6.52–6.58

(m, 2 H), 2.90 and 2.91 (2 s, 6 H), 2.62 and 2.65 (2 s, 3 H) ppm.

¹³C NMR [101 MHz, CDCl₃, two sets of signals for (E) and (Z)

isomers]: δ = 197.6 and 197.8, 164.2 and 164.7, 147.5 and 147.7,

144.7, 142.3, 140.1, 140.0, 139.8, 137.8, 136.8, 136.5, 130.4, 129.9,

129.4, 129.0, 128.8, 128.6, 128.4, 128.2, 128.1, 128.0, 123.1 and

123.6, 112.4 and 112.6, 40.6 and 40.7, 26.6 and 26.8 ppm.

˜

(m), 1226 (m), 1164 (m), 1122 (m), 1090 (s), 958 (m), 820 (vs), 702

(vs), 670 (w) cm^–1.

N-[{4-(Dimethylamino)phenyl}(phenyl)methylene]-NЈ,NЈ-dimethyl-

p-phenylenediamine (4aad): Compound 4aad was synthesized ac-

cording to the general procedure described above from 5a (368 mg,

1.20 mmol) and 2-bromo-N,N-dimethylaniline (3d) (200 mg,

1.00 mmol). After purification by column chromatography (hex-

ane/ethyl acetate, 80:20), 4aad (170 mg, 50%) was obtained as an

1

orange solid (m.p. 173 °C). H NMR [400 MHz, CDCl₃, two sets

of signals for (E) and (Z) isomers, ratio approx. 2.1:1]: δ = 7.61–

7.69 and 7.71–7.76 (2 m, 2 H), 7.26–7.34 and 7.36–7.47 (2 m, 3 H),

7.03–7.10 and 7.16–7.23 (2 m, 2 H), 6.52–6.84 (m, 6 H), 2.99 and

3.04 (2 s, 6 H), 2.87 and 2.91 (2 s, 6 H) ppm. ¹³C NMR [101 MHz,

CDCl₃, two sets of signals for (E) and (Z) isomers]: δ = 166.1 and

166.7, 151.7, 150.1, 146.8 and 147.0, 142.1, 141.8, 141.6, 137.8,

131.5, 130.4, 129.7, 129.6, 129.4, 128.2, 127.9, 127.8, 124.0, 123.1,

122.9, 112.9 and 113.1, 111.0 and 111.1, 41.0, 40.1 and 40.2 ppm.

HRMS (EI): calcd. for C₂₃H₂₅N₃[M]⁺343.2048; found 343.2051.

MS (70 eV): m/z (%) = 344 (31), 343 (100) [M]⁺, 342 (21), 328 (12),

C

₂₃H₂₂N₂O (342.44): calcd. C 80.67, H 6.48, N 8.18; found C

80.19, H 6.55, N 8.65. HRMS (EI): calcd. for C₂₃H₂₂N₂O [M]⁺

342.1732; found 342.1720. MS (70 eV): m/z (%) = 344 (35), 343

(100) [M]⁺, 342 (19), 282 (19), 266 (23), 224 (24), 208 (35). IR

(KBr): ν = 1683 (vs), 1607 (vs), 1511 (vs), 1443 (m), 1399 (m), 1355

˜

266 (19), 208 (22), 77 (15). IR (KBr): ν = 1617 (m), 1583 (s), 1507

˜

(s), 1264 (vs), 1230 (s), 1184 (m), 1062 (m), 954 (m), 822 (s), 708

(s), 1441 (m), 1369 (m), 1343 (m), 1320 (m), 1224 (s), 1198 (m),

1164 (m), 1142 (m), 1058 (m), 942 (m), 914 (w), 816 (vs), 700 (s),

670 (m) cm^–1.

(vs), 670 (m), 604 (w), 592 (w) cm^–1.

N-[(4-Cyanophenyl)(phenyl)methylene]-NЈ,NЈ-dimethyl-p-phenyl-

enediamine (4aah): Compound 4aah was synthesized according to

the general procedure described above from 5a (368 mg,

1.20 mmol) and 4-bromobenzonitrile (3h) (182 mg, 110 μL,

1.00 mmol). After purification by column chromatography (hex-

ane/ethyl acetate, 80:20), 4aah (250 mg, 77%) was obtained as a red

solid (m.p. 148 °C). ¹H NMR [400 MHz, CDCl₃, two sets of signals

for (E) and (Z) isomers]: δ = 7.61–7.65 and 7.82–7.87 (2 m, 2 H),

7.65–7.70 (m, 2 H), 7.35–7.49 (m, 3 H), 7.14–7.19 and 7.27–7.33 (2

m, 2 H), 6.63–6.68 and 6.71–6.76 (2 m, 2 H), 6.52–6.58 (m, 2 H),

2.92 (s, 6 H) ppm. ¹³C NMR [101 MHz, CDCl₃, two sets of signals

for (E) and (Z) isomers]: δ = 162.9 and 163.6, 147.7 and 148.0,

144.6, 142.2, 139.7, 139.4, 139.3, 136.4, 132.0, 131.8, 130.6, 130.3,

129.3, 129.2, 128.7, 128.6, 128.3, 123.8, 123.1, 118.8, 118.4, 113.0,

112.5, 112.2, 112.0. 40.56 and 40.62 ppm. C₂₂H₁₉N₃(325.41):

calcd. C 81.20, H 5.89, N 12.91; found C 81.24, H 5.85, N 12.97.

MS (70 eV): m/z (%) = 327 (35), 326 (100), 325 (12) [M]⁺, 249 (16),

N-[(2-Methoxyphenyl)(phenyl)methylene]-NЈ,NЈ-dimethyl-p-phen-

ylenediamine (4aae): Compound 4aae was synthesized according to

the general procedure described above from 5a (368 mg,

1.20 mmol) and 2-bromoanisole (3e) (187 mg, 125 μL, 1.00 mmol).

After purification by column chromatography (hexane/ethyl acet-

ate, 80:20), 4aae (190 mg, 58%) was obtained as an orange solid

(m.p. 93 °C). ¹H NMR (400 MHz, CDCl₃): δ = 7.72–7.77 (m, 2 H),

7.26–7.41 (m, 4 H), 6.97–7.02 (m, 1 H), 6.83–6.92 (m, 2 H), 6.71–

6.76 (m, 2 H), 6.51–6.57 (m, 2 H), 3.59 (s, 3 H), 2.84 (s, 6 H) ppm.

¹³C NMR (101 MHz, CDCl₃): δ = 163.8, 156.9, 147.4, 141.3, 140.0,

130.0, 129.9, 129.6, 128.2, 126.7, 122.2, 120.4, 112.5, 110.9, 55.3,

40.9 ppm. C₂₂H₂₂N₂O (330.43): calcd. C 79.97, H 6.71, N 8.48;

found C 80.05, H 6.69, N 8.49. MS (70 eV): m/z (%) = 331 (25),

330 (97) [M]⁺, 167 (21), 136 (100), 135 (69), 121 (23), 77 (25). IR

(KBr): ν = 1605 (s), 1509 (vs), 1485 (s), 1443 (s), 1345 (m), 1248

˜

(s), 1228 (s), 1166 (m), 1108 (m), 1046 (w), 1022 (m), 956 (m), 816

224 (34), 208 (18), 77 (26), 51 (14). IR (KBr): ν = 2227 (m), 1609

˜

(m), 754 (s), 698 (s) cm^–1.

(s), 1513 (vs), 1443 (s), 1359 (s), 1318 (m), 1284 (w), 1230 (m), 1170

(m), 1066 (w), 950 (m), 814 (s), 782 (m), 698 (s) cm^–1.

N,N-Dimethyl-NЈ-[(2-naphthyl)(phenyl)methylene]-p-phenylenedi-

amine (4aaf): Compound 4aaf was synthesized according to the

general procedure described above from 5a (368 mg, 1.20 mmol)

and 2-bromonaphthalene (3f) (207 mg, 1.00 mmol). After purifica-

tion by column chromatography (hexane/ethyl acetate, 85:15), 4aaf

N-[{4-(Ethoxycarbonyl)phenyl}(phenyl)methylene]-NЈ,NЈ-dimethyl-

p-phenylenediamine (4aai): Compound 4aai was synthesized ac-

cording to the general procedure described above from 5a (368 mg,

1.20 mmol) and ethyl 4-bromobenzoate (3i) (229 mg, 160 μL,

1.00 mmol). After purification by column chromatography (hex-

ane/ethyl acetate, 80:20), 4aai (260 mg, 70%) was obtained as a red

1

(185 mg, 53%) was obtained as an orange solid (m.p. 119 °C). H

NMR [400 MHz, CDCl₃, two sets of signals for (E) and (Z) iso-

mers, ratio approx. 1.2:1]: δ = 7.99–8.02 and 8.11–8.15 (2 m, 1 H),

7.35–7.56 and 7.71–7.93 (2 m, 5 H), 6.73–6.82 and 7.23–7.29 (2 m,

2 H), 6.49–6.56 and 6.56–6.63 (2 m, 1 H), 2.86 and 2.91 (2 s, 6 H)

1

solid (m.p. 81 °C). H NMR [400 MHz, CDCl₃, two sets of signals

for (E) and (Z) isomers]: δ = 7.96–8.11 (m, 2 H), 7.67–7.82 (m, 2

H), 7.15–7.48 (m, 5 H), 6.66–6.78 (m, 2 H), 6.52–6.60 (m, 2 H),

ppm. ¹³C NMR [101 MHz, CDCl₃, two sets of signals for (E) and 4.36–4.47 (m, 2 H), 2.895 and 2.905 (2 s, 6 H), 1.38–1.47 (m, 3 H)

(Z) isomers]: δ = 165.7 and 165.8, 147.4, 140.8, 140.7, 140.6, 138.0,

137.3, 134.9, 134.3, 132.9, 132.8, 130.1, 129.9, 129.7, 129.3, 129.2,

128.9, 128.3, 128.2, 128.1, 127.8, 127.7, 127.6, 127.1, 127.0, 126.6,

126.2, 126.1, 125.6, 123.3 and 123.4, 112.6 and 112.7, 40.7 and

40.8 ppm. C₂₅H₂₂N₂(350.46): calcd. C 85.68, H 6.33, N 7.99; found

C 85.52, H 6.13, N 7.96. MS (70 eV): m/z (%) = 352 (36), 351 (100),

ppm. ¹³C NMR [101 MHz, CDCl₃, two sets of signals for (E) and

(Z) isomers]: δ = 166.2 and 166.3, 164.5 and 164.9, 147.5 and 147.7

142.0, 140.2, 140.1, 139.9, 136.9, 131.4, 130.3, 130.1, 129.6, 129.4,

129.3, 129.2, 128.84, 128.82, 128.5, 128.3, 128.2, 123.1 and 123.5,

112.4 and 112.6, 61.05 and 61.09, 40.67 and 40.70, 14.3 ppm.

C₂₄H₂₄N₂O₂(372.47): calcd. C 77.39, H 6.49, N 7.52; found C

349 (13) [M]⁺, 274 (19), 224 (16), 208 (15), 136 (30), 77 (20). IR 77.37, H 6.48, N 7.51. MS (70 eV): m/z (%) = 373 (35), 372 (100)

(KBr): ν = 1605 (m), 1507 (s), 1441 (m), 1347 (m), 1226 (m), 1180 [M]⁺, 344 (31), 299 (13), 223 (21), 135 (14), 77 (15). IR (KBr): ν =

˜

2793 (w), 1719 (s), 1607 (m), 1507 (s), 1443 (m), 1272 (vs), 1228

(s), 1100 (vs), 1014 (m), 958 (m), 820 (s), 782 (m), 710 (s) cm^–1.

(m), 1166 (w), 1116 (w), 1060 (w), 936 (w), 896 (w), 818 (vs), 750

(m), 704 (vs) cm^–1.

6494

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Eur. J. Org. Chem. 2011, 6486–6501

Decarboxylative Coupling for the Synthesis of Azomethines and Ketones

N,N-Dimethyl-NЈ-[{4-(trifluoromethyl)phenyl}(phenyl)methylene]-

p-phenylenediamine (4aaj): Compound 4aaj was synthesized ac-

cording to the general procedure described above from 5a (368 mg,

1.20 mmol) and ethyl 4-bromo-4-(trifluoromethyl)benzene (3j)

(227 mg, 142 μL, 1.00 mmol). After purification by column

chromatography (hexane/ethyl acetate, 85:15), 4aaj (303 mg, 82%)

was obtained as a red solid (m.p. 117 °C). ¹H NMR [400 MHz,

CDCl₃, two sets of signals for (E) and (Z) isomers]: δ = 7.69–7.74

and 7.84–7.89 (2 m, 2 H), 7.58–7.68 (m, 2 H), 7.27–7.52 (m, 4 H),

7.16–7.22 (m, 1 H), 6.67–6.78 (m, 2 H), 6.54–6.61 (m, 2 H), 2.92

(s, 6 H) ppm. ¹³C NMR [101 MHz, CDCl₃, two sets of signals for

(E) and (Z) isomers]: δ = 163.9 and 164.2, 147.6 and 147.8, 141.0,

(m), 1262 (vs), 1104 (vs), 1086 (vs), 1026 (s), 820 (vs), 802 (vs), 708

(m) cm^–1.

N,N-Dimethyl-NЈ-[(phenyl)(3-pyridyl)methylene]-p-phenylenedi-

amine (4aam): Compound 4aam was synthesized according to the

general procedure described above from 5a (368 mg, 1.20 mmol)

and 3-bromopyridine (3m) (158 mg, 96.3 μL, 1.00 mmol). The

crude product was purified by Kugelrohr distillation in vacuo

(Ͼ250 °C, 2.4ϫ10^–2mbar), which yielded 4aam (254 mg, 84%) as

1

a red oil. H NMR [400 MHz, CDCl₃, two sets of signals for (E)

and (Z)isomers]: δ = 8.60–8.64 and 8.81–8.85 (2 m, 1 H), 8.38–8.42

and 8.51–8.54 (2 m, 1 H), 7.65–7.72 (m, 1 H), 7.35–7.49 (m, 2 H),

7.27–7.35 (m, 2 H), 7.20–7.24 and 8.03–8.08 (2 m, 1 H), 7.12–7.18

(m, 1 H), 6.61–6.75 (m, 2 H), 6.48–6.55 (m, 2 H), 2.86 and 2.87 (2

s, 6 H) ppm. ¹³C NMR [101 MHz, CDCl₃, two sets of signals for

(E) and (Z) isomers]: δ = 162.9 and 163.0, 150.6, 150.4, 150.2,

149.2, 147.6 and 147.7, 140.1, 139.8, 139.7, 137.1, 136.2, 136.2,

135.9, 133.0, 130.5, 129.3, 128.8, 128.7, 128.6, 128.4, 128.3, 123.5,

122.96 and 123.00, 112.4 and 112.7, 40.6 and 40.7 ppm. HRMS

(EI): calcd. for C₂₀H₁₉N₃[M]⁺301.1579; found 301.1594. MS

(70 eV): m/z (%) = 302 (27), 301 (100) [M]⁺, 300 (21), 224 (21), 223

1

140.0, 139.9, 139.8, 133.5 (q, J_C,F= approx. 630 Hz), 130.2 and

2

131.5 (q, J_C,F= 32.7 and 32.1 Hz), 130.0, 129.4, 129.2, 128.8,

128.6, 128.4, 128.2, 125.0 and 125.1 (q, ³J_C,F= 3.69 Hz), 123.1 and

123.5, 122.5 and 122.7, 112.4 and 112.6, 40.6 and 40.7 ppm. ¹⁹F

NMR (376 MHz, CDCl₃): δ = –62.6 (s, 3 F) ppm. C₂₂H₁₉F₃N₂

(368.40): calcd. C 71.73, H 5.20, N 7.60; found C 71.75, H 5.26, N

7.69. MS (70 eV): m/z (%) = 369 (35), 368 (100) [M]⁺, 291 (15), 223

(28), 135 (14), 77 (19), 42 (10). IR (KBr): ν = 1609 (s), 1507 (vs),

˜

1443 (m), 1407 (m), 1351 (m), 1320 (vs), 1166 (s), 1128 (vs), 1108

(s), 1064 (vs), 1014 (m), 960 (w), 948 (w), 860 (m), 818 (m), 706

(m), 678 (w) cm^–1.

(31), 135 (29), 77 (30). IR (NaCl): ν = 1659 (s), 1613 (vs), 1503

˜

(vs), 1443 (vs), 1413 (s), 1351 (vs), 1228 (s), 1166 (s), 1062 (m),

1026 (m), 948 (s), 822 (s), 752 (m), 706 (m) cm^–1.

N-[(4-Fluorophenyl)(phenyl)methylene]-NЈ,NЈ-dimethyl-p-phenylene-

diamine (4aak): Compound 4aak was synthesized according to the

general procedure described above from 5a (368 mg, 1.20 mmol)

and 1-bromo-4-fluorobenzene (3k) (175 mg, 110 μL, 1.00 mmol).

After purification by column chromatography (hexane/ethyl acet-

ate, 85:15), 4aak (240 mg, 75%) was obtained as an orange solid

N-[(2-Mesityl)(phenyl)methylene]-NЈ,NЈ-dimethyl-p-phenylenedi-

amine (4aan): Compound 4aan was synthesized according to the

general procedure described above from 5a (368 mg, 1.20 mmol)

and 2-bromomesitylene (3n) (199 mg, 153 μL, 1.00 mmol). GC

yield: 10%. MS (70 eV): m/z (%) = 343 (27), 342 (100) [M]⁺, 341

(55), 325 (21), 207 (29), 192 (22), 77 (24).

1

(m.p. 95 °C). H NMR [400 MHz, CDCl₃, two sets of signals for

General Procedure for the One-Pot Three-Component Azomethine

Synthesis: An oven-dried 20 mL vessel was charged with potassium

2-aryl-2-oxoacetate (1a–i, 1.20 mmol), copper(I) bromide (21.5 mg,

0.15 mmol), palladium(II) 1,1,1,3,3,3-hexafluoroacetylacetonate

(5.2 mg, 0.01 mmol), 1,10-phenanthroline (27.0 mg, 0.15 mmol),

1,1Ј-bis(diphenylphosphanyl)ferrocene (5.7 mg, 0.01 mmol) and ac-

tivated ground 3 Å molecular sieves (200 mg). The reaction vessel

was evacuated and flushed with nitrogen three times. Subsequently,

a solution of the appropriate aryl halide (3a–t, 1.00 mmol), amine

(2a–j, 1.20 mmol) and n-tetradecane (50 μL) in NMP (2 mL) was

added by syringe. The resulting mixture was stirred at 100 °C for

16 h, diluted with saturated sodium hydrogencarbonate solution

(20 mL) and extracted repeatedly with ethyl acetate (20 mL por-

tions). The combined organic layers were washed with saturated

sodium hydrogencarbonate solution, water and brine, dried with

MgSO₄, filtered, and the volatiles were removed in vacuo. The resi-

due was purified by Kugelrohr distillation in vacuo (130 °C/

4ϫ10^–3mbar), which yielded the corresponding azomethine 4.

(E) and (Z) isomers, ratio approx. 1.1:1]: δ = 7.66–7.75 (m, 2 H),

7.26–7.35 and 7.35–7.46 (2 m, 3 H), 6.95–7.09 and 7.10–7.19 (2 m,

4 H), 6.64–6.72 (m, 2 H), 6.49–6.60 (m, 2 H), 2.86 and 2.88 (2 s, 6

H) ppm. ¹³C NMR [101 MHz, CDCl₃, two sets of signals for (E)

1

and (Z) isomers]: δ = 164.6 and 165.0, 162.3 and 164.1 (d, J_C,F

=

248.8 and 250.6 Hz), 147.4, 140.6, 140.5, 140.4, 137.0, 133.1 and

4

3

136.7 (d, J_C,F= 3.7 and 2.8 Hz), 131.0 and 131.6 (2d, J_C,F

=

8.3 Hz), 130.2, 129.5, 129.0, 128.4, 128.1 and 128.2, 123.0 and

2

123.2, 115.0 and 115.2 (2d, J_C,F= 21.3 and 22.2 Hz), 112.6 and

112.7, 40.8 ppm. ¹⁹F NMR [376 MHz, CDCl₃, two sets of signals

for (E) and (Z) isomers]: δ = –110.8 and –112.1 (s, 1 F) ppm.

C₂₁H₁₉FN₂(318.39): calcd. C 79.22, H 6.01, N 8.80; found C 79.22,

H 6.39, N 8.90. MS (70 eV): m/z (%) = 319 (29), 318 (100) [M]⁺,

317 (15), 241 (28), 223 (19), 135 (23), 77 (22). IR (KBr): ν = 1611

˜

(m), 1595 (m), 1507 (vs), 1441 (m), 1353 (m), 1288 (m), 1224 (s),

1166 (m), 1064 (m), 958 (m), 846 (m), 806 (s), 690 (s), 534 (m) cm^–1.

N-[(4-Chlorophenyl)(phenyl)methylene]-NЈ,NЈ-dimethyl-p-phenylene-

diamine (4aal): Compound 4aal was synthesized according to the

general procedure described above from 5a (368 mg, 1.20 mmol)

and 1-bromo-4-chlorobenzene (3l) (175 mg, 110 μL, 1.00 mmol).

After purification by column chromatography (hexane/ethyl acet-

ate, 80:20), 4aal (298 mg, 86%) was obtained as an orange solid

N-[(Phenyl)(4-tolyl)methylene]cyclohexanamine (4aba): Compound

4aba was synthesized according to the general procedure described

above from potassium 2-oxo-2-phenylacetate (1a) (226 mg,

1.20 mmol), cyclohexanamine (2b) (119 mg, 137 μL, 1.20 mmol)

and 4-bromotoluene (3a) (171 mg, 122 μL, 1.00 mmol). After distil-

lation, 4aba (252 mg, 91%) was obtained as a pale yellow oil. The

spectroscopic data (NMR, GC–MS, IR) were identical to those

reported in the literature.^[35]

1

(m.p. 127 °C). H NMR [400 MHz, CDCl₃, two sets of signals for

(E) and (Z) isomers]: δ = 7.66–7.74 (m, 2 H), 7.26–7.48 (m, 5 H),

7.11–7.19 (m, 2 H), 6.67–6.74 (m, 2 H), 6.52–6.62 (m, 2 H), 2.90

and 2.92 (2 s, 6 H) ppm. ¹³C NMR [101 MHz, CDCl₃, two sets of

signals for (E) and (Z) isomers]: δ = 164.5 and 164.7, 147.4 and

147.5, 140.4, 140.3, 140.2, 139.0, 136.8, 136.1, 135.6, 134.2, 131.1,

130.3, 129.4, 128.9, 128.4, 128.3, 128.1, 123.1 and 123.3, 112.5 and

112.7, 40.7 and 40.8 ppm. C₂₁H₁₉ClN₂(334.85): calcd. C 75.33, H

N-[(4-Methoxyphenyl)(phenyl)methylene]cyclohexanamine (4abb):

Compound 4abb was synthesized according to the general pro-

cedure described above from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 4-bromoanisole (3b) (187 mg, 126 μL,

5.72, N 8.37; found C 75.01, H 5.82, N 8.46. MS (70 eV): m/z (%) 1.00 mmol). After distillation, 4abb (263 mg, 90%) was obtained as

= 337 (35), 336 (36), 335 (100), 334 (12) [M]⁺, 258 (24), 224 (26),

a yellow oil. The spectroscopic data (NMR, GC–MS, IR) were

136 (23), 77 (29). IR (KBr): ν = 1607 (m), 1507 (s), 1441 (m), 1339

identical to those reported in the literature.^[35]

˜

Eur. J. Org. Chem. 2011, 6486–6501

www.eurjoc.org

6495

F. Collet, B. Song, F. Rudolphi, L. J. Gooßen

FULL PAPER

N-[(4-Methylsulfanylphenyl)(phenyl)methylene]cyclohexanamine

(4abc): Compound 4abc was synthesized according to the general

procedure described above from 1a (226 mg, 1.20 mmol), 2b

(119 mg, 137 μL, 1.20 mmol) and 4-bromothioanisole (3c) (203 mg,

1.00 mmol). After distillation, 4abc (285 mg, 92%) was obtained as

1.3:1]: δ = 8.29 and 8.38 (2 s, 1 H), 7.63–7.69 and 7.75–7.86 (2 m,

2 H), 7.54–7.63 (m, 2 H), 7.24–7.37 and 7.38–7.54 (2 m, 3 H), 7.10–

7.16 and 7.16–7.23 (2 m, 2 H), 3.12–3.29 (m, 2 H), 1.50–1.89 (m,

14 H), 1.05–1.45 (m, 6 H) ppm. ¹³C NMR [101 MHz, CDCl₃, two

sets of signals for (E) and (Z) isomers]: δ = 164.9 and 165.0, 157.9

a pale yellow oil. The spectroscopic data (NMR, GC–MS, IR) were and 158.1, 142.0, 139.9, 139.4, 137.4, 137.1, 136.3, 129.6, 128.5,

identical to those reported in the literature.^[35]

128.3, 128.2, 128.1, 128.0, 127.9, 127.7, 127.6, 127.5, 69.9 and 70.0,

61.4 and 61.5, 34.2 and 34.3, 33.8, 25.55 and 25.58, 24.67 and

24.71, 24.3 ppm. HRMS (EI): calcd. for C₂₆H₃₂N₂[M]⁺372.2565;

found 372.2545. MS (70 eV): m/z (%) = 374 (38), 372 (100) [M]⁺,

N-{[4-(Dimethylamino)phenyl](phenyl)methylene}cyclohexanamine

(4abd): Compound 4abd was synthesized according to the general

procedure described above from 1a (226 mg, 1.20 mmol), 2b

(119 mg, 137 μL, 1.20 mmol) and 4-bromo-N,N-dimethylaniline

(3d) (200 mg, 1.00 mmol). After distillation, 4abd (260 mg, 85%)

was obtained as an orange oil. The spectroscopic data (NMR, GC–

MS, IR) were identical to those reported in the literature.^[35]

296 (90), 291 (29), 290 (97), 207 (29), 55 (60). IR (NaCl): ν = 2925

˜

(vs), 2851 (s), 1641 (m), 1485 (w), 1447 (m), 1381 (w), 1345 (w),

1294 (w), 1148 (w), 1068 (m), 1010 (w), 966 (w), 888 (w), 854 (w),

830 (w), 820 (w), 776 (w), 756 (w), 696 (w) cm^–1.

N-[(4-Cyanophenyl)(phenyl)methylene]cyclohexanamine (4abh):

Compound 4abh was synthesized according to the general pro-

cedure described above from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 4-bromobenzonitrile (3h) (182 mg,

1.00 mmol). After distillation, 4abh (274 mg, 95%) was obtained as

a pale yellow oil. The spectroscopic data (NMR, GC–MS, IR) were

identical to those reported in the literature.^[35]

N-[(2-Methoxyphenyl)(phenyl)methylene]cyclohexanamine (4abe):

Compound 4abe was synthesized according to the general pro-

cedure described above from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 2-bromoanisole (3e) (187 mg, 125 μL,

1.00 mmol). After distillation, 4abe (251 mg, 86%) was obtained as

a pale yellow oil. The spectroscopic data (NMR, GC–MS, IR) were

identical to those reported in the literature.^[35]

Ethyl 4-[(Cyclohexylimino)(phenyl)methyl]benzoate (4abi): Com-

pound 4abi was synthesized according to the general procedure de-

scribed above from 1a (226 mg, 1.20 mmol), 2b (119 mg, 137 μL,

1.20 mmol) and ethyl 4-bromobenzoate (3i) (229 mg, 160 μL,

1.00 mmol). After distillation, 4abi (277 mg, 83%) was obtained as

a pale yellow oil. The spectroscopic data (NMR, GC–MS, IR) were

identical to those reported in the literature.^[35]

N-[(2-Naphthylphenyl)methylene]cyclohexanamine (4abf): Com-

pound 4abf was synthesized according to the general procedure

described above from 1a (226 mg, 1.20 mmol), 2b (119 mg, 137 μL,

1.20 mmol) and 2-bromonaphthalene (3f) (207 mg, 1.00 mmol).

After distillation, 4abf (292 mg, 93%) was obtained as a yellow oil.

The spectroscopic data (NMR, GC–MS, IR) were identical to

those reported in the literature.^[35]

N-{(Phenyl)[4-(trifluoromethyl)phenyl]methylene}cyclohexanamine

(4abj): Compound 4abj was synthesized according to the general

procedure described above from 1a (226 mg, 1.20 mmol), 2b

(119 mg, 137 μL, 1.20 mmol) and 4-bromobenzotrifluoride (3j)

(227 mg, 142 μL, 1.00 mmol). After distillation, 4abj (215 mg, 65%)

was obtained as a red oil. The spectroscopic data (NMR, GC–MS,

IR) were identical to those reported in the literature.^[35]

N-[(1-Naphthyl)(phenyl)methylene]cyclohexanamine (4abo): Com-

pound 4abo was synthesized at 100 °C according to the general

procedure described above from 1a (226 mg, 1.20 mmol), 2b

(119 mg, 137 μL, 1.20 mmol) and 1-bromonaphthalene (3o)

(207 mg, 140 μL, 1.00 mmol). After distillation, 4abo (183 mg,

1

58%) was obtained as an orange oil. H NMR (400 MHz, CDCl₃,

some split signals for the cyclohexane ring): δ = 7.93–7.99 (m, 2

H), 7.64–7.72 (m, 3 H), 7.56–7.63 (m, 1 H), 7.50–7.56 (m, 1 H),

7.40–7.46 (m, 1 H), 7.26–7.40 (m, 4 H), 3.05–3.11 (m, 1 H), 1.50–

1.82 (m, 7 H), 0.91–1.40 (m, 3 H) ppm. ¹³C NMR (101 MHz,

CDCl₃, some split signals for the cyclohexane ring): δ = 164.5,

140.1, 135.6, 133.3, 130.8, 129.7, 128.3, 128.2, 128.1, 127.9, 126.5,

126.2, 125.6, 125.14, 125.08, 61.8, 33.8 and 33.7, 25.6, 24.3 and

24.1 ppm. HRMS (EI): calcd. for C₂₃H₂₃N [M]⁺313.1830; found

313.1819. MS (70 eV): m/z (%) = 315 (30), 314 (100), 313 (81)

N-[(4-Nitrophenyl)(phenyl)methylene]cyclohexanamine (4abr): Com-

pound 4abr was synthesized according to the general procedure

described above from 1a (226 mg, 1.20 mmol), 2b (119 mg, 137 μL,

1.20 mmol) and 1-bromo-4-nitrobenzene (3r) (202 mg, 1.00 mmol).

After distillation, 4abr (175 mg, 57%) was obtained as an orange

oil. The spectroscopic data (NMR, GC–MS, IR) were identical to

those reported in the literature.^[35]

N-[(4-Chlorophenyl)(phenyl)methylene]cyclohexanamine (4abl):

Compound 4abl was synthesized according to the general pro-

cedure described above from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 1-bromo-4-chlorobenzene (3l) (175 mg,

110 μL, 1.00 mmol). After distillation, 4abl (280 mg, 94%) was ob-

tained as a pale yellow oil. The spectroscopic data (NMR, GC–

MS, IR) were identical to those reported in the literature.^[35]

[M]⁺, 232 (17), 231 (44), 216 (36), 128 (23). IR (NaCl): ν = 3057

˜

(m), 2927 (vs), 2853 (s), 1619 (m), 1505 (w), 1445 (m), 1286 (w),

1254 (w), 1214 (w), 1176 (w), 1026 (w), 960 (w), 800 (m), 758 (m),

694 (w) cm^–1.

N-[(9-Phenanthryl)(phenyl)methylene]cyclohexanamine (4abp):

Compound 4abp was synthesized according to the general pro-

cedure described above from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 9-bromophenanthrene (3p) (257 mg,

1.00 mmol). After distillation, 4abp (240 mg, 66%) was obtained as

a yellow oil. The spectroscopic data (NMR, GC–MS, IR) were

identical to those reported in the literature.^[35]

N-[(Phenyl)(3-pyridyl)methylene]cyclohexanamine (4abm): Com-

pound 4abm was synthesized according to the general procedure

described above from 1a (226 mg, 1.20 mmol), 2b (119 mg, 137 μL,

1.20 mmol) and 3-bromopyridine (3m) (158 mg, 96 μL, 1.00 mmol).

After distillation, 4abm (240 mg, 91%) was obtained as a pale yel-

low oil. The spectroscopic data (NMR, GC–MS, IR) were identical

to those reported in the literature.^[35]

N-{4-[N-(Cyclohexylcarboximidoyl)phenyl](phenyl)methylene}-

cyclohexanamine (4abq): Compound 4abq was synthesized accord-

ing to the general procedure described above from 1a (226 mg,

1.20 mmol), 2b (218 mg, 252 μL, 2.20 mmol) and 4-bromobenz-

N-[(Phenyl)(2-pyridyl)methylene]cyclohexanamine (4abs): Com-

pound 4abs was synthesized according to the general procedure

described above from 1a (226 mg, 1.20 mmol), 2b (119 mg, 137 μL,

aldehyde (3q) (185 mg, 1.00 mmol). After distillation, 4abq

1

(200 mg, 54%) was obtained as a yellow oil. H NMR [400 MHz, 1.20 mmol), and 1-bromopyridine (3s) (158 mg, 96 μL, 1.00 mmol).

CDCl₃, two sets of signals for (E) and (Z) isomers, ratio approx.

After distillation, 4abs (123 mg, 47%) was obtained as a light yel-

6496

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Eur. J. Org. Chem. 2011, 6486–6501

Decarboxylative Coupling for the Synthesis of Azomethines and Ketones

low oil. ¹H NMR [400 MHz, CDCl₃, two sets of signals for (E)

and (Z) isomers, ratio approx. 1.3:1]: δ = 8.53–8.60 and 8.69–8.76

(2 m, 1 H), 7.85–7.95 and 8.00–8.09 (2 m, 1 H), 7.63–7.81 (m, 1

H), 7.50–7.61 (m, 1 H), 7.36–7.50 (m, 2 H), 7.12–7.24 and 7.26–

7.36 (2 m, 3 H), 3.07–3.18 and 3.25–3.37 (2 m, 1 H), 1.50–1.81 (m,

7 H), 1.02–1.31 (m, 3 H) ppm. ¹³C NMR [101 MHz, CDCl₃, two

sets of signals for (E) and (Z) isomers]: δ = 163.9 and 165.8, 156.3

and 157.8, 149.8, 149.0, 136.6, 136.1, 136.0, 130.9, 129.7, 128.2,

128.11, 128.06, 128.0, 127.7, 123.6, 123.0, 122.9, 122.7, 61.4 and

61.6, 33.7, 25.5, 24.29, 24.33 ppm. HRMS (EI): calcd. for

approx. 1.6:1]: δ = 7.44–7.48 and 7.50–7.56 (2 m, 2 H), 7.25–7.28

and 7.40–7.44 (2 m, 2 H), 7.00–7.05 and 7.07–7.15 und 7.22–7.25

(3 m, 4 H), 3.13–3.30 (m, 1 H), 2.35 and 2.43 (2 s, 3 H), 1.54–1.79

(m, 7 H), 1.10–1.33 (m, 3 H) ppm. ¹³C NMR [101 MHz, CDCl₃,

two sets of signals for (E) and (Z) isomers]: δ = 164.1 and 164.5,

139.1 and 139.8, 137.3 and 138.0, 135.5 and 135.9, 133.8 and 133.9,

129.6, 129.1, 128.7, 128.6, 128.2, 128.0, 127.5, 61.3 and 61.4, 33.9,

25.6, 24.3, 21.2 and 21.3 ppm. HRMS (EI): calcd. for C₂₀H₂₂³⁵ClN

[M]⁺311.1441; found 311.1426, and calcd. for C₂₀H₂₂³⁷ClN [M]⁺

313.1411; found 313.1409. MS (70 eV): m/z (%) = 312 (100), 311

C₁₈H₂₀N₂[M]⁺264.1626; found 264.1622. MS (70 eV): m/z (%) = (36), 310 (82) [M]⁺, 268 (33), 256 (43), 200 (56), 179 (31). IR

264 (35) [M]⁺, 222 (20), 221 (100), 208 (23), 207 (19), 168 (21), 167

(17). IR (NaCl): ν = 2927 (vs), 2853 (s), 1665 (s), 1579 (m), 1445

(NaCl): ν = 2927 (vs), 2853 (vs), 1659 (w), 1619 (s), 1589 (m), 1567

˜

(m), 1509 (m), 1485 (s), 1447 (m), 1397 (m), 1288 (m), 1174 (w),

˜

(m), 1433 (m), 1304 (m), 1282 (m), 1246 (m), 1162 (m), 994 (m), 1090 (m), 1068 (w), 1014 (m), 968 (m), 888 (w), 824 (m), 792 (w),

970 (w), 940 (m), 744 (w), 696 (m), 652 (w) cm^–1.

756 (m), 732 (m) cm^–1.

N-[(Phenyl)(3-thienyl)methylene]cyclohexanamine (4abt): Com-

pound 4abt was synthesized according to the general procedure

described above from 1a (226 mg, 1.20 mmol), 2b (119 mg, 137 μL,

1.20 mmol) and 3-bromothiophene (3t) (163 mg, 94 μL,

1.00 mmol). After distillation, 4abt (230 mg, 85%) was obtained as

a pale yellow oil. The spectroscopic data (NMR, GC–MS, IR) were

identical to those reported in the literature.^[35]

N-{[2-(2-Furyl)](4-tolyl)methylene}cyclohexanamine (4fba): Com-

pound 4fba was synthesized according to the general procedure

described above from potassium 2-(2-furyl)-2-oxoacetate (1f)

(214 mg, 1.20 mmol), 2b (119 mg, 137 μL, 1.20 mmol) and 3a

(171 mg, 123 μL, 1.00 mmol). After distillation, 4fba (230 mg,

85%) was obtained as a brown oil. The spectroscopic data (NMR,

GC–MS, IR) were identical to those reported in the literature.^[35]

N-[Bis(4-tolyl)methylene]cyclohexanamine (4bba): Compound 4bba

was synthesized according to the general procedure described

above from potassium 2-oxo-2-(4-tolyl)acetate (1b) (243 mg,

1.20 mmol), 2b (119 mg, 137 μL, 1.20 mmol) and 3a (171 mg,

123 μL, 1.00 mmol). After distillation, 4bba (80 mg, 62%) was ob-

tained as a red oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.51–7.57 (m,

2 H), 7.23–7.30 (m, 2 H), 7.05–7.11 (m, 2 H), 7.11–7.17 (m, 2 H),

N-[(2-Thienyl)(4-tolyl)methylene]cyclohexanamine (4gba): Com-

pound 4gba was synthesized according to the general procedure

described above from potassium 2-oxo-2-(2-thienyl)acetate (1g)

(233 mg, 1.20 mmol), 2b (119 mg, 137 μL, 1.20 mmol) and 3a

(171 mg, 123 μL, 1.00 mmol). After distillation, 4gba (150 mg,

53 %) was obtained as a brown solid (m.p. 78 °C). ¹H NMR

[400 MHz, CDCl₃, two sets of signals for (E) and (Z) isomers, ratio

approx. 9:1]: δ = 7.31–7.37 and 7.50–7.56 (2 m, 1 H), 7.24–7.39 and

7.44–7.48 (2 m, 2 H), 7.10–7.16 (m, 2 H), 6.90–6.95 and 7.00–7.02

(2 m, 1 H), 6.70–6.75 (m, 1 H), 3.21 and 3.44–3.53 (q and m, ³J_H,H

= 7.1 Hz, 1 H), 2.37 and 2.44 (2 s, 3 H), 1.53–1.80 (m, 7 H), 1.10–

1.30 (m, 3 H) ppm. ¹³C NMR [101 MHz, CDCl₃, two sets of sig-

nals for (E) and (Z) isomers]: δ = 160.5, 147.9, 138.1, 133.6, 129.7,

128.9, 128.7, 128.3, 127.5, 126.9, 60.7, 33.8 und 34.1, 25.6 und 25.7,

24.3 und 24.4, 21.3 ppm. HRMS (EI): calcd. for C₁₈H₂₁NS [M]⁺

283.1395; found 283.1391. MS (70 eV): m/z (%) = 283 (74) [M]⁺,

282 (99), 250 (100), 240 (36), 192 (46), 186 (41), 171 (47). IR

3

3.30 (q, J_H,H= 7.1 Hz, 1 H), 2.44 (s, 3 H), 2.36 (s, 3 H), 1.57–1.84

(m, 7 H), 1.14–1.39 (m, 3 H) ppm. ¹³C NMR (101 MHz, CDCl₃):

δ = 165.4, 139.3, 137.9, 137.5, 134.5, 128.8, 128.5, 128.2, 127.5,

61.1, 33.9, 25.6, 24.3, 21.2, 21.1 ppm. HRMS (EI): calcd. for

C₂₁H₂₅N [M]⁺291.1987; found 291.1977. MS (70 eV): m/z (%) =

292 (32), 291 (39) [M]⁺, 290 (100), 200 (85), 179 (34), 118 (37), 91

(31). IR (NaCl): ν = 2919 (vs), 2853 (vs), 1659 (m), 1621 (s), 1605

˜

(s), 1505 (s), 1447 (s), 1405 (m), 1310 (s), 1292 (s), 1256 (m), 1180

(s), 1112 (m), 1068 (m), 1038 (w), 1020 (m), 968 (m), 932 (w), 890

(w), 822 (m), 778 (m), 756 (m), 732 (m) cm^–1.

N-[(4-Methoxyphenyl)(4-tolyl)methylene]cyclohexanamine (4cba):

Compound 4cba was synthesized according to the general pro-

cedure described above from potassium 2-(4-methoxyphenyl)-2-

oxoacetate (1c) (262 mg, 1.20 mmol), 2b (119 mg, 137 μL,

1.20 mmol) and 3a (171 mg, 123 μL, 1.00 mmol). After distillation,

4cba (105 mg, 34%) was obtained as a pale yellow oil. The spectro-

scopic data (NMR, GC–MS, IR) were identical to those reported

in the literature.^[35]

(NaCl): ν = 2921 (s), 2849 (s), 1601 (vs), 1445 (vs), 1429 (vs), 1290

˜

(s), 1260 (s), 1230 (s), 1108 (s), 1068 (vs), 1046 (s), 1018 (s), 842 (s),

818 (s), 804 (s), 780 (m), 700 (s) cm^–1.

N-[(2,5-Dimethylphenyl)(p-tolyl)methylene]cyclohexanamine (4hba):

Compound 4hba was synthesized according to the general pro-

cedure described above from potassium 2-(2,5-dimethylphenyl)-2-

oxoacetate (1h) (260 mg, 1.20 mmol), 2b (119 mg, 137 μL,

1.20 mmol) and 3a (171 mg, 123 μL, 1.00 mmol). After distillation,

4hba (200 mg, 66%) was obtained as a colourless solid (m.p. 87 °C).

The spectroscopic data (NMR, GC–MS, IR) were identical to

those reported in the literature.^[35]

4-[(Cyclohexylimino)(4-tolyl)methyl]benzonitrile (4dba): Compound

4dba was synthesized according to the general procedure described

above from potassium 2-(4-cyanophenyl)-2-oxoacetate (1d)

(256 mg, 1.20 mmol), 2b (119 mg, 137 μL, 1.20 mmol) and 3a

(171 mg, 123 μL, 1.00 mmol). After distillation, 4dba (285 mg,

94%) was obtained as a colourless solid (m.p. 112.2 °C). The spec-

troscopic data (NMR, GC–MS, IR) were identical to those re-

ported in the literature.^[35]

N-[(tert-Butyl)(p-tolyl)methylene]pentanamine (4ica): Compound

4ica was synthesized in 36 h according to the general procedure

described above from potassium trimethyl pyruvate (1i) (202 mg,

1.20 mmol), pentanamine (2c) (106 mg, 140 μL, 1.20 mmol) and 3a

(171 mg, 123 μL, 1.00 mmol). After distillation, 4ica (63.0 mg,

26%) was obtained as a pale yellow oil. The spectroscopic data

(NMR, GC–MS, IR) were identical to those reported in the litera-

ture.^[35]

N-[(4-Chlorophenyl)(4-tolyl)methylene]cyclohexanamine (4eba):

Compound 4eba was synthesized according to the general pro-

cedure described above from potassium 2-(4-chlorophenyl)-2-

oxoacetate (1e) (267 mg, 1.20 mmol), 2b (119 mg, 137 μL,

1.20 mmol), and 3a (171 mg, 123 μL, 1.00 mmol). After distillation, N-[(Isopropyl)(p-tolyl)methylene]cyclohexanamine (4jba): Com-

4eba (276 mg, 89%) was obtained as a colourless oil. ¹H NMR pound 4jba was synthesized according to the general procedure de-

[400 MHz, CDCl₃, two sets of signals for (E) and (Z) isomers, ratio

scribed above from potassium 3,3-dimethyl-2-oxobutyrate (1j)

6497

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F. Collet, B. Song, F. Rudolphi, L. J. Gooßen

(185 mg, 1.20 mmol), 2b (119 mg, 137 μL, 1.20 mmol) and 3a N-[(Phenyl)(p-tolyl)methylene]aniline (4aea): Compound 4aea was

FULL PAPER

(171 mg, 123 μL, 1.00 mmol). GC yield: 46%. Upon distillation, a

mixture of the product (86%) and the corresponding ketone (10%)

was obtained (see GC spectrum in the Supporting Information).

synthesized according to the general procedure described above

from 1a (226 mg, 1.20 mmol), aniline (2e) (112 mg, 109 μL,

1.20 mmol) and 3a (171 mg, 123 μL, 1.00 mmol). After distillation,

MS (70 eV): m/z (%) = 244 (15), 243 (7) [M]⁺, 242 (17), 200 (26), 4aea (144 mg, 53%) was obtained as a yellow oil. The spectroscopic

118 (100), 91 (12).

data (NMR, GC–MS, IR) were identical to those reported in the

literature.^[35]

N-[(Phenyl)(p-tolyl)methylene]pentanamine (4aca): Compound 4aca

was synthesized according to the general procedure described

above from 1a (226 mg, 1.20 mmol), pentanamine (2c) (106 mg,

140 μL, 1.20 mmol) and 3a (171 mg, 123 μL, 1.00 mmol). After dis-

tillation, 4aca (232 mg, 87%) was obtained as a yellow-orange oil.

4-Chloro-N-[(phenyl)(4-tolyl)methylene]aniline (4afa): Compound

4afa was synthesized according to the general procedure described

above from 1a (226 mg, 1.20 mmol), p-anisidine (2f) (156 mg,

1.20 mmol), and 3a (171 mg, 123 μL, 1.00 mmol). After distillation,

The spectroscopic data (NMR, GC–MS, IR) were identical to 4afa (229 mg, 75%) was obtained as a yellow oil. ¹H NMR

those reported in the literature.^[35]

[400 MHz, CDCl₃, two sets of signals for (E) and (Z) isomers, ratio

approx. 1.2:1]: δ = 7.61–7.68 and 7.71–7.79 (2 m, 2 H), 7.17–7.34

und 7.36–7.51 (2 m, 2 H), 7.05–7.15 (m, 4 H), 6.96–7.03 (m, 1 H),

6.61–6.71 (m, 2 H), 2.33 und 2.41 (2 s, 3 H) ppm. ¹³C NMR

[101 MHz, CDCl₃, two sets of signals for (E) and (Z) isomers]: δ

= 168.8 and 169.0, 149.8 and 149.9, 141.3, 139.6, 138.8, 136.6,

136.0, 132.8, 130.8, 129.5, 129.32, 129.28, 128.9, 128.7, 128.6,

128.52, 128.46, 128.25, 128.21, 128.1, 128.0, 122.3 und 122.4, 21.3

and 21.4 ppm. HRMS (EI): calcd. for C₂₀H₁₆³⁵ClN [M]⁺305.0971;

found 305.0951, and calcd. for C₂₀H₁₆³⁷ClN [M]⁺307.0942; found

307.0916. MS (70 eV): m/z (%) = 307 (36), 306 (33), 305 (100)

(+)-(1S)-1-Phenyl-N-[(phenyl)(p-tolyl)methylene]ethanamine (4aga):

Compound 4aga was synthesized according to the general pro-

cedure described above from 1a (226 mg, 1.20 mmol), (–)-l-α-meth-

ylbenzylamine (2 g) (147 mg, 94 μL, 1.20 mmol) and 3a (171 mg,

123 μL, 1.00 mmol). After distillation, 4aga (191 mg, 64%) was ob-

tained as a colourless oil. The spectroscopic data (NMR, GC–MS,

IR) were identical to those reported in the literature.^[35]

2,4-Dimethoxy-N-[(phenyl)(p-tolyl)methylene]aniline (4aha): Com-

pound 4aha was synthesized according to the general procedure

described above from 1a (226 mg, 1.20 mmol), 2,4-dimethoxyan-

iline (2h) (184 mg, 171 μL, 1.20 mmol) and 3a (171 mg, 123 μL,

1.00 mmol). After distillation, 4aha (312 mg, 94%) was obtained

as a brown oil. The spectroscopic data (NMR, GC–MS, IR) were

identical to those reported in the literature.^[35]

[M]⁺, 290 (34), 228 (42), 179 (41), 75 (43). IR (NaCl): ν = 3079

˜

(m), 3055 (m), 3025 (m), 2919 (m), 1605 (vs), 1481 (vs), 1445 (m),

1314 (s), 1296 (s), 1222 (s), 1182 (m), 1142 (s), 1092 (s), 1010 (m),

960 (m), 834 (s), 774 (m), 722 (m), 702 (s), 670 (w) cm^–1.

N-[(Phenyl)(p-tolyl)methylene]-4-(trifluormethyl)aniline

(4aja):

N,N-Dimethyl-NЈ-[(phenyl)(p-tolyl)methylene]-p-phenylenediamine

(4aaa): Compound 4aaa was synthesized according to the general

procedure described above from 1a (226 mg, 1.20 mmol), N,N-di-

methyl-p-phenylenediamine (2a) (163 mg, 1.20 mmol) and 3a

(171 mg, 123 μL, 1.00 mmol). After distillation, 4aaa (190 mg,

60%) was obtained as an orange solid (m.p. 99 °C). The spectro-

scopic data (NMR, GC–MS, IR) were identical to those reported

in the literature.^[35]

Compound 4aja was synthesized according to the general pro-

cedure described above from 1a (226 mg, 1.20 mmol), 4-(trifluoro-

methyl)aniline (2j) (193 mg, 149 μL, 1.20 mmol) and 3a (171 mg,

123 μL, 1.00 mmol). GC yield: 16%. MS (70 eV): m/z (%) = 341

(38), 340 (100), 339 (22) [M]⁺, 325 (33), 263 (57), 249 (22), 180 (45).

Synthesis of N-[(Phenyl)(p-tolyl)methyl]cyclohexanamine (7a): A

20 mL vessel was charged with 4aba (277 mg, 1.00 mmol), lithium

aluminum hydride (120 mg, 3.00 mmol) and THF (2 mL). The re-

sulting mixture was stirred at 60 °C for 16 h, diluted with saturated

sodium hydrogencarbonate solution (20 mL) and extracted repeat-

edly with ethyl acetate (20 mL portions). The combined organic

layers were washed with water and brine, dried with MgSO₄, fil-

tered, and the volatiles were removed in vacuo, which yielded 7a as

N-[(Phenyl)(4-tolyl)methylene]-p-anisidine (4ada): Compound 4ada

was synthesized according to the general procedure described

above from 1a (226 mg, 1.20 mmol), p-anisidine (2d) (148 mg,

1.20 mmol) and 3a (171 mg, 123 μL, 1.00 mmol). After distillation,

4ada (165 mg, 55%) was obtained as an orange oil. ¹H NMR

[400 MHz, CDCl₃, two sets of signals for (E) and (Z) isomers, ratio

approx. 1.1:1]: δ = 7.62–7.68 and 7.73–7.78 (2 m, 2 H), 7.18–7.31

and 7.36–7.48 (2 m, 4 H), 7.01–7.17 (m, 3 H), 6.67–6.75 (m, 4 H),

3.71 and 3.73 (2 s, 2 H), 2.34 and 2.41 (2 s, 3 H) ppm. ¹³C NMR

[101 MHz, CDCl₃, two sets of signals for (E) and (Z) isomers]: δ

= 167.6 and 167.8, 155.6 and 155.7, 144.4 and 144.5, 140.7, 140.2,

138.3, 137.2, 136.7, 133.5, 130.3, 129.5, 129.4, 129.14, 129.08,

128.8, 128.6, 128.3, 128.0, 127.9, 122.5, 122.4, 113.6 and 113.7,

55.2, 21.27 and 21.33 ppm. HRMS (EI): calcd. for C₂₁H₁₉NO

[M]⁺301.1467; found 301.1469. MS (70 eV): m/z (%) = 302 (38),

301 (100) [M]⁺, 287 (16), 225 (8), 224 (17), 210 (11), 179 (8). IR

1

a yellowish oil (262 mg, 94%). H NMR (400 MHz, CDCl₃): δ =

7.23–7.30 (m, 2 H), 7.12–7.20 (m, 4 H), 7.03–7.09 (m, 1 H), 6.95–

7.01 (m, 2 H), 4.89 (s, 1 H), 2.24–2.34 (m, 1 H), 2.18 (s, 3 H), 1.79–

1.88 (m, 2 H), 1.37–1.65 (m, 3 H), 1.20–1.36 (br., 1 H), 0.91–1.13

(m, 5 H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 144.9, 141.8,

136.2, 129.0, 128.3, 127.2, 126.6, 63.3, 53.9, 33.9, 26.2, 25.1,

21.0 ppm. HRMS (EI): calcd. for C₂₀H₂₅N [M]⁺279.1987; found

279.1976. MS (70 eV): m/z (%) = 279 (5) [M]⁺, 202 (29), 188 (14),

182 (23), 181 (100), 167 (17), 166 (26), 165 (28). IR (NaCl): ν =

˜

3021 (m), 2923 (vs), 2849 (vs), 1601 (w), 1509 (m), 1491 (m), 1449

(s), 1339 (w), 1176 (w), 1110 (m), 1028 (w), 890 (w), 846 (w), 806

(m), 698 (m) cm^–1.

(NaCl): ν = 2929 (m), 2833 (m), 1605 (vs), 1567 (s), 1503 (vs), 1443

˜

(s), 1290 (s), 1242 (vs), 1220 (s), 1180 (m), 1106 (m), 1036 (s), 960

General Procedure for the One-Pot Synthesis of Ketones: An oven-

dried 20 mL vessel was charged with potassium α-aryl-α-oxo-

(m), 832 (m), 778 (m), 700 (m) cm^–1.

N-[(Phenyl)(p-tolyl)methylene]-o-anisidine (4aia): Compound 4aia

was synthesized according to the general procedure described

above from 1a (226 mg, 1.20 mmol), o-anisidine (2i) (148 mg,

135 μL, 1.20 mmol) and 3a (171 mg, 123 μL, 1.00 mmol). After dis-

carboxylate

1

(1.20 mmol), copper(I) bromide (21.5 mg,

0.15 mmol), palladium(II) 1,1,1,3,3,3-hexafluoroacetylacetonate

(5.2 mg, 0.01 mmol), 1,10-phenanthroline (27.0 mg, 0.15 mmol),

1,1Ј-bis(diphenylphosphanyl)ferrocene (5.7 mg, 0.01 mmol) and

tillation, 4aia (220 mg, 73%) was obtained as a yellow-orange oil. 3 Å molecular sieves (200 mg). The reaction vessel was evacuated

The spectroscopic data (NMR, GC–MS, IR) were identical to

and flushed with nitrogen three times. A degassed solution of the

corresponding aryl halide 3 (1.00 mmol), amine 2 (1.20 mmol) and

those reported in the literature.^[35]

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Decarboxylative Coupling for the Synthesis of Azomethines and Ketones

n-tetradecane (50 μL) in quinoline (2 mL) was added by syringe.

The resulting mixture was stirred at 100 °C for 10 h. A 2 m HCl/

THF (3 mL, 1:1) solution was added by syringe, and the mixture

was stirred at 80 °C for 1 h. After addition of 6 m HCl solution

(20 mL), the mixture was extracted three times with ethyl acetate

(20 mL portions). The combined organic layers were washed with

saturated sodium hydrogencarbonate solution, water and brine,

dried with MgSO₄, filtered, and the volatiles were removed in

vacuo. The residue was purified by column chromatography (SiO₂;

hexane/ethyl acetate, 80:20), affording the corresponding ketone 6.

3-Benzoylthiophene (6h): Ketone 6h was synthesized according to

the general procedure from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 3t (163 mg, 94 μL, 1.00 mmol). Com-

pound 6h was purified by column chromatography (SiO₂; hexane/

ethyl acetate, 80:20) and isolated as a yellow oil (182 mg, 97%). The

spectroscopic data (NMR, GC–MS, IR) matched those reported in

the literature (CAS: 6453-99-2).

3-Benzoylpyridine (6i): Ketone 6i was synthesized according to the

general procedure from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 3m (158 mg, 96 μL, 1.00 mmol). After ad-

dition of dilute sodium hydrogencarbonate solution, the reaction

mixture was extracted three times with ethyl acetate (20 mL). The

combined organic layers were dried with magnesium sulfate, and

the volatile components were removed at 130 °C and 2ϫ10^–2mbar.

The residue was purified by column chromatography (SiO₂; hexane/

ethyl acetate, 80:20) to afford 6i (166 mg, 91%) as a brown oil. The

spectroscopic data (NMR, GC–MS, IR) matched those reported

in the literature (CAS: 5424-19-1).

4-Methylbenzophenone (6a): Ketone 6a was synthesized according

to the general procedure from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 3a (175 mg, 126 μL, 1.00 mmol). Com-

pound 6a was purified by column chromatography (SiO₂; hexane/

ethyl acetate, 90:10) and isolated as a pale yellow solid (190 mg,

97%) (m.p. 55–56 °C). The spectroscopic data (NMR, GC–MS,

IR) matched those reported in the literature (CAS: 134-84-9).

4-Methoxybenzophenone (6b): Ketone 6b was synthesized according

to the general procedure from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 3b (187 mg, 126 μL, 1.00 mmol). Com-

pound 6b was purified by column chromatography (SiO₂; hexane/

ethyl acetate, 90:10) and isolated as a yellow oil (184 mg, 87%). The

spectroscopic data (NMR, GC–MS, IR) matched those reported in

the literature (CAS: 611-94-9).

1,3-Diphenylprop-2-en-1-one (Chalcone) (6j): Ketone 6j was synthe-

sized according to the general procedure from 1a (226 mg,

1.20 mmol), 2b (119 mg, 137 μL, 1.20 mmol) and 2-(bromovinyl)-

benzene (3u) (183 mg, 129 μL, 1.00 mmol). Compound 6j was puri-

fied by column chromatography (SiO₂; hexane/ethyl acetate, 90:10)

and isolated as a yellow oil (88 mg, 42%). The spectroscopic data

(NMR, GC–MS, IR) matched those reported in the literature

(CAS: 94-41-7).

2-Benzoylnaphthalene (6c): Ketone 6c was synthesized according to

the general procedure from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 3f (207 mg, 1.00 mmol). Compound 6c

was purified by column chromatography (SiO₂; hexane/ethyl acet-

ate, 90:10) and isolated as a pale yellow solid (220 mg, 95%) (m.p.

83–84 °C). The spectroscopic data (NMR, GC–MS, IR) matched

those reported in the literature (CAS: 644-13-3).

4,4Ј-Dimethylbenzophenone (6k): Ketone 6k was synthesized ac-

cording to the general procedure from 1b (243 mg, 1.20 mmol), 2b

(119 mg, 137 μL, 1.20 mmol) and 3a (175 mg, 126 μL, 1.00 mmol).

Compound 6k was purified by column chromatography (SiO₂; hex-

ane/ethyl acetate, 85:15) and isolated as a yellow solid (115 mg,

55%) (m.p. 72–73 °C). The spectroscopic data (NMR, GC–MS,

IR) matched those reported in the literature (CAS: 611-97-2).

4-Benzoylbenzonitrile (6d): Ketone 6d was synthesized according to

the general procedure from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 3h (182 mg, 1.00 mmol). Compound 6d

was purified by column chromatography (SiO₂; hexane/ethyl acet-

ate, 80:20) and isolated as a white solid (195 mg, 94%) (m.p. 114–

115 °C). The spectroscopic data (NMR, GC–MS, IR) matched

those reported in the literature (CAS: 1503-49-7).

4-Methoxy-4Ј-methylbenzophenone (6l): Ketone 6l was synthesized

according to the general procedure from 1c (262 mg, 1.20 mmol),

2b (119 mg, 137 μL, 1.20 mmol) and 3a (175 mg, 126 μL,

1.00 mmol). Compound 6l was purified by column chromatography

(SiO₂; hexane/ethyl acetate, 90:10) and isolated as a pale yellow

solid (160 mg, 71%) (m.p. 89–90 °C). The spectroscopic data

(NMR, GC–MS, IR) matched those reported in the literature

(CAS: 23886-71-7).

4-Nitrobenzophenone (6e): Ketone 6e was synthesized according to

the general procedure from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 3r (202 mg, 1.00 mmol). Compound 6e

was purified by column chromatography (SiO₂; hexane/ethyl acet-

ate, 85:15) and isolated as a pale yellow solid (148 mg, 65%) (m.p.

138–139 °C). The spectroscopic data (NMR, GC–MS, IR) matched

those reported in the literature (CAS: 1144-74-7).

(4-Methylbenzoyl)benzonitrile (6m): Ketone 6m was synthesized ac-

cording to the general procedure from 1d (256 mg, 1.20 mmol), 2b

(119 mg, 137 μL, 1.20 mmol) and 3a (175 mg, 126 μL, 1.00 mmol).

Compound 6m was purified by column chromatography (SiO₂;

hexane/ethyl acetate, 90:10) and isolated as a white solid (132 mg,

60%) (m.p. 166–167 °C). The spectroscopic data (NMR, GC–MS,

IR) matched those reported in the literature (CAS: 35776-95-5).

4-(Trifluoromethyl)benzophenone (6f): Ketone 6f was synthesized

according to the general procedure from 1a (226 mg, 1.20 mmol),

2b (119 mg, 137 μL, 1.20 mmol) and 3j (227 mg, 142 μL,

1.00 mmol). Compound 6f was purified by column chromatog-

raphy (SiO₂; hexane/ethyl acetate, 95:5) and isolated as a white so-

lid (220 mg, 88%) (m.p. 116–117 °C). The spectroscopic data

(NMR, GC–MS, IR) matched those reported in the literature for

(CAS: 728-86-9).

4-Chloro-4Ј-methylbenzophenone (6n): Ketone 6n was synthesized

according to the general procedure from 1e (267 mg, 1.20 mmol),

2b (119 mg, 137 μL, 1.20 mmol) and 3a (175 mg, 126 μL,

1.00 mmol). Compound 6n was purified by column chromatog-

raphy (SiO₂; hexane/ethyl acetate, 95:5) and isolated as a white so-

lid (69 mg, 30%) (m.p. 127–128 °C). The spectroscopic data (NMR,

GC–MS, IR) matched those reported in the literature (CAS: 5395-

79-9).

4-Chlorobenzophenone (6g): Ketone 6g was synthesized according

to the general procedure from 1a (226 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 3l (191 mg, 116 μL, 1.00 mmol). Com-

pound 6g was purified by column chromatography (SiO₂; hexane/

ethyl acetate, 95:5) and isolated as a white solid (200 mg, 92%)

(m.p. 76–77 °C). The spectroscopic data (NMR, GC–MS, IR)

matched those reported in the literature (CAS: 134-85-0).

2-Furyl 4-Tolyl Ketone (6o): Ketone 6o was synthesized according

to the general procedure from 1f (214 mg, 1.20 mmol), 2b (119 mg,

137 μL, 1.20 mmol) and 3a (175 mg, 126 μL, 1.00 mmol). Com-

pound 6o was purified by column chromatography (SiO₂; hexane/

ethyl acetate, 90:10) and isolated as a yellow oil (135 mg, 73%). The

Eur. J. Org. Chem. 2011, 6486–6501

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F. Collet, B. Song, F. Rudolphi, L. J. Gooßen

FULL PAPER

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103, 811–891; b) G. Masson, C. Housseman, J. Zhu, Angew.

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2007, 36, 1581–1588; d) Y.-L. Shi, M. Shi, Eur. J. Org. Chem.

2007, 2905–2916; e) V. Singh, S. Batra, Tetrahedron 2008, 64,

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a) M. B. Smith, J. March, March’s Advanced Organic Chemis-

try, 6th ed., Wiley, Hoboken, New Jersey, 2007, pp. 1263–1267;

b) A. R. Hajipour, S. Khoee, A. E. Ruoho, Org. Prep. Proced.

Int. 2003, 35, 527–581.

a) R. K. Thalji, K. A. Ahrendt, R. G. Bergman, J. A. Ellman,

J. Am. Chem. Soc. 2001, 123, 9692–9693; b) C. H. Jun, C. W.

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a) B. L. Small, M. Brookhart, A. M. A. Bennett, J. Am. Chem.

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2007, 26, 988–999.

spectroscopic data (NMR, GC–MS, IR) matched those reported in

the literature (CAS: 13365-62-3).

2,4Ј-Dimethylpropiophenone (6p): Ketone 6p was synthesized ac-

cording to the general procedure from 1j (185 mg, 1.20 mmol), 2b

(119 mg, 137 μL, 1.20 mmol) and 3a (175 mg, 126 μL, 1.00 mmol)

at 100 °C for 36 h. Compound 6p was purified by column

chromatography (SiO₂; hexane/ethyl acetate, 95:5) and isolated as

a colourless oil (138 mg, 85%). The spectroscopic data (NMR,

GC–MS, IR) matched those reported in the literature (CAS: 50390-

51-7).

[7]

[8]

2,2,4Ј-Trimethylpropiophenone (6q): Ketone 6q was synthesized ac-

cording to the general procedure from 1i (202 mg, 1.20 mmol), 2b

(119 mg, 137 μL, 1.20 mmol) and 3a (175 mg, 126 μL, 1.00 mmol)

at 100 °C for 36 h. Compound 6q was purified by column

chromatography (SiO₂; hexane/ethyl acetate, 100:0) and isolated as

a colourless oil (78 mg, 44%). The spectroscopic data (NMR, GC–

MS, IR) matched those reported in the literature (CAS: 30314-44-

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Received: July 28, 2011

Published Online: September 15, 2011

Eur. J. Org. Chem. 2011, 6486–6501

www.eurjoc.org

6501

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Development of decarboxylative coupling processes for the synthesis of azomethines and ketones

DOI: 10.1002/ejoc.201101103

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