FR2602508A1 - Process for the synthesis of heterocycles from palladocyclic complexes - Google Patents

Abstract

The subject of the invention is a process for the synthesis of heterocycles from palladocyclic complexes, by reaction with alkynes, characterised in that the palladocyclic complexes are used in the form of iodinated or cationic complexes. This process applies in particular to the synthesis of nitrogenous heterocycles.

Description

 The present invention relates to a process for synthesizing heterocycles from palladocyclic complexes.

For the purpose of carrying out organic syntheses, cyclic organometallic complexes of transition metals have been developed for several years in which the carbon metal bond is stabilized by an intramolecular coordination bond between the metal and a donor (N, P) atom. , O, S ...)
These compounds are known to lead to easy reaction with various reagents due to the high reactivity of the metal-carbon bond.

 Among these, palladium II complexes which can undergo a large number of insertion reactions have been developed in particular A. Bahsoun and Coll (J. Chem.

Soc. Dalton Trains, 1979 47) have thus described the reaction of chlorinated or brominated palladocyclic complexes with alkynes. They showed that according to the nature of the alkyne we obtain a mono or di-insertion of the alkyne in the Pd-C bond. In addition, they observed only in a single case a spontaneous demetallation leading to the formation of a heterocyclic compound.

 One could think to obtain a general way of demetallation of such organometallic compounds using conventional reducing agents such as hydrides (LiAl H4, NaH) but the use of these reducers may induce these parasitic reactions (reduction of ~ liai - multiple sounds for example).

 The present invention aims to provide a general method for effective depalladation during the reaction of palladocyclic complexes with alkynes, thereby leading to the production of heterocycles by formation of a carbon-heteroatom bond. The inventors have discovered that it is possible to activate the pallodocyclic complexes by putting them in the form of iodine complexes or of cationic complexes and to obtain during the reaction with the alkynes an elimination of palladium by reduction of this palladium metallic state.

 The subject of the present invention is thus a process for the synthesis of heterocycles from palladocyclic complexes, by reaction with alkynes, characterized in that the palladocyclic complexes are used in the form of iodinated or cationic complexes.

complexe cationique

The palladocyclic complexes that are used in the present invention can be represented by the following schematic formulas: iodized complex

cationic complex

In these formulas Y - X represents an organic remainder
When bound to palladium on the Y side by a nitrogen or sulfur atom and on the X side by a carbon atom, Z1 and Z2 represent two weakly coordinated ligands.

In these complexes of formula I and II the palladium together with the Y - X residue form a ring having generally 5 to 7 knuckles (including palladium), as an example of Y - X residues having a coordination bond.
N + Pd are those derived from the following compounds
- alkylamines
- benzylamines
- arylamines
- naphthylamines
- imines
azobenzenes
- Schiff bases
- hydrazones
- pyroles
- aminoferrocene
- oximes
pyridines
- quinolines
substituted pyridines
Analogous pallatocyclic nitrogen complexes are described in particular in the article by A. Ryabov "Cyclopalladated Complexes in Organic Synthesis" Synthesis No. 3, page 233, March 1985.

Examples of nitrogen compounds forming such complexes include more particularly:
8-methylquinoline (8-mq)
N, N-dimethyl naphthylamine (dmna)
benzylpyridine (BP)
N, N-dimethylbenzylamine (dmba)
Examples of Y - X residues having S> Pd coordination binding include those derived from the following compounds
- arylthioketones
benzylalkylthioethers
naphthylalkylthioethers
aryl alkyltioethers
thiophene derivatives such as 2-phenyl
thiophene
In the complexes of formula II, the weakly-coordinated ligands Z1 and Z2 may in particular be weakly coordinating solvent molecules such as RCN nitriles, RO-R 'ethers, R-S'-R' thioethers and R-CO ketones.
R ', ROH alcohols, THF, DMSO, DMF (in these formulas R and R' may be C1 to
C6 or aryl).

The alkynes which can be reacted according to the invention with iodinated or cationic complexes are especially compounds of formula
Wherein R1 and R2 are independently selected from hydrogen, aryl groups such as phenyl, alkyl groups, especially C1 to C6 groups, and C1-C6 haloalkyl; C2-C6 alkenyl groups; groups of formula -COOR3 or -GO-R3 in which R3 is a C1-C6 alkyl or aryl group; of the
groups of formula -CR4R5 OH in which R4 and R5
are selected from hydrogen, alkyl groups
C1-C6 and aryl groups; a -CHO group; groups
of formula -NR6R7 in which R6 and R7 are chosen
from hydrogen and C1 to C6 alkyl groups; of the
groups of formula -SR8 or -SO2R8 in which
R8 is selected from C1 to C6 alkyl groups and
aryl groups; a trimethylsilyl group; as well as
such groups linked to the triple bond by a chain
C1 to C6 alkylene.

The reaction of the complexes of formula I or II with
the alkynes of formula III leading to depalladation
complex and the formation of a heterocycle can gener-
typically beech by simple heating in soil
such as chlorobenzene, toluene or chlorine
roform, at atmospheric pressure, usually at a temperature
from 125 to 135 ° C, and especially in refluxing chlorobenzene.

The main interest of the process according to the present
invention is that it allows starting tertiary amines and
substituted alkynes to obtain heterocycles function
nalisables in a few steps. The intermediate compound of the pal
ladium is usually done with excellent yields and
it is not usually necessary to isolate it. Moreover these compounds are easily manipulated (their synthesis can be done in air and at room temperature is 20 to 25-C) without special precautions.

 With regard to the step of the formation of the heterocycle it is done under sufficiently mild conditions so that there is no parasitic reaction on other functional groups present on the metallated amine. The process is applicable to a variety of amines. The choice of this and the type of reaction used makes it possible to obtain heterocycles whose size generally varies from 6 to 8 chains.

 The reaction is selective. In most cases only one product is identified after the reaction without the need for additional purifications. When a non-symmetrical alkyne is used the reaction is regioselective and often regiospecific. The reaction is stoichiometric palladium but it is obviously recoverable and can easily be recycled.

 The method can be used for the synthesis of heterocycles difficult to access by conventional organic synthesis methods. The structure of the heterocycles obtained is reminiscent of certain alkaloids.

Thus the complex ioaé (dmna) (- I) 3 2 # reacts with alkynes to give heterocycles according to the following reaction scheme

On the other hand, in the case of the corresponding chlorine complex [{Pd (dmna) (--Cl)} 2], a reaction is observed only with hexafluorobut-2-yne. With the other alkynes no reaction is observed after refluxing in chlorobenzene for several days.

The complex [Pd (dmna) (MeCN) 2] BF4 also reacts with alkynes to give heterocycles according to the following scheme:

The following examples illustrate the present invention.

Part A illustrates the preparation of the starting materials and Part B the heterocycles. In Part B, Examples 1-7 illustrate the use of iodinated complexes and Examples 8-14 illustrate the use of cationic complexes.

A Preparation of starting materials
1. Preparation of iodinated complexes
at. Preparation of the complexCPd (dmba) (t 1323

 To a suspension of the corresponding chlorinated pallodocyclic complex [{Pd (dmba) (- Cl)} 2] (0.552 g, 1 mmol in acetone (50 ml)) is added sodium iodide (0.6 g, 4 mmol) A strong orange solution is obtained After stirring for 5 minutes, the solvent is removed in vacuo and extracted with CH 2 Cl 2 (50 ml) and CH 2 Cl 2 is removed in vacuo.

I1 est obtenu comme sous 1 a a partir du complexe chloré correspondant.NMR spectrum (CDCl3) 3.99 and 3.96 (2s, 2H, CH2-N); 2.91 and 2.88 (2s, 6H, N-CH3) b. Preparation of the complex [{Pd (8-mq) (-I)} 2]

It is obtained as under 1 from the corresponding chlorinated complex.

NMR (CDCl3): 9.29 (s (broad), 1H, Ho); 8.25 (dd, 1H, Hp, 3 # Hp-Hm = 7.4); 3.88 (s (broad), 2H, CH 2).

I1 est obtenu comme sous 1 a a partir du complexe chloré correspondant
RMN1 H (CDC13) : 3,57 et 3,52 (2s, 6H, N-CH3) 2. Préparation de complexes cationiques
a. Préparation du complexe de formule

c. Preparation of the complex [{Pd (dmna)

It is obtained as under 1 from the corresponding chlorinated complex
1 H NMR (CDCl3): 3.57 and 3.52 (2s, 6H, N-CH3) 2. Preparation of cationic complexes
at. Preparation of the formula complex

To a solution of Ag BF4 (0.39 g, 2 mmol) in CH 2 Cl 2 /
Me CN (15 ml / 1.5 ml) is added a solution of [{Pd (dmba) (-Cl)} 2] (0.55 g, 1 mmol) in CH 2 Cl 2 (25 ml), which immediately gives a precipitate AgCl The reaction mixture is filtered through a column of Celite (1 = 3cm).

The colorless filtrate was concentrated in vacuo to 2 ml, yielding pentane (30 ml) of the cationic complex as a white solid (0.65 g, 80%).

IR, (nujol): # C # N = 2332.2300 (w) cm
1 H NMR (CDCl 3): 3.91 (s, 2H, CH 2 -N); 2.80 (s, 6H,
N-CH3) t 2.47 and 2.28 (2s, 6H, CH3-CN).

b. Preparation of the formula complex

;1 est préparé comme sous 2a à partir du complexe chloré
Pd (dmna) ( -Cl)}2]
I.R (nujol) : #C#N=2310,2290 (w) cm-1
RMN 1H (CDCl3) : 3,36 (s,6H,N-CH3) ; 2,55 et 2,33 (2s, 6H,CH3-CN). It is prepared as 2a from the chlorinated [{Pd (8-mq) (-Cl)} 2 complex (this compound was described by Brausstein et al in J Am Chem Soc, 1984, 106, 410).
c. Preparation of the formula complex

1 is prepared as under 2a from the chlorinated complex
Pd (dmna) (-Cl)} 2]
IR (nujol): # C # N = 2310.2290 (w) cm-1
1 H NMR (CDCl 3): 3.36 (s, 6H, N-CH 3); 2.55 and 2.33 (2s, 6H, CH3-CN).

(composé 1)
On condense de l'héxafluorobut-2-yne (0,65g, 4 mmole) a la température de l'azote liquide dans un tube de Schlenk contenant une solution deLEPd (dmna) ( -I)}2]obtenu sous 1 c (0,30g, 0,37 mmole) dans du chlorobenzène (25ml). On chauffe le mélange réactionnel à la température de reflux pendant 15h. On filtre la solution a travers une colonne de Celite (1 = 5cm) et on amène à sec sous vide. On obtient un solide vert. Une extraction avec le pentane (3xlO ml) fournit une solution orangé-rouge, qui après élimination du solvant donne le composé du titre à l'état pur sous la forme d'un solide rouge (0,12g, rendement 50%).Les caractéristiques du produit sont données dans le tableau I
Exemple 2
Préparation du composé de formule

(composé 2)
On ajoute du diphénylacétylène (0,35g, 1,96 mmole) a une solution de [{Pd (dmna) ( -I)}2](0,30g, 0,37 mmole) dans du chlorobenzène (40 ml). On chauffe le mélange au reflux pendant 24h et on filtre la solution noire obtenue sur une colonne de Celite (1 = 4cm) pour éliminer toute trace de palladium métallique. On amène la solution à siccité, ce qui fournit un produit brut consistant en le composé du titre et en diphénylacétylène n'ayant pas réagi. On élimine ce dernier par chromatographie sur colonne d'alumine (1 = 12cm) en utilisant du pentane (230 ml) comme éluant.B. Preparation of heterocycles
Example 1
Preparation of the compound of formula

(compound 1)
Hexafluorobut-2-yne (0.65 g, 4 mmol) is condensed at the temperature of the liquid nitrogen in a Schlenk tube containing a solution of LEPd (dmna) (-I)} 2] obtained under 1 c ( 0.30 g, 0.37 mmol) in chlorobenzene (25 ml). The reaction mixture is heated at the reflux temperature for 15 hours. The solution is filtered through a column of Celite (1 = 5cm) and brought to dryness under vacuum. A green solid is obtained. Extraction with pentane (3 × 10 ml) gives an orange-red solution, which after removal of the solvent gives the title compound in pure form as a red solid (0.12 g, 50% yield). Product characteristics are given in Table I
Example 2
Preparation of the compound of formula

(compound 2)
Diphenylacetylene (0.35 g, 1.96 mmol) was added to a solution of [{Pd (dmna) (- I)} 2] (0.30 g, 0.37 mmol) in chlorobenzene (40 ml). The mixture is refluxed for 24 hours and the resulting black solution is filtered through a column of celite (1 = 4 cm) to remove any trace of palladium metal. The solution is brought to dryness to provide a crude product consisting of the title compound and unreacted diphenylacetylene. The latter is removed by column chromatography on alumina (1 = 12 cm) using pentane (230 ml) as eluent.

The pure product is then extracted with ether (40 ml) in the form of a yellow-green solid (0.12 g, 49% yield) which can be crystallized at -200 ° C. from a solution in an ether mixture. pentane giving fluorescent yellow crystals. F = 201 C. The other characteristics are listed in Table I.

(composé 3)
On chauffe au reflux un mélange de [{Pd(dmna) ( -I)}2] (0,40g, 0,49 mmole) dans du chlorobenzène (45ml) avec du 3-phénylpropiOlate d'éthyle (0,35g, 2 mmole) pendant 2 heures. On élimine le palladium métallique formé par filtration sur une colonne de celte (1=4cm). On élimine le solvant sous vide et on lave le solide couleur kaki obtenu avec de l'hexane (5 ml) ce qui donne le composé dp titre sous forme d'un solide vert (0,32g, rendement 96%) contaminé avec de l'alcyne libre. Une cristallisation dans une solution dans un mélange éther/pentane à - 20 C donne des cristaux jaune-vert fluorescents du composé (0,13g, rendement 40%) F = 1170C. La liqueur mère est amenée a siccité et le résidu est purifié par chromatographie sur une colonne d'aluminé (1 = 20cm). On extrait d'abord l'alcyne libre avec du pentane (500 ml).Example 3
Preparation of the compound of formula

(compound 3)
A mixture of [{Pd (dmna) (- I)} 2] (0.40 g, 0.49 mmol) in chlorobenzene (45 ml) was refluxed with ethyl 3-phenylpropionate (0.35 g, 2 g). mmol) for 2 hours. The palladium metal formed is removed by filtration on a column of celtic (1 = 4 cm). The solvent is removed in vacuo and the resulting khaki solid is washed with hexane (5 ml) to give the title compound as a green solid (0.32 g, 96% yield) contaminated with water. alkyne free. Crystallization from a solution in ether / pentane at -20 ° C gave fluorescent yellow-green crystals of the compound (0.13 g, 40% yield) mp = 1170 ° C. The mother liquor is brought to dryness and the residue is purified by chromatography on a column of alumina (1 = 20 cm). The free alkyne is first extracted with pentane (500 ml).

Extraction with ethyl ether (250 ml) afforded the pure product (0.09 g, 30% yield), giving a total yield of 70%. The characteristics of the compound are given in Table I.

(composé 4)
On ajoute de l'acétylène dicarboxylate de diméthyle (0,20g, 1,4 mmole) à une solution de [{Pd(dmna) ( -I)}2] (0,30g, 0,37 mmole) dans du chlorobenzène (40ml). Après agitation a la température de reflux pendant 70 minutes la couleur devient vert foncé. On filtre la solution à travers une colonne de Celite et on évapore le solvant sous vide. On lave le résidu vert avec de l'hexane t5 ml).Example 4
Preparation of the compound of formula

(compound 4)
Dimethyl acetylene dicarboxylate (0.20 g, 1.4 mmol) is added to a solution of [{Pd (dmna) (- I)} 2] (0.30 g, 0.37 mmol) in chlorobenzene ( 40ml). After stirring at reflux temperature for 70 minutes the color becomes dark green. The solution is filtered through a column of Celite and the solvent evaporated in vacuo. The green residue is washed with hexane (5 ml).

extraction. with CH 2 Cl 2 / hexane (2 ml / 15 ml) gives an orange solution which after removal of the solvent gives the title compound as an orange solid (0.22 g, 50% yield). When the solution is concentrated in CH 2 Cl 2 / hexane and cooled to -200 ° C., the compound is obtained in the form of bright orange crystals (0.05 g, 23% yield) mp = 920 ° C.

(composé 5) T A B L E A U I caractéristiques des composés de formule générale

Other characteristics are given in Table I
Example 5
Preparation of the compound of formula

(compound 5) TABLEAUI characteristics of the compounds of general formula

Example <SEP> Compound <SEP> Color <SEP> IR (KBr) cm-1 <SEP> 1H <SEP> NMR
<tb><SEP>#<SEP> C <SEP> = <SEP> O <SEP> N-Me <SEP> CO2R <SEP> H9 <SEP> H4
<tb> 1 <SEP> R = R = CF3 <SEP> red
<tb><SEP> 3.21 (g) <SEP> 6.35
<tb><SEP> 5 # HF = 2.2 <SEP> 3 # H9-H8 = 6.6
<tb> 2 <SEP> R = R = Ph <SEP> yellow <SEP> green <SEP> 3,87 (s) <SEP> 6,23 (d) <SEP> 6,13 (d)
<tb><SEP> 3 # H9-H8 = 7.9 <SEP> 3 # H4-H5 = 7.1
<tb> 3 <SEP> {R = CO2Et <SEP> yellow <SEP> green <SEP> 1695 (vs) <SEP> 3.86 (s) <SEP> 3.80 (q) <SEP> 6.25 (dd)
<tb><SEP> R = Ph <SEP> 0.77 (t) <SEP> 3 # H9-H8 = 7.5
<tb> 4 <SEP> R = R = CO2Me <SEP> orange <SEP> 1730.1690 (vs) <SEP> 3.09) <SEP> 3.93 (s) <SEP> 6.30 (dd)
<tb><SEP> 3.81 (s). <SEP> 3 # H9-H8 = 6.9
<Tb>
Diphenylacetylene (0.27 g, 1.52 mmol) [{Pd (8-m) (-I)}] (0.31 g, 0.41 mmol) is reacted in chlorobenzene (50 ml) under reflux for half a minute. -hour.

The palladium metal formed (0.04 g, 63% relative to Pd) was filtered off on a Celite column (1 = 4 cm). The resulting purple solution is evaporated under vacuum and the residue is washed with pentane (3 × 10 ml) and dissolved in the minimum amount of CH 2 Cl 2
Addition of pentane gives the title compound in pure form (0.24 g, 8% yield based on iodine). It is recrystallized from a CH 2 Cl 2 / pentane mixture at room temperature and purple crystals (0.16 g, 59% yield) are obtained.

NMR: (CDCl 3): 9.23 (dd, 1H, Ho, 3H-Hm = 7.5), 8.65 (dd, 1H, Hp, 3H-Hm = 6.0, 4Hp-Ho = 0) 8), 8.36 (dd, 1H, Hm); 5.14 and 4.09 (2d, 2H, CH 2, 2 # HA-HB = 16.3)
13 C NMR (CDCl 3): 34.7 (CH 2).

a) Préparation du composé de formule

(composé 6')
On fait réagir du 3-phénylpropiolate d'éthyle
(0,35 g, 2 mmoles) avec [{Pd(dmba)( -Cl)}2] (0,55 g,
1 mmole) dans le dichlorométhane (50 ml) à la tempé
rature ambiante pendant l heure. Le solvant est alors
éliminé sous vide et le résidu est lavé avec du n-pentane
(3 x 10 ml). On obtient un solide jaune qui est dissout
dans CH2C12 (10 ml). On ajoute du pentane (15 ml) à cette
solution et le mélange est refroidi à -20'C. Après 48 h,
on obtient le composé [{Pd(dmba)c(CO2Et)=C(Ph)( -Cl)}2[(6")
sous forme de cristaux jaune (0,53 g, 60%).Example 6
Preparation of compounds of formula

a) Preparation of the compound of formula

(6 'compound)
Ethyl 3-phenylpropiolate is reacted
(0.35 g, 2 mmol) with [{Pd (dmba) (- Cl)} 2] (0.55 g,
1 mmol) in dichloromethane (50 ml) at room temperature
ambient temperature for 1 hour. The solvent is then
removed in vacuo and the residue is washed with n-pentane
(3 x 10 ml). A yellow solid is obtained which is dissolved
in CH2Cl2 (10 mL). Pentane (15 ml) is added to this
solution and the mixture is cooled to -20 ° C. After 48 hours,
the compound [{Pd (dmba) c (CO2Et) = C (Ph) (-Cl)} 2 [(6 ") is obtained
in the form of yellow crystals (0.53 g, 60%).

The compound 6 'is obtained as under Ala sous for
me an orange product from the chlorinated compound 6 ".

NMR (CDCl3 + # Py-05) = 4.13 and 3.04 (2d, 2H, CH2-N, 2 # HH = 10.7H2) 3.65 (q, 2H, CH2 (OE1)), 3.10 and 3.06 (2s, 6H, CH3N), 0.61 (t, 3H, CH3 (OEt)) # HH = 7.2
Hz).

b) Preparation of the title compounds
Refluxed for 3 hours a solution of the pro
obtained in (0.45 g, 0.42 mmol) in chloroben
zen (50ml). The black solution thus obtained is filtered
on a Celite column (l = 4cm). The solvent is evaporated
under reduced pressure of the purple solution thus obtained
naked. Pentane (35ml) is added and the mixture is shaken
3 hours. The solution obtained is filtered to separate a
dark solid of a yellow solution. The solid is then
crystallized at ambient temperature in a CH 2 Cl 2 /:
pentane. Compound 6a is obtained in the form of screams
purple rate (O, Olg yield 14% compared to the dmba).

The evaporation of pentane under vacuum leads to an oil
composed of compound 6b (0.1 g, 60% yield
report to the Dmba).

Example 7
Preparation of compounds of formula

A slight excess of diphenylacetylene (0.14 g,
0.77 mmol) with the complex [{Pd (BP) (- I)} 22 (0.24 g,
0.30 mmol) in chlorobenzene (40 ml) at reflux
0.5 hours. The black solution obtained is filtered on
a column of Celite (1 = 4cm) to eliminate palla
metal dium. The solvent is then removed and washed
the purple residue with pentane (2 x 10ml). The compound
7a crystallized from a solution in CH 2 Cl 2 (15 ml)
in the form of deeply purple crystals (0.06g, ren
36% relative to iodine). We concentrate the liquor
mother under vacuum and compound 7b then precipitates with
pentane as an orange solid (0.08 g, 43%).
compound 7b can be crystallized in a mixture CH2 Cl2 /
pentane (0.05 g, 25%).

(composé 8)
On ajoute du diphénylacétylène (0,25g, 1,4 mmole) à une solution de [Pd (dmna) (Me CN)2]BF4 (0,23g, 0,51 mmole) dans du chlorobenzène (60ml). On chauffe le mélange réactionnel au reflux pendant 1 heure, on filtre sur une colonne de Celite (1 = 5cm) pour éliminer le palladium métallique. On évapore sous vide la solution rouge foncé obtenue, ce qui fournit un solide qu'on lave avec du pentane (2 x lOml). Le composé cristallise à partir d'un mélange CH2 Cl2 /pentane à température ambiante sous forme de cristaux pourpre foncé (0,04g, rendement 18%).Compound 7a
NMR (CD3CN): 8.54 (dd, 1H, Ho, 3H-Hm = 5.4), 8.42 (td, 1H, Hp, 3Hp-Hm = 7.9, 4Hp-Ho = 1.4), 8.17 (dd, 1H, Hm ', 3Hm-Hp = 7.9, Hm'-Hm = 1.1), 4.70 and 4.59 (2d, 2H, CH2, 2 # HA-HB = 13.8)
Compound 7b
1 H NMR (CDCl 3): 8.81 (dd, 1H, Ho, 3 # Ho-Hm = 6.6, 4 # Ho-Hp = 1.1)
8.73 (dd, 1H, Hm ', 3 # Hm'-Hp = 8.1, 4 # Hm'-Hm = 1.2), 8.39 (td, 1H, Hp, 3 # Hp-Hm = 7.8), 5.08 and 4.47 (2d, 2H, CH 2, 2HA-HB = 13.5)
Example 8
Preparation of the compound of formula

(compound 8)
Diphenylacetylene (0.25 g, 1.4 mmol) is added to a solution of [Pd (dmna) (Me CN) 2] BF4 (0.23 g, 0.51 mmol) in chlorobenzene (60 ml). The reaction mixture was refluxed for 1 hour, filtered through a column of Celite (1 = 5cm) to remove the palladium metal. The dark red solution obtained is evaporated under vacuum, which gives a solid which is washed with pentane (2 × 10 ml). The compound crystallizes from a CH 2 Cl 2 / pentane mixture at room temperature in the form of dark purple crystals (0.04 g, 18% yield).

(composé 9)
On ajoute du 3-phénylpropiolate d'éthyle (O,15g, 0,86 mmole) à une solution de LPd (dmna) (MeCN)w]BF4 (0,20g, 0,46 mmole) dans du chlorobenzene (50 ml). On chauffe le mélange réactionnel au reflux pendant deux heures, puis on élimine le palladium métallique par filtration sur une colonne de
Celite (1 = 4cm). On obtient une solution vert foncé. On évapore sous vide le solvant et on lave le résidu ainsi obtenu avec du pentane (2 x 10ml) puis avec de l'éther (15ml) pour éliminer toutes traces de composé 3 formé lors de la réaction.Le solide vert restant consiste en le composé du titre, contaminé avec [{Pd (dmna) ( Cl} lié à l'utilisation du solvant chloré.IR (KBr): # BF = 1050 (s, broad) cm-1
NMR (CD3CN): 6.92 (d, 1H, H4.3 H4-H5 = 6.4), 3.76 (s, 6H, N-CH3)
Example 9
Preparation of the compound of formula

(compound 9)
Ethyl 3-phenylpropiolate (0.15 g, 0.86 mmol) was added to a solution of LPd (dmna) (MeCN) w] BF4 (0.20 g, 0.46 mmol) in chlorobenzene (50 ml). . The reaction mixture is refluxed for two hours and then the palladium metal is removed by filtration through a column of
Celite (1 = 4cm). A dark green solution is obtained. The solvent is evaporated under vacuum and the residue thus obtained is washed with pentane (2 × 10 ml) and then with ether (15 ml) in order to remove any traces of compound 3 formed during the reaction. The remaining green solid consists of composed of the title, contaminated with [{Pd (dmna) (Cl} related to the use of the chlorinated solvent.

IR (KBr): # C = O = 1720 (s) cm-1 # BF = 1050 (s, broad) cm-1
1 H NMR (CDCl 3): 4.02 (q, 2H, O-CH 2), 3.89 (s, 6H, N-CH 3), 0.91 (t, 3H, CH 3).

(compose 10)
On fait réagir du diphénylacétylêne (0,30g, 1,68 mmole) avec le complexe [Pd(8-mq) (Me CN)23 BF4 (0,27g, 0,65 mmole) dans du chlorobenzène (50ml). On chauffe le mélange au reflux pendant 70 minutes et on filtre sur une colonne de
Celite (1 = 5cm). On évapore le solvant sous vide et on lave le résidu avec du pentane (2 x 10ml). Le solide incolore obtenu est séché, ce qui fournit le composé du titre (0,32g, rendement 85%).On effectue ensuite une chromatoqraphie sur une colonne d'alumine (1 = 6cm). L'é-
lution . avec CH2 Cl2 (20ml) élimine certaines impuretés. Example 10
Preparation of the compound of formula

(dials 10)
Diphenylacetylene (0.30 g, 1.68 mmol) is reacted with the complex [Pd (8-mc) (Me CN) 23 BF4 (0.27 g, 0.65 mmol) in chlorobenzene (50 ml). The mixture is refluxed for 70 minutes and filtered through a column of
Celite (1 = 5cm). The solvent is evaporated in vacuo and the residue is washed with pentane (2 × 10 ml). The colorless solid obtained is dried, which gives the title compound (0.32 g, 85% yield) and is then chromatographed on a column of alumina (1 = 6 cm). The-
lution. with CH2 Cl2 (20ml) eliminates certain impurities.

 Elution with acetone (40ml) provides a colorless solution. The acetone is evaporated under vacuum and the residue is dissolved in the minimum amount of ethyl ether. Cooling to 200C gives a white solid.

1 H NMR: (CDCl 3): 9.06 (dd, 1H, Ho, 3 Ho Ho-Hm = 7.2): 8.69 (dd, 1H, Hp, 3 H Hp-Hm = 6.1); 8.24 (d (broad), 1H, Hm); 4.62 and 4.06 (2d, 2H, CH 2, 2 # HA-HB = 16.4).

(composé 11)
A une solution de [Pd(dmba) (Me CN)2] BF4 (0,25g, 0,61 mmole)
dans du chlorobenzène (50ml) on ajoute du diphénylacé
tylène (0,25g, 1,40 mmole) et on chauffe le mélange au
reflux pendant 2,5 heures. On sépare par filtration sous une colonne de Celite (1 = 5cm) le palladium métallique ainsi formé. On évapore sous vide le solvant et on lave le résidu orangé avec du pentane (2 x 10 ml), on redissout avec la quantité minimale de CH2 Cl2 et on pré- cipite par addition de pentane (25 ml), ce qui fournit le composé du titre sous forme d'un solide orangé, avec un rendement quantitatif.Ce produit est purifié par cristallisation dans un mélange CH2 C12/pentane à -200C ce qui fournit des cristaux jaune brillant (0,13g, rendement 37,58) F = 2040C
IR (KBr) #B-F = 1070(s, large), cm-1
RMNH (CDCl3) : 5,83 (d,1H, proton aromatique, 3#H=H = 7 4,21 et 3,88 (2d,2H,CH2-N, 2#HA-HB = 13,6), 2,70 et 1,74 (2s (large), 6H,N-CH3).Example 11
Preparation of the compound of formula

(compound 11)
To a solution of [Pd (dmba) (Me CN) 2] BF4 (0.25 g, 0.61 mmol)
in chlorobenzene (50ml) is added diphenylaceous
tylene (0.25 g, 1.40 mmol) and the mixture is heated to
reflux for 2.5 hours. The palladium metal thus formed is filtered off under a column of celite (1 = 5 cm). The solvent is evaporated under vacuum and the orange residue is washed with pentane (2 × 10 ml), redissolved with the minimum amount of CH 2 Cl 2 and precipitated by addition of pentane (25 ml), which gives the compound of the title in the form of an orange solid, with a quantitative yield.This product is purified by crystallization in a CH2 C12 / pentane mixture at -200C which provides bright yellow crystals (0.13 g, yield 37.58) F = 2040C
IR (KBr) #BF = 1070 (s, broad), cm-1
NMR (CDCl 3): 5.83 (d, 1H, aromatic proton, 3H = H = 4.21 and 3.88 (2d, 2H, CH 2 -N, 2H-HA = HB = 13.6), 2.70 and 1.74 (2s (broad), 6H, N-CH 3).

(composé 12)
On ajoute du 3-phénylpropiolate d'éthyle (0,26g, 1,49 mmole) à une solution de [Pd(dmba) (MeCN)2]BF4 (0,25g, 0,61 mmole) dans du chlorobenzène (40ml). On chauffe le mélange au reflux pendant 70 minutes. On obtient une solution noire.Example 12
Preparation of the compound of formula

(compound 12)
Ethyl 3-phenylpropiolate (0.26 g, 1.49 mmol) is added to a solution of [Pd (dmba) (MeCN) 2] BF4 (0.25 g, 0.61 mmol) in chlorobenzene (40 ml) . The mixture is refluxed for 70 minutes. A black solution is obtained.

The palladium metal formed is removed by filtration on a Celite column (1 = 4 cm) and the solvent is evaporated in vacuo. The resulting solid product is purified by chromatography under a column of alumina (1 = 6cm) using CH 2 Cl 2 as eluent. The solution is evaporated under vacuum and an orange waxy solid product is obtained.

IR (KBr): # C = O = 1720 (s) (CO2R), 1615 (m) (CO2-) cm-1.

 1H NMR (CD 2 Cl 2): 7.70-6.94 (m, 14H, aromatic protons), 2-chloro-1H NMR (CDCl3): HA-HB-2,16 (s, 6H, N-CH 3), 0.77 (t, m.p. 3H, CH3).

Example 13
Preparation of the compound of formula

(compound 13)
The procedure is as in Example 12 starting from [Pd (8-mq) (MeCN) 4]
BF4 (0.21 g, 0.5 mmol) and ethyl 3-phenylpropiolate (0.21 g, 1.2 mmol) in chlorobenzene (50 ml)
IR (KBr): # C = O = 1715 (s) (CO 2 R), 1615 (m) (CO2 -1)
1 H NMR (CD 2 Cl 2): 8.80 (dd, 1H, Ho, 3 Ho Ho-Hm = 4.2, 4 Ho Ho-Hp = 1.8), 8.14 (dd, 1H, Hp, 3 H Hp-Hm = 8.3), 7.70-7.17 (m, 14H, aromatic protons), 4.38 (s (broad), 2H, CH2), 3.79 (q, 2H, O-CH2), 0, 80 (t, 3H, CH3).

(composé 14) a) préparation du composé de formule

(composé 14')
Le composé 14' est obtenu comme sous A 2a à partir
du composé chloré 6".Example 14
Preparation of the compound of formula

(Compound 14) a) Preparation of the Formula Compound

(14 'compound)
The compound 14 'is obtained as under A 2a from
chlorine compound 6 ".

NMR (CDCl 3): 3.95 and 3.22 (2d, 2H, CH 2 -N, 2 # HH = 13.5Hz), 3.84 (q, 2H,
CH2 (OEt)), 2.80 and 2.57 (2s, 6H, CH3-N), 2.16 and 2.03 (2s, 6H, CH3-CN), 0.77 (t, 3H,
CH3 (OEt), 3 HH - 7.1 Hz).

 b) preparation of the title compound.

The compound obtained in (0.65 g, 1 mmol) is heated in
chlorobenzene (40ml) under reflux for 0.75 hours.

We obtain a quantitative formation of palladium metal
lic. The reaction mixture is filtered through a column of
Celite (1 = 4cm) and the solvent is evaporated under vacuum. The re
sidu thus obtained is purified by chromatography on co
alumina (1 = 7cm). CH2 C12 (50 ml)
eluent to remove impurities and then extracted
with acetone (35ml). After removal of the solvent
gets a colorless solid (O, 18g, 41%).

IR (KBr): # C = O = 1725 (s) (CO2R) cm-1; BF = 1060 (s, broad)
cm-1
NMR (CDCl3): 5.06 (s, 2H, CH2-N), 3.99 (q, 2H, O-CH2), 3.26
(s, 6H, N-CH 3), 0.85 (t, 3H, CH 3).

Claims (8)

 1. A process for synthesizing heterocycles from ladocyclic complexes by reaction with alkynes, which is carried out in that the palladocyclic complexes are used in the form of iodinated or cationic complexes.  2. Process according to claim 1, characterized in that an iodinated complex of formula

 wherein Y - X represents an organic radical bonded to palladium on the Y side by a nitrogen or sulfur atom and on the X side by a carbon atom.  3. Process according to claim 1, characterized in that a cationic complex of formula

 wherein Y - X represents an organic radical bonded to palladium on the Y side by a nitrogen or sulfur atom and on the X side by a carbon atom, andZlet Z2 represent two weakly coordinated ligands.  4. Process according to claim 2 or claim 3, characterized in that Y - X is a residue derived from 8-methylquinoline, N, N-dimethyl naphthylamine, benzylpyridine and N, -dimethylbenzylamine.  5. Process according to any one of Claims 1 to 4, characterized in that an alkyne of formula  Wherein R1 and R2 are independently selected from hydrogen, aryl groups; such as phenyl, alkyl groups, especially C1 to C6, and C1 to C6 haloalkyl groups; alkenyl groups; C2-C6; groups of the formula -COOR3 or sCO-R3 in which R3 is a C1-C6 alkyl or aryl group; groups of formula -CR 4 R 5 OH wherein R 4 and R 5 are selected from hydrogen, alkyl groups of C1-C6 and aryl groups; a -CHO group; groups of formula -NR6R7 wherein R6 and R7 are selected from hydrogen and C1-C6 alkyl groups; groups of formula -SR8 or -SO2R8 in which R8 is selected from C1 to C6 alkyl and aryl groups; a trimethylsilyl group; as well as such groups linked to the triple bond by a C1 to C6 alkylene chain.  6. Process according to any one of the claims  1 to 5, characterized in that the reaction is carried out by  heating in an inert solvent.  7. Process according to claim 5, characterized in  what is reacted an iodized complex of formula

 with an alkyne of formula  R - C # C - R R and R having the meaning given in claim 5, and a heterocycle of formula

R1 and R2 having the meaning given above.  8. Process according to claim 5, characterized in that a cationic complex of formula

 with an alkyne of formula  R - C # C - R R and R having the meaning given in claim 5 and a heterocycle of formula

 in which R1 and R2 have the meaning given above.