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Title:
SYNTHESES OF METAL HETEROCYCLIC CARBENE ENOLATES AS COUPLING REACTIONS CATALYSTS
Document Type and Number:
WIPO Patent Application WO/2017/099693
Kind Code:
A1
Abstract:
The invention relates to the synthesis methods of N-heterocyclic carbene NHCE metal complexes and their catalytic activities in carbon-carbon coupling reactions.

Inventors:
COSKUN, Nejdet (Dumlupinar Mah. Kayabasi Sok. Tepebasi Cad. 72 Bilbeyler Sitesi 390e Kat:4 D:8 Gorukle Nilufer, Bursa, TR)
CETIN KORUKCU, Meliha (Yüzüncüyıl Mah. Prof. Dr. Erdal İnönü Cad. Lokman Hekim Sitesi No:38 D: 3 Nilüfer, Bursa, TR)
Application Number:
TR2016/050487
Publication Date:
June 15, 2017
Filing Date:
December 07, 2016
Export Citation:
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Assignee:
COSKUN, Nejdet (Dumlupinar Mah. Kayabasi Sok. Tepebasi Cad. 72 Bilbeyler Sitesi 390e Kat:4 D:8 Gorukle Nilufer, Bursa, TR)
CETIN KORUKCU, Meliha (Yüzüncüyıl Mah. Prof. Dr. Erdal İnönü Cad. Lokman Hekim Sitesi No:38 D: 3 Nilüfer, Bursa, TR)
International Classes:
C07F15/00
Domestic Patent References:
WO2008156451A12008-12-24
Foreign References:
JPH02165155A1990-06-26
Other References:
CO_KUN N ET AL: "Thermal rearrangements of tetrahydroimidazo[1,5-b]isoxazole-2,3-dicarboxylates. Synthesis of 3H-imidazol-1-ium ylides and their silver derivatives", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 66, no. 11, 13 March 2010 (2010-03-13), pages 2053 - 2060, XP026906886, ISSN: 0040-4020, [retrieved on 20100118], DOI: 10.1016/J.TET.2010.01.037
T. MIZOROKI; K. MORI; A. OZAKI, BULL. CHEM. SOC. JPN, vol. 44, 1971, pages 581 - 581
R. F. HECK; J. P. NOLLEY, J. ORG. CHEM., vol. 37, 1972, pages 2320 - 2322
W. CABRI; I. CANDIANI, ACC. CHEM. RES, vol. 28, 1995, pages 2 - 7
A. DE MEIJERE; F.E.MEYER, ANGEW. CHEM., INT. ED. ENGL, vol. 33, 1994, pages 2379 - 2411
I.P. BELETSKAYA; A.V. CHEPRAKOV, CHEM. REV., vol. 100, 2000, pages 3009 - 3066
J.G. VRIES, CAN. J. CHEM, vol. 79, 2001, pages 1086 - 1092
N. J. WHITCOMBE; K. K. HII; S. E. GIBSON, TETRAHEDRON, vol. 57, 2001, pages 7449 - 7476
N. CO KUN; S. TUNGMAN, TETRAHEDRON, vol. 62, 2006, pages 1345 - 1350
N. CO KUN; A. OZTURK, TETRAHEDRON, vol. 62, 2006, pages 12057 - 12063
N. CO KUN; M. QETIN, TETRAHEDRON, vol. 66, 2010, pages 2053 - 2060
O. GUERRET; S. SOLÉ; H. GORNITZKA; M. TEICHERT; G. TRINQUIER; G. BERTRAND, J. AM. CHEM. SOC., vol. 119, 1997, pages 6668 - 6669
H. M. J. WANG; I. J. B. LIN, ORGANOMETALLICS, vol. 17, 1998, pages 972 - 975
A. A. D. TULLOCH; A. A. DANOPOULOS; S. WINSTON; S. KLEINHENZ; G. EASTHAM, J. CHEM. SOC., DALTON TRANS., 2000, pages 4499 - 4506
P. L. ARNOLD, HETEROAT. CHEM, vol. 13, 2002, pages 534 - 539
I. J. B. LIN; C. S. VASAM, COMMENTS INORG. CHEM, vol. 25, 2004, pages 75 - 129
J. C. GARRISON; W. J. YOUNGS, CHEM. REV., vol. 105, 2005, pages 3978 - 4008
W. A. HERRMANN; C. KOCHER, ANGEW. CHEM., INT. ED. ENGL, vol. 36, 1997, pages 2163 - 2187
T. WESKAMP; V.P.W. BOHM; W.A. HERRMANN, J. ORGANOMET. CHEM., vol. 600, 2000, pages 12 - 22
FRISTRUP, P.; LE QUEMENT, S.; TANNER, D.; NORRBY, P.O, ORGANOMETALLICS, vol. 23, 2004, pages 6160 - 6265
CO KUN, N, TETRAHEDRON, vol. 55, 1999, pages 475 - 484
DONTHIRI, R. R.; PAPPULA, V.; REDDY, N. N. K.; BAIRAGI, D.; ADIMURTHY, S, J. ORG. CHEM., vol. 79, 2014, pages 11277 - 11284
BHARGAVA, S.; CHOUDHARY, A, INT. J. PHARM. PHARM. SCI., vol. 6, 2014, pages 553 - 557
BAGDI, A. K.; RAHMAN, M.; SANTRA, S.; MAJEE, A.; HAJRA, A, ADV. SYNTH. CATAL., vol. 355, 2013, pages 1741 - 1747
MARHADOUR, S.; MARCHAND, P.; PAGNIEZ, F.; BAZIN, M. A.; PICOT, C.; LOZACH, O.; RUCHAUD, S.; MAUD, A.; MEIJER, L.; RACHIDI, N., EUR. J. MED. CHEM., vol. 58, 2012, pages 543 - 556
SUGIHARA, T.; SATOH, T.; MIURA, M.; NOMURA, M, ANGEW. CHEM. INT. ED., vol. 42, 2003, pages 4672
KAMAL, A.; SRINIVASULU,V.; SESHADRI, B. N.; MARKANDEYA, N.; ALARIFIB, A.; SHANKARAIAH, N, GREEN CHEM., vol. 14, 2012, pages 2513
KIM, B.R.; LEE, H.G.; KIM, E.J.; LEE, S.G.; YOON, Y.J, J. ORG. CHEM., vol. 75, 2010, pages 484
CASTELLS, J.; FONT, J.; VIRGILI, A, J. CHEM. SOC. PERKIN TRANS I: ORGANIC AND BIOORGANIC CHEM, vol. 1, 1979, pages 1
XU, H.J.; ZHAO, Y.Q.; ZHOU, X.F., J. ORG. CHEM., vol. 76, 2011, pages 8036
XUE, J.Q.; FENG, Y.Q.; WANG, L.; WU, L.H, CHIN. CHEM. LETT., vol. 18, 2007, pages 1319
CHATURBHUJ, G.U; AKAMANCHI, K.G, TETRAHEDRON LETT., vol. 52, 2011, pages 4950
FAN, X.H.; YANG, L.M, EUR. J. ORG. CHEM., vol. 8, 2011, pages 1467
TAO, B.; BOYKIN, D, J. ORG. CHEM., vol. 69, 2004, pages 4330
DEMIR, A.S.; FINDIK, H.; SAYGILI, N.; TUNA S.N, TETRAHEDRON, vol. 66, 2010, pages 1308
NIU, L.; ZHANG, H; YANG, H.; FU H, SYNLETT, vol. 25, 2014, pages 995
MIURA, M.; KOIKE, T.; ISHIHARA, T.; SAKAMOTO, S.; OKADA, M.; OHTA, M.; TSUKAMOTO, S, SYNTH. COMMUN, vol. 37, 2007, pages 667
KIRAI, N.; YAMAMOTO, Y, EUR. J. ORG. CHEM., vol. 12, 2009, pages 1864
CO KUN N, TETRAHEDRON, vol. 55, 1999, pages 475
HIEBEL, M.; FALL, Y.; SCHERRMANN, M.; BERTEINA-RABOIN, S, EUR. J. ORG. CHEM., vol. 21, 2014, pages 4643
Attorney, Agent or Firm:
DESTEK PATENT, INC. (Lefkose Cad. NM Ofis Park B Blok No: 36/5 Besevler, Bursa, 16110, TR)
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Claims:
CLAIMS

1.

alkyl, aryl, heteroaryls

the hydrogen, alkyl, aryl, heteroaryl groups the electron-withdrawing groups such as ester, formyl, acyl, amide, nitrile the heteroatoms

X= an anion

M = a transition metal cation Are metal-mono HCE complexes. 2. According to claim 1 the compounds are metal-mono HCE complexes wherein R1 is being substituted phenyl.

3. According to claim 1 the compounds are metal-mono HCE complexes wherein R2 is being hydrogen, R3 is being Ph.

4. According to claim 1 the compounds are metal-mono HCE complexes wherein R4 and R5 are being methoxycarbonyl groups.

5. According to claim 1 the compounds are metal-mono HCE complexes wherein A, B and D are being nitrogen.

6. According to claim 1 the compounds are metal-mono HCE complexes wherein M is being Ag (I). 7. A method for the preparation of metal-mono HCE complexes mentioned in claim 1 includes the steps given below; a) Stirring the precursor compound 3/- -imidazol-1 -ium ylide (I) in a solvent at room temperature, in the presence of MX2 salts, b) Seperation of the precipitating compound by filtration and evaporation of the solvent under vacuum,

c) Extraction of the residual solid by a solvent and combining the extracts, d) Evaporation of the solvent of the combined extracts and trituation of the residue with a solvent selected from the ethers group,

e) Filtration of the precipitated amorphous solid and drying under vacuum

8. According to claim 7, a preparation method wherein the solvent in step a is CH2CI2. 9. According to claim 7, a preparation method wherein the mentioned stirring time in step a is 1 -10 hours.

10. According to claim 7, a preparation method wherein the solvent mentioned in step c is toluene.

1 1. l, heteroaryl groups

g groups such as ester, formyl, acyl,

M = a transition metal cation are metal-bisHCE complexes.

12. According to claim 1 1 the compounds are metal-bis HCE complexes wherein R1 is being substituted phenyl. 13. According to claim 1 1 the compounds are metal-bis HCE complexes wherein R2 is being hydrogen, R3 is being Ph.

14. According to claim 1 1 the compounds are metal-bis HCE complexes wherein R4 and R5 are being methoxycarbonyl groups.

15. According to claim 1 1 the compounds are metal-bis HCE complexes wherein A and B are being nitrogen.

16. According to claim 1 1 the compounds are metal-bis HCE complexes wherein the mentioned transition metal is being Pd(ll), Pt(ll), Ni(ll).

17. A method for the preparation of metal-bis HCE complexes mentioned in claim 1 1 includes the steps given below; a) Dissolving the metal-mono HCE complexes mentioned in claim 1 in a solvent, b) Keeping the formed solution at room temperature for a while,

c) Subjecting the solution to a thin layer plate or column and eluating with solvents

18. According to claim 17, a preparation method of the mentioned metal-bis HCE complexes, wherein the solvents mentioned in step c are ethyl acetate and petroleum ether.

19. The metal-mono HCE complexes mentioned in claim 1 and metal-bis HCE complexes mentioned in claim 1 1 are being used as catalysts in coupling reactions. 20. The catalysts mentioned in claim 19 are being used in the preparation of substituted ethenes.

21. The catalysts mentioned in claim 18 are being used in the preparation of biaryls.

Description:
DESCRIPTION

SYNTHESES OF METAL HETEROCYCLIC CARBENE ENOLATES AS COUPLING

REACTIONS CATALYSTS

Field of the invention

The present invention relates to the synthesis of organic and organometalic compounds having catalyst properties. Specifically, the invention relates to a method for the synthesis of N-heterocyclic carbene enolate (NHCE) metal complexes and their catalytic activities in carbon-carbon coupling reactions.

State of the present art

The carbon-carbon bond forming reaction between alkenes and aryl halides in the presence of a palladium catalyst has found an extensive usage following the pioneering reports of Mizoroki [1] and Heck [2] from the early 1970s. Numerous excellent surveys on a wide variety of different aspects of the Heck reaction have been published. 131 A variety of ligands [3al have been developed for the reaction, and it has been a key step in the total synthesis of many natural products and commercially important products. [3b ' 3dl The selectivity and mechanistic aspects of the Heck reaction have also been thoroughly reviewed. [3c ' 41

Our laboratory has recently described the utility of isoxazolo[3,2-a]isoquinolines as precursors for the synthesis of stable azomethine ylides; [5a] while the adducts of acyclic nitrones were shown to undergo a cascade reaction leading to the formation of iminocarbenes. [5bl We have also reported the rearrangement of isoxazolines from the reaction of imidazoline 3-oxides with dimethyl acetylenedicarboxylate to give the corresponding 3/- -imidazol-1 -ium ylides. The reaction of the latter with AgNC>3 in the presence of Et 3 N at room temperature provides C-2 metallated A/-heterocyclic carbene enolates (Pd-NHCE) precursors such as 1 (Scheme 1 ). [61 The silver compounds reported so far in the formation of Ag(l)-NHC complexes are AgOAc, [7] Ag 2 0 [8] and Ag 2 C0 3 . [91 Silver N- heterocyclic carbene complexes have been important in the development of other metal- carbene systems due to facile transmetallation reactions from the silver carbenes to a wide range of other transition metals 1101 and their application in synthetic systems. 1111 Palladium complexes of NHC ligands, in particular, have proved to be excellent catalysts not only for the Heck reactions but also for the Suzuki, Stille and Sonagashira cross-couplings. 141 In the state of the present art, as mentioned above, the N-heterocyclic carbene complexes as catalysts have some disadvantages. These are, the high catalysts loads, long reaction times, low selectivity and yields, and the use of highly toxic phosphorus based ligands in some catalytic systems, running the reactions in oxygen and moisture free conditions, and the lack of the kinetically supported data for the reaction mechanisms.

As a result, due to the disadvantages described above and the unsufficiencies of the present solutions, an improvement in the field of the art by preparing organic and organometallic compounds having catalytic activities was necessary.

Aim of the invention

The present invention relates to the synthesis of metal heterocyclic carbene enolates catalyzing the coupling reactions, addressing the above mentioned necessities and boosting all disadvantages and adding some more advantages.

The preferred aim of the invention is the synthesis of organic and organometallic compounds having catalytic properties.

An aim of the invention is the synthetic method for a new class of N-heterocyclic carbene enolates (NHCE) metal complexes and their catalytic activities in carbon-carbon coupling reactions.

Another aim of the invention is to provide low catalyst loads, to decrease the reaction times, to provide high selectivity and yields, to avoid the use of highly toxic phosphorus based ligands, running the reactions in oxygen and moisture insensitive catalytic reactions, and to gain mechanistic knowledge about the catalytic cycle.

Similar aim of the invention is the use of the developed catalysts in the synthesis of important medicines.

The structural and characteristic features and all the advantages will be understood more clearly by the figures as well as by the notes made to them. Therefore, it is necessary the evaluation to be done having in mind the detailed description and the explanations made to the figures. Figures to be in help to understand the invention

Figure 1 : Effect of changing A/-Aryl substituents of the Pd-NHCE catalyst on the rate at 80 °C in NMP. for 2a, H = 1 ; 2b, Me = 3.38; 2c, MeO = 4.79; 2d, CI = 0.33; 2e, Br = 0.34.

Figure 2: Effect of arylbromide (a) 6a, H = 1 ; 6b, 4-Me = 0.8; 6c, 4-MeO = 0.6; 6d, 3-CHO = 8; 6e, 4-CHO = 15) and styrene (b) (k rel =[6]X/[6]X=H 6e, H = 1 ; 6f, 4-Me = 0.95; 6g, 4-MeO = 0.12; 6i, 4-CI = 0.05) structures on the rate of Heck coupling reaction in NMP.

Figure 3: Kinetic plots for the reaction of bromobenzaldehyde and styrene at different reactant ratios (a-c) and initial rate plots for the same (d).

Figure 4: Mercury poisoning experiments with catalyst 2b (left, 0.5 mol%, at 80 and 100°C) and 3b (right, 0.5 mol %, at 80°C) in NMP.

Figure 5: Effect of arylbromide (a) and boronic acid (b) and catalyst (3a-d) structures on the rate of Suzuki coupling reaction. Effect of reactant concentration on the initial rates (d) in the coupling of 4-bromobenzaldehyde and phenylboronic acid.

Figure 6: Comparison of the reaction rates of 4-bromobenzaldehyde with phenylboronic acid (dark circles) with 2b (0.01 mol%, at room temperature) and the same in the presence of Hg (red circles) in DMF-H 2 0.

Figure 7: 1 H NMR (400 MHz, CDCI 3 ) spectrum of compound 3a.

Figure 8: 13 C NMR (100 MHz, CDCI 3 ) spectrum of compound 3a.

Figure 9: 1 H NMR (400 MHz, CDCI 3 ) spectrum of compound 3b.

Figure 10: 13 C NMR (100 MHz, CDCI 3 ) spectrum of compound 3b.

Figure 11 : Ή NMR (400 MHz, CDCI 3 ) spectrum of compound 3c.

Figure 12 13 C NMR (100 MHz, CDCI 3 ) spectrum of compound 3c.

Figure 13 Ή NMR (400 MHz, CDCI 3 ) spectrum of compound 3d.

Figure 14 3 C NMR (100 MHz, CDCI 3 ) spectrum of compound 3d.

Figure 15 H NMR (400 MHz, CDCI 3 ) spectrum of compound 3e.

Figure 16 3 C NMR (100 MHz, CDCI 3 ) spectrum of compound 3e.

Figure 17 H NMR (400 MHz, CDCI 3 ) spectrum of compound 6a.

Figure 18 3 C NMR (100 MHz, CDCI 3 ) spectrum of compound 6a.

Figure 19 H NMR (400 MHz, CDCI 3 ) spectrum of compound 6b.

Figure 20 3 C NMR (100 MHz, CDCI 3 ) spectrum of compound 6b.

Figure 21 H NMR (400 MHz, CDCI 3 ) spectrum of compound 6c. Figui e 22: 13 C NMR (100 MHz , CDCI 3 ) spectrum of compound 6c.

Figui e 23: 1 H NMR (400 MHz, CDCI3) spectrum of compound 6d.

Figui e 24: 13 C NMR (100 MHz , CDCI3) spectrum of compound 6d.

Figui e 25: 1 H NMR (400 MHz, CDCI3) spectrum of compound 6e.

Figui e 26: 13 C NMR (100 MHz , CDCI3) spectrum of compound 6e.

Figui e 27: 1 H NMR (400 MHz, CDCI3) spectrum of compound 6f.

Figui e 28: 13 C NMR (100 MHz , CDCI3) spectrum of compound 6f.

Figui e 29: 1 H NMR (400 MHz, CDCI3) spectrum of compound 6g.

Figui e 30: 13 C NMR (100 MHz , CDCI3) spectrum of compound 6g.

Figui e 31 : Ή NMR (400 MHz, CDCI3) spectrum of compound 6h.

Figui e 32: 13 C NMR (100 MHz , CDCI3) spectrum of compound 6h.

Figui e 33: Ή NMR (400 MHz, CDCI3) spectrum of compound 6i.

Figui e 34: 13 C NMR (100 MHz , CDCI3) spectrum of compound 6i.

Figui e 35: Ή NMR (400 MHz, CDCI3) spectrum of compound 8a.

Figui e 36: 13 C NMR (100 MHz , CDCI3) spectrum of compound 8a.

Figui e 37: Ή NMR (400 MHz, CDCI3) spectrum of compound 8b.

Figui e 38: 13 C NMR (100 MHz , CDCI3) spectrum of compound 8b.

Figui e 39: 1 H NMR (400 MHz, CDCI3) spectrum of compound 8c.

Figui e 40: 13 C NMR (100 MHz , CDCI3) spectrum of compound 8c.

Figui e 41 : 1 H NMR (400 MHz, CDCI3) spectrum of compound 8d.

Figui e 42: 13 C NMR (100 MHz , CDCI3) spectrum of compound 8d.

Figui e 43: 1 H NMR (400 MHz, CDCI3) spectrum of compound 8e.

Figui e 44: 13 C NMR (100 MHz , CDCI3) spectrum of compound 8e.

Figui e 45: 1 H NMR (400 MHz, CDCI3) spectrum of compound 8f.

Figui e 46: 13 C NMR (100 MHz , CDCI3) spectrum of compound 8f.

Figui e 47: Ή NMR (400 MHz, CDCI3) spectrum of compound 8g.

Figui e 48: 13 C NMR (100 MHz , CDCI3) spectrum of compound 8g.

Figui e 49: 1 H NMR (400 MHz, CDCI3) spectrum of compound 8h.

Figui e 50: 13 C NMR (100 MHz , CDCI3) spectrum of compound 8h.

Figui e 51 : Ή NMR (400 MHz, CDCI3) spectrum of compound 8i.

Figui e 52: 13 C NMR (100 MHz , CDCI3) spectrum of compound 8i.

Figui e 53: Ή NMR (400 MHz, CDCI3) spectrum of compound 10. Figure 54: 13 C NMR (100 MHz, CDCI 3 ) spectrum of compound 10.

Figure 55: 1 H NMR (400 MHz, DMSO-d 6 ) spectrum of compound 11 .

Figure 56: 13 C NMR (100 MHz, DMSO-d 6 ) spectrum of compound 11 .

Figure 57: 1 H NMR (400 MHz, CDCI 3 ) spectrum of compound 12.

Figure 58: 13 C NMR (100 MHz, CDCI 3 ) spectrum of compound 12.

Figure 59: 1 H NMR (400 MHz, CDCI 3 ) spectrum of compound 13.

Figure 60: 13 C NMR (100 MHz, CDCI 3 ) spectrum of compound 13.

It is not necessary the figures to be scaled up and some details which are not important to understand the invention might be dismissed. Moreover, the compounds having to great extend the same properties are given by the same number.

Detailed description of the invention

In the present detailed description of the invention the preferred embodiments for the synthesis of metal heterocyclic carbene enolates catalyzing coupling reactions, are selected only for better understanding of the invention and are described so that not to affect any rectriction.

The invention relates to the synthetic methods of metal-monoHCE (heterocyclic carbene enolates) and their metal-bis-HCE complexes having catalyst properties. C-2 Metallated 3H- imidazol-1 -ium ylide (1 ) (6) was used as a precursor for the synthesis of the related compounds. n, R 3 =Ph nitrile;

C= O or S; preferably O

M = a transition metal cation; preferably Ag (I)

Scheme 1 : General formula of C2-metallated 3/- -imidazol-1 -ium ylides

The screen of the present compounds in coupling reactions (e.g. Heck and Suzuki) in the 80 to 120 °C range revealed their high catalytic efficiencies in the Heck reaction, while the same compounds were found to be highly efficient at room temperature and aqueous medium in the Suzuki reaction.

Hammett type correlations revealed that the effect of substituents on the halide and alkene are opposite. Electron donating groups on the halide accelerate while the same substituents on the alkene decelerate the reaction rate. Similar effects were observed in the Suzuki reaction.

Based on these results the mechanisms for the both, Heck and Suzuki reactions in the presence of the new catalysts were elucidated. The synthetic applications of the catalysts were shown in the syntheses of stilbene, biaryl and medicinally important compounds. groups hydrogen, R 3 =Ph l, amide, nitrile;

C= 0 or S; preferably 0

X= an anion, preferably CI " or AcO "

M = a transition metal cation; preferably Pd(ll), t, (II), Ni(ll)

Scheme 2: General formula of metal-monoHCE complexes

Metal-monoHCE compound, the subject of the invention, is a metallacyclic which is formed by the bonding of a ligand having carbene and enolate sites to a metal centre. The carbene unit is located between the two heteroatoms of a heteroaromatic cycle, while the enolate site is bonded to atom B and contacts with the metal centre via atom C.

Substituent R1 , bounded to atom A of the heterocycle; can be any alkyl, aryl or heteroaryl

Substituents R2 and R3, can be any combination of the hydrogen, alkyl, aryl and heteroaryl groups

Substituents R4 and R5, can be a combination of electron-withdrawing groups such as ester, formyl, acyl, amide, nitrile etc.

R6, can be an aliphatic or aromatic group

A, B, D atoms are selected from one of the 5A group elements; such as nitrogen and phosphorus

Atom C4 is selected from 4A group elements There may be bonds between neighboring substituents R1 -R5 to form different size cycles.

X group bonded to the metal can be a conjugated base of an acid

Atom M is a transion metal cation in its second oxidation state oups

R 2 =hydrogen, R 3 =Ph acyl, amide, nitrile;

: a transition metal cation; preferably Pd(ll), Pt,(ll), Ni(ll)

Scheme 3: General formula of metal-bisHCE complexes

Metal-bisHCE compound, the subject of the invention, is a metallacyclic which is formed by the bonding of two ligands having carbene and enolate sites to a metal centre. The carbene unit is located between the two heteroatoms of a heteroaromatic cycle, while the enolate site is bonded to atom B and contacts with the metal centre via atom C. · Substituent R1 , bounded to atom A of the heterocycle can be any alkyl, aryl or heteroaryl

• Substituents R2 and R3 can be any combination of the hydrogen, alkyl, aryl and heteroaryl groups

• Substituents R4 and R5 can be a combination of electron withdrawing groups such as ester, formyl, acyl, amide, nitrile etc.

• A, B, D atoms are selected from one of the 5A group elements; such as nitrogen and phosphorus

• Atom C4 is selected from 4A group elements

• There may be bonds between neighboring substituents R1 -R5 to form different size cycles

• Atom M is a transion metal cation in its second oxidation state

C-2 Metallated 3/- -imidazol-1 -ium ylide (1 ) was used as a precursor for the synthesis of the mentioned metal-heterocyclic carbene enolate complexes. The reaction of the mentioned precursor with MX 2 in a solvent at room temperature provides compound 2. In the preferred embodiment of the invention Pd is used as M. In the preferred embodiment of the invention CH2CI2 is used as a solvent and the performed reactions are given below.

As shown below, the reaction of 1 with Pd(ll) salts in CH2CI2 at room temperature provides 3/-/-imidazol-1 -ium-2-yliden Pd(ll) complexes (2-3a-e)

NHCE precursor 1

Scheme 4: Synthesis of NHCE based palladacyclic compounds (2-3a-e)

Experimental Data:

Syntheses of the compounds that are the subject of the invention:

Melting points were recorded on an Electrothermal Digital melting point apparatus. Infrared spectra were recorded on a Thermo-Nicolet 6700 FTIR. 1 D and 2D NMR experiments were performed on a Varian Mercury Plus 400 MHz spectrometer. The elemental analyses were performed on a EuroEA 3000 CHNS analyser. Thermogravimetric (TG) and differential thermogravimetric (DTG) curves were obtained using a Sll Exstar TG/DTA 6200 analyzer in the range 25-1000 °C in platinum crucibles under nitrogen at a heating rate of 10 °C min 1 using alumina as reference. The Hammett correlation reaction series were run as each triplicated parallel reactions, in 10 mL screw cap vials and the initial rates for the substituted and unsubstituted cases were compared by monitoring the reactions by 1 H NMR. Hg(0) Poisoning experiments. Two identical parallel Heck or Suzuki reactions were run and followed for a specified time by 1 H NMR. Then mercury (300 times excess relative to the catalyst amount) was added. Aliquots from the reactions were analyzed by 1 H NMR and the percentages of the products were plotted versus time. Synthesis of 3H-imidazol-1-ium 2-yliden Pd(ll) complexes (2). General Procedure:

To a solution of 1a-e (0.25 mmol) in CH 2 CI 2 (5 mL), Pd(CH 3 CN) 2 CI 2 (0.288 mmol, 0.075 g, 99%) was added and the reaction mixture stirred for 1 -10 h in dark. The precipitated AgCI was removed by filtration and the solvent evaporated under reduced pressure at room temperature. The residual solid was extracted preferably with toluene (3 X 5 mL) and the extracts were combined. The solvent of the combined extracts was evaporated and the precipitated amorphous mass trituated preferably with diethylether. The amorphous solid was filtered and dried under vacuum. The obtained compounds 2 are isolable. Compounds 2 are in equilibria in organic solvents.

NHCE-Pd(ll) complex 2a.

2a Yield 0.085 g, 55% (The yield determined by Ή NMR is 88%). Dark orange powder, mp 140- 142 °C (decomposition). IR (KBr) v c =o 1738, 1695; v c =c 1613 cm 1 ; 1 H NMR (400 MHz, DMSO-de) : δ 1 .01 (t, J = 7.2 Hz, 9H), 2.69 (q, J = 7.2 Hz, 6H), 3.19 (s, 3H), 3.65 (s, 3H), 7.35-7.72 (m, 8H), 8.10 (s, 1 H), 8.25 (d, J = 7.6 Hz, 2H). Anal Calcd for C 2 7H 32 CIN 3 05Pd (620.43) C, 52.27; H, 5.20; N, 6.77; Found C, 52.30; H, 5.1 1 ; N, 6.64.

NHCE-Pd(ll) complex 2b (X = CI ).

2b

Yield 0.1 1 1 g, 70% (The yield determined by 1 H NMR is 77%). Yellow powder, mp 138-140 °C (decomposition). 161 .5 °C by TGA. IR (KBr) v c =o 1739, 1694; v c =c 161 1 cm 1 ; Ή NMR (400 MHz, DMSO-de) : δ 0.95 (t, J = 7.6 Hz, 9H), 2.42 (s, 3H), 2.52 (q, J = 7.6 Hz, 6H), 3.19 (s, 3H), 3.65 (s, 3H), 7.34-7.38 (m, 3H), 7.47-7.50 (m, 4H), 8.05 (s, 1 H), 8.13 (d, J = 8.0 Hz, 2H). 13 C NMR (100 MHz, DMSO-d 6 ): δ 1 1 .5, 21 .2, 46.1 , 49.8, 51 .5, 121 .4, 124.8, 128.1 , 128.8, 128.4, 128.6, 129.2, 130.7, 135.9, 139.1 , 147.5, 165.9, 167.7, 169.4. Anal Calcd for CssH^CINaOsPd (634.46) C, 53.01 ; H, 5.40; N, 6.62; Found C, 52.90; H, 5.04; N, 6.66.

NHCE-Pd(ll) complex 2b (X = AcO).

2b'

Yield 0.272 g, 86% (The yield determined by 1 H NMR is 100%). Brown powder, mp 128 °C (decomposition). IR (KBr) v c =o 1735, 1687; v c =c 161 1 cm 1 ; 1 H NMR (400 MHz, DMSO-d 6 ): δ 1 .02 (t, J = 6.8 Hz, 9H), 1 .89 (s, 3H), 2.42 (s, 3H), 2.72 (q, J = 6.8 Hz, 6H), 3.33 (s, 3H), 3.68 (s, 3H), 7.14-7.20 (m, 2H), 7.35-7.50 (m, 5H), 8.05 (s, 1 H), 8.64-8.67 (m, 2H). Anal Calcd for CaoHa NaO Pd (658.06) C, 54.76; H, 5.67; N, 6.39; Found C, 54.80; H, 5.62; N, 6.41 .

NHCE-Pd(ll) complex 2'b.

2'b

1 H NMR (400 MHz, DMSO-d 6 ): δ 1 .07 (t, J = 7.6 Hz, 9H,), 2.41 (s, 3H), 2.85 (q, J = 7.6 Hz, 6H), 3.16 (s, 3H), 3.65 (s, 3H), 7.34-7.38 (m, 3H), 7.44-7.50 (m, 4H), 7.92 (s, 1 H), 8.13 (d, J = 8.4 Hz, 2H).

NHCE-Pd(ll) complex 2c.

2c Yield 0.119 g, 73% (The yield determined by 1 H NMR is 91%). Orange powder, mp 134-136 °C (decomposition). 163.7 °C by TGA. IR (KBr) v c =o 1738, 1700; v c =c 1611 cm 1 ; 1 H NMR (400 MHz, DMSO-de): δ 0.96 (t, J= 6.8 Hz, 9H), 2.69 (q, J= 7.2 Hz, 6H), 3.19 (s, 3H), 3.66 (s, 3H), 3.85 (s, 3H), 7.11-7.50 (m, 7H), 8.01 (s, 1H), 8.15 (d, J= 6.8 Hz, 2H). Anal Calcd for C28H 3 4CIN 3 06Pd (650.46) C, 51.70; H, 5.27; N, 6.46; Found C, 51.50; H, 5.45; N, 6.58.

NHCE-Pd(ll) complex 2d.

2d Yield 0.098 g, 60% (The yield detected by 1 H NMR is 90%). Dark orange powder, mp 135- 138 °C (decomposition). 169.6 °C by TGA. IR (KBr) v c =o 1738, 1694; v c =c 1613 cm 1 ; Ή NMR (400 MHz, DMSO-d 6 ): δ 0.98 (t, J= 7.2 Hz, 9H), 2.63 (q, J = 7.2 Hz, 6H), 3.19 (s, 3H), 3.65 (s, 3H), 7.35-7.55 (m, 5H), 7.80 (d, J= 8.4 Hz, 2H), 8.11 (s, 1H), 8.28 (d, J= 6.8 Hz, 2H). Anal Calcd for CsyHaiClsNaOsPd (654.88) C, 49.52; H, 4.77; N, 6.42; Found C, 49.48; H, 4.93; N, 6.43.

NHCE-Pd(ll) complex 2e.

2e Yield 0.131g, 75% (yield detected by 1 H NMR is 100%). Yellow powder, mp 141-143 °C (decomposition).170.0 °C by TGA. IR (KBr) v c =o 1738, 1694; v c =c 1613 cm 1 ; 1 H NMR (400 MHz, DMSO-de): δ 0.99 (t, J= 7.2 Hz, 9H), 2.65 (q, J= 7.2 Hz, 6H), 3.19 (s, 3H), 3.65 (s, 3H), 7.14-7.54 (m, 5H), 7.93 (d, J= 8.0 Hz, 2H), 8.11 (s, 1H), 8.21 (d, J= 6.0 Hz, 2H). Anal Calcd for CsyHaiBrCINaOsPd (699.33) C, 46.37; H, 4.47; N, 6.01 ; Found C, 44.36; H, 4.42; N, 6.00.

Compound 2 (0.25 mmol) was dissolved in 1 mL CHCI3 and after waiting 30 min at room temperature, was subjected to silicagel coated thin layer plates. The plates were developed in the eluent and dried. The layer containing the compound 3 is washed with CHCI3. The solvent is evaporated and the pure compound is dried under vacuum.

S/s-NHCE-Pdfll) complex 3a:

3a

The compound was isolated by subjecting 2a (0.240 g) to preparative TLC. 0.022 g, 20%. Yelowish powder, mp 179 °C (decomposition). IR (KBr) v c =o 1 39, 1698 v c =c 1630 cm 1 ; Ή NMR (400 MHz, CDCI 3 ): δ 3.14 (s, 6H), 3.94 (s, 6H), 6.77 (s, 2H), 7.25-7.37 (m, 16H), 7.54 (d, J = 8.0 Hz, 4H). 13 C NMR (100 MHz, CDCI 3 ): δ 50.3, 52.6, 106.3, 120.0, 125.0, 126.8, 128.2, 128.6, 128.8, 129.0, 129.3, 135.4, 138.1 , 156.8, 163.5, 166.3, 168.5. Anal Calcd for C42H 3 4N 4 OioPd (861 .16) C, 58.58; H, 3.98; N, 6.51 ; Found C, 59.01 ; H, 4.05; N, 6.48. S/s-NHCE-Pdfll) complex 3b

3b

The compound was isolated by subjecting 2b (X=CI) to preparative TLC. 0.022 g, 20%. White powder, mp 220 °C (decomposition). IR (KBr) v c =o 1740, 1708 v c =c 1628 cm 1 ; 1 H NMR (400 MHz, DMSO-d 6 ): δ 2.29 (s, 6H), 2.95 (s, 6H), 3.78 (s, 6H), 7.16 (t, J = 7.6 Hz, 4H) 7.34-7.38 (m, 6H), 7.47-7.50 (m, 8H), 7.57 (s, 2H).

1 H NMR (400 MHz, CDCI 3 ): δ 2.35 (s, 6H), 3.10 (s, 6H), 3.94 (s, 6H), 6.74 (s, 2H), 7.09 (d, J = 8.4 Hz, 4H,), 7.25 (d, J = 6.8 Hz, 4H), 7.31 (t, J = 6.8 Hz, 2H), 7.37 (t, J = 7.2 Hz, 4H), 7.46 (d, J = 8.4 Hz, 4H). 13 C NMR (100 MHz, CDCI 3 ): δ 21 .1 , 50.3, 52.5, 106.1 , 120.0, 124.8, 126.7, 128.5, 128.8, 129.3, 129.6, 135.3, 135.7, 138.3, 156.9, 163.6, 166.3, 168.8. Anal Calcd for C 4 4H38N 4 OioPd (889.21 ) C, 59.43; H, 4.31 ; N, 6.30; Found C, 59.45; H, 4.37; N, 6.38. S/s-NHCE-Pd(ll) complex 3b: The compound was isolated by subjecting 2b (X=OAc) to preparative TLC. Ή NMR (400 MHz, DMSO-d 6 ): δ 2.29 (s, 6H), 2.96 (s, 6H), 3.79 (s, 6H), 7.36-7.48 (m, 18H), 7.59 (s, 2H). 1 H NMR (400 MHz, CDCI 3 ): δ 2.35 (s, 6H), 3.10 (s, 6H), 3.94 (6H, s), 6.74 (2H, s), 7.13 (d, J = 8.8 Hz, 4H), 7.24-7.26 (m, 6H), 7.33-7.38 (m, 4H), 7.45 (d, J= 8.4 Hz, 4H,).

S/s-NHCE-Pdfll) complex 3c

The compound was isolated by subjecting 2c (0.065 g) to preparative TLC. 0.029 g, 25%. Yellowish powder, mp 159 °C (decomposition). IR (KBr) v c =o 1739, 1694 v c =c 1615 cm 1 ; Ή NMR (400 MHz, CDCI 3 ): δ 3.12 (s, 6H), 3.82 (s, 6H), 3.94 (s, 6H), 6.76 (s, 2H), 6.85 (d, J = 8.8 Hz, 4H), 7.25-7.27 (m, 4H), 7.31 (t, J = 7.2 Hz, 2H), 7.36 (d, J = 7.2 Hz, 4H), 7.48 (d, J = 8.8 Hz, 4H). 13 C NMR (100 MHz, CDCI 3 ): δ 50.5, 52.5, 55.6, 106.4, 1 14.0, 120.2, 126.1 , 126.8, 128.6, 128.7, 129.5, 131 .1 , 135.2, 156.9, 159.4, 163.5, 166.4, 168.4. Anal Calcd for C 4 4H 38 N 4 Oi2Pd (921 .21 ) C, 57.37; H, 4.16; N, 6.08; Found C, 57.80; H, 4.27; N, 6.28. S/s-NHCE-Pdfll) complex 3d

3d

The compound was isolated by subjecting 2d (0.155 g) to preparative TLC. 0.027 g, 23%. Yellowish powder, mp 190 °C (decomposition). IR (KBr) v c =o 1739, 1707 v c =c 1629 cm 1 ; 1 H NMR (400 MHz, CDCI 3 ): δ 3.10 (s, 6H), 3.93 (s, 6H), 6.80 (s, 2H), 7.27 (d, J = 8.4 Hz, 4H), 7.34-7.41 (m, 10H), 7.55 (d, J = 9.2 Hz, 4H). 13 C NMR (100 MHz, CDCI 3 ): δ 50.5, 52.6, 106.1 , 1 19.7, 126.1 , 126.9, 128.9, 129.0, 129.2, 133.4, 134.4, 136.1 , 136.5, 156.9, 163.4, 166.1 , 168.7. Anal Calcd for C42H 3 2Cl2N 4 OioPd (930.05) C, 54.24; H, 3.47; N, 6.02; Found C, 54.45; H, 3.25; N, 6.18.

S/s-NHCE-Pdfll) complex 3e

3e

The compound was isolated by subjecting 2e (0.260 g) to preparative TLC. 0.024 g, 19%. Yellowish powder, mp 170 °C (decomposition). IR (KBr) v c =o 1739, 1696 v c =c 1622 cm 1 ; 1 H NMR (400 MHz, CDCI 3 ): δ 3.1 1 (s, 6H), 3.93 (s, 6H), 6.82 (s, 2H), 7.30 (d, J = 8.0 Hz, 4H), 7.34 (t, J = 7.2 Hz, 2H), 7.39 (d, J = 7.2 Hz, 4H), 7.51 (s, 8H). 13 C NMR (100 MHz, CDCI 3 ): δ 50.6, 52.7, 106.2, 1 19.7, 122.3, 126.3, 127.0, 128.9, 129.0, 129.2, 132.1 , 136.2, 136.9, 156.7, 163.5, 166.1 , 168.7. Anal Calcd for C 4 2H 3 2Br 2 N40ioPd (1018.95) C, 49.51 ; H, 3.17; N, 5.50; Found C, 50.05; H, 3.27; N, 5.35. The obtained compounds 3 are in equilibrium in organic solvents as well.

Examples of compounds prepared by the use of compounds, the subject of the invention, having catalyst properties.

Synthesis of substituted ethenes 6. General procedure:

In the preferred embodiment of the invention 1 ,2-diarylethenes (stibenes) are synthesized 4-Bromobenzaldehyde derivative (0.5 mmol) and styrene (0.75 mmol) were heated in the presence of the corresponding catalysts at the conditions specified in the Tables 2 and 3. The isolation in the solvent free conditions involves extraction with ether (3X5 mL). In other cases, crushed ice (3 g) was added to the reaction mixtures under stirring and the formed solids were filtered and washed with water (3X5 mL). Nearly pure compounds 6 were recrystallized from ether.

(E)-1 ,2-diphenylethene 6a

White crystals, Mp 122-123 °C . Lit 17a Mp 123-125 °C. Ή NMR (400 MHz, CDCI 3 ): 5 7.12 (s, 2H), 7.24-7.28 (m, 2H), 7.37 (dt, J = 6.0; 1 .6 Hz, 4H) Hz), 7.52 (dd, J = 6.8; 1 .6 Hz, 4H). 13 C NMR (100 MHz, CDCI 3 ): δ 126.5, 127.6, 128.69, 128.70, 137.3.

(E)-1-methyl-4-styrylbenzene 6b

6b Pal yellow crystals, Mp 1 17-1 19 °C Lit 17b Mp 1 19-122 °C. IR (KBr) v c =c 1592 cm 1 ; 1 H NMR (400 MHz, CDCI 3 ): 5 2.37 (s, 3H); 7.07 (d, J = 2.4 Hz, 2H), 7.17 (d, J = 7.6 Hz, 2H), 7.24- 7.26 (m, 1 H), 7.35 (t, J= 6.8 Hz, 2H), 7.42 (d, J= 8.4 Hz, 2H), 7.50 (dd, J= 9.6; 1.2 Hz, 2H). 13 C NMR (100 MHz, CDCI 3 ): δ 21.3, 126.40, 126.42, 127.4, 127.7, 128.6, 128.7, 129.4, 134.5, 137.50, 137.54. (E)-1-methoxy-4-styryl benzene 6c

6c

Pal yellow crystals, Mp 129-130 °C . Lit 17b Mp 131-134°C. IR (KBr) v c =c 1600 cm 1 ; 1 H NMR (400 MHz, CDCI3): δ 3.84 (s, 3H), 6.90 (d, J= 9.2 Hz, 2H), 6.97 (d, J= 16.4 Hz, 1H), 7.07 (d, J = 16.4 Hz, 1H), 7.22-7.25 (m, 1H), 7.35 (t, J= 8.0 Hz, 2H), 7.47 (d, J= 5.2 Hz, 2H), 7.50 (2H, d, J = 6.8 Hz). 13 C NMR (100 MHz, CDCI 3 ): δ 55.3, 114.1, 126.3, 126.6, 127.2, 127.7, 128.2, 128.7, 130.1, 137.6, 159.3.

(E)-4-styrylbenzaldehyde 6d

6d

Pal yellow crystals, Mp 108-109 °C. Lit 17c Mp 107-109 °C. IR (KBr) v c =o 1692, v c =c 1589 cnr 1 ; Ή NMR (400 MHz, CDCI 3 ): δ 7.15 (d, J= 16.4 Hz, 1H), 7.25 (d, J= 16.4 Hz, 1H), 7.32 (t, J= 6.8 Hz, 1H), 7.40 (t, J= 6.8 Hz, 2H), 7.56 (t, J= 6.8 Hz, 2H), 7.67 (d, J= 8.4 Hz, 2H), 7.88 (d, J= 8.4 Hz, 2H), 10.00 (s, 1H). 13 C NMR (100 MHz, CDCI 3 ): δ 126.8, 126.9, 127.3, 128.5, 128.9, 130.3, 132.2, 135.3, 136.5, 143.4, 191.7.

(E)-3-styrylbenzaldehyde 6e

Pal yellow crystals, Mp 100-101 °C. Lit 17d Mp 101-103 < C. IR (KBr) v c =o 1692, v c =c 1589cnr 1;(400 MHz, CDCI 3 ) δ 7.15 (d, J= 16.4 Hz, 1H), 7.22 (d, J= 16.4 Hz, 1H), 7.30 (t, J= 8.0 Hz, 1H), 7.39 (t, J= 8.0 Hz, 2H), 7.52-7.55 (m, 3H), 7.61-7.78 (M 2H), 8.04 (s, 1H), 10.06 (s, 1H). 13 C NMR (101 MHz, CDCI 3 ) δ 126.7, 127.1, 127.2, 128.2, 128.8, 128.9, 129.4, 130.5, 132.3, 136.7, 136.8, 138.3, 192.4.

(E)-4-(4-methylstyryl)benzaldehyde 6f

Pal yellow crystals, Mp 183-184 °C. Lit 17e Mp 182.1-182.8 < C IR (KBr) v c =o 1693, v c =c 1597 cm 1 ; 1 H NMR (400 MHz, CDCI 3 ) δ 2.38 (s, 3H), 7.10 (d, J= 16.3 Hz, 1H), 7.19-7.28 (m, 3H), 7.45 (d, J= 8.0 Hz, 2H), 7.64 (d, J= 8.2 Hz, 2H), 7.86 (d, J= 8.2 Hz, 2H), 9.99 (s, 1H). 13 C NMR (101 MHz, CDCI 3 ) δ 21.3, 126.3, 126.80, 126.82, 129.5, 130.2, 132.2, 133.8, 135.1, 138.6, 143.7, 191.6. (E)-4-(4-methoxystyryl)benzaldehyde 6g

Pal yellow crystals, Mp 144-146 °C. Lit 17 ' 146-147 < C. IR (KBr) v c =o 1690, v c =c 1596 cm 1 ; 1 H NMR (400 MHz, CDCI 3 ) δ 3.84 (s, 3H), 6.90 - 6.95 (m, 2H), 7.01 (d, J = 16.3 Hz, 1H), 7.22 (d, J = 16.3 Hz, 1 H), 7.46 - 7.51 (m, 2H), 7.62 (d, J = 8.2 Hz, 2H), 7.85 (d, J = 8.3 Hz, 2H), 9.98 (s, 1H). 13 C NMR (101 MHz, CDCI 3 ) δ 55.4, 114.3, 125.1, 126.56, 128.2, 129.3, 130.2, 131.8, 135.0, 143.8, 159.9, 191.6. (E)-4-(3-nitrostyryl)benzaldehyde 6h

Pal yellow crystals, Mp 179-180 °C. IR (KBr) v c =o 1694, v c =c 1599 cm "1 ; 1 H NMR (400 MHz, CDCI3) δ 7.28 (s, 2H), 7.57 (t, J= 8.0 Hz, 1H), 7.70 (d, J= 8.3 Hz, 2H), 7.83 (d, J= 7.8 Hz, 1H), 7.91 (d, J= 8.3 Hz, 2H), 8.15 (dd, J= 8.2, 1.3 Hz, 1H), 8.41 (t, J= 1.9 Hz, 1H), 10.02 (s, 1H). 13 C NMR (101 MHz, CDCI3) δ 121.2, 122.8, 127.3, 129.4, 129.8, 130.2, 130.4, 132.6, 135.9, 138.3, 142.1, 191.5. Anal Calcd for Ci 5 HnN0 3 (253.25) C, 71.14; H, 4.38; N, 5.53; Found C, 71.00; H, 4.50; N, 5.45. (E)-4-(4-chlorostyryl)benzaldehyde 6i

Pal yellow crystals, Mp 139-140 °C. Lit 17b Mp 129-131 < C. IR (KBr) v c =o 1693, v c =c 1597 cnr 1 ; 1 H NMR (400 MHz, CDCI 3 ) 57.11 (d, J= 16.3 Hz, 1H), 7.20 (d, J= 16.4 Hz, 1H), 7.35 (d, J = 8.5 Hz, 2H), 7.47 (d, J= 8.6 Hz, 2H), 7.64 (d, J= 8.2 Hz, 2H), 7.87 (d, J= 8.3 Hz, 2H), 10.00 (s, 1H). 13 C NMR (101 MHz, CDCI3) δ 126.9, 127.9, 128.0, 129.0, 130.2, 130.8, 134.1, 135.0, 135.5, 143.0, 191.6.

Synthesis of biaryls 8. General procedure: Aryl bromide (0.5 mmol) and arylboronic acid (0.75 mmol) were stirred in the presence of 0.1 mol% catalyst 2 (0.0005 mmol, 0.0003 g) and Cs 2 C0 3 or Na 2 C0 3 (1 mmol) in DMF-H 2 0 (1 :1) (1.6 mL, 0.8 mL DMF and 0.8 mL H 2 0) at room temperature (25 °C). After adding crushed ice (3 g) the precipitated biaryls were filtered and washed with water (3 X 3 mL). All compounds except 8f were isolated by this way and dried under vacuum. As an exception, compound 8f was purified by extraction with CHCI 3 (3X5mL) and following chromatographic methods. Biphenyl 8a

Mp 68-69 °C. Lit 18a mp 69-70 °C. 1 H NMR (400 MHz, CDCI 3 ) δ 7.35 (t, J= 7.6 Hz, 2H), 7.44 (t, J= 7.6 Hz, 4H), 7.60 (d, J= 6.8 Hz, 4H). 13 C NMR (101 MHz, CDCI 3 ) δ 127.1, 127.2, 128.7, 141.2.

4-Methyl biphenyl 8b

Mp 41-42 °C. Lit 18b mp 41-42 °C. 1 H NMR (400 MHz, CDCI 3 ) δ 2.40 (s, 3H), 7.24-7.26 (m, 2H), 7.32 (t, J= 7.2 Hz, 1 H), 7.42 (t, J= 8.0 Hz, 2H), 7.49 (d, J= 8.0 Hz, 2H), 7.59 (d, J= 8.0 Hz, 2H). 13 C NMR (101 MHz, CDCI 3 ) δ 21.2, 126.97, 126.99, 128.7, 128.8, 129.5, 137.0, 138.3, 141.1.

Biphenyl-4-yl methyl ether 8c

Mp 86-87 °C. Lit 18b mp 85-86 °C. Ή NMR (400 MHz, CDCI 3 ) δ 3.86 (s, 3H), 6.98 (d, J= 9.2 Hz, 2H), 7.30 (t, J= 7.2 Hz, 1H), 7.42 (t, J= 8.0 Hz, 2H), 7.53-7.57 (m, 4H). 13 C NMR (101 MHz, CDCI 3 ) δ55.3, 114.2, 126.70, 126.74, 128.2, 128.7, 133.8, 140.8, 159.1. Bi henyl-4-carbaldehyde 8d

Mp 60-61 °C. Lit 18c mp 59-60 °C. 1 H NMR (400 MHz, CDCI 3 ) δ 7.42-7.51 (m, 3H), 7.64 (d, J = 9.6 Hz, 2H), 7.75 (d, J= 8.0 Hz, 2H), 7.95 (d, J= 8.0 Hz, 2H), 10.06 (s, 1H). 13 C NMR (101 MHz, CDCI 3 ) δ 127.4, 127.7, 128.5, 129.0, 130.3, 135.2, 139.7, 147.2, 191.9.

Biphenyl-3-carbaldehyde 8e

Mp 52-53 °C. Lit 18d mp 53-54 °C. 1 H NMR (400 MHz, CDCI 3 ) δ 7.40 (t, J= 7.2 Hz, 1H), 7.48 (t, J= 7.2 Hz, 2H), 7.59-7.64 (m, 3H), 7.86 (dd, J= 9.6; 1.6 Hz, 2H), 8.10 (m, 1H), 10.09 (s, 1H). 13 C NMR (101 MHz, CDCI 3 ) δ 127.2, 128.0, 128.2, 128.7, 129.0, 129.5, 133.1, 136.9, 139.7, 142.1, 192.4. 3'-Methylbiphenyl-4-carbaldehyde 8f

Mp 57-58 °C. (Lit 186 , given as colorless oily product). 1 H NMR (400 MHz, CDCI 3 ) δ 2.44 (s, 3H), 7.23-7.25 (m, 1H), 7.37 (t, J= 8.0 Hz, 1H), 7.43-7.45 (m, 2H), 7.73-7..75 (m, 2H), 7.93- 7.95 (m, 2H), 10.05 (s, 1H). 13 C NMR (101 MHz, CDCI 3 ) δ 23.7, 126.7, 129.8, 130.3, 131.1, 131.4, 132.4, 137.3, 140.9, 141.9, 149.5, 194.2. 4'-Methoxybiphenyl-4-carbaldehyde 8g

Mp 103-104 °C. Lit 18 ' mp 103-104°C. 1 H NMR (400 MHz, CDCI 3 ) δ 3.87 (s, 3H), 7.02 (t, J = 5.7 Hz, 2H), 7.60 (t, J =5.1 Hz, 2H), 7.71 (d, J= 8.2 Hz, 2H), 7.92 (d, J= 8.0 Hz, 2H), 10.03 (s, 1H). 13 C NMR (101 MHz, CDCI 3 ) δ 55.4, 114.5, 127.0, 128.5, 130.3, 132.0, 134.6, 146.8, 160.1, 191.9.

Biphenyl-4,4'-dicarbaldehyde 8h

Mp 145-147 °C. Lit 18 ^ mp 148-150 °C. 1 H NMR (400 MHz, CDCI 3 ) δ 7.80 (d, J= 8.2 Hz, 4H), 8.00 (d, J= 8.2 Hz, 4H), 10.09 (s, 2H). 13 C NMR (101 MHz, CDCI 3 ) δ 128.0, 130.4, 135.9, 145.5, 191.7. '-Chlorobiphenyl-4-carbaldehyde 8i

Mp 113-115 °C. Lit 18 ' mp 114-115 °C. 1 H NMR (400 MHz, CDCI 3 ) δ 7.45-7.47 (m, 2H), 7.56 - 7.58 (m, 2H), 7.71-7.73 (m, 2H), 7.95 - 7.97 (m, 2H), 10.06 (s, 1H). 13 C NMR (101 MHz, CDCI 3 ) δ 127.6, 128.6, 129.2, 130.4, 134.7, 135.4, 138.1, 145.9, 191.8

Synthesis of 3,4-diphenyl-1-p-tolyl-1H-imidazol-2(3H)-one 9.

The compound was synthesized according to the literature procedure. 19 Synthesis of 4-(2-oxo-3,4-diphenyl-1 -p-tolyl-2,3-dihydro-1 H-imidazol-5-yl)benzaldehyde 10.

According to the general procedure, to the solution of 9 (0.2 mmol, 0.065 g) and 4- bromobenzaldehyde (0.3 mmol, 0.056 g) in DMF (0.3 mL) NaOAc (0.8 mmol, 0.066 g) and the catalyst 2b' (0.002 mmol, 0.001 g) were added and the mixture heated in a screw cap vial at 120 °C for 75 h. The reaction mixture was extracted with CDCI 3 (3X15 mL). After drying and filtering was subjected to preparative TLC (using ethyl acetate / hexane as eluent system) to give the pure compound as light yellow solid. The product was recrystallized from diethyl ether / petroleum ether.

Mp 194-195 °C. IR (KBr) v c =o 1708, 1693; V C =N 1600 cm 1 ; 1 H NMR (400 MHz, CDCI 3 ): δ 2.33 (s, 3H), 6.99 (d, J = 6.8 Hz, 2H ), 7.09-7.19 (m, 8H), 7.20-7.33 (m, 6H), 7.62 (d, J = 8.4 Hz, 2H), 9.90 (s, 1 H). 13 C NMR (100 MHz, CDCI 3 ): δ 21 .1 , 120.3, 123.3, 127.2, 127.4, 127.6, 128.2, 128.3, 128.5, 128.8, 129.4, 129.6, 130.3, 130.4, 132.3, 134.8, 134.8, 135.0, 137.4, 152.4, 191 .6. Anal Calcd for C29H22N2O2 (430.50) C, 80.91 ; H, 5.15; N, 6.51 ; Found C, 80.71 ; H, 5.25; N, 6.40

Synthesis of 2-amino-1-(2-hydroxyimino-2-phenyl-ethyl)-pyridinium bromide 11.

To a solution of 2-aminopyridine (10 mmol, 0.941 g) in EtOH (20 mL) 2-bromo-1 -phenyl- ethanone oxime (10 mmol, 2.130 g) was added and the reaction mixture stirred for 45 min. The precipitating solid was filtered and dried under vacuum.

Yield 2.202 g, 71%. White powder, mp 156-157 °C. IR (KBr) v NH 3310 ve 3273; V N -OH 3137; VC=N 1662 cm 1 ; 1 H NMR (400 MHz, DMSO-d 6 ): δ 5.31 (s, 2H), 6.89 (t, J= 6.8 Hz, 1H), 7.06 (d, J= 8.4 Hz, 1H), 7.41-7.47 (m, 3H), 7.69 (dd, J= 9.2, 1.6 Hz, 2H), 7.85 (t, J= 8.4 Hz, 1H), 8.11 (d, J= 6.4 Hz, 1H), 8.52 (br s, 2H), 11.41 (s, 1H). 13 C NMR (100 MHz, DMSO-d 6 ): δ 55.0, 113.1, 115.4, 128.5, 129.0, 129.9, 131.3, 141.2, 143.0, 147.3, 154.9. Anal. Calcd for Ci 3 Hi 4 BrN 3 0 (308.17 ) C, 50.67; H, 4.58; N, 13.64; Found C, 50.92; H, 4.28; N, 13.73.

Synthesis of 2-phenyl-1 H-imidazo[1 ,2-a]pyridine 12. 2-Amino-1-(2-hydroxyimino-2-phenyl-ethyl)-pyridinium bromide (6.5 mmol) was treated with NH 4 OH (5.5 mL, 26%) at room temperature for 10 min. Water was added (30 mL) to the suspension and the mixture extracted with CHCI3 (6 X 20 mL). The combined extracts were dried over Na 2 S0 4 and filtered. The organic solvent was evaporated under vacuum and the residue crystallized from diethyl ether.

Yield 1.200 g, 95%. Colorless crystals, mp 135-136 °C. Lit 20 mp 131.6-132.6 °C. IR (KBr) VC=N 1631; vc = c 1503 cm 1 ; 1 H NMR (400 MHz, CDCI 3 ): δ 6.76 (dd, J= 7.6, 1.2 Hz, 1H), 7.14- 7.18 (m, 1H), 7.31-7.35 (m, 1H), 7.44 (t, J= 7.2 Hz, 2H), 7.63 (d, J= 9.6 Hz, 1H), 7.85 (s, 1H), 7.95 (d, J= 9.6 Hz, 1H), 8.10 (d, J= 8.4 Hz, 2H). 13 C NMR (100 MHz, CDCI 3 ): δ 108.1, 112.4, 117.6, 124.6, 125.6, 126.0, 126.8, 127.9, 128.7, 133.7, 145.8. 1 H NMR (400 MHz, DMSO-de): δ 6.87 (dt, J= 8.0, 1.2 Hz, 1H), 7.20-7.24 (m, 1H), 7.28-7.32 (m, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.56 (dt, J= 10.0, 0.8 Hz, 1H), 7.93-7.96 (m, 2H), 8.38 (s, 1H), 8.50 (dt, J= 6.8, 1.2 Hz, 1H)

Synthesis of 4-(2-phenyl-1H-imidazo[1,2-a]pyridin-3-yl)benzaldehyde 13.

To a solution of heterocycle 12 (0.2 mmol, 0.039 g) and 4-bromobenzaldehyde (0.3 mmol, 0.056 mg) in DMF (0.3 mL) NaOAc (0.8 mmol, 0.066 g) and the catalyst 2b' (0.002 mmol, 0.001 g) were added and the mixture heated in a screw cap vial at 120 °C for 75 h. The reaction mixture was poured into crushed ice and the precipitated products filtered and dried.

Pal yellow powder, mp 190-191 < C. Lit 20 mp 189.7-192.2 < C. IR (KBr) v c =o 1695; V C =N 1604; vc=c 1568 cm 1 , 1 H NMR (400 MHz, CDCI3): δ 6.82 (1 H, t, J = 6.8 Hz), 7.25-7.32 (4H, m), 7.60-7.62 (2H, m), 7.66 (2H, d, J = 8.4 Hz), 7.72 (1 H, d, J = 9.2 Hz), 8.03 (2H, d, J = 8.4 Hz), 8.09 (1 H, d, J = 6.8 Hz), 10.10 (1 H, s). 13 C NMR (100 MHz, CDCI 3 ): δ 1 12.9, 1 17.9, 1 19.7, 123.0, 125.4, 127.9, 128.4, 128.5, 130.7, 130.9, 133.7, 135.9, 136.1 , 143.9, 145.5, 191 .6.

Synthetic method for the invention subject compounds.

In the preferred embodiment of the invention Pd is used for . The reaction of NHCE (N-heterocyclic carbene enolates) precursors C-2 metallated 3H- imidazol-1 -ium ylides 1 with Pd(ll) salts (Pd(CH 3 CN) 2 CI 2 and Pd(OAc) 2 etc.) in CH 2 CI 2 , provided orange colored amorphous solids 2 in good to moderate yields (Table 1 ). The elemental analyses (CHN) confirm the stoichiometry of complex 2 to be as depicted in Scheme 4. The FTIR spectra of 2 (KBr) show the presence of v c =o and v c =c at ca 1738, 1695 and 1613 cm 1 , respectively. The monoligated examples 2 have characteristic patterns (Figure 1 ) in their 1 H NMR (DMSO-cfe) spectra at ca. 0.95 (9H, t, J = 7.6 Hz) and 2.52 (6H, q, J = 7.6 Hz), due to the coordinated Et 3 N (Scheme 5). Three proton singlets at ca. 3.19 and 3.65 ppm correspond to the methyl carboxylate groups. In the 13 C NMR spectra the carbonyls of the ester functional groups have signals at ca. 168 and 169 while the ketone carbonyl appears at ca. 166 ppm. The comparison of the 1 H NMR spectra of 2b and 2b' (Scheme 5) provides a clue for the orientation of the X ligand in the latter compounds. The downfield shift of the A/-o-aryl protons as well as the CH 2 protons of the Et 3 N can be assumed to arise from the acetoxy group's anisotropic magnetic field. The one proton singlets at ca. 8.05 for the C-4H of the imidazolium ring are the other characteristic peaks of compounds 2. Finally, the orffto-protons of the A/-aromatic rings are shifted downfield by ca 0.4 ppm with respect to the corresponding protons of 1 . Closer inspection of the 1 H NMR spectra in DMSO-d6 reveals (Table 1 ) that 2 are in equilibrium with 2' and 3. Compounds 2' were assumed to arise from the chloride displacement by the solvent molecule. NOE experiments confirm the assigned geometries (Scheme 5) for the latter. The ratios of 2 in equilibrium with 2'b and 3 were determined (Table 1 ).

2b 2b' 2'b

Scheme 5: Characteristic chemical shifts of 2b, 2b' and 2'b.

Table 1. Mono 2 and bis-Pd-NHCE complexes 3 equilibria in DMSO-d 6 and CDCI 3 at 20 °C

a C 6 H5 CI 55 20 67:20 48:52 45:55 b 4-MeC 6 H 4 CI 70 20 69:28 c 35:65 9 30:70 b' 4-MeC 6 H 4 AcO 86 25 69:31 60:40 60:40 c 4-MeOC 6 H 4 CI 73 25 66:23 52:48 49:51 d 4-CIC 6 H 4 CI 60 23 68:20 d 50:50 48:52 e 4-BrC 6 H 4 CI 75 19 73:18 65:34 56:44 a Isolated yield of 2 and 3 in %. b The ratios of the corresponding compounds were determined by the integration of the corresponding peaks at 3.78 (3); 3.67(2'); 3.65(2); in the 1 H NMR spectra of the mixtures in DMSO-de at 20 °C. c The ratio of 2b:2'b:3b after a week became 9:77:14. d Compound 2'(See Figure 1 ) was present in ca 10% in all cases except in the case with X=AcO. e The ratios of the corresponding compounds were determined by the integration of the corresponding peaks at 7.13 and 6.74 ppm in the 1 H NMR spectra of the mixtures in CDC at 20 °C. 'The values are after 25 hrs at 20 °C. 9 The ratio of the products from the reaction of 1b with 0.5 eqv Pd(ll) was the same, however the amount of the hydrolysed 1b was 42%.

The formation of the latter leads to an equimolar amount of Pd(Et 3 N) 2 X2, which has characteristic peaks at ca 1 .35 and 3.19 ppm in the 1 H NMR spectra corresponding to coordinated Et 3 N. Compounds 3a-e were isolated and purified by preparative TLC or column chromatography and characterized (the yields are given in Table 1 ).

Scheme 6: Characteristic NMR data for 3b in CDCI 3 .

Compounds 2a-e were screened for their catalytic efficiencies in a Heck cross-coupling between 4-bromobenzaldehyde and styrene in NMP at 80 Ό (Scheme 7). The changing N- aryl substituent of the catalyst was correlated in a Hammett plot, which demonstrated that electron-donating groups accelerated the reaction while electron-withdrawing ones decelerated the reaction. The plot of σ ρ constants versus log k re i provided a p constant equal to -2.32.

Ο. . Ό · kat (NHCE-Pd) jr

Scheme 7: Heck-Mizoroki reaction catalyzed by compounds 2 and 3.

A series of aryl halides were reacted with styrene in the presence of 0.5 mol % catalyst 2b, and the relative stilbene formation rates were correlated with the Hammett σ constants (Scheme 2). The magnitude of the reaction constant p is 2.05. The reaction of 4-bromobenzaldehyde with a series of substituted styrenes confirmed that the styrene structure is also affecting the coupling rate as the aryl halide. Thus, reaction constant pi of magnitude -1 .54 from the correlation of p-substituted (Scheme 2) styrenes with σι constants was produced. The latter correlations clearly reveal that both reactants are involved in the rate determining step of the coupling reaction. This fact is in controversy with the observations that only a- substitution at styrene is substituent dependent process. 12

Kinetic plots for the reaction of 4-bromobenzaldehyde and styrene at different reactant concentrations revealed that the reaction is 1 st order according to each reactant, and 2 nd order in total (Scheme 3).

In view of the Pd(ll)-NHCE catalyzed Heck reaction, the probable mechanism is depicted in Scheme 8.

2

NHCE NHCE B B '

Pd(NHCE) 2

NHCE

Β ' )

Scheme 8: Probable catalytic cycle in the reaction of aryl bromides with styrene in the presence of Pd-NHCEs.

We assume that compounds 3 may undergo dissociation to give both nucleophilic species A and electrophilic species A'. The latter activated palladium-carbene species can transfer Pd(0) to the corresponding aryl halide and styrene to give C and C, respectively. The reactions of C and C with styrene and aryl halide will provide D. Generally proposed steps in the classical Heck reaction mechanism will provide the product stilbene and E. The HBr elimination of the later probably produces Pd(0) species, which undergo reactions with anion- carbene B' and cation-carbene B to give the corresponding A and A', respectively. The reactions of the latter with their counter-ions B and B' completes the catalytic cycle. Mercury metal suppressed (Scheme 4) the catalysts 2b as well as 3b activities, which is in agreement with the proposed active species to be Pd(0) or its soluble carbene-enol and -enolate complexes. The presence of colloidal palladium is also not excluded.

The above discussed mechanism can to some extent explain the effect of both reactants on the reaction rate by assuming the activation energies for C and C conversions to D to be equal, however the effect of catalyst with p = -2.32 clearly is in controversy with the proposed independent equivalent energy transition states. We can not expect the catalyst substituents to have the same effect on transition states with opposite charges. Therefore, a more reasonable mechanism is depicted in Scheme 8. The species from the reactions of A and A' with the corresponding aryl halide and styrene were assumed to combine in a transition state H (Scheme 8) to undergo synchronous conversion to I and A.

Stilbenes 6a-i are synthesized by using catalyst 2b (Scheme 7, Table 2).

Table 2. 2 Optimization of the Heck-Mizoroki reaction catalyzed by compounds 2 and 3 at 120 °C.

Conversion

Entry Cat.(%) a X Base 15 Solvent Time (h)

(%)

68

1 2b (1 ) CI Cs 2 C0 3 DMF 42

72

2 2b (1 ) CI Na 2 C0 3 DMF 42

46

4 2b (1 ) CI NaHC0 3 DMF 42

34

5 2b (1 ) CI NaAcO DMF 42

52

6 2b (1 ) CI Na 2 C0 3 DMAA 42

90

7 2b (1 ) CI Na 2 C0 3 NMP 42

72

8 2b (1 ) CI Na 2 C0 3 DMF-H 2 0 42

100

9 2b (0.1 ) CI Na 2 C0 3 NMP 75

100

10 2b (0.01 ) CI Na 2 C0 3 NMP 75

57

1 1 2b (0.001 ) CI Na 2 C0 3 NMP 75

84

12 2b (1 ) AcO Cs 2 C0 3 DMF 42

67

13 2b (1 ) AcO Na 2 C0 3 DMF 42

37

14 2b (1 ) AcO K 2 C0 3 DMF 42

60

15 2b (1 ) AcO NaHC0 3 DMF 42

67

16 2b (1 ) AcO NaAcO DMF 42 43

17 2b (1) AcO Na 2 C0 3 DM A A 42

74

18 2b (1) AcO Na 2 C0 3 NMP 42

82

19 2b (1) AcO Na 2 C0 3 DMF-H 2 0 42

65

20 2b (0.1) AcO Na 2 C0 3 DMF 75

13

21 2b (0.01) AcO Na 2 C0 3 DMF 75

0

22 2b (0.001) AcO Na 2 C0 3 DMF 75

100

23 3b (0.1) CI Na 2 C0 3 NMP 44

100

24 3b (0.01) CI Na 2 C0 3 NMP 44

69

25 3b (0.001) CI Na 2 C0 3 NMP 44

12

26 3b (0.0001) CI Na 2 C0 3 NMP 44

100

27 3b (0.001) CI Na 2 C0 3 NMP 99

28 3b (0.0001) CI Na 2 C0 3 NMP 99 35

a Catalyst mol%; b NaHC03 and NaAcO were used 4 eqvs, all other are 2 eqvs; c No palladium black formations were observed except entries 3,13,16-17. Compound 2c was randomly selected from the catalyst series to explore its potential as a catalyst in Suzuki coupling reaction. Thorough investigation of solvents and bases for the reaction revealed that Cs 2 C0 3 and Na 2 C0 3 can be used in DMF-H 2 0 (1:1) at room temperature (Table 4) Table 4. Room temperature Suzuki coupling reaction in DMF-H 2 0 (1 :1).

Cat Time Conversion krel

Entry R R 2

(mol%) (min) (%)

1 3a (0.01) 4-CHO H 120 32 1

2 3b (0.01) 4-CHO H 120 66 2.06

3 3c(0.01) 4-CHO H 120 71 2.22

4 3d(0.01) 4-CHO H 120 83 2.59

5 3e(0.01) 4-CHO H 120 17 0.53

6 2b(0.01) H H 120 18 1

7 2b(0.01) 4-Me H 120 15 0.83

8 2b(0.01) 4-MeO H 120 9 0.5

9 2b(0.01) 4-CHO H 120 37 2.05

10 2b(0.01) 3-CHO H 120 24 1.33 1 1 2b(0.01 ) 4-CHO H 120 45 1

12 2b(0.01 ) 4-CHO 3-Me 120 40 0.89

13 2b(0.01 ) 4-CHO 4-MeO 120 96 2.13

14 2b(0.01 ) 4-CHO 4-CI 120 5 0.1 1

15 2b(0.01 ) 4-CHO 4-CHO 120 7 0.16

16 2b(0.01 ) 4-CHO 4-MeO 30 100

17 2b(0.01 ) 4-CHO 4-MeO 120 100

18 2b(0.001 ) 4-CHO 4-MeO 1320 67 b

19 2b(0.0001 ) 4-CHO 4-MeO 1320 12

a Cat mol% / base 2eqv Na 2 C0 3 ; b 88% at 72 h.

The latter solvent mixture is about 150 times more efficient than the other solvents tested (e.g. 1 ,4-dioxane, NMP, dimethylacetamide (DMAA), DMF, H 2 0). The correlations performed with aryl halide, arylboronic acid and catalyst series provided p constants having the same sign with those in the Heck reaction (0.83, -1 .63, -0.79, respectively). Initial rate measurements revealed that doubling the arylboronic acid concentration doubles the reaction initial rate while doubling the concentration of the aryl halide slightly decreased the initial rate.

It is clear that the mechanism for the Suzuki coupling in the presence of NHCE-Pd complexes involves steps similar to those of the Heck reaction mechanism. However, the negative mercury poisoning test and the surprising concentration effect of the aryl halide requires some discussions. The probable mechanism for the Suzuki reaction is depicted in Scheme 1 1 . The oppositely charged species A and A' may undergo insertions onto the aryl halide and arylboronic acid to give the corresponding adducts, which in turn can combine with arylboronic acid and aryl halide, respectively, to give the Pd (IV) species. The disproportionation of the latter will provide the biaryl 8 and the initial catalyst structure 3.

Biaryls 8a-i were prepared by using catalyst 2b at room temperature in excellent yield (Scheme 9,Table 3).

Scheme 9: Concerted mechanism for the ambident palladium catalysed Heck reaction Table 3. Synthesis of stilbenes 6a-i by Pd-NHCEs catalysis. 3

Solvent / Temperature Time Conversion

Entry 6 R R 1 Yield c base" (°C) ( ) (%)

1 a H H none/Cs 2 C0 3 120 42 93 90

2 b 4-Me H none/Cs 2 C0 3 120 42 96 92

3 c 4-MeO H none/Cs 2 C0 3 120 42 93 80

4 d 3-CHO H NMP/Na 2 C0 3 120 20 100 89

5 e 4-CHO H NMP/Na 2 C0 3 120 5 100 98

6 e 4-CHO H NMP/Na 2 C0 3 80 20 100 98

7 e 4-CHO H none/Cs 2 C0 3 100 18 100 98

8 f 4-CHO 4-Me NMP/Na 2 C0 3 80 24 95 90

4-

9 g 4-CHO NMP/Na 2 C0 3 100 20 100 97

MeO

10 h 4-CHO 3-N0 2 NMP/Na 2 C0 3 120 52 100 91

1 1 1 4-CHO 4-CI NMP/Na 2 C0 3 120 20 100 95

2b (0.5 mol%) was used in all entries; b Base 2eqv; isolated yield (%).

Scheme 10: Suzuki reaction catalyzed by Pd-NHCE complexes. Table 5. Synthesis of biaryls 8 by Pd-NHCEs catalysis. 3

Time

Entry R R 1 Yield c Mp

(min) b

1 H H 75 93 68-69

2 4-Me H 300 91 41 -42

3 4-MeO H 120 93 86-87

4 4-CHO H 40 95 60-61

5 3-CHO H 300 90 52-53

6 4-CHO 3-Me 40 97 57-58

7 4-CHO 4-MeO 40 91 103-104

8 4-CHO 4-CHO 75 90 143-145

9 4-CHO 4-CI 40 96 1 13-1 15

a Catalyst 2b (0.1 mol%) at 25°C in DMF:H 2 0 (1 :1 ) and Na 2 C0 3 (2eqv) were used in all of the entries. b The times for the quantitative conversions determined by 1 H NMR; C Isolated yield (%). 1 ,3,4,5-Tetraaryl-1 /- -imidazol-2(3/-/)-one derivatives are important materials for design and preparation of electrophotographic photoreceptors. 03 ' 3,4-Diphenyl-1 -p-tolyl-1 H-imidazol- 2(3H)-one 9 was prepared by the method that was formerly reported by the applicants and inventors and converted to 10 quantitatively. 04 ' The isolation procedure simply contains pouring the reaction mixture in ice-water and filtering the precipitating product 10.

2-Phenyl-1 H-imidazo[1 ,2-a]pyridine° 5 ' 12 was prepared by a simple high yielding method given in Scheme 1 1 . There is an abundance of biologically active compounds involving 2- phenyl-1 /- -imidazo[1 ,2-a]pyridine core in the literature. (15b) 2,3-Diarylimidazo[1 ,2-a]pyridines are achieved by C-H arylation (20) and their antileishmanial activities are also reported. 06 ' In our case we have demonstrated the C-H arylation of 12 with aryl bromide 4d in the presence of 2b' to give 4-(2-phenyl-1 H-imidazo[1 ,2-a]pyridin-3-yl) benzaldehyde 13 in quantitative yield (Scheme 1 1 ). ©

NHCE NHCE B B '

Ar 2 -F†d(NHCE) 2

Ar

Scheme 11 : Probable catalytic cycle in the reaction of arylbromides with arylboronic acids in the presence of Pd-NHCEs

REFERANSLAR

(1 ) T. Mizoroki, K. Mori, A. Ozaki. Bull. Chem. Soc. Jpn 1971 , 44, 581 -581 . (2) R. F. Heck, , J. P. Nolley. J. Org. Chem. 1972, 37, 2320-2322.

(3) a) W. Cabri, I. Candiani, Acc. Chem. Res. 1995, 28, 2-7. b) A. de Meijere, F.E.Meyer, Angew. Chem., Int. Ed. Engl. 1994, 33, 2379-241 1 . c) I. P. Beletskaya, A.V. Cheprakov, Chem. Rev. 2000, 100, 3009-3066. d) J.G. Vries, Can. J. Chem. 2001 , 79, 1086-1092.

(4) N. J. Whitcombe, K. K. Hii, S. E. Gibson, Tetrahedron 2001 , 57, 7449-7476.

(5) a) N. Coskun, S. Tungman, Tetrahedron 2006, 62, 1345-1350. b) N. Coskun, A. Ozturk, Tetrahedron 2006, 62, 12057-12063.

(6) N. Coskun, M. Qetin, Tetrahedron 2010, 66, 2053-2060.

(7) O. Guerret, S. Sole, H. Gornitzka, M. Teichert, G. Trinquier, G. Bertrand, J. Am. Chem.

Soc. 1997, 1 19, 6668-6669.

(8) H. M. J. Wang, I. J. B. Lin, Organometallics 1998, 17, 972-975.

(9) A. A. D. Tulloch, A. A. Danopoulos, S. Winston, S. Kleinhenz, G. Eastham, J. Chem.

Soc, Dalton Trans. 2000, 4499-4506.

(10) For recent reviews on Ag-NHC complexes see a) P. L. Arnold, Heteroat. Chem. 2002, 13, 534-539. b) I. J. B. Lin, C. S. Vasam, Comments Inorg. Chem. 2004, 25, 75-129. c) J. C. Garrison, W. J. Youngs, Chem. Rev. 2005, 105, 3978-4008. (1 1 ) a) W. A. Herrmann, C. Kocher, Angew. Chem., Int. Ed. Engl. 1997, 36, 2163-2187. b) T. Weskamp, V.P.W. Bohm, W.A. Herrmann, J. Organomet. Chem. 2000, 600,12-22.

(12) Fristrup, P.; Le Quement, S.; Tanner, D.; Norrby, P.O. Organometallics 2004, 23, 6160-6265.

(13) Murakami,Y.; Niigae, R.; Hisada, H.; Takeda, H.; Nakatani, Y.; Kumon, A. Jpn. Kokai Tokkyo Koho, 1990, JP 02165155 A 19900626. (14) Co§kun, N. Tetrahedron 1999, 55, 475-484.

(15) a) Donthiri, R. R.; Pappula, V.; Reddy, N. N. K.; Bairagi, D.; Adimurthy, S. J. Org. Chem. 2014, 79, 1 1277-1 1284. b) Bhargava, S.; Choudhary, A. Int. J. Pharm. Pharm. Sci. 2014, 6, 553-557. c) Bagdi, A. K.; Rahman, M.; Santra, S.; Majee, A.; Hajra, A. Adv. Synth. Catal. 2013, 355, 1741 -1747.

(16) Marhadour, S.; Marchand, P.; Pagniez, F.; Bazin, M. A.; Picot, C; Lozach, O.; Ruchaud, S.; Maud, A.; Meijer, L; Rachidi, N.; Le Pape, P. Eur. J. Med. Chem. 2012, 58, 543-556.

(17) . (a) Sugihara, T.; Satoh, T.; Miura, M.; Nomura, M. Angew. Chem. Int. Ed. 2003, 42, 4672. (b) Kamal, A.; Srinivasulu,V.; Seshadri, B. N.; Markandeya, N.; Alarifib, A.; Shankaraiah, N. Green Chem., 2012, 14, 2513. (c) Kim, B.R.; Lee, H.G.; Kim, E.J.; Lee, S.G.; Yoon, Y.J. J. Org. Chem. 2010, 75, 484. (d) Castells, J.; Font, J.; Virgili, A. J. Chem. Soc. Perkin Trans I: Organic and Bioorganic Chem 1979, 1 , 1 . (e) Xu, H.J.; Zhao, Y.Q.; Zhou, X.F. J. Org. Chem. 2011 , 76, 8036 (f) Xue, J.Q.; Feng, Y.Q.; Wang, L; Wu, L.H. Chin. Chem. Lett. 2007, 18, 1319.

(18) (a) Chaturbhuj, G.U.; Akamanchi, K.G. Tetrahedron Lett. 2011 , 52, 4950. (b) Fan, X.H.; Yang, L.M. Eur. J. Org. Chem. 2011 , 8, 1467. (c) Tao, B.; Boykin, D. J. Org. Chem.

2004, 69, 4330. (d) Demir, A.S.; Findik, H.; Saygili, N.; Tuna S.N. Tetrahedron 2010, 66, 1308. (e) Niu, L; Zhang, H. Yang, H.; Fu H. Synlett, 2014, 25, 995. (f) Miura, M.; Koike, T.; Ishihara, T.; Sakamoto, S.; Okada, M.; Ohta, M.; Tsukamoto, S. Synth. Commun. 2007, 37, 667. (g) Kirai, N.; Yamamoto, Y. Eur. J. Org. Chem. 2009, 12, 1864.

(19) Co§kun N. Tetrahedron, 1999, 55, 475.

(20) Hiebel, M.; Fall, Y.; Scherrmann, M.; Berteina-Raboin, S. Eur. J. Org. Chem. 2014, 21 , 4643.