Synthesis and reactivity of ortho-palladated arylureas. Synthesis and catalytic activity of a C,N,C pincer complex. Stoichiometric syntheses of some N-heterocycles

DOI: 10.1021/om050451y

Source and publish data:

Organometallics p. 5044 - 5057 (2005)

Update date:2022-08-04

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Authors:

Vicente, Jose

Abad, Jose-Antonio

Lopez-Serrano, Joaquin

Jones, Peter G.

Najera, Carmen

Botella-Segura, Luis

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Article abstract of DOI:10.1021/om050451y

1-(2-Iodophenyl)-3-p-tolylurea (1) reacts with Pd(dba)₂ ([Pd₂(dba)₃]·dba; dba = dibenzylide-neacetone) in the presence of the appropriate ligands to give the ortho-palladated arylureas [Pd{C₆H₄NHC(O)NHTo-2}IL₂] (To = C ₆H₄Me-4; L₂ = tbubpy (4,4′-di-tert-butyl- 2,2′-bipyridine) (2a), tmeda (N,N,N′,N′- tetramethylethylenediamine) (2b); L = PPh₃ (2c)). Reaction of 2b with Tl(TfO) (TfO = triflate, CF₃SO₃) results in the formation of cyclopalladated [Pd{κ²C,O-C₆H ₄NHC(O)NHTo-2}(tmeda)]OTf (3b). The latter reacts with PPh ₃ to yield [Pd{C₆H₄NHC-(O)NHTo-2}(tmeda) (PPh₃)]OTf (4b). Treatment of 2b with CO gives the corresponding acyl derivative [Pd{C(O)C₆H₄NHC(O)NHTo-2}I(tmeda)] (5b). If Tl(TfO) is added after the bubbling of CO, the C,N coupling product 3-p-tolyl-1H-quinazoline-2,4-dione (6) is formed. Complex 5b reacts with XyNC (Xy = 2,6-dimethylphenyl) to yield trans-[Pd{C(O)C₆H ₄NHC-(O)NHTo-2}I(CNXy)₂] (7). Both 5b and 7 decompose in solution to give 6. Complex 2b reacts with isocyanides to give the iminoacyl derivatives trans-[Pd{C(=NR)C₆H₄NHC(O)NHTo-2}I(CNR) ₂] (R = Xy (8x), ^tBu (8t)). The complex 8x gives the C,N coupling product 4-(xylylimino)-3-p-tolyl-3,4-dihydro-1H-quinazolin-2-one (9) after treatment with TlOTf. 8x also reacts with bases (K₂CO ₃ and Tl₂CO₃) to yield the iminoacyl amido carbene C,N,C pincer palladium complex [Pd{κ³C,N,C-C(=NXy) C₆H₄NC(O)NToC(NHXy)-2}(CNXy)] (10); this complex is an active precatalyst in Heck and Suzuki reactions. The reaction of 2b with R′C≡ CR″ and TlOTf gives [Pd{κ²C,N-CR′= CR″C₆H₄NHC(O)NHTo-2}(tmeda)]OTf (R′ = R″ = Et (11be), CO₂Me (11bm), Ph (11bp); R′ = Ph, R″ = CO₂Me (11bq)). These complexes decompose in solution, and in the case of 11bp, 2,3-diphenylindole-1-carboxylic acid p-tolylamide (12p) was isolated, 11bq reacts with PPh₃ to give 3-phenyl-1H-indole-2-carboxylic acid methyl ester (13q). 11bp and 11bq decompose in the presence of CO to yield 3,4-diphenyl-2-quinolone (14po) and 2-oxo-4-phenyl-l,2-dihydroquinoline-3- carboxylic acid methyl ester (14qo), respectively. Similarly, when 11bq is reacted with XyNC, the C,N coupling compound 2-xylyl-4-phenyl-1,2- dihydroquinoline-3-carboxylic acid methyl ester (14qnx) is formed. The crystal and molecular structures of 3b, 10·0.5CDCl₃, 11bp·OEt₂, 11bq, and 14po have been determined.

Full text of DOI:10.1021/om050451y

5044

Organometallics 2005, 24, 5044-5057

Synthesis and Reactivity of Ortho-Palladated Arylureas.

Synthesis and Catalytic Activity of a C,N,C Pincer

Complex. Stoichiometric Syntheses of Some

N-Heterocycles

Jose´ Vicente,* Jose´-Antonio Abad, and Joaqu´ın Lo´pez-Serrano

Grupo de Quı´mica Organometa´lica, Departamento de Qu´ımica Inorga´nica, Facultad de

Quı´mica, Universidad de Murcia, Apartado 4021, E-30071 Murcia, Spain

Peter G. Jones^†

Institut fu¨r Anorganische und Analytische Chemie der Technischen Universita¨t,

Postfach 3329, 38023 Braunschweig, Germany

Carmen Na´jera and Luis Botella-Segura^‡

Departamento de Quı´mica Orga´nica and Instituto de S´ıntesis Orga´nica (ISO),

Facultad de Ciencias, Universidad de Alicante, Apartado 99, E-03080 Alicante, Spain

Received June 3, 2005

1-(2-Iodophenyl)-3-p-tolylurea (1) reacts with Pd(dba)₂([Pd₂(dba)₃]‚dba; dba ) dibenzylide-

neacetone) in the presence of the appropriate ligands to give the ortho-palladated arylureas

[Pd{C₆H₄NHC(O)NHTo-2}IL₂] (To ) C₆H₄Me-4; L₂) tbubpy (4,4′-di-tert-butyl-2,2′-bipyridine)

(2a), tmeda (N,N,N′,N′-tetramethylethylenediamine) (2b); L ) PPh₃(2c)). Reaction of 2b

with Tl(TfO) (TfO ) triflate, CF₃SO₃) results in the formation of cyclopalladated [Pd{κ²C,O-

C₆H₄NHC(O)NHTo-2}(tmeda)]OTf (3b). The latter reacts with PPh₃to yield [Pd{C₆H₄NHC-

(O)NHTo-2}(tmeda)(PPh₃)]OTf (4b). Treatment of 2b with CO gives the corresponding acyl

derivative [Pd{C(O)C₆H₄NHC(O)NHTo-2}I(tmeda)] (5b). If Tl(TfO) is added after the

bubbling of CO, the C,N coupling product 3-p-tolyl-1H-quinazoline-2,4-dione (6) is formed.

Complex 5b reacts with XyNC (Xy ) 2,6-dimethylphenyl) to yield trans-[Pd{C(O)C₆H₄NHC-

(O)NHTo-2}I(CNXy)₂] (7). Both 5b and 7 decompose in solution to give 6. Complex 2b reacts

with isocyanides to give the iminoacyl derivatives trans-[Pd{C(dNR)C₆H₄NHC(O)NHTo-

2}I(CNR)₂] (R ) Xy (8x), Bu (8t)). The complex 8x gives the C,N coupling product

4-(xylylimino)-3-p-tolyl-3,4-dihydro-1H-quinazolin-2-one (9) after treatment with TlOTf. 8x

also reacts with bases (K₂CO₃and Tl₂CO₃) to yield the iminoacyl amido carbene C,N,C pincer

palladium complex [Pd{κ³C,N,C-C(dNXy)C₆H₄NC(O)NToC(NHXy)-2}(CNXy)] (10); this

complex is an active precatalyst in Heck and Suzuki reactions. The reaction of 2b with R′Ct

CR′′ and TlOTf gives [Pd{κ²C,N-CR′dCR′′C₆H₄NHC(O)NHTo-2}(tmeda)]OTf (R′ ) R′′ ) Et

(11be), CO₂Me (11bm), Ph (11bp); R′ ) Ph, R′′ ) CO₂Me (11bq)). These complexes

decompose in solution, and in the case of 11bp, 2,3-diphenylindole-1-carboxylic acid

p-tolylamide (12p) was isolated. 11bq reacts with PPh₃to give 3-phenyl-1H-indole-2-

carboxylic acid methyl ester (13q). 11bp and 11bq decompose in the presence of CO to yield

3,4-diphenyl-2-quinolone (14po) and 2-oxo-4-phenyl-1,2-dihydroquinoline-3-carboxylic acid

methyl ester (14qo), respectively. Similarly, when 11bq is reacted with XyNC, the C,N

coupling compound 2-xylyl-4-phenyl-1,2-dihydroquinoline-3-carboxylic acid methyl ester

(14qnx) is formed. The crystal and molecular structures of 3b, 10‚0.5CDCl₃, 11bp‚OEt₂,

11bq, and 14po have been determined.

Introduction

in the catalytic syntheses of some carbo- or heterocycles;

in these reactions, the ortho substituents play a key

Arylpalladium(II) complexes are postulated as inter-

mediates in many catalytic reactions.^1,2In particular,

ortho-substituted arylpalladium derivatives are involved

(2) Tsuji, J. Palladium Reagents and Catalysts; Wiley: Chichester,

U. K., 1995. Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2047.

Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem.

Res. 1998, 31, 805. Whitcombe, N. J.; Hii, K. K.; Gibson, S. E.

Tetrahedron 2001, 57, 7449. Li, G. Y.; Zheng, G.; Noonan, A. F. J. Org.

Chem. 2001, 66, 8677. Yin, J. J.; Buchwald, S. L. J. Am. Chem. Soc.

2002, 124, 6043. Mann, G.; Shelby, Q.; Roy, A.; Hartwig, J. F.

Organometallics 2003, 22, 2775. Mann, G.; Baranano, D.; Hartwig, J.

F.; Rheingold, A. L.; Guzei, I. A. J. Am. Chem. Soc. 1998, 120, 9205.

* To whom correspondence should be addressed. E-mail: jvs1@um.es.

WWW: http://www.um.es/gqo/.

^†E-mail: p.jones@tu-bs.de.

^‡E-mail: cnajera@ua.es.

(1) Heck, R. F. Palladium Reagents in Organic Synthesis; Academic

Press: New York, 1985.

Publication on Web 09/07/2005

Ortho-Palladated Arylureas

Organometallics, Vol. 24, No. 21, 2005 5045

role.³The importance of such catalytic processes

prompted us to prepare and isolate ortho-functionalized

arylpalladium derivatives and to study their reactivity

toward unsaturated molecules. Thus, we have previ-

ously reported the syntheses of palladium complexes

with ortho-functionalized aryl ligands such as C₆H-

(OMe)₃-2,3,4-X-6 (X ) CHO, C(O)Me, CH₂OEt, C(O)-

NH^tBu), C₆H₃(CHO)₂-2,5, C₆H₄NH₂-2, and C₆H₄X-2 (X

) NH₂, OH, CHdCH₂, CHO, C(O)Me, CN, CHdCHR,

NdPPh₃, Ph₂PdNR, NdCdNR, NdNPh, SPh, CH(SR)₂)

and also ortho-palladated benzyl- and phenethylamines.

We have also studied the reactivity of some of these

palladium complexes with alkynes, carbon monoxide,

and isocyanides to give interesting new organopalla-

dium(II) complexes and organic compounds.^4-10

This paper describes the synthesis and isolation of

arylpalladium derivatives bearing a urea group at the

ortho position. Urea derivatives can coordinate through

the oxygen or, less frequently, through nitrogen;¹¹

arylpalladium complexes that contain a urea group in

the ortho position are thus candidates to form metal-

lacycles. Another interesting feature of ureas is the

occurrence in the same functional group of two nucleo-

philic nitrogens and one electrophilic carbon. Conse-

quently, C-C and C-N coupling processes may take

place from the above-mentioned palladium urea-aryl

complexes. Thus, a hydantoin synthesis from cyclohex-

anecarboxaldehyde, ureas, and CO has been reported,¹²

as has the palladium-catalyzed formation of benzoimi-

dazolones via the C-N coupling of (o-bromophenyl)-

ureas.¹³In at least one case, Alper’s palladium-catalyzed

quinazolinone synthesis, some of the postulated inter-

mediates are arylpalladium derivatives with urea groups

at the ortho position.¹⁴However, to the best of our

knowledge, the complexes here reported are the first

isolated examples of such intermediates.

Some of the arylpalladium derivatives prepared in

this work react with CO to yield unstable, but isolable,

acylpalladium complexes that decompose to give a

quinazolinone derivative. These stoichiometric reactions

may serve as models for one of the above-mentioned

catalytic processes.¹⁴Reactions with isocyanides have

also been studied, allowing us to isolate iminoacyl

derivatives that decompose to give quinazolinone imi-

nes. The insertion of isocyanides to form iminoacyl

palladium complexes is well documented.^{6,7,9,10,15,16}There

are, however, fewer examples in which the initial

iminoacyl complex evolves, giving a new type of pal-

ladium complex.^16,17In some cases, further transforma-

tion of the insertion intermediates takes place, giving

organic products in stoichiometric^6,10,18,19or catalytic

reactions.²⁰One of the isolated iminoacyl complexes was

reacted with a base to give an iminoacyl amido carbene

C,N,C pincer, which is an active precatalyst in Heck and

Suzuki reactions. It is well-known that different types

of palladacycles have proved to be very efficient cata-

lysts or precatalysts in cross-coupling proceses.²¹

The insertion of alkynes into Pd-C bonds is also well-

known.^5,6,8,9,22In the present paper, we report the

synthesis of some complexes resulting from the monoin-

sertion of alkynes into the Pd-C bond of one of the

ortho-palladated arylureas. The vinylpalladium deriva-

tives thus obtained undergo a C-N coupling process to

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Vicente et al.

H, Me). ¹³C{¹H} NMR: the compound is not soluble enough

in common deuterated solvents to record its ¹³C{¹H} NMR

spectrum. Anal. Calcd for C₁₄H₁₃IN₂O: C, 47.75; H, 3.72; N,

7.95. Found: C, 48.13; H, 3.58; N, 7.95.

of indoles, both stoichiometric^19,23and catalytic,²⁴are

documented in the literature. In some of these reactions

the mechanism may include a C-N coupling process

from similar vinylpalladium derivatives.²⁵We also

report the synthesis of a 2-quinolone as the decomposi-

tion product of the complex resulting from a sequential

insertion of an alkyne and carbon monoxide into an

ortho urea-substituted arylpalladium complex. Recently,

the palladium-catalyzed annulation of internal alkynes

by N-substituted o-iodoanilines under 1 atm of carbon

monoxide has been reported to give 3,4-disubstituted

2-quinolones.²⁶

Synthesis of [Pd{C₆H₄NHC(O)NHTo-2}I(tbubpy)] (2a).

Pd(dba)₂(254 mg, 0.42 mmol) and 4,4′-di-tert-butyl-2,2′-

bipyridine (tbubpy; 129 mg, 0.48 mmol) were stirred in freshly

distilled toluene (20 mL) under N₂. After 10 min, 1 (200 mg,

0.57 mmol) was added and the mixture stirred for 30 min. The

solvent was removed under reduced pressure, Et₂O (15 mL)

was added, and the suspension was filtered through anhydrous

MgSO₄. The solution was concentrated to ca. 1 mL and

subjected to silica gel preparative thin-layer chromatography.

Elution with Et₂O/n-hexane (2:1) gave an orange band, which

was collected and extracted with CH₂Cl₂; the solution was

dried over anhydrous MgSO₄, filtered, and evaporated to

dryness. The resulting solid was stirred with Et₂O and filtered

and the solid washed with Et₂O (3 × 3 mL) to give 2a as an

orange solid. Yield: 145 mg, 50%. Mp: 138-140 °C. IR (Nujol,

Experimental Section

Conductivity was measured in Me₂CO solutions (ca. 10^-5

M).²⁷NMR measurements were performed on Bruker AVANCE

spectrometers (200, 300, and 400 MHz). When needed, NMR

signals were assigned with the help of standard DEPT, COSY,

and ¹³C-¹H HMQC and HMBC techniques. The infrared

spectra were recorded using a Perkin-Elmer 16F PC FT-IR

spectrometer. The mass spectra were recorded on a Fisons VG-

Autospec apparatus. C, H, N, and S microanalyses were

performed on a Carlo Erba 1108 instrument. Pd(dba)₂([Pd₂-

(dba)₃]‚dba, dba ) dibenzylideneacetone) was prepared as

described previously.^1,282-Iodoaniline, p-tolyl isocyanate, 3-hex-

yne, and 2-butyne were purchased from Aldrich, XyNC (Xy )

cm^-1): 1704 ν(CdO). H NMR (200 MHz, CDCl₃): δ 9.41 (d,

³J_HH) 6.5 Hz, 1 H), 7.93 (d, J_HH) 5 Hz, 2 H), 7.67 (d, J_HH

) 7.5 Hz, 1 H), 7.59 (s, 1 H, NH), 7.49 (td, ³J_HH) 7.5 Hz, ⁴J_HH

) 1.5 Hz, 2 H), 7.39 (d, J_HH) 7.5 Hz, 1 H), 7.25 (dd, 1 H),

7.15 (d, J_HH) 8.5 Hz, 2 H, p-tolyl), 7.01 (t, J_HH) 6.5 Hz, 1

H), 6.89 (d, J_HH) 8.5 Hz, 3 H, p-tolyl + C₆H₄), 6.58 (s, 1 H,

NH), 2.16 (s, 3 H, Me), 1.53 (s, 9 H, Bu), 1.43 (s, 9 H, Bu).

¹³C{¹H} NMR (50 MHz, CDCl₃): δ 163.43 (C), 163.33 (C),

155.72 (C), 153.93 (C), 153.50 (C), 152.10 (CH), 149.60 (CH),

141.07 (C), 136.88 (CH), 135.96 (C), 132.42 (C), 129.27 (CH,

p-tolyl), 124.13 (CH), 123.89 (CH), 123.80 (CH), 122.80 (CH),

121.16 (CH), 121.01 (CH, p-tolyl), 118.40 (CH), 118.01 (CH),

2,6-dimethylphenyl), BuNC and PhCtCPh from Fluka, and

MeO₂CCtCCO₂Me and HCtCCO₂Me from Acros; PhCtCCO₂-

Me was obtained from Lancaster and ¹³CO from Isotec.

Products obtained from commercial sources were used without

further purification. The syntheses of the compounds were

carried out without precautions against air and moisture,

unless otherwise stated. The preparative thin-layer chromato-

graphic separations were performed using silica gel 60 ACC

(70-200 µm). In the case of colorless substances fluorescent

silica gel (GF₂₅₄) was added (approximately 5%). Gas chro-

matographic analyses were performed on a HP-5890 instru-

ment equipped with a WCOT HP-1 fused silica capillary

column.

35.43 (C, Bu), 30.32 (Me, Bu), 30.13 (Me, Bu), 20.68 (Me,

To). Anal. Calcd for C₃₂H₃₇IN₄OP₂Pd: C, 52.87; H, 5.13; N, 7.71.

Found: C, 52.47; H, 5.32; N, 7.42.

Synthesis of [Pd{C₆H₄NHC(O)NHTo-2}I(tmeda)] (2b).

Pd(dba)₂(1.17 g, 2.00 mmol) and N,N,N′,N′-tetramethyleth-

ylenediamine (tmeda; 342 µL, 2.28 mmol) were stirred in

freshly distilled toluene (10 mL) under N₂. After 10 min, 1

(0.95 mg, 2.71 mmol) was added and the mixture stirred under

N₂for 4 h. The solvent was removed under reduced pressure,

CH₂Cl₂(20 mL) was added, and the resulting suspension was

filtered through anhydrous MgSO₄. The solvent was removed

and the residue treated with Et₂O (20 mL), precipitating a

solid, which was collected by filtration, washed with Et₂O (3

× 4 mL), and dried under a stream of air to give impure 2b as

a pink powder. This solid contains approximately 5% of [PdI₂-

(tmeda)] (NMR). Analytically pure 2b was obtained by layering

Et₂O over a concentrated solution of the crude product in CH₂-

Cl₂until small crystals began to form; after the mixture was

left overnight, the crystals were collected by filtration and air-

dried. Yield: 880 mg, 64% (crude); 440 mg, 32% (pure). Mp:

Synthesis of IC₆H₄NHC(O)NHTo-2 (1). 2-Iodoaniline

(1.94 g, 8.9 mmol) and p-tolyl isocyanate (ToNCO, 1.67 g, 8.9

mmol) were mixed in Et₂O (10 mL) and stirred at room

temperature overnight. n-Hexane (5 mL) was added to the

colorless suspension and filtered. The resulting solid was

collected by filtration, washed with Et₂O and n-hexane, and

air-dried to yield 1 as a colorless powder. Yield: 2.80 g, 90%.

Mp: 199-201 °C. IR (Nujol, cm^-1): 3278 ν(NH), 1644

ν(CdO). ¹H NMR (200 MHz, d₆-acetone): δ 8.75 (br, 1 H, NH),

8.08 (dd, J_HH) 8.2 Hz, J_HH) 1.5 Hz, 1 H, C₆H₄), 7.82 (dd,

177-179 °C. IR (Nujol, cm^-1): 3324 ν(NH), 1682 ν(CdO). H

³J_HH) 8.2 Hz, ⁴J_HH) 1.5 Hz, 1 H, C₆H₄), 7.5-7.3 (several m,

NMR (400 MHz, CDCl₃): δ 7.75 (s, 1 H, NH), 7.47 (d, J_HH

)

4 H, C₆H₄+ NH + p-tolyl), 7.09 (d, J_HH) 8.2, 2 H, p-tolyl),

7 Hz, 1 H, C₆H₄), 7.32 (d, J_HH) 8.4 Hz, 2 H, p-tolyl), 7.18

6.82 (td, J_HH) 8.2 Hz, J_HH) 1.5 Hz, 1 H, C₆H₄), 2.25 (s, 3

(dd, J_HH) 7 Hz, J_HH) 1.5 Hz, 1 H, C₆H₄), 7.13 (d, J_HH

)

8.4 Hz, 2 H, p-tolyl), 6.91 (td, ³J_HH) 7 Hz, ⁴J_HH) 1.5 Hz, 1 H,

(23) Onitsuka, K.; Segawa, M.; Takahashi, S. Organometallics 1998,

17, 4335.

C₆H₄), 6.79 (td, J_HH) 7 Hz, J_HH) 1.5 Hz, 1 H, C₆H₄), 6.74

(m, 1 H, NH), 2.80-2.29 (several m, 4 H, CH₂), 2.65 (s, 3 H,

Me), 2.45 (s, 3 H, Me), 2.39 (s, 3 H, Me), 2.29 (s, 3 H, Me), 2.19

(s, 3 H, Me). ¹³C{¹H} APT NMR (75 MHz, CDCl₃): δ 154.00

(CdO), 141.03 (C), 135.75 (CH, C₆H₄), 135.26 (C), 134.86 (C),

133.50 (C), 129.45 (CH, p-tolyl), 123.83 (CH, C₆H₄), 122.94 (CH,

C₆H₄), 122.21 (CH, p-tolyl), 121.74 (CH, C₆H₄), 62.08 (CH₂),

58.35 (CH₂), 50.67 (Me, tmeda), 50.22 (Me, tmeda), 48.96 (Me,

tmeda), 20.76 (Me, p-tolyl). Anal. Calcd for C₂₄H₂₉IN₄OPd: C,

41.79; H, 5.09; N, 9.75. Found: C, 41.84; H, 5.35; N, 9.90.

[PdI₂(tmeda)] was independently prepared by addition of

tmeda to a stirred acetone solution of [PdCl₂(NCMe)₂] (molar

ratio 2:1) and an excess of NaI. The resulting reddish suspen-

sion was stirred for 10 min. The suspension was filtered

through Celite, and the solution was evaporated to dryness.

(24) Siebeneicher, H.; Bytschkov, I.; Doye, S. Angew. Chem., Int. Ed.

2003, 42, 3042. Banwell, M. G.; Kelly, B. D.; Kokas, O. J.; Lupton, D.

W. Org. Lett. 2003, 5, 2497. Kamijo, S.; Yamamoto, Y. Angew. Chem.,

Int. Ed. 2002, 41, 3230. Fujita, K.; Yamamoto, K.; Yamaguchi, R. Org.

Lett. 2002, 4, 2691. Soderberg, B. C.; Shriver, J. A. J. Org. Chem. 1997,

62, 5838. Fagnola, M. C.; Candiani, I.; Visentin, G.; Cabri, W.; Zarini,

F.; Mongelli, N.; Bedeschi, A. Tetrahedron Lett. 1997, 38, 2307. Yu,

Y.; Ostresh, J. M.; Houghten, R. A. Tetrahedron Lett. 2003, 44, 2569.

Larock, R. C.; Pace, P.; Yang, H.; Russell, C. E.; Cacchi, S.; Fabrizi, G.

Tetrahedron 1998, 54, 9961. Roesch, K. R.; Larock, R. C. Org. Lett.

1999, 1, 1551. Shen, M.; Li, G. S.; Lu, B. Z.; Hossain, A.; Roschangar,

F.; Farina, V.; Senanayake, C. H. Org. Lett. 2004, 6, 4129.

(25) Larock, R. C.; Yum, E. K. J. Am. Chem. Soc. 1991, 113, 6689.

(26) Kadnikov, D. V.; Larock, R. C. J. Org. Chem. 2004, 69, 6772.

(27) Geary, W. J. Coord. Chem. Rev. 1971, 7, 81.

(28) Takahashi, Y.; Ito, S.; Sakai, S.; Ishii, Y. J. Chem. Soc., Chem.

Commun. 1970, 1065.

Ortho-Palladated Arylureas

Organometallics, Vol. 24, No. 21, 2005 5047

The red residue was treated with Et₂O (10 mL) and filtered.

The solid was washed with Et₂O (3 × 2 mL) and air-dried to

give [PdI₂(tmeda)] as a red powder. ¹H NMR (200 MHz,

CDCl₃): δ 2.96 (s, 12 H, Me), 2.68 (s, 4 H, CH₂). Anal. Calcd

for C₆H₁₆N₂I₂Pd C, 15.13; H, 3.38; N, 5.88. Found: C, 15.36;

H, 3.46; N, 5.83. Addition of a small amount of this solid to a

CDCl₃solution of crude 2b caused an increase in the intensity

of the crystals obtained as described above were suitable for

single-crystal X-ray determination studies. Mp: 160 °C dec.

Λ_M) 145 Ω^-1cm²mol^-1IR (Nujol, cm^-1): 3288, 3192 ν(NH),

1634 ν(CdO), 1296, 1028 ν(OTf). ¹H NMR (300 MHz, CDCl₃):

δ 9.48 (s, 1 H, NH), 9.16 (s, 1 H, NH), 7.20 (d, J_HH) 8.2 Hz,

2 H, p-tolyl), 7.06 (d, J_HH) 8.2 Hz, 2 H, p-tolyl), 7.01-7.88

(m, 4 H, C₆H₄), 2.81-2.75 (m, 2H, CH₂), 2.75 (s, 6 H, Me),

2.60-2.54 (m, 2 H, CH₂), 2.33 (s, 6 H, Me), 2.92 (s, 3 H, Me

p-tolyl). ¹³C{¹H} NMR (75 MHz, CDCl₃): δ 155.98 (CdO),

136.16 (C), 135.03 (C), 133.92 (C), 132.43 (CH), 129.32 (CH,

p-tolyl), 126.23 (CH), 124.57 (C), 123.61 (CH), 123.04 (CH,

p-tolyl), 116.34 (CH), 65.57 (CH₂), 57.30 (CH₂), 51.34 (Me,

tmeda), 47.56 (Me, tmeda), 20.91 (Me, p-tolyl). Anal. Calcd for

C₂₁H₂₉F₃N₄O₄PdS: C, 42.25; H, 4.90; N, 9.39; S, 5.37. Found:

C, 41.85; H, 5.20; N, 9.17; S, 5.17.

of the 2.93 ppm signal in the H NMR spectrum.

Synthesis of trans-[Pd{C₆H₄NHC(O)NHTo-2}I(PPh₃)₂]

(2c). Method A. Pd(dba)₂(0.92 g, 1.59 mmol) and PPh₃(1.00

g, 3.81 mmol) were stirred in freshly distilled toluene (10 mL)

under N₂. After 10 min, 1 (0.75 g, 2.13 mmol) was added and

the mixture stirred under N₂for 3 h. The solvent was removed

under reduced pressure, CH₂Cl₂(15 mL) was added, and the

resulting suspension was filtered through anhydrous MgSO₄.

The solvent was removed and the residue treated with Et₂O

(15 mL) and n-hexane (5 mL). A solid precipitated, which was

collected by filtration, washed with Et₂O (3 × 4 mL), and air-

dried to give an orange solid. Yield: 1.30 g. This crude product

contains between 15 and 20% of 1 and 5% of [PdI₂(PPh₃)₂] by

NMR (δ 13.31 ppm, ³¹P NMR) and microanalysis data. Re-

crystallization of the crude sample from CH₂Cl₂/n-hexane

results in a greater proportion of 1.

Synthesis of [Pd{C₆H₄NHC(O)NHTo-2}(tmeda)(PPh₃)]-

OTf (4b). PPh₃(44 mg, 0.17 mmol) was added to a CH₂Cl₂(5

mL) solution of 3b (100 mg, 0.17 mmol). After 15 min, the

solution was filtered through anhydrous MgSO₄, the solvent

was removed, and the residue was vigorously stirred in Et₂O

(10 mL). The resulting solid was filtered, washed with Et₂O

(3 × 3 mL), and air-dried to yield 4b as a pale yellow powder.

Yield: 100 mg, 70%. Mp: 135-137 °C. Λ_M) 112 Ω^-1cm²

mol^-1. IR (Nujol, cm^-1): 3322, 3294 ν(NH), 1702 ν(CdO), 1188,

1028 ν(OTf). ¹H NMR (400 MHz, CDCl₃): δ 8.57 (s, 1 H, NH),

7.76 (s, 1 H, NH), 7.57 (d, ³J_HH) 8 Hz, 2 H, H2 + H6, p-tolyl)

7.48-7.39 (m, 9 H, ortho and para H’s PPh₃), 7.35-7.31 (m, 7

H, meta H’s PPh₃+ H3 C₆H₄), 7.27 (d, ³J_HH) 4 Hz, 1 H, H6),

Method B. PPh₃(138 mg, 0.53 mmol) was added to a

solution of pure 2b (120 mg, 0.21 mmol) in acetone (10 mL). A

colorless precipitate began to form after 15 min. The mixture

was stirred for 1 h and then diluted with Et₂O (5 mL) and

filtered. The solid was washed with Et₂O (3 × 2 mL) and air-

dried to yield 2c as a colorless powder. This solid was

recrystallized by addition of Et₂O to a concentrated solution

of the crude sample in CH₂Cl₂(122 mg in 5 mL) until a

turbidity appeared. The suspension was stored in a refrigerator

overnight, and the colorless crystals were collected by filtration

and air-dried to give analytically pure 2c‚0.21CH₂Cl₂. After

18 h under high vacuum the crystals contain 0.17 mol of CH₂-

Cl₂/mol of 2c, in agreement with the NMR and microanalysis

data. No [PdI₂(PPh₃)₂] was formed during the reaction if pure

2b was used. If 2b contaminated with [PdI₂(PPh₃)₂] was used

instead, more [PdI₂(PPh₃)₂] was formed but could be removed

during the recrystallization. Yield: 142 mg (crude), 89 mg, 51%

(pure 2c‚0.17CH₂Cl₂). Mp: 181-183 °C. IR (Nujol, cm^-1): 1682

7.08 (d, J_HH) 8 Hz, 2 H, H3 + H5, p-tolyl), 6.78 (t, J_HH

)

7.8 Hz, 1 H, H4, C₆H₄), 6.53 (t, ³J_HH) 7.8 Hz, 1 H, H5, C₆H₄),

3.42 (m, 1 H, CH₂), 2.94 (m, 1 H, CH₂), 2.52-2.41 (m, 2 H,

CH₂), 2.52 (s, 3 H, Me, tmeda), 2.48 (s, 3 H, Me, tmeda), 2.29

(s, 3 H, Me, p-tolyl), 2.03 (s, 3 H, Me, tmeda), 1.99 (s, 3 H, Me,

tmeda). ¹³C{¹H} APT NMR (100 MHz, CDCl₃): δ 153.04 (Cd

O), 142,34 (C, C2, C₆H₄), 140.56 (d, J_CP) 12.5 Hz, C-Pd),

137.93 (C, C1, p-tolyl), 134.74 (d, J_CP) 11.1 Hz, ortho CH’s

PPh₃), 134.59 (C6H), 131.66 (para CH’s, PPh₃), 131.47 (C, C4,

p-tolyl), 129.45 (s, C3H + C5H, p-tolyl), 129.11 (d, ³J_CP) 10.8

Hz, meta CH’s, PPh₃), 128.57 (d, J_CP) 50.7 Hz, ipso C’s,

PPh₃), 125.41 (C4H, C₆H₄), 123.09 (C3H, C₆H₄), 122.12 (C5H,

C₆H₄), 119.85 (C2H + C6H, p-tolyl), 62.26 (CH₂), 60.91 (CH₂),

51.95 (Me, tmeda), 50.73 (Me, tmeda), 49.00 (Me, tmeda), 48.60

(Me, tmeda), 21.18 (Me, p-tolyl). ³¹P{¹H} NMR (81 MHz,

CDCl₃): δ 4.66 (s, PPh₃). Anal. Calcd for C₃₉H₄₄F₃N₄O₄PPdS:

C, 54.51; H, 5.16; N, 6.52; S, 3.73. Found: C, 54.24; H, 5.25;

N, 6.33; S, 3.42.

ν(CdO). H NMR (300 MHz, CDCl₃): δ 7.48-7.41 (m, 12 H,

ortho or meta H’s, PPh₃), 7.38-7.31 (m, 7 H, para H’s PPh₃+

NH), 7.27-7.21 (m, 12 H, ortho or meta H’s, PPh₃), 7.16 (d,

³J_HH) 8 Hz, 2 H, p-tolyl), 7.07 (d, J_HH) 8 Hz, 2 H, p-tolyl),

6.91 (d, J_HH) 8 Hz, 1 H, H3 or H6, C₆H₄), 6.78 (apparent d,

³J_HH) 8 Hz, 1 H, H3 or H6, C₆H₄), 6.57 (t, J_HH) 8 Hz, 1 H,

Synthesis of [Pd{C(O)C₆H₄NHC(O)NHTo-2}I(tmeda)]

(5b). CO was bubbled for 10 min through a stirred solution of

2b (120 mg, 0.21 mmol) in THF (20 mL). The solution was

stirred for a further 20 h under a CO atmosphere, giving some

palladium metal. The suspension was filtered through anhy-

drous MgSO₄, and the filtrate was concentrated to ca. 1 mL

and treated with n-pentane (10 mL). The resulting mixture

was stirred vigorously, precipitating a solid, which was col-

lected by filtration, washed with n-pentane (3 × 2 mL), and

dried under a stream of air to give 5b containing 4% of [PdI₂-

(tmeda)] (NMR and microanalysis), which was recrystallized

from acetone/Et₂O to give 5b as yellow-orange crystals. Yield:

76 mg, 60%. Mp: 159-161 °C dec. IR (Nujol, cm^-1): 1666

ν(CdO). ¹H NMR (300 MHz, CDCl₃): δ 10.51 (s, 1 H, NH),

H4 or H5, C₆H₄), 6.18 (t, J_HH) 8 Hz, 1 H, H4 or H5, C₆H₄),

5.66 (s, 1 H, NH), 5.30 (s, 0.34 H, CH₂Cl₂), 2.33 (s, 3 H, Me).

³¹P{¹H} NMR (121 MHz, CDCl₃): δ 22.68 (s, PPh₃). Anal. Calcd

for C_50.21H_43.42Cl_0.42IN₂OP₂Pd: C, 59.82; H, 4.33; N, 2.84.

Found: C, 59.91; H, 4.34; N, 2.84.

[PdI₂(PPh₃)₂] was independently prepared by treatment of

[PdCl₂(NCMe)₂] with PPh₃(molar ratio 1:2) and an excess of

NaI. The mixture was stirred in acetone for 1 h, the solvent

was removed, and CH₂Cl₂was added. The red suspension was

filtered through Celite to give a red solution. After 2 h the red

needles thus formed were collected by filtration, washed with

CH₂Cl₂and Et₂O, and air-dried to yield [PdI₂(PPh₃)₂] as

shining deep red crystals. ¹H NMR (300 MHz, CDCl₃): δ 7.73-

7.66 (m, 12 H, H ortho or H meta PPh₃), 7.39-7.35 (m, 18 H,

ortho or meta H’s, PPh₃+ para H’s PPh₃). ³¹P{¹H} NMR (121

MHz, CDCl₃): δ 13.30 (s, PPh₃).

9.08 (d, J_HH) 8 Hz, 1 H, H3 or H6), 8.32 (d, J_HH) 8 Hz, 1

H, H3 or H6), 7.38 (td, J_HH) 8 Hz, J_HH) 2 Hz, 1 H, H4 or

H5), 7.31 (d, J_HH) 8 Hz, 2 H, p-tolyl), 7.18-7.10 (m, 3 H,

Synthesis of [Pd{K²C,O-C₆H₄NHC(O)NHTo-2}(tmeda)]-

OTf (3b). TlOTf (60 mg, 0.17 mmol) was added to a stirred

solution of 2b (100 mg, 0.17 mmol) in acetone (10 mL), the

green suspension was stirred for a further 2 h and then filtered

through Celite, and the solution was concentrated to ca. 1 mL.

Et₂O (10 mL) was slowly added, precipitating yellow crystals.

The solvent was decanted, and the crystals were washed with

Et₂O and air-dried to give yellow 3b. Yield: 70 mg, 70%. Some

p-tolyl + H4 or H5), 6.65 (s, 1 H, NH), 2.95 (0.46 H, Me [PdI₂-

(tmeda)]), 2.73-2.66 (m, 2 H, CH₂), 2.60 (s, 6 H, 2Me), 2.54-

2.50 (m, 2 H, CH₂), 2.40 (s, 6 H, 2Me), 2.32 (s, 3 H, Me). ¹³C{¹H}

NMR: the compound decomposes during the experiment. Anal.

Calcd for C₂₁H₂₉IN₄O₂Pd: C, 41.84; H, 4.85; N, 9.29. Found:

C, 41.58; H, 4.74; N, 9.21.

Synthesis of 3-p-Tolyl-1H-quinazoline-2,4-dione (6). CO

was bubbled through an acetone (10 mL) solution of 2b (200

5048 Organometallics, Vol. 24, No. 21, 2005

Vicente et al.

mg, 0.35 mmol) for 5 min. TlOTf (123 mg, 0.35 mmol) was

added. After 20 min the black suspension was filtered through

anhydrous MgSO₄, the solvent was removed under reduced

pressure, and the residue was stirred in Et₂O (10 mL). The

precipitate was removed by filtration; the solution was con-

centrated to ca. 1 mL and subjected to silica gel preparative

thin-layer chromatography. Elution with n-hexane/AcOEt (3:

1) gave a band (R_f) 0.75) which was collected and extracted

with CH₂Cl₂; the solution was dried over anhydrous MgSO₄,

filtered, and evaporated to dryness to yield 6 as a colorless

solid. Yield: 53 mg, 60%. The same compound was identified

among the decomposition products of 5b and 7. Mp: 264-266

°C. IR (Nujol, cm^-1): 3194 ν(NH), 1732 ν(CdO). ¹H NMR (400

MHz, CDCl₃+ DMSO-d₆): δ 9.97 (s, 1 H, NH), 8.03 (dd, ³J_HH

(5 mL) was added, precipitating a solid, which was collected

by filtration, washed with n-pentane (3 × 3 mL) and n-pen-

tane-Et₂O (1:1) (3 × 2 mL) and dried in a stream of air to yield

pale-yellow 8t. Yield: 242 mg, 85%. Mp: 88-90 °C. IR (Nujol,

cm^-1): 3340 ν(NH), 2198 ν(CtN), 1672 ν(CdO), 1590

ν(CdN). ¹H NMR (300 MHz, CDCl₃): δ 12.88 (br s, 1 H, NH),

8.87 (d, J_HH) 8 Hz, 1 H, H6, C₆H₄), 8.71 (d, J_HH) 8 Hz,

⁴J_HH) 1.2 Hz, 1 H, H3, C₆H₄), 7.31-7.23 (m, 3 H, H2 + H6,

p-tolyl + H4, C₆H₄), 7.12-7.03 (m, 3 H, H3 + H5, p-tolyl +

H5, C₆H₄), 6.17 (s, 1 H, NH), 2.31 (s, 3 H, Me), 1.66 (s, 9 H,

^tBu), 1.37 (s, 18 H, Bu). ¹³C{¹H} NMR (75 MHz, CDCl₃): δ

176.5 (CdN^tBu), 153.0 (CdO), 137.6 (C6H, C₆H₄), 137.1 (C),

136.1 (C1, p-tolyl), 132.6 (C4, p-tolyl), 129.5 (C3H + C5H,

p-tolyl), 129.3 (C4H, C₆H₄), 129.0 (C), 120.8 (C5H), 119.3 (C2H

+ C6H, p-tolyl), 118.4 (C3H, C₆H₄), 57.9 (CdNCMe₃), 57.8

(Pd-CdNCMe₃), 31.4 (CdNMe₃), 29.7 (Pd-CdNCMe₃), 20.7

(Me, p-tolyl). Anal. Calcd for C₂₉H₃₁IN₅OPd: C, 49.20; H, 5.69;

N, 9.89. Found: C, 48.94; H, 5.81; N, 9.85.

) 6.6 Hz, J_HH) 1.3 Hz, 1 H, H5), 7.73-7.68 (m, 3 H, H2 +

H6, p-tolyl + H7), 7.39 (d, J_HH) 8 Hz, 1 H, H8), 7.26 (m, 1

H, H6), 7.17 (d, J_HH) 8 Hz, 2 H, H3 + H8, p-tolyl), 2.36 (s,

3 H, Me). ¹³C{¹H} APT NMR (100 MHz, CDCl₃+ DMSO-d₆):

δ 158.3 (C4dO), 149.61 (C2dO), 148.71 (C4a), 135.28 (C7H),

134.21 (C1, p-tolyl), 131.20 (C4, p-tolyl), 127.91 (C5H + C3H,

p-tolyl), 127.00 (C5H), 123.48 (C8H), 122.64 (C6H), 118.55

(C2H + C6H, p-tolyl), 112.53 (C8a), 19.50 (Me). EI-MS (%):

m/z 252.00 (M⁺, 47), 252.95 (M⁺, 8). The NMR data are in

accord with those reported in the literature.¹⁴

Synthesis of 4-(Xylylimino)-3-p-tolyl-3,4-dihydro-1H-

quinazolin-2-one (9). TlOTf (84 mg, 0.24 mmol) was added

to a CH₂Cl₂(10 mL) solution of 8x (200 mg, 0.24 mmol) and

the volume of the reaction mixture was made up to 20 mL

with acetone, precipitating a green solid. The mixture was

stirred for 7 h, the resulting suspension was filtered through

Celite, the filtrate was concentrated to dryness, and the

residue was treated with Et₂O. The solution was decanted,

concentrated to ca. 1 mL, and placed on a silica gel chromato-

graphic column. Elution with Et₂O/n-hexane (1:2) gave crude

9 (R_f) 0.80 by TLC), which was crystallized by cooling (-34

°C) a saturated Et₂O/n-hexane solution. The crystals thus

formed were collected by filtration, washed with cold Et₂O (1

mL), and dried under high vacuum for 2 h. Yield: 47 mg, 55%

for the crude product; 21 mg, 25% for the crystals of 9‚0.2H₂O.

Synthesis of trans-[Pd{C(O)C₆H₄NHC(O)NHTo-2}I(C-

NXy)₂] (7). XyNC (65 mg, 0.50 mmol) was added to a solution

of 5b (100 mg, 0.17 mmol) in CH₂Cl₂(5 mL). The solvent was

removed, and the residue was triturated with Et₂O (10 mL).

The resulting solid was collected by filtration, washed with

Et₂O (3 × 2 mL), and dried under high vacuum for 6 h to yield

7‚0.6Et₂O as a pale yellow solid. Yield: 118 mg, 95%. Mp:

129-131 °C dec. IR (Nujol, cm^-1): 2182 ν(CtN), 1708

ν(CdO). ¹H NMR (200 MHz, CDCl₃): δ 10.38 (br s, 1 H, NH),

Mp: 151 °C. IR (Nujol, cm^-1): 3370 ν(NH), 1698 ν(CdO). H

9.00 (d, J_HH) 8 Hz, 1 H, H3 or H6, C₆H₄), 8.50 (d, J_HH) 8

Hz, 1 H, H3 or H6, C₆H₄), 7.49 (t, ³J_HH) 8 Hz, 1 H, H4 or H5,

C₆H₄), 7.32 (d, ³J_HH) 10 Hz, 2 H, p-tolyl), 7.27-7.14 (several

m, 5 H, H4 or H5, C₆H₄+ 2 H, p-tolyl + para H’s Xy), 7.04 (d,

³J_HH) 8 Hz, 4 H, meta H’s Xy), 6.54 (br s, 1 H, NH), 3.48 (q,

³J_HH) 8 Hz, 2.5 H, CH₂, Et₂O), 2.34 (s, 3 H, Me, p-tolyl), 2.27

NMR (400 MHz, CDCl₃): δ 8.26 (d, J_HH) 7.5 Hz, 1 H), 7.53

(td, J_HH) 7.5 Hz, J_HH) 1.5 Hz, 1 H, H6 or H7), 7.28-7.16

(m, 4 H), 7.09 (d, J_HH) 7.5 Hz, 2 H), 7.02-6.96 (m, 3 H),

6.67 (s, 1 H, NH), 2.28 (s, 3 H, Me), 2.15 (s, 6 H, Me), 1.55 (s,

0.4 H, H₂O. ¹³C{¹H} NMR (75 MHz, CDCl₃): δ 149.35 (C),

145.37 (C), 145.36 (C), 144.17 (C), 134.62 (C), 133.95 (CH),

133.26 (C), 129.63 (CH), 128.09 (C), 127.81 (CH), 126.92 (CH),

124.60 (CH), 124.45 (CH), 123.25 (CH), 119.37 (CH), 116.21

(s, 12 H, Me, Xy), 1.21 (t, J_HH) 8 Hz, 3.75 H, Me, Et₂O).

¹³C{¹H} NMR: the compound decomposes during the experi-

ment. Anal. Calcd for C_40.4H₃₇IN₄O_2.6Pd: C, 53.59; H, 4.70; N,

7.06. Found: C, 53.23; H, 4.93; N, 6.93.

(C), 18.37 (Me), 18.37 (Me, Xy). Anal. Calcd for C₂₃H_21.4

N₃O_1.2: C, 76.94; H, 6.01; N, 11.70. Found: C, 76.88; H, 6.07;

N, 11.59.

Synthesis of trans-[Pd{C(dNXy)C₆H₄NHC(O)NHTo-2}-

I(CNXy)₂] (8x). XyNC (92 mg, 0.70 mmol) was added to a CH₂-

Cl₂(5 mL) solution of 2b (100 mg, 0.17 mmol). After 20 min

the solution was concentrated to ca. 1 mL and Et₂O (10 mL)

added. A solid precipitated, which was collected by filtration,

washed with Et₂O (3 × 3 mL), and dried under a stream of

air to yield pale yellow 8x. Yield: 130 mg, 90%. Mp: 142-

143 °C. IR (Nujol, cm^-1): 2184 ν(CtN), 1674 ν(CdO). ¹H NMR

Synthesis of [Pd{K³C,N,C-C(dNXy)C₆H₄{NC(O)NToC-

(NHXy)}-2}(CNXy)] (10). 8x (100 mg, 0.12 mmol) was dis-

solved in acetone/CH₂Cl₂(2:1). Excess K₂CO₃was added, and

the mixture was stirred overnight (16 h). The suspension was

filtered through anhydrous MgSO₄, the filtrate was concen-

trated to ca. 1 mL, and Et₂O (5 mL) was added. After a few

minutes yellow crystals began to form. n-Pentane (10 mL) was

added and the flask cooled (4 °C) overnight. The yellow crystals

were collected by filtration, washed with Et₂O (3 × 3 mL) and

n-pentane (3 × 2 mL), and air-dried to yield crystalline 10‚

0.7CH₂Cl₂. A sample of this solid was dried under high vacuum

overnight. The NMR of the dried solid showed approximately

0.2 mol of CH₂Cl₂/mol of complex. Yield: 55 mg, 58% for 10‚

0.7CH₂Cl₂. Single crystals of 10‚0.5CDCl₃, suitable for an X-ray

diffraction study, were obtained by liquid diffusion of n-

pentane into a solution of 10 in CDCl₃. Mp: 157-159 °C. IR

(Nujol, cm^-1): 3240 ν(NH), 2176 ν(CtN), 1682 ν(CdO). ¹H

NMR (400 MHz, CDCl₃): δ 8.56 (d, ³J_HH) 7.7 Hz, 1 H, C₆H₄),

8.07 (dd, ³J_HH) 8 Hz, ⁴J_HH) 1.4 Hz, 1 H, C₆H₄), 7.37 (d, ³J_HH

(400 MHz, CDCl₃): δ 11.75 (s, 1 H, NH), 8.79 (dd, J_HH) 8

Hz, J_HH) 1.5 Hz, 1 H, H3 or H6, C₆H₄), 8.54 (dd, J_HH) 8

Hz, J_HH) 1.5 Hz, 1 H, H3 or H6, C₆H₄), 7.39 (td, J_HH) 8

Hz, J_HH) 1.5 Hz, 1 H, H4 or H5, C₆H₄), 7.20 (t, J_HH) 7.5

Hz, 2 H, Pd-CNXy), 7.15 (td, J_HH) 8 Hz, J_HH) 1.5 Hz, 1

H, H4 or H5) 7.05 (t, J_HH) 7.5 Hz, 6 H, p-tolyl + Pd-CNXy),

6.94-6.89 (m, 3 H CdNXy), 6.74 (d, ³J_HH) 8 Hz, 2 H, p-tolyl),

6.13 (s, 1 H, NH), 2.17 (s, 12 H, Me, Pd-CNXy), 2.01 (s, 3 H,

Me, p-tolyl), 1.94 (s, 6 H, Me, CdNXy). ¹³C{¹H} NMR (101

MHz, CDCl₃): δ 183.18 (C), 154.60 (C), 148.41 (C), 137.42 (CH),

137.31 (C), 136.84 (C), 135.97 (C), 135.58 (C), 133.78 (C),

130.50 (CH), 130.05 (CH), 129.67 (CH), 128.16 (CH), 128.01

(CH), 127.19 (C), 124.40 (CH), 123.97 (CH), 121.15 (CH),

119.18 (CH), 20.78 (Me), 19.04 (Me), 18.83 (Me), 18.56 (Me).

Anal. Calcd for C₄₁H₄₀IN₅OPd: C, 57.79; H, 4.73; N, 8.22.

Found: C, 57.91; H, 4.61; N, 8.01.

) 8 Hz, 2 H, p-tolyl), 7.27 (td, J_HH) 7.7 Hz, J_HH) 1.4 Hz,

1 H, C₆H₄), 7.25 (d, J_HH) 8 Hz, 2 H, p-tolyl), 7.05 (t, J_HH

)

7.7 Hz, 1 H, Xy), 6.92 (t, J_HH) 7.7 Hz, 1 H, C₆H₄), 6.83 (d,

Synthesis of trans-[Pd{C(dN^tBu)C₆H₄NHC(O)NHTo-

³J_HH) 7.7 Hz, 2 H, Xy), 6.55 (d, J_HH) 7.6 Hz, 2 H, p-tolyl),

2}I(CN^tBu)₂] (8t). BuNC (184 µL, 1.64 mmol) was added to

6.50 (d, J_HH) 7.5 Hz, 2 H, p-tolyl), 6.09 (t, J_HH) 7.6 Hz, 1

a CH₂Cl₂(5 mL) solution of 2b (240 mg, 0.41 mmol). After 20

min, the solution was concentrated to ca. 1 mL and n-pentane

H, Xy), 5.86 (t, J_HH) 7.5 Hz, 1 H, Xy), 5.30 (s, 0.28 H, CH₂-

Cl₂), 2.40 (s, 3 H, Me), 2.22 (s, 6 H, Me, Xy), 2.10 (s, 6 H, Me,

Ortho-Palladated Arylureas

Organometallics, Vol. 24, No. 21, 2005 5049

Xy), 1.98 (s, 6 H, Me, Xy). ¹³C{¹H} NMR (50 MHz, CDCl₃): δ

204.83 (C, carbene), 160.27 (C), 152.88 (C), 152.30 (C), 143.87

(C), 139.92 (C), 136.23 (C), 134.98 (C), 133.43 (C), 132.81 (C),

131.29 (CH, p-tolyl), 131.11 (CH, C₆H₄), 128.62 (CH, p-tolyl),

128.09 (CH, Xy), 127.98 (CH, Xy), 127.97 (CH, Xy) 127.15 (CH,

Xy), 126.87 (CH, Xy), 125.64 (C), 124.83 (CH, C₆H₄), 121.63

(CH, C₆H₄), 121.51 (CH, Xy), 119.05 (CH, C₆H₄), 21.24 (Me,

p-tolyl), 19.24 (Me, Xy), 18.96 (Me, Xy), 18.24 (Me, Xy). Anal.

Calcd for C₄₁H₃₉N₅OPd‚0.7CH₂Cl₂: C, 63.91; H, 5.20; N, 8.94.

Found: C, 64.10; H, 5.21; N, 9.01. Calcd for C_41.14H_39.28Cl_0.28N₅-

OPd: C, 67.13; H, 5.38; N, 9.51. Found: C, 67.14; H, 5.69; N,

9.66.

was collected by filtration, washed with Et₂O (3 × 2 mL), and

air-dried to give 11bq as a yellow powder. Yield: 222 mg, 86%.

Crystals suitable for an X-ray study were obtained by slow

diffusion of Et₂O into a CDCl₃solution of 11bq. Λ_M) 135 Ω^-1

cm²mol^-1. Mp: 160-162 °C. IR (Nujol, cm^-1): 3298 ν(NH),

1682, 1634 ν(CdO), 1030 (OTf). H NMR (400 MHz, CDCl₃):

δ 8.83 (s, 1 H, NH), 8.81 (s, 1 H, NH), 7.45-7.35 (m, 3 H),

7.34-7.29 (m, 1 H), 7.25-7.01 m, 9 H), 3.47 (s, 3 H, OMe),

2.87 (s, 3 H, Me, tmeda), 2.66 (s, 3 H, Me, tmeda), 2.69-2.55

(m, 2 H, CH₂), 2.28 (s, 3 H, Me, p-tolyl), 2.26 (s, 3 H, Me,

tmeda), 2.30-2.14 (m, 2 H, CH₂), 1.87 (s, 3 H, Me, tmeda).

¹³C{¹H} APT NMR (75 MHz, CDCl₃): δ 171.40 (CO₂Me),

160.30 (NHCO), 144.10 (C), 140.80 (C), 138.90 (C), 138.8 (C),

135.1 (C), 134.00 (C), 133.3 (C4 p-tolyl), 129.50 (CH), 129.40

(CH), 129.10 (C3H + C5H, p-tolyl), 128.50 (CH), 128.20 (ortho

or meta CH’s, Ph), 127.40 (ortho or meta CH’s Ph), 127.20

(CH), 120.80 (C2H + C6H, p-tolyl), 64.40 (CH₂), 57.60 (CH₂),

54.00 (Me, tmeda), 51.50 (OMe), 49.50 (Me, tmeda), 48.80 (Me,

tmeda), 46.10 (Me, tmeda), 20.80 (Me, p-tolyl). Anal. Calcd for

C₃₁H₃₇F₃N₄O₆PdS: C, 49.18; H, 4.93; N, 7.40; S, 4.23. Found:

C, 48.81; H, 4.92; N, 7.27; S, 3.92.

Synthesis of [Pd{K²C,N-C(Et)dC(Et)C₆H₄NHC(O)NHTo-

2}(tmeda)]OTf (11be). 3-Hexyne (80 µL, 0.70 mmol) and

TlOTf (61 mg, 0.17 mmol) were added to a solution of 2b (100

mg, 0.17 mmol) in THF (5 mL). After 10 min, the solvent was

removed and the residue was treated with CH₂Cl₂(5 mL). The

suspension was filtered over Celite, the filtrate was concen-

trated to 1 mL, and n-pentane was added. The mixture was

stirred until a solid formed; this was collected by filtration,

washed with n-pentane, and dried under a stream of air to

yield 11be as a brown powder. Yield: 70 mg. IR (Nujol, cm^-1):

Synthesis of [Pd{K²C,N-C(Ph)dC(Ph)C₆H₄NHC(O)-

NHTo-2}(tmeda)]OTf (11bp) and 2,3-Diphenylindole-1-

carboxylic acid p-Tolylamide (12p). TlOTf (62 mg, 0.18

mmol) was added to a solution of diphenylacetylene (124 mg,

0.70 mmol) and 2b (100 mg, 0.17 mmol) in THF (10 mL). The

resulting suspension was stirred for 5 min, the solvent was

removed under reduced pressure, and CH₂Cl₂(10 mL) was

added. The suspension was filtered through Celite, the filtrate

concentrated to dryness, and the solid vigorously stirred

overnight in Et₂O. The resulting solid was collected by filtra-

tion, washed with Et₂O (3 × 3 mL), and dried under a stream

of air to yield yellow 11bp, which was used without further

purification in the synthesis of 12p. Yield: 110 mg, 82%. Single

crystals were obtained by liquid diffusion of Et₂O into a

solution of 11bp in CDCl₃. Mp: 118-120 °C. IR (Nujol, cm^-1):

3256, 3250 ν(NH), 1650, 1634 ν(CO), 1026 ν(OTf). H NMR

(400 MHz, CDCl₃): δ 8.74 (s, 1 H, NH), 8.47 (s, 1 H, NH), 7.37

(td, J_H,H) 7 Hz, J_H,H) 1.3 Hz, 1 H), 7.28-7.24 (m, 4 H),

7.19-7.15 (m, 1 H), 7.03 (d, ³J_H,H) 8.5 Hz, 2 H, p-tolyl), 2.70-

2.78 (several multiplets, 8 H, CH₂), 2.66 (s, 3 H, Me), 2.44 (s,

3 H, Me), 2.31 (s, 3 H, Me), 2.27 (s, 3 H, Me), 1.79 (s, 3 H, Me),

1.07 (t, ³J_H,H) 7.5 Hz, 3 H, MeCH₂), 0.83 (t, ³J_H,H) 7.5 Hz, 3

H, MeCH₂). Because this compound is unstable, minor reso-

nances are also observed that increase with time. ¹³C{¹H}

NMR: the compound decomposes during the experiment. All

attempts to purify the compound to get good elemental

analyses failed.

Synthesis of [Pd{K²C,N-C(CO₂Me)dC(CO₂Me)C₆H₄NHC-

(O)NHTo-2}(tmeda)]OTf (11bm). dmad (85 µL, 0.79 mmol)

and TlOTf (61 mg, 0.17 mmol) were added to a solution of 2b

(100 mg, 0.17 mmol) in THF (10 mL). After 10 min, the solvent

was removed and the residue was treated with CH₂Cl₂(10 mL).

The suspension was filtered over Celite, and the filtrate was

concentrated to dryness. The solid was triturated with Et₂O

(5 mL), collected by filtration, washed with Et₂O, and dried

under a stream of air to yield 11bm as a yellow powder.

Yield: 80 mg. IR (Nujol, cm^-1): 3254, 3246 ν(NH), 1698, 1632

3300, 3222 ν(NH), 1634 ν(CdO), 1026 (OTf). H NMR (400

MHz, CDCl₃): δ 8.84 (s, 1 H, NH), 8.48 (br s, 1 H, NH), 7.70

(d, ³J_HH) 7.5 Hz, 1 H), 7.52 (t, ³J_HH) 7.5 Hz, 1 H), 7.41-7.34

(m, 3 H), 7.28-7.23 (m, 4 H), 7.13 (d, J_HH) 8.5 Hz, 2 H),

7.10-7.05 (m, 3 H), 7.01-6.93 (m, 6 H), 2.54 (s, 3 H, Me), 2.34

(s, 3 H, Me), 2.30 (s, 3 H, Me), 1.97 (s, 3 H, Me), 1.80 (s, 3 H,

Me), 2.64-2.04 (several m, 4H, CH₂). ¹³C{¹H} NMR: the

compound decomposes during the experiment.

ν(CdO), 1028 (OTf). H NMR (400 MHz, CDCl₃): δ 8.78 (s, 1

Complex 11bp (200 mg, 0.26 mmol) was dissolved in CH₂-

Cl₂(10 mL). After 15 min a black precipitate began to appear.

After 48 h the mixture was filtered through Celite and the

solution concentrated to ca. 1 mL and placed on a silica gel

chromatographic column. Elution with Et₂O/n-hexane (1:2)

rendered a colorless solid, which was dissolved in acetone, and

n-hexane was added. Slow evaporation of the solvents gave

crystals, which were filtered off, washed with n-hexane, and

air-dried to give 12p as a colorless crystalline solid. Yield: 75

mg, 72% (crude); 30 mg, 29% (pure). Mp: 203-205 °C. IR

(Nujol, cm^-1): 3296 ν(NH), 1676 ν(CdO). ¹H NMR (400 MHz,

H, NH), 8.59 (s, 1 H, NH), 7.51-7.38 (m, 3 H), 7.28 (d, ³J_HH

)

7.5 Hz, 1 H), 7.17 (d, J_HH) 8 Hz, 2 H, p-tolyl), 7.07 (d, J_HH

) 8 Hz, 2 H, p-tolyl), 3.76 (s, 3 H, OMe), 3.61 (s, 3 H, OMe),

2.78 (s, 3 H, Me), 2.73-2.15 (several m, 4 H, CH₂), 2.59 (s, 3

H, Me), 2.30 (s, 3 H, Me), 2.20 (s, 3 H, Me), 1.18 (s, 3 H, Me).

Other signals appear, and their intensity increases with time.

¹³C{¹H} NMR: the compound decomposes during the experi-

ment. Anal. Calcd for C₂₇H₃₅F₃N₄O₈PdS: C, 43.88; H, 4.77; N,

7.58; S, 4.34. Found: C, 43.44; H, 4.65; N, 7.32; S, 3.56. All

attempts to purify the compound resulted in an increase of

the amount of impurities. See Results and Discussion.

Synthesis of [Pd{K²C,N-C(Ph)dC(CO₂Me)C₆H₄NHC(O)-

NHTo-2}(tmeda)]OTf (11bq). Method A. TlOTf (61 mg, 0.17

mmol) was added to a solution of methyl phenylpropiolate (96

µL, 0.70 mmol) and 2b in THF (5 mL), and the resulting

suspension was stirred for 10 min. The solvent was removed

under reduced pressure, and CH₂Cl₂(10 mL) was added. The

suspension was filtered through Celite, the filtrate was

concentrated to ca. 1 mL, and Et₂O was added, precipitating

a solid, which was collected by filtration, washed with Et₂O

(3 × 3 mL), and dried under a stream of air to yield pale yellow

11bq. Yield: 95 mg, 72%.

CDCl₃): δ 8.33 (d, J_HH) 8 Hz, 1 H), 7.64 (d, J_HH) 8 Hz, 1

H), 7.44-7.39 (several m, 6 H), 7.32-7.26 (several m, 6 H),

7.03 (d, J_HH) 8 Hz, 2 H, p-tolyl), 6.88 (d, J_HH) 8 Hz, 2 H,

p-tolyl), 6.59 (s, 1 H, NH), 2.27 (s, 3 H, Me). ¹³C{¹H} APT NMR

(100 MHz, CDCl₃): δ 149.40 (CdO), 137.06 (C7a), 134.25 (C),

134.21 (C), 133.27 (C), 133.00 (C), 131.37 (C), 130.73 (CH),

130.09 (CH), 129.45 (CH), 129.21 (C3′H + C5′H, p-tolyl),

129.05 (CH), 128.61 (C3a), 128.34 (CH), 126.84 (CH), 124.89

(C6H), 122.82 (C5H), 121.50 (C3), 119.71 (CH), 129.68 (CH),

114.72 (CH), 20.79 (Me). Anal. Calcd for C₂₈H₂₂N₂O: C, 83.56;

H, 5.51; N, 6.69. Found: C, 83.21; H, 5.70; N, 6.94.

Synthesis of 3-Phenyl-1H-indole-2-carboxylic acid

Methyl Ester (13q). PPh₃(278 mg, 1.06 mmol) was added to

a solution of 11bq (200 mg, 0.26 mmol) in CH₂Cl₂(10 mL).

The yellow solution was stirred overnight (16 h), and the

solvent was removed under reduced pressure. The residue was

Method B. Methyl phenylpropiolate (192 µL, 1.34 mmol)

was added to a solution of 3b (200 mg, 0.34 mmol) in CH₂Cl₂

(5 mL). The solution was stirred for 20 min and concentrated

to ca. 1 mL and Et₂O (5 mL) added, precipitating a solid, which

5050 Organometallics, Vol. 24, No. 21, 2005

Vicente et al.

placed on a silica gel chromatographic column. Elution with

n-hexane/Et₂O (3:1) rendered a fraction (R_f) 0.6 by TLC),

which was collected, dried over anhydrous MgSO₄, filtered, and

evaporated to dryness to give crude 13q. This solid was

crystallized by addition of n-hexane (1 mL) to a solution in

the minimum amount of Et₂O. The resulting suspension was

concentrated to ca. 0.5 mL and placed in a refrigerator at -34

°C overnight. The resulting crystals were collected by filtration

and dried under high vacuum for 12 h to yield 13q‚0.2H₂O as

a yellow crystalline solid. Yield: 34 mg, 51% (crude); 5 mg, 8%

(pure). Mp: 129-131 °C. IR (Nujol, cm^-1): 3332 ν(NH), 1674

ν(CdO). ¹H NMR (400 MHz, CDCl₃): δ 8.95 (s, 1 H, NH), 7.64

C₁₇H₁₃NO₃: C, 73.11; H, 5.02; N, 4.69. Found: C, 72.72; H,

4.99; N, 5.04.

Synthesis of 2-Xylyl-4-phenyl-1,2-dihydroquinoline-3-

carboxylic Acid Methyl Ester (14qnx). XyNC (50 mg, 0.38

mmol) was added to a solution of 11bq (280 mg, 0.37 mmol)

in CH₂Cl₂(10 mL) under N₂. The mixture was stirred for 24

h, as the yellow solution turned into a green suspension. The

suspension was filtered through Celite, and the filtrate was

concentrated to dryness. The solid was placed on a silica gel

chromatographic column. Elution with n-hexane/acetone (5:

1) rendered a yellow solid (R_f) 0.45 by TLC). The resulting

solid was crystallized by cooling concentrated pentane solu-

tions (-34 °C) overnight. The crystals were collected by

filtration, washed with cold pentane (2 × 1 mL), and dried

under high vacuum to give colorless crystals of 14qnx. Yield:

46 mg, 32% (crude); 5 mg, 3% (pure). Mp: 146-148 °C. IR

(Nujol, cm^-1): 3394 ν(NH), 1712 ν(CdO), 1598 ν(CdN). ¹H

NMR (200 MHz, CDCl₃): δ 7.96 (br s, 1 H, NH), 7.6 (dd, ³J_HH

) 8 Hz, ⁴J_HH) 1 Hz, 1 H), 7.55-7.43 (m, 4 H), 7.39-7.32 (m,

3 H), 7.14-7.07 (m, 4 H), 3.43 (s, 3 H, OMe), 2.31 (s, 6 H, 3Me,

Xy). ¹³C{¹H} APT NMR (100 MHz, CDCl₃): δ 169.36 (CdO),

151.90 (CdN), 151.24 (C), 148.59 (C), 137.69 (C), 136.77 (C-

N, Xy), 135.34 (C-Me, Xy), 130.96 (CH), 128.80 (CH), 128.035

(CH), 128.01 (CH), 127.91 (CH), 127.23 (CH), 125.83 (CH),

122.79 (CH), 122.52 (C), 113.30 (C, C3), 51.95 (OMe), 19.00

(Me). Anal. Calcd for C₂₅H₂₂N₂O₂: C, 78.51; H, 5.80; N, 7.32.

Found: C, 78.71; H, 6.14; N, 7.33.

Heck Coupling of 4-Chloroiodobenzene with Methyl

Acrylate. Method A. A 25 mL round-bottom flask was

charged with 4-chloroiodobenzene (476 mg, 2 mmol), methyl

acrylate (216 µL, 2.4 mmol), Et₃N (393 µL, 2.8 mmol), complex

10 (145 µg, 2 × 10^-4mmol, 0.01 mol % Pd), and DMF (4 mL).

The solution was stirred at 110 °C in air, and the reaction

progress was analyzed by GLC. After completion the reaction

mixture was cooled and poured into water (30 mL) and this

mixture was extracted with AcOEt (2 × 20 mL). The resulting

organic phase was washed with water (3 × 30 mL) and dried

over Na₂SO₄, and the solvents were evaporated to obtain the

corresponding methyl cinnamate in 95% yield.

(d, J_HH) 8 Hz, 1 H, H4 or H7), 7.57-7.55 (m, 2 H), 7.49-

7.45 (several m, 3 H), 7.41-7.35 (several m, 2 H), 7.15 (td,

³J_HH) 8 Hz, ⁴J_HH) 1 Hz, H5 or H6), 3.82 (s, 3 H, OMe), 1.55

(s, 0.4 H, H₂O). ¹³C{¹H} APT NMR (100 MHz, CDCl₃): δ 162.40

(CdO), 135.73 (C), 133.37 (C), 130.52 (CH, Ph), 127.85 (CH,

Ph), 127.24 (CH), 125.88 (CH), 124.40 (C), 122.36 (C), 121.77

(CH), 120.89 (CH), 111.68 (CH), 51.77 (OMe). EI-MS (m/z

(%)): 251.1 (M⁺, 92.4), 220.1 (M⁺- OMe, 100), 192.1 (M⁺

CO₂Me, 98.7). Anal. Calcd for C₁₆H_13.4NO_2.2: C, 75.40; H, 5.30;

N, 5.50. Found: C, 75.61; H, 5.51; N, 5.69.

Synthesis of 3,4-Diphenyl-2-quinolone (14po). CO was

bubbled through a solution of 12p (120 mg, 0.163 mmol) in

CH₂Cl₂(10 mL). After a few minutes a black precipitate was

formed. The suspension was stirred for 2 h under a CO

atmosphere and filtered through Celite and the filtrate

concentrated to dryness. The residue was placed on a silica

gel chromatographic column. Elution with n-hexane/Et₂O

(1:1) gave a fraction (R_f) 0.7 by TLC) which was collected

and dried over anhydrous MgSO₄, and the solvents were

removed to give crude 14po. This solid was recrystallized by

addition of n-hexane to a solution in the minimum amount of

AcOEt until small crystals began to form. After the mixture

was cooled (-34 °C) overnight, the resulting crystals were

collected by filtration and dried under high vacuum for 2 h to

yield 14po‚0.4H₂O as a colorless crystalline solid. Single

crystals suitable for X-ray diffraction studies were obtained

by slow diffusion of Et₂O into concentrated solutions of

amorphous 14po in CDCl₃. Yield: 40 mg, 88% (crude); 5 mg,

11% (pure). Mp: 272-274 °C. IR (Nujol, cm^-1): 1652 ν(CdO).

¹H NMR (400 MHz, CDCl₃): δ 11.89 (br s, 1H, NH), 7.45 (td,

Method B. A 25 mL round-bottom flask was charged with

4-bromonitrobenzene (404 mg, 2 mmol), methyl acrylate (216

µL, 2.4 mmol), potassium carbonate (386 mg, 2.8 mmol), (n-

Bu₄N)Br (129 mg, 0.4 mmol), complex 10 (8.3 mg, 1.15 × 10^-2

mmol, 0.6 mol % Pd), and DMF (4 mL). The solution was

stirred at 110 °C in air, and the reaction progress was analyzed

by GLC. After completion the reaction mixture was cooled and

poured into water (30 mL) and the mixture was extracted with

AcOEt (2 × 20 mL). The resulting organic phase was washed

with water (3 × 30 mL) and dried over Na₂SO₄, and the

solvents were evaporated to obtain the corresponding methyl

cinnamate in 97% yield.

³J_HH) 7 Hz, J_HH) 1 Hz, 1 H), 7.33 (d, J_HH) 7 Hz, 1 H),

7.29-7.04 (m, 12 H), 1.55 (s, 0.8 H, H₂O). ¹³C{¹H} APT NMR

(50 MHz, CDCl₃): δ 163.00 (CdO), 149.70 (C), 137.80 (C), 136.3

(C), 135.20 (C), 131.90 (C), 130.80 (CH), 130.20 (CH), 129.8

(CH), 128.00 (CH), 127.60 (CH), 127.50 (CH), 127.00 (CH),

122.3 (CH), 120.90 (CH), 115.80 (CH). HRMS: calcd for C₂₁H₁₅-

NO, 297.114; found, 297.115. Anal. Calcd for C₂₁H_15.8NO_1.4: C,

82.82; H, 5.23; N, 4.60. Found: C, 82.89; H, 5.28; N, 4.75.

Synthesis of 2-Oxo-4-phenyl-1,2-dihydroquinoline-3-

carboxylic Acid Methyl Ester (14qo). CO was bubbled

through a CH₂Cl₂(5 mL) solution of 11bq (144 mg, 0.19 mmol),

giving palladium metal. The suspension was stirred overnight

under a CO atmosphere, and the resulting suspension was

filtered through anhydrous MgSO₄. The solution was concen-

trated and placed on a silica gel chromatographic column.

Elution with n-hexane/AcOEt (1:2) gave a fraction which was

collected, dried over anhydrous MgSO₄, filtered, and concen-

trated to dryness to yield a colorless solid. This crude sample

was recrystallized from CH₂Cl₂/Et₂O/n-hexane to give 14qo

as colorless crystals. Yield: 59 mg, 57%. Mp: 226-228 °C. IR

(Nujol, cm^-1): 1736 ν(CdO). ¹H NMR (300 MHz, CDCl₃): δ

12.88 (br s, 1 H, NH), 7.56-7.47 (several m, 5 H), 7.41-7.37

(m, 2 H), 7.31 (d, J_HH) 8 Hz, 1 H), 7.14 (ddd, J_HH) 8 Hz, J_HH

) 5 Hz, J_HH) 3 Hz, 1 H, C₆H₄), 3.65 (s, 3 H, OMe). ¹³C{¹H}

APT NMR (50 MHz, CDCl₃): δ 166.21 (CO₂), 161.14 (CdO),

150.83 (C), 138.46 (C), 134.57 (C), 131.62 (CH), 128.91 (CH),

128.63 (CH), 128.39 (CH), 127.62 (CH), 125.96 (C), 122.96

(CH), 119.41 (C), 116.91 (CH), 52.30 (s, OMe). Anal. Calcd for

General Procedure for Suzuki Couplings. A 25 mL

round-bottom flask was charged with the corresponding aryl

halide (2 mmol), arylboronic acid (366 mg, 3 mmol), K₂CO₃

(553 mg, 4 mmol), (n-Bu₄N)Br (322 mg, 1 mmol, only for aryl

chlorides), complex 10 (see Table 2), and solvent (7 mL, see

Table 2). The mixture was heated (see Table 2) and stirred in

air, and the reaction progress was analyzed by GLC. After

completion the reaction mixture was cooled and poured into

AcOEt (40 mL) and the mixture was washed with aqueous 2

M NaOH (2 × 20 mL) and water (3 × 20 mL). The organic

layer was dried over Na₂SO₄, and the solvents were evaporated

to obtain the corresponding biphenyl.

X-ray Structure Determinations. Data were obtained

using Mo KR radiation on a Bruker SMART 1000 CCD

diffractometer. Absorption corrections were based on indexed

faces (3b and 10) or multiple scans (program SADABS; 11bp

and 11bq). Structures were refined anisotropically on F²

(program SHELXL-97, G. M. Sheldrick, University of Go¨ttin-

gen, Go¨ttingen, Germany). Hydrogens of NH groups were

refined freely but with N-H distance restraints (SADI).

Ortho-Palladated Arylureas

Scheme 1

Organometallics, Vol. 24, No. 21, 2005 5051

Scheme 2

Methyl hydrogens were identified in difference syntheses and

refined as rigid groups allowed to rotate but not tip; other

hydrogens were included using a riding model. Crystal data

are presented in Table 3. Special features/exceptions: The

solvent methyl groups in 11bp were set ideally staggered and

refined using a riding model. To improve the stability of the

refinement, restraints to light atom displacement parameters

were employed (DELU, SIMU). For 11bq and 14po, NH

hydrogens were refined freely without restraints.

complex mixtures. On the other hand, addition of PPh₃

to 3b resulted in the opening of the metallacycle to yield

[Pd{C₆H₄NHC(O)NHTo-2}(tmeda)(PPh₃)]OTf (4b).

Reactions with CO and Isocyanides. Synthesis

of Quinazolinones. Complex 2b reacts with CO to give

the acylpalladium derivative [Pd{C(O)C₆H₄NHC(O)-

NHTo-2}I(tmeda)] (5b) (Scheme 2). If Tl(TfO) is added

after the bubbling of CO, the C,N coupling product 3-p-

tolyl-1H-quinazoline-2,4-dione (6) is formed. The analo-

gous reaction using 2c gave complex mixtures. Treat-

ment of 5b with XyNC (1:3 molar ratio) gave trans-

[Pd{C(O)C₆H₄NHC(O)NHTo-2}I(CNXy)₂] (7). The reac-

tion of 5b with PPh₃(1:2 molar ratio) resulted in the

substitution of the tmeda by PPh₃; the resulting complex

was identified in solution as trans-[Pd{C(O)C₆H₄NHC-

(O)NHTo-2}I(PPh₃)₂] but could not be isolated because

of its low stability. An analytically pure sample of 5b

gives, after 24 h in CDCl₃at room temperature, a

palladium mirror and a solution containing 5b and 6

in an approximately 1:1 molar ratio, ca. 20 mol % [PdI₂-

(tmeda)], free tmeda, and minor quantities of other

unidentified products. Similarly, a CDCl₃solution of 7

forms, after 24 h, a palladium mirror, compound 6, free

XyNC, and another compound (¹H NMR δ 2.57 ppm),

probably the isocyanide-palladium(I) complex [Pd₂I₂-

(CNXy)₂].²⁹Elution of the mixture in a GC/MS ap-

paratus confirmed the presence of XyNC (m/e 131, M⁺)

and 6 (m/e 253, M⁺). Compound 6 was also formed in

the decomposition of trans-[Pd{C(O)C₆H₄NHC(O)NHTo-

Results and Discussion

Synthesis of Ortho-Palladated Arylureas. 2-Io-

doaniline and p-tolyl isocyanate were reacted to give the

(iodoaryl)urea IC₆H₄NHC(O)NHTo-2 (1; To ) C₆H₄Me-

4). This compound adds oxidatively to Pd(dba)₂([Pd₂-

(dba)₃]‚dba, dba ) dibenzylideneacetone), in the pres-

ence of 1 equiv of 4,4′-di-tert-butyl-2,2′-bipyridine (tbubpy)

or N,N,N′,N′-tetramethylethylenediamine (tmeda) or 2

equiv of PPh₃, to yield the corresponding complexes [Pd-

{C₆H₄NHC(O)NHTo-2}IL₂] (L₂) tbubpy (2a), tmeda

(2b), L ) PPh₃(2c)) (Scheme 1). Complexes 2b,c were

obtained contaminated with [PdI₂(tmeda)] (ca. 5%) and

with 1 plus [PdI₂(PPh₃)₂] (ca. 5%), respectively. These

impurities seem to form as decomposition products of

some intermediate in the synthesis of 2b and 2c, as the

isolated complexes are stable in solution at room tem-

perature. Analytically pure samples of 2b and 2c were

obtained by recrystallization and by reaction of pure 2b

with PPh₃, respectively. An X-ray diffraction study of

2b confirmed the proposed structure, but it could not

be refined adequately because of disorder in the tmeda

ligand.

Complex 2b reacts with TlOTf to give the cationic

cyclometalated complex [Pd{κ²C,O-C₆H₄NHC(O)NHTo-

2}(tmeda)]OTf (3b). The urea group at the ortho position

coordinates to the palladium atom through the oxygen

to form a six-membered metallacycle (see below). Other

attempts to obtain metallacycles were fruitless. Thus,

oxidative addition of 1 to Pd(dba)₂in the absence of

other ligands or in the presence of 1 equiv of PPh₃gave

(29) Dura´ Vila, V.; Mingos, D. M. P.; Vilar, R.; White, A. J. P.;

Williams, D. J. J. Organomet. Chem. 2000, 600, 198.

5052 Organometallics, Vol. 24, No. 21, 2005

Vicente et al.

Table 1. Heck Reaction

Scheme 3

TON/TOF conversn

reacn conditions

10^-2mol % Pd, Et₃N,

DMF, 110 °C, 2 h

(h^-1

)

(%)^a

9500/4250

NO₂Br 0.6 mol % Pd, K₂CO₃,

(n-Bu₄N)Br, DMF, 130 °C, 2 h

162/81

^aIsolated yields.

result was obtained using Tl₂CO₃. The pathway for this

reaction may include abstraction of the acidic proton of

one of the NH groups by the base and formation of the

amide complex A with replacement of iodide. Complex

A may undergo cyclization after nucleophilic attack of

the remaining NH to the isocyanide ligand.³⁰Unfortu-

nately, attempts to obtain similar complexes from 5b,

7, or 8t resulted in complex mixtures.

One of the interesting features of pincer compounds,

including NHC (N-heterocyclic carbene) pincers, is their

ability to catalyze carbon-carbon or carbon-heteroatom

coupling reactions,³¹such as the Heck,³²Suzuki,³³and

amination reactions,³⁴along with other catalytic reac-

tions.³⁵Apart from this, amido complexes of palladium

seem to be intermediates in palladium-catalyzed ami-

nation reactions.³⁶Also described are amido diphosphino

complexes that catalyze the Heck reaction.³⁷We there-

fore decided to study the activity of 10 as a precatalyst

in cross-coupling processes under the reaction conditions

previously described for the Heck³⁸and Suzuki³⁹reac-

tions using oxime-derived palladacycles as precatalysts.

Thus, methyl acrylate reacted with 4-chloroiodobenzene,

using triethylamine as base and complex 10 (0.01 mol

%) as catalyst in DMF at 110 °C (method A), to give

methyl 4-chlorocinnamate in 95% yield (Table 1). In the

case of the arylation of methyl acrylate with 4-bromo-

nitrobenzene, K₂CO₃as base, (n-Bu₄N)Br as additive,

and higher loading of complex 10 (0.6 mol %) at 130 °C

were used (method B), affording after 2 h methyl

4-nitrocinnamate in 97% yield (Table 1). These TON and

TOF values were similar to those obtained with oxime-

derived palladacycles.³⁸

2}I(PPh₃)₂] in solution. As mentioned in the Introduc-

tion, a work by Alper et al. on the synthesis of quino-

lones describes the preparation of 6 from 2-iodoaniline,

isocyanates, CO, and a palladium catalyst.¹⁴This work

postulates the formation of ortho-palladated arylureas

and their acyl derivatives as intermediates in the

reaction. Here we confirm this proposal, isolating and

characterizing some of these intermediates and proving

that the acyl derivatives (5b and 7) undergo a C,N

coupling to give the quinolone 6.

The complex 2b reacts with isocyanides RNC (R )

Xy ()2,6-dimethylphenyl), ^tBu; 1:4 molar ratio), to give

the corresponding iminoacyl derivatives trans-[Pd-

{C(dNR)C₆H₄NHC(O)NHTo-2}I(CNR)₂] (R ) Xy (8x),

^tBu (8t)). An X-ray diffraction study of 8t confirmed the

proposed structure, but the X-ray data could not be

refined. The complex 8x can also be obtained in low yield

(12%) from 2c (120 mg, 0.12 mmol) and XyNC in CH₂-

Cl₂. The orange solid obtained from this reaction

contained impure 8x, which was isolated after recrys-

tallization from CH₂Cl₂/n-pentane. These iminoacyl

complexes are more stable in solution than their acyl

counterparts; nevertheless, treatment of 8x with TlOTf

resulted in the formation of the quinazolinone imine

4-(xylylimino)-3-p-tolyl-3,4-dihydro-1H-quinazolin-2-

one (9). The yield of this reaction is low (40% for the

crude, 25% for the pure sample), but no other com-

pounds appeared in the GC/MS spectra of crude samples

of the reaction mixture, and the low yield may be partly

due to losses during the workup. 9 was also identified

among the products of the reaction between 2b and

XyNC in a 1:1 molar ratio, which takes place with

formation of palladium metal.

Complex 10 also catalyzed the cross-coupling of phen-

ylboronic acid and bromo- or chloroarenes in water and

organic solvents, giving the corresponding biaryls (Table

2). This reaction takes place at 100-110 °C but not at

room temperature, which indicates the necessity of

(30) Vicente, J.; Chicote, M. T.; Huertas, S.; Jones, P. G. Inorg.

Chem. 2003, 42, 4268. Michelin, R. A.; Pombeiro, A. J. L.; Guedes da

Silva, M. F. C. Coord. Chem. Rev. 2001, 218, 75.

(31) Albrecht, M.; van Koten, G. Angew. Chem., Int. Ed. 2001, 40,

3750. van der Boom, M. E.; Milstein, D. Chem. Rev. 2003, 103, 1759.

(32) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009.

(33) Loch, J. A.; Albrecht, M.; Peris, E.; Mata, J.; Faller, J. W.;

Crabtree, R. H. Organometallics 2002, 21, 700.

Synthesis of an Amido Carbene C,N,C Pincer

Compound. Catalytic Activity. All acyl and imino-

acylpalladium derivatives described here (5b, 7, 8x, and

8t) exhibit one low-field resonance (δ > 10.30 ppm) in

their proton NMR spectra. These resonances were

assigned to one of the NH protons of their urea frag-

ment. This prompted us to investigate the behavior of

these complexes toward bases. Thus, reaction of 8x with

K₂CO₃resulted in the formation of the amido carbene

C,N,C pincer complex [Pd{κ³C,N,C-C(dNXy)C₆H₄{NC-

(O)NToC(NHXy)}-2}(CNXy)] (10) (Scheme 3). The same

(34) Viciu, M. S.; Kissling, R. M.; Stevens, E. D.; Nolan, S. P. Org.

Lett. 2002, 4, 2229.

(35) Poyatos, M.; Mata, J. A.; Falomir, E.; Crabtree, R. H.; Peris, E.

Organometallics 2003, 22, 1110. Mas-Marza´, E.; Poyatos, M.; Sanau´,

M.; Peris, E. Organometallics 2004, 23, 323.

(36) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 4708.

Muller, T. E.; Beller, M. Chem. Rev. 1998, 98, 675.

(37) Huang, M.-H.; Liang, L.-C. Organometallics 2004, 23, 2813.

(38) Alonso, D. A.; Najera, C.; Pacheco, M. C. Adv. Synth. Catal.

2002, 344, 172.

(39) Botella, L.; Najera, C. J. Organomet. Chem. 2002, 663, 46.

Alonso, D. A.; Najera, C.; Pacheco, M. C. J. Org. Chem. 2002, 67, 5588.

Ortho-Palladated Arylureas

Table 2. Suzuki Reaction

Organometallics, Vol. 24, No. 21, 2005 5053

Scheme 4

TON/TOF conversn

reacn conditions

(h^-1

)

(%)^a

C(O)Me

Br 10^-2mol % Pd, KOH,

MeOH/H₂O (3:1),

room temp, 1 day

CH₂CO₂H Br 0.1 mol % Pd, K₂CO₃,

H₂O, room temp, 1 day

OMe

Br 1.1 × 10^-2mol % Pd, K₂CO₃, 7818/6014

toluene, 100 °C, 1.3 h

Br 1.1 × 10^-2mol % Pd, K₂CO₃, 8727/6713

toluene/H₂O (95:5), 110 °C,

1.3 h

C(O)Me

Cl 1.3 × 10^-2mol % Pd, K₂CO₃, 7308/2943

Bu₄NBr, H₂O, reflux, 2.5 h

^aIsolated yields.

generating the catalytically active species. Deactivated

4-methoxybromobenzene could be coupled with phenyl-

boronic acid either in toluene or in a 95:5 mixture of

toluene and water with K₂CO₃as base, with high TON

and TOF values. In the case of the coupling of phenyl-

boronic acid and 4-chloroacetophenone, the reaction was

performed in neat water with (n-Bu₄N)Br as additive

to give 4-acetylbiphenyl in 95% yield with efficiency

similar to that for oxime-derived palladacycles.³⁹In

conclusion, complex 10 is an efficient precatalyst for the

Suzuki and Heck reactions, in water or organic solvents,

and under an air atmosphere.

Reactions with Alkynes. The complex 2b reacts

with internal alkynes and TlOTf at room temperature,

to give the cationic complexes [Pd{κ²C,N-CR′dCR′′C₆H₄-

NHC(O)NHTo-2}(tmeda)]OTf (R′ ) R′′ ) Et (11be),

CO₂Me (11bm), Ph (11bp); R′ ) Ph, R′′ ) CO₂Me

(11bq)) (Scheme 4). In these reactions, only one mol-

ecule of alkyne inserts into the palladium-carbon bond,

despite the use of a 4-fold excess of alkyne. All com-

plexes 11, except 11bq, are unstable in solution, which

precludes recording their ¹³C NMR spectra and recrys-

tallization to obtain analytically pure species. However,

(using GC/MS) PPh₃, 12q (the homologue of 12p with

R′ ) Ph, R′′ ) CO₂Me), p-tolyl isocyanate, and 3-phenyl-

1H-indole-2-carboxylic acid methyl ester (13q). This

indole could be isolated in 52% yield. The reaction

pathway for the formation of the indole derivatives 12p

and 13q (Scheme 5) may include a C,N coupling

involving the vinylic carbon attached to palladium and

the appropriate NH of the urea group. The indole 13q

is the product of the decomposition of the corresponding

12q, in agreement with the GC/MS data of the corre-

sponding reaction mixture.

all could be identified unequivocally by H NMR spec-

troscopy, and 11bp and 11bq were also identified by

X-ray diffraction studies. Interestingly, the insertion of

MeO₂CCtCPh into the Pd-C bond of 2b to give 11bq

is regioselective. The isomer is that in which the CCO₂-

Me moiety is attached to the palladium atom. This

behavior is an exception to that generally observed for

unsymmetrical alkynes.⁸11bq was also synthesized by

reaction of 3b with a 3-fold excess of MeO₂CCtCPh.

The same reaction using the stoichiometric amount of

alkyne also gave 11bq, but longer reaction times (24 h

instead of 5 min) were necessary. Reactions with other

internal (2-butyne) or terminal alkynes (phenylacety-

lene, methyl propiolate) gave compounds that decom-

posed rapidly and could not be identified. The reaction

of 2b with MeO₂CCtCCO₂Me (DMAD), CO, and TlOTf

gave 6 (Scheme 2), indicating that the insertion of

carbon monoxide is faster than that of the alkyne.

When a sample of 11bp was stirred in CH₂Cl₂

overnight and the mixture separated by chromatogra-

phy, the decomposition product 2,3-diphenylindole-1-

carboxylic acid p-tolylamide (12p) (Scheme 4) was

isolated (72% yield). As mentioned above, complex 11bq

is stable in solution, but addition of PPh₃to a solution

of the compound in CH₂Cl₂led to a mixture containing

The vinylpalladium complexes 11bp and 11bq react

with carbon monoxide to give palladium and the qui-

nolone derivatives 14po and 14qo (Scheme 4). The ¹³

NMR spectrum of the resulting quinolone using ¹³CO

showed that the CO group of 14qo originates from

carbon monoxide. In addition, as p-tolyl isocyanate was

detected by GC/MS in the reaction mixtures of 11bp

and 11bq with CO, the reaction pathway depicted in

Scheme 5 can explain the formation of 14po and 14qo:

CO inserts into the Pd-C_vinylbond of 11 to give an acyl

palladium derivative, which undergoes a C,N coupling

with loss of Pd and p-tolyl isocyanate. Similarly, the

reaction of 11bq and XyNC gave the quinolone imine

14qnx. In this case, no palladium precipitate was

observed, presumably because of the formation of some

palladium(0)-isocyanide complex. The mechanism of

the reaction may be similar to that proposed for the

insertion of CO (Scheme 5).

Spectroscopic Data. The infrared spectra of the

arylurea 1, complexes 2a-c, 3b, 4b, 5b, 7, 8x,t, 10, and

11, and the organic products 6, 9, 12p, 13q, and 14 show

one or two bands in the region 1632-1736 cm^-1assign-

able to the ν(CdO) mode. Complexes 7, 8x,t, and 10

5054 Organometallics, Vol. 24, No. 21, 2005

Vicente et al.

Scheme 5

Figure 1. Thermal ellipsoid plot (30% probability) of one

of the two independent formula units of 3b. Selected bond

lengths (Å) and angles (deg) for this formula unit: Pd(1)-

C(11) ) 2.0030(17), Pd(1)-O(1) ) 2.0227(12), Pd(1)-N(1)

) 2.0752(15), Pd(1)-N(2) ) 2.1703(15), N(3)-C(10) )

1.338(2), N(3)-C(12) ) 1.423(2), N(4)-C(10) ) 1.353(2),

N(4)-C(21) ) 1.422(2), O(1)-C(10) ) 1.257(2); C(11)-

Pd(1)-O(1) ) 89.56(6), C(11)-Pd(1)-N(1) ) 98.88(7),

O(1)-Pd(1)-N(2)

84.48(6).

)

87.07(5), N(1)-Pd(1)-N(2)

)

exhibit bands assignable to the ν(CtN) mode of the

isocyanide ligands in the range 2176-2198 cm^-1

The NMR spectra of the new compounds are in

agreement with the proposed structures. Thus, the H

NMR spectra of 2b, 4b, and 11 show four signals in the

methyl region corresponding to the tmeda ligand, while

in the spectra of 3b and 5b there are only two. In the

case of 2b and 4b, the four signals are due to the

restricted rotation of the aryl group around the Pd-C

bond, whereas in the case of 5b the insertion of the CO

allows the free rotation of the acyl ligand. The metal-

lacycle in 11 must be rigid enough to prevent the

equivalence of two methyl groups of each nitrogen atom.

Complexes 5b, 7, and 8 show one very low-field

resonance (δ >10.3 ppm) assignable to one of their NH

protons, probably that involved in a six-membered

intramolecular hydrogen bond⁴⁰with the CdO oxygen

(5b and 7) or the CdN nitrogen (8), respectively. In

complexes 3b, 4b, and 11 both NH protons appear at

low field (δ >7.8 ppm) because of the formation of

hydrogen bonds in solution with the triflate anion.

These hydrogen bonds have been observed in the solid

state in the case of 3b, 11bp, and 11bq (see below). In

the ¹³C NMR of 10 the resonance at 204.83 ppm,

corresponding to a quaternary carbon, is tentatively

assigned to the carbene carbon.

Figure 2. Thermal ellipsoid plot (30% probability) of one

of the two independent molecules of 10‚0.5CDCl₃. The

molecule of CDCl₃is omitted for clarity. Selected bond

lengths (Å) and angles (deg) for this molecule: Pd(1)-C(40)

) 1.9435(16), Pd(1)-N(1) ) 1.9968(13), Pd(1)-C(30) )

2.0579(15), Pd(1)-C(50) ) 2.1045(15), N(1)-C(10) )

1.346(2), N(1)-C(11)

)

1.4027(19), N(2)-C(50)

1.455(2), N(3)-C(30)

)

1.3585(19), N(2)-C(10)

)

1.269(2), N(4)-C(40) ) 1.157(2), N(5)-C(50) ) 1.323(2),

O(1)-C(10) ) 1.2122(19); C(40)-Pd(1)-C(30) ) 97.23(6),

N(1)-Pd(1)-C(30)

) 82.08(6), C(40)-Pd(1)-C(50) )

101.18(6), N(1)-Pd(1)-C(50) ) 79.46(6).

(Figure 2), 11bp‚0.5OEt₂(Figure 3), 11bq (Figure 4),

and 14po (Figure 5) have been determined by X-ray

diffraction studies. Crystallographic data for all of these

complexes are given in Table 3. In complexes 3b and

10 there are two independent formula units in the

asymmetric unit; the cations are closely similar except

for ring rotations, with rms deviations of 0.09 Å,

excluding peripheral ring atoms, in both cases. The

palladium complexes 3b, 10, 11bp, and 11bq show

slightly distorted square planar structures. In complexes

3b, 11bp, and 11bq the triflate is connected to the

X-ray Structures of Complexes 3b, 10‚0.5CDCl₃,

11bp‚OEt₂, 11bq, and 14po. The crystal and molecular

structures of the compounds 3b (Figure 1), 10‚0.5CDCl₃

(40) Gu¨nther, H. NMR Spectroscopy; Wiley: New York, 1996.

Ortho-Palladated Arylureas

Organometallics, Vol. 24, No. 21, 2005 5055

Figure 5. Thermal ellipsoid plot (50% probability) of 14po.

Selected bond lengths (Å) and angles (deg): O-C(2) )

Figure 3. Thermal ellipsoid plot (30% probability) of

11bp‚OEt₂. The hydrogen atoms not involved in hydrogen

bonds and the molecule of Et₂O are omitted for clarity.

Selected bond lengths (Å) and angles (deg): Pd-C(3) )

2.0009(19), Pd-N(4) ) 2.0635(17), Pd-O(1) ) 2.0720(13),

Pd-N(3) ) 2.1632(16), O(1)-C(1) ) 1.264(2), N(1)-C(1)

) 1.342(2), N(1)-C(12) ) 1.437(2), N(2)-C(1) ) 1.349(2);

C(3)-Pd-N(4) ) 94.93(7), C(3)-Pd-O(1) ) 91.60(7), N(4)-

Pd-N(3) ) 85.24(6), O(1)-Pd-N(3) ) 88.39(6), C(1)-O(1)-

Pd ) 127.30(12).

1.2506(16), N(1)-C(2)

) 1.3623(18), N(1)-C(8A) )

1.3850(18), C(2)-C(3) ) 1.471(2), C(3)-C(4) ) 1.3735(18),

C(4)-C(4A) ) 1.454(2), C(4A)-C(8A) ) 1.406(2); C(2)-

N(1)-C(8A) ) 125.05(12), O-C(2)-N(1) ) 119.87(13),

O-C(2)-C(3) ) 123.44(13), N(1)-C(2)-C(3) ) 116.69(13),

C(4)-C(3)-C(2)

)

119.95(13), C(4)-C(3)-C(11)

)

122.59(13), C(2)-C(3)-C(11) ) 117.44(12), C(3)-C(4)-

C(4A) ) 120.84(13), C(3)-C(4)-C(21) ) 120.70(13), C(4A)-

C(4)-C(21) ) 118.43(12), C(8A)-C(4A)-C(5) ) 117.61(13),

C(8A)-C(4A)-C(4) ) 118.27(13), C(5)-C(4A)-C(4) )

124.11(13).

has a contact within the asymmetric unit from H(25)

to the ether oxygen, but this is rather long at 2.75 Å;

again, there are no C-H‚‚‚O < 2.6 Å. Compound 11bq

has one extremely short C(3)-H(3B)‚‚‚O5 interaction of

2.29 Å, which links the residues to form chains parallel

to [110], but no other C-H‚‚‚O < 2.57 Å. In 14po,

N-H‚‚‚O interactions lead to dimers, which are ar-

ranged in layers parallel to the xz plane at y ≈ 0, ¹/₂, 1;

the quinolone moieties are parallel to the layers, and

the phenyl substituents project between them.

The NHC(O)NH group in the palladium complexes

3b, 11bp, and 11bq shows a high degree of delocaliza-

tion. Thus, the C-NHC(O)NH-C systems are es-

sentially planar (mean deviation of non-H atoms e0.06

Å) and the C-N distances (range 1.338-1.352 Å) are

intermediate between single C-N (for example, 1.48 Å

in the tmeda ligands of the same complexes) and double

CdN (1.28 Å)⁴¹bond lengths. In PhNHC(O)NHPh the

(O)C-NH distances are similar (1.340, 1.358 Å) but the

C-O distance (1.233 Å)⁴²is shorter than in our com-

plexes (range 1.257(2)-1.264(2) Å) because of the O

coordination to Pd. There is no reported crystal struc-

ture of a metal complex containing an O-bonded ArN-

HC(O)NHAr (Ar ) aryl) ligand to compare with our

C-O(Pd) distancer, nor is there a crystal structure of

any palladium complex with an O-bonded urea ligand.

In complex 10, there is delocalization over the O-C-

N(1) (N(1)-C(10) ) 1.346(2), 1.3443(19) Å; cf. N(2)-

C(10) ) 1.455(2), 1.4410(19) Å) and carbene groups

(N(2)-C(50) ) 1.3585(19), 1.3541(18) Å; N(5)-C(50) )

1.323(2), 1.3197(19) Å).

Figure 4. Thermal ellipsoid plot (30% probability) of

11bq. Selected bond lengths (Å) and angles (deg): Pd-

C(18) ) 1.9997(11), Pd-O(1) ) 2.0388(9), Pd-N(1) )

2.0567(11), Pd-N(2)

1.3466(15), N(4)-C(28)

)

2.1416(10), N(3)-C(28)

1.3490(15), O(1)-C(28)

)

1.2595(14), O(2)-C(19) ) 1.2140(15); C(18)-Pd-O(1) )

90.34(4), C(18)-Pd-N(1) ) 96.18(5), O(1)-Pd-N(2) )

88.57(4), N(1)-Pd-N(2) ) 85.34(4).

cation through two N-H‚‚‚O hydrogen bonds involving

the two NH groups of the urea moiety of the cation and

two oxygen atoms of the triflate anion (details of the

hydrogen bonds may be found in the Supporting Infor-

mation). These interactions seem also to be present in

solution, as mentioned above. The crystal packing of 3b

also involves six C-H‚‚‚O interactions with H‚‚‚O_triflate

e 2.6 Å that may be regarded as hydrogen bonds.

Cations 1 (unprimed) and cations 2 (primed atom

The Pd-O bond distance in the palladium complex

3b or 11bq (range 2.0221(12)-2.0388(9) Å) is, surpris-

ingly, significantly shorter than in 11bp (2.0720(13) Å)

names) occupy the regions at y ≈ 0, /₂, 1 and /₄, /₄,

respectively, and are linked by the anions to form tubes

or layers. In 10‚0.5CDCl₃there is a Cl₃CD‚‚‚OdC

interaction to the second independent molecule, with a

short D‚‚‚O distance of 2.41 Å but a narrow angle of

124°; surprisingly, there are no short contacts from the

N-H groups and no C-H‚‚‚O < 2.6 Å. Compound 11bp

(41) Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen,

A. G.; Taylor, R. J. Chem. Soc., Perkin Trans. 2 1987, S1.

(42) Dannecker, W.; Kopf, J.; Rust, H. Cryst. Struct. Commun. 1979,

8, 429.

5056 Organometallics, Vol. 24, No. 21, 2005

Vicente et al.

Table 3. Crystallographic Data for Complexes 3b, 10‚0.5CDCl₃, 11bp‚OEt₂, 11bq, and 14po

10‚0.5CDCl₃

11bp‚OEt₂

11bq

14po

C₂₁H₁₅NO

formula

₂₁H₂₉F₃N₄O₄-

C_39.5H₄₀D_0.5Cl_1.5

N₅OPd

761.34

C₃₉H₄₉F₃N₄O₅-

PdS

849.28

0.20 × 0.16 × 0.11

monoclinic

P2₁/n

C₃₁H₃₇F₃N₄O₆-

PdS

757.11

PdS

M_r

596.94

297.34

cryst size (mm)

cryst syst

space group

cell constants

a, Å

0.36 × 0.28 × 0.08

monoclinic

P2₁/c

0.36 × 0.35 × 0.20

0.35 × 0.20 × 0.19

0.17 × 0.13 × 0.03

monoclinic

P2₁/c

triclinic

P1h

11.4308(6)

36.692(2)

12.6396(8)

103.788(4)

13.2337(9)

16.0883(9)

18.6439(11)

77.246(4)

74.208(4)

78.201(4)

3681.0

14.6886(12)

13.9976(12)

19.3570(16)

92.820(3)

11.2565(6)

12.1297(6)

12.7493(6)

96.519(4)

94.892(4)

105.625(4)

1653.34

12.494(2)

8.2559(14)

14.828(3)

93.018(8)

b, Å

c, Å

R, deg

â, deg

γ, deg

V, Å³

5148.5

3975.1

1527.4

λ, Å

0.71073

1.540

0.71073

1.374

0.71073

1.419

0.71073

1.521

0.71073

1.293

0.08

F(calcd), Mg m^-3

µ, mm^-1

0.86

0.65

0.58

0.69

F(000)

T, K

2432

1568

1760

776

624

133

2θ_max, deg

no. of rflns measd

no. of indep reflns

transmissn

R_int

52.7

108 507

15 062

0.74-0.93

0.050

77 572

21 464

0.79-0.89

0.033

81 564

11 642

0.87-0.96

0.045

32 571

9591

13 845

3127

0.81-0.93

0.019

0/429

no cor

0.051

0/212

0.0100

0.0391

0.98

no. of restraints/params

R_w(F²) (all rflns)

R(F) (>4σ(F))

6/639

1/923

121/491

0.0851

0.0314

1.01

0.0656

0.0275

0.98

0.0742

0.0274

1.05

0.0571

0.0208

1.04

max ∆F, e Å^-3

0.60

0.86

0.81

0.57

0.24

despite the similarities between these complexes and,

in particular, of the same ligand in a trans position. In

these three complexes, the tmeda N-Pd bond distance

trans to oxygen (range 2.0752(15)-2.0567(11) Å) is

shorter than that trans to carbon (range 2.1703(15)-

2.1416(10) Å) because of the greater trans influence of

the aryl or vinyl ligands.

Complexes 11bp‚Et₂O and 11bq (Figures 3 and 4)

show eight-membered palladacycles adopting a “boat”

conformation. In the case of 11bq, the crystal structure

confirms that the isolated isomer is that in which the

CCO₂Me moiety is attached to the palladium atom. The

crystal structure of 14po (Figure 5) exhibits a planar

disposition of the quinoline ring system. The bond

lengths and angles are similar to those of 2-quinolone

and some of its derivatives.⁴⁹Single crystals of 8t‚

0.7Et₂O and 2b were obtained and studied by X-ray

diffraction, supporting the suggested structures; how-

ever, the data could not be refined adequately because

of disorder phenomena.

The reported Pd-N distances in amido palladium

complexes are in the broad range 2.348-1.923 Å (mean

value 2.025 Å) because of the very different natures of

the ligands in trans positions.⁴³The Pd-N distances in

complex 10 (1.9968(13), 2.0037(12) Å) are in the range

of amido palladium complexes containing ligands with

little trans influence (Cl, imino (bpy or phen), or

amido).⁴⁴

Conclusions

Most of the data for trans-C-Pd^II-C_{CN -carbene}com-

plexes correspond to trans-“Pd(CN₂-carbene)₂” species.⁴³

We report the first ortho-palladated arylurea com-

plexes, obtained by oxidative addition reactions, and

have studied their reactivity toward different reagents.

Thus, with Tl(TfO) a cyclopalladated complex is formed

after coordination of the urea oxygen atom. The reaction

with CO gives the corresponding acyl derivative and, if

Tl(TfO) is added after the bubbling of CO, the C,N

coupling product 3-p-tolyl-1H-quinazoline-2,4-dione is

formed. Alkynes monoinsert, giving complexes that

decompose to result in indole derivatives, or react with

CO or XyNC, giving quinolone derivatives. Iminoacyl

complexes are obtained by reacting isocyanides with

The broad range of Pd-C_{CN carbene}distances in these

complexes (range 2.004⁴⁵- 2.137⁴⁶Å, mean value 2.045

Å) implies that they depend mainly on steric factors.

There are only a few such carbene complexes having

other carbon donor ligands, such as Me or π-allyl, in

trans positions; the corresponding range of Pd-C_{CN carbene}

distances (2.028⁴⁷-2.090⁴⁸Å, mean value 2.053 Å) lies

below that of our complex 10 (2.1045(15), 2.1029(15) Å).

(43) CSD version 5.25; CCDC, Dec 2004.

(44) See for example: Mazet, C.; Gade, L. H. Chem. Eur. J. 2003,

9, 1759. Paul, F.; Fischer, J.; Ochsenbein, P.; Osborn, J. A. Angew.

Chem., Int. Ed. 1993, 32, 1638. Khoury, R. G.; Senge, M. O.; Colchester,

J. E.; Smith, K. M. J. Chem. Soc., Dalton Trans. 1996, 3937. Vogel,

E.; Michels, M.; Zander, L.; Lex, J.; Tuzun, N. S.; Houk, K. N. Angew.

Chem., Int. Ed. 2003, 42, 2857. Liu, Q.; Thorne, L.; Kozin, I.; Song,

D.; Seward, C.; D’Iorio, M.; Tao, Y.; Wang, S. Dalton Trans. 2002, 3234.

Tian, G.; Boyle, P. D.; Novak, B. M. Organometallics 2002, 21, 1462.

(45) Grundemann, S.; Albrecht, M.; Loch, J. A.; Faller, J. W.;

Crabtree, R. H. Organometallics 2001, 20, 5485.

(47) Viciu, M. S.; Navarro, O.; Germaneau, R. F.; Kelly, R. A., III;

Sommer, W.; Marion, N.; Stevens, E. D.; Cavallo, L.; Nolan, S. P.

Organometallics 2004, 23, 1629.

(48) Douthwaite, R. E.; Green, M. L. H.; Silcock, P. J.; Gomes, P. T.

Dalton Trans. 2002, 1386.

(49) Chen, Y.-L.; Wang, T.-C.; Fang, K.-C.; Chang, N.-C.; Tzeng, C.-

C. Heterocycles 1999, 50, 453. Ribar, B.; Janic, I.; Kalman, A.; Argay,

G. Cryst. Struct. Commun. 1977, 6, 677. Kido, M.; Nakagawa, K. Chem.

Pharm. Bull. 1982, 30, 1488.

(46) Fehlhammer, W. P.; Bliss, T.; Kernbach, U.; Brudgam, I. J.

Organomet. Chem. 1995, 490, 149.

Ortho-Palladated Arylureas

Organometallics, Vol. 24, No. 21, 2005 5057

[Pd{C₆H₄NHC(O)NHTo-2}I(tmeda)]. The product of the

reaction with XyNC reacts with TlOTf to give the C,N

coupling product 4-(xylylimino)-3-p-tolyl-3,4-dihydro-

1H-quinazolin-2-one. An amido carbene C,N,C pincer

complex is obtained, which is a precatalyst in Heck and

Suzuki cross-coupling processes.

grateful to the Fundacio´n Se´neca (Comunidad

Auto´noma de la Regio´n de Murcia, Spain) for a grant.

Supporting Information Available: Text giving experi-

mental details of the preparation of 11be and 11bm, listings

of all refined and calculated atomic coordinates, anisotropic

thermal parameters, and bond lengths and angles, and CIF

files for 3b, 10‚0.5CDCl₃, 11bp‚Et₂O, 11bq, and 14po. This

material is available free of charge via the Internet at

http://pubs.acs.org.

Acknowledgment. We are grateful for the financial

support of the former Ministerio de Ciencia y Tecnolo-

g´ıa, FEDER (Grant No. BQU2001-0133). J.L.-S. is

OM050451Y

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Synthesis and reactivity of ortho-palladated arylureas. Synthesis and catalytic activity of a C,N,C pincer complex. Stoichiometric syntheses of some N-heterocycles

DOI: 10.1021/om050451y

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