Ortho-palladation of (Z)-2-Aryl-4-Arylidene-5(4H)-oxazolones. structure and functionalization

Article abstract of DOI:10.1021/om901068f

Ortho-palladated complexes of (Z)-2-aryl-4-arylidene-5(4H)-oxazolones have been prepared through oxidative addition. The reaction of (Z)-2-phenyl-4-(2- bromobenzylidene)-5(4H)-oxazolone (4) with Pd₂(dba)₃ · CHCl₃ gives the six-membered cyclopalladated dinuclear complex [Pd(μ-Br)(o-C₆H₄CH=CNC(O)OCPh)]₂ (7). The reaction of 7 with PPh₃ gives dinuclear 9, which incorporates one phosphine per Pd atom through cleavage of the Pd-N bond, and preserves the bromide bridging system. However, reaction with PPh₂Me gives mononuclear 8, which incorporates two phosphines as a results of the cleavage of the μ-Br system and N displacement. In contrast, the reaction of 7 with pyridine gives complex 12 due to simple cleavage of the Br bridge, leaving the N-bonding intact. Therefore, three different reaction pathways have been characterized. The reactivity of the Pd-C bond in 7 has also been examined, and functionalized oxazolones can be obtained. The reaction of 7 with PhI(OAc)₂ in acetic acid gives the starting oxazolone C ₆H₄-2-Br-CH=CNC(O)OCPh (4), through the presumed oxidation of the Pd center and C-Br bond formation by reductive coupling. In contrast, the reaction of the acetate dlmer 14 with PhI(OAc)2 in acetic acid gives C ₆H₄-2-OAcCH=CNC(O)OCPh (20) through C-O coupling. When treatment of 7 with PhI(OAc)₂ is performed in MeOH or EtOH, the oxazolones C₆H₄-2-OR-CH=CNC(O)OCPh (R = Me (18), Et (19)) are obtained. The reaction of 7 with CO in alcohols ROH gives cleanly the oxazolones C₆H₄-2-CO₂RCH=CNC(O)OCPh (R = Me (21), ⁱPr (22)) through CO migratory insertion into the Pd-C bond and further nucleophilic attack of the RO^-fragment.

Full text of DOI:10.1021/om901068f

1428 Organometallics 2010, 29, 1428–1435
DOI: 10.1021/om901068f
Ortho-Palladation of (Z)-2-Aryl-4-Arylidene-5(4H)-Oxazolones.
Structure and Functionalization
Gheorghe-Doru Roiban,†,‡ Elena Serrano,§ Tatiana Soler,^ Maria Contel, Ion Grosu,†
Carlos Cativiela,‡ and Esteban P. Urriolabeitia*,§
†Organic Chemistry Department, Faculty of Chemistry and Chemical Engineering, Babes-Bolyai University,
‡
Arany Janos 11, 400028 Cluj-Napoca, Romania, Departamento de Quımica Organica, Instituto de Ciencia
´
ꢀ
de Materiales de Aragoꢀn, CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain, §Departamento de
ꢀ
ꢀ
Compuestos Organometalicos, Instituto de Ciencia de^Materiales de Aragon, CSIC-Universidad de
ꢀ
ꢀ
Zaragoza, c/Pedro Cerbuna 12, 50009 Zaragoza, Spain, Servicios Tecnicos de Investigacion, Facultad de
Ciencias Fase II, 03690 San Vicente de Raspeig, Alicante, Spain, and Chemistry Department, Brooklyn
College and The Graduate Center (CUNY), 2900 Bedford Avenue, Brooklyn, New York 11210
Received December 14, 2009
Ortho-palladated complexes of (Z)-2-aryl-4-arylidene-5(4H)-oxazolones have been prepared
through oxidative addition. The reaction of (Z)-2-phenyl-4-(2-bromobenzylidene)-5(4H)-oxazolone
(4) with Pd2(dba)3 CHCl3 gives the six-membered cyclopalladated dinuclear complex [Pd(μ-Br)-
3
(o-C6H4CHdCNC(O)OCPh)]2 (7). The reaction of 7 with PPh3 gives dinuclear 9, which incorporates
one phosphine per Pd atom through cleavage of the Pd-N bond, and preserves the bromide bridging
system. However, reaction with PPh2Me gives mononuclear 8, which incorporates two phosphines as
a results of the cleavage of the μ-Br system and N displacement. In contrast, the reaction of 7 with
pyridine gives complex 12 due to simple cleavage of the Br bridge, leaving the N-bonding intact.
Therefore, three different reaction pathways have been characterized. The reactivity of the Pd-C
bond in 7 has also been examined, and functionalized oxazolones can be obtained. The reaction of 7
with PhI(OAc)2 in acetic acid gives the starting oxazolone C6H4-2-Br-CHdCNC(O)OCPh (4),
through the presumed oxidation of the Pd center and C-Br bond formation by reductive coupling. In
contrast, the reaction of the acetate dimer 14 with PhI(OAc)2 in acetic acid gives C6H4-2-OAc-
CHdCNC(O)OCPh (20) through C-O coupling. When treatment of 7 with PhI(OAc)2 is performed
in MeOH or EtOH, the oxazolones C6H4-2-OR-CHdCNC(O)OCPh (R = Me (18), Et (19)) are
obtained. The reaction of 7 with CO in alcohols ROH gives cleanly the oxazolones C6H4-2-CO2R-
CHdCNC(O)OCPh (R = Me (21), iPr (22)) through CO migratory insertion into the Pd-C bond
and further nucleophilic attack of the RO- fragment.
Introduction
processes. Other applications have focused on their use in
optical devices, biological applications, and other interesting
properties.1 The most important method for the synthesis of
ortho-palladated complexes is C-H bond activation,1-3
mainly at an aromatic ring. This reaction has been exten-
sively studied, since it is a fundamental step in the catalytic or
stoichiometric ortho functionalization of a large diversity of
Ortho-palladated complexes1 are considered to be useful
reagents in a variety of chemical transformations, most of
them being Pd-mediated catalytic or stoichiometric organic
*To whom correspondence should be addressed. Fax: (þ34)
976761187. E-mail: esteban@unizar.es.
(1) Urriolabeitia, E. P. in Palladacycles: Synthesis, Characterization
and Applications; Dupont, J., Pfeffer, M. Eds.; Wiley-VCH: Weinheim,
Germany, 2008; Chapter 3: Oxidative Addition and Transmetallation.
(2) Selected recent reviews on ortho palladation: (a) Dupont, J.;
Consorti, C.; Spencer, J. Chem. Rev. 2005, 105, 2527. (b) Yu, J.-Q.; Giri,
R.; Chen, X. Org. Biomol. Chem. 2006, 4, 4041. (c) Fairlamb, I. J. S. Chem.
Soc. Rev. 2007, 36, 1036. (d) Omae, I. J. Organomet. Chem. 2007, 692,
2608. (e) Nishiyama, H. Chem. Soc. Rev. 2007, 36, 1133. (f) Gagliardo, M.;
Snelders, D. J. M.; Chase, P. A.; Klein Gebbink, R. J. M.; van Klink, G. P. M.;
van Koten, G. Angew. Chem., Int. Ed. 2007, 46, 8558. (g) Horino, Y. Angew.
Chem., Int. Ed. 2007, 46, 2144. (h) Ma, L.; Wong, E. L.-M.; Che, C.-M.
Dalton Trans. 2007, 4884. (i) Chatani, N. In Directed Metallation; Springer:
New York, 2007; Topics in Organometallic Chemistry 24. (j) Leis, W.; Mayera,
H. A.; Kaska, W. C. Coord. Chem. Rev. 2008, 252, 1787. (k) Djukic, J. P.;
Hijazi, A.; Flack, H. D.; Bernardinelli, G. Chem. Soc. Rev. 2008, 37, 406.
(l) Djukic, J. P.; Sortais, J. B.; Barloy, L.; Pfeffer, M. Eur. J. Inorg. Chem.
2009, 817. (m) Albrecht, M. Chem. Rev. 2010, 110, 576. (n) Lyons, T. W.;
Sanford, M. S. Chem. Rev. 2010, 110, 1147.
(3) Selected recent reviews on CH bond activation and applications:
(a) Godula, K.; Sames, D. Science 2006, 312, 67. (b) Dick, A. R.; Sanford,
M. S. Tetrahedron 2006, 62, 2439. (c) Deprez, N. R.; Sanford, M. S. Inorg.
Chem. 2007, 46, 1924. (d) Alberico, D.; Scott, M. E.; Lautens, M. Chem.
Rev. 2007, 107, 174. (e) Park, Y. J.; Park, J.-W.; Jun, C.-H. Acc. Chem. Res.
2008, 41, 222. (f) Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013.
(g) Thansandote, P.; Lautens, M. Chem. Eur. J. 2009, 15, 5874. (h) Chen,
X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48,
5094. (i) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res. 2009, 42,
1074. (j) Giri, R.; Shi, B.-F.; Engle, K. M.; Maugel, N.; Yu, J.-Q. Chem. Soc.
Rev. 2009, 38, 3242. (k) Storr, T. E.; Baumann, C. G.; Thatcher, R. J.;
De Ornellas, S.; Whitwood, A. C.; Fairlamb, I. J. S. J. Org. Chem. 2009, 74,
5810. (l) Zhang, M. Adv. Synth. Catal. 2009, 351, 2243. (m) Vedernikov,
~
A. N. Chem. Commun. 2009, 4781. (n) Muniz, K. Angew. Chem., Int. Ed.
2009, 48, 9412. (o) Roger, J.; Gottumukkala, A. L.; Doucet, H. ChemCat-
Chem 2010, 2, 20. (p) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem.
Rev. 2010, 110, 624. (q) Bellina, F.; Rossi, R. Chem. Rev. 2010, 110, 1082.
r
pubs.acs.org/Organometallics
Published on Web 02/22/2010
2010 American Chemical Society

Article
Organometallics, Vol. 29, No. 6, 2010 1429
Scheme 1.a
We present here the synthesis of ortho-palladated unsatu-
rated 5(4H)-oxazolones. These compounds are relevant
organic precursors and intermediates in the preparation of
heterocyclic compounds of pharmacological interest, more
specifically in the synthesis of amino acids.17 Saturated
5(4H)-oxazolones are easily obtained from N-acylamino
acids, and they have been used in coupling reactions as
synthetic equivalents of R-amino acids in the synthesis of
peptides. Asymmetric alkylation reactions have been reported
in the enantioselective synthesis of acyclic R,R-quaternary
amino acids.18 Unsaturated 5(4H)-oxazolones have been
known for years. Many applications have been found for
these compounds, and the reactivity of the exocyclic double
bond makes them especially attractive intermediates for the
asymmetric synthesis of non-proteinogenic amino acids.19 In
spite of the extensive chemistry developed with 5(4H)-oxazo-
lones, ortho-metalated complexes are restricted to Ir and Pd
examples with saturated precursors,20 while metalated un-
saturated 5(4H)-oxazolones are unknown. Only very recently
have we reported21a the first example of ortho palladation of
unsaturated 5(4H)-oxazolones.
Due to the interest in unsaturated 5(4H)-oxazolones as
strategic intermediates, we have studied the ortho pallada-
tion of a special class of oxazolones, namely the (Z)-2-aryl-4-
arylidene-5(4H)-oxazolones. Our aim was to provide an
alternative synthetic route to their functionalization, com-
plementary to classical organic methods. We have recently
employed this strategy for the successful functionalization of
R-amino acids.21b Gratifyingly, we have found in the present
case that the regioselective modification of the ortho position
of the arylidene ring in oxazolones is easily achievable. This
fact could provide a selective reaction path to high added
value modified amino acids that are not easily prepared by
conventional methods.
a R1 = Br, R2 = H (4), R1 = H, R2 = Br (5), R1 = H, R2 = I (6).
organic substrates.2-16 The C-H bond activation-
functionalization methodology allows the formation of a
wide range of C-X bonds (X = C, O, N, S, P, halogen),
and the regiospecific addition of a large number of func-
tional groups to a given substrate has been achieved. In this
context, methyl,4 acetate and/or methoxy,5 arylsulfonyl,6
ethoxycarbonyl,7 halogen,8 amide9 or amine,10 alkynyl,11
alkenyl,12 acyl,13 and aryl14 functional groups, as well as
intramolecular cyclization processes15 and mechanistic
studies,16 have been reported.
(4) (a) Chen, X.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006,
128, 12634. (b) Giri, R.; Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.;
Saunders, L. B.; Yu, J.-Q. J. Am. Chem. Soc. 2007, 129, 3510.
(5) (a) Desai, L. V.; Malik, H. A.; Sanford, M. S. Org. Lett. 2006, 8,
1141. (b) Desai, L. V.; Stowers, K. J.; Sanford, M. S. J. Am. Chem. Soc.
2008, 130, 13285. (c) Powers, D. C.; Geibel, M. A. L.; Klein, J. E. M. N.;
Ritter, T. J. Am. Chem. Soc. 2009, 131, 17050.
(6) Zhao, X.; Dimitrijevic, E.; Dong, V. M. J. Am. Chem. Soc. 2009,
131, 3466.
(7) Yu, W. Y.; Sit, W. N.; Lai, K. M.; Zhou, Z.; Chan, A. S. C. J. Am.
Chem. Soc. 2008, 130, 3304.
(8) (a) Wang, X.; Mei, T.-S.; Yu, J.-Q. J. Am. Chem. Soc. 2009, 131,
7520. (b) Li, J. J.; Mei, T. S.; Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47,
6452. (c) Whitfield, S. R.; Sanford, M. S. J. Am. Chem. Soc. 2007, 129,
15142. (d) Hull, K. L.; Anani, W. Q.; Sanford, M. S. J. Am. Chem. Soc. 2006,
128, 7134. (e) Powers, D. C.; Ritter, T. Nat. Chem. 2009, 1, 302.
(9) (a) Thu, H.-Y.; Yu, W.-Y.; Che, C.-M. J. Am. Chem. Soc. 2006,
ꢀ
128, 9048. (b) Houlden, C. E.; Bailey, C. D.; Ford, J. G.; Gagne, M. R.; Lloyd-
Jones, G. C.; Booker-Milburn, K. I. J. Am. Chem. Soc. 2008, 130, 10066.
(10) Dick, A. R.; Remy, M. S.; Kampf, J. W.; Sanford, M. S.
Organometallics 2007, 26, 1365.
Results and Discussion
(11) Tobisu, M.; Ano, Y.; Chatani, N. Org. Lett. 2009, 11, 3250.
(12) (a) Rauf, W.; Thompson, A. L.; Brown, J. M. Chem. Commun.
2009, 3874. (b) Lee, G. T.; Jiang, X.; Prasad, K.; Repic, O.; Blacklock, T. J.
Adv. Synth. Catal. 2005, 347, 1921.
(13) Jia, X.; Zhang, S.; Wang, W.; Luo, F.; Cheng, J. Org. Lett. 2009,
11, 3120.
1. Synthesis of the 5(4H)-Oxazolones. Our first step was to
find the reactive positions of the oxazolones, since two aryl
rings can be palladated. Surprisingly, the simplest case
(Scheme 1, R1 = R2 = H)22 showed a total lack of reactivity
(14) (a) Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 9651.
ꢀ
´
(b) Liegault, B.; Lapointe, D.; Caron, L.; Vlassova, A.; Fagnou, K. J. Org.
(17) (a) Cativiela, C.; Dıaz-de-Villegas, M. D. In The Chemistry of
Heterocyclic Compounds; Palmer, D. C., Ed.; Wiley: New York, 2004; Vol.
60, p 129. (b) Fisk, J. S.; Mosey, R. A.; Tepe, J. J. Chem. Soc. Rev. 2007, 36,
1432. (c) Boyd, G. V. In Comprehensive Heterocyclic Chemistry; Potts,
K. T., Ed.; Pergamon Press: Oxford, U.K., 1984; Vol. 6, pp 177-234.
(d) Hartner, F. W., Jr. In Comprehensive Heterocyclic Chemistry II; Shinkai,
I., Ed.; Pergamon Press: Oxford, U.K., 1996; Vol. 3, p 261. (e) Rao, Y. S.;
Filler, R. Oxazoles. In The Chemistry of Heterocyclic Compounds; Turchi,
I. J., Ed.; Wiley: New York, 1986; Vol. 45, p 363.
Chem. 2009, 74, 1826. (c) Campeau, L. C.; Schipper, D. J.; Fagnou, K.
J. Am. Chem. Soc. 2008, 130, 3266. (d) Hull, K. L.; Sanford, M. S. J. Am.
Chem. Soc. 2007, 129, 11904. (e) Lafrance, M.; Gorelsky, S. I.; Fagnou, K.
J. Am. Chem. Soc. 2007, 129, 14570. (f) Daugulis, O.; Zaitsev, V. G. Angew.
Chem., Int. Ed. 2005, 44, 4046. (g) Lazareva, A.; Daugulis, O. Org. Lett.
2006, 8, 5211. (h) Shabashov, D.; Daugulis, O. Org. Lett. 2006, 8, 4947.
(i) Daugulis, O.; Zaitsev, V. G.; Shavashov, D.; Pham, Q. N.; Lazareva, A.
Synlett 2006, 3382. (j) Scarborough, C. C.; McDonald, R. I.; Hartmann, C.;
Sazama, G. T.; Bergant, A.; Stahl, S. S. J. Org. Chem. 2009, 74, 2613.
(k) Zhou, H.; Chung, W.-J.; Xu, Y.-H.; Loh, T.-P. Chem. Commun. 2009,
3472. (l) Zhou, H.; Xu, Y.-H.; Chung, W.-J.; Loh, T.-P. Angew. Chem., Int.
Ed. 2009, 48, 5355. (m) Watanabe, T.; Oishi, S.; Fujii, N.; Ohno, H. J. Org.
Chem. 2009, 74, 4720. (n) Kalyani, D.; Deprez, N. R.; Desai, L. V.; Sanford,
M. S. J. Am. Chem. Soc. 2005, 127, 7330. (o) Hull, K. L.; Lanni, E. L.;
Sanford, M. S. J. Am. Chem. Soc. 2006, 128, 14047.
(18) (a) Mosey, R. A.; Fisk, J. S.; Friebe, T. L.; Tepe, J. J. Org. Lett.
2008, 10, 825. (b) Cabrera, S.; Reyes, E.; Aleman, J.; Milelli, A.; Kobbelgaard,
S.; Jorgensen, K. A. J. Am. Chem. Soc. 2008, 130, 12031.
(19) (a) Cativiela, C.; Dı
metry 1998, 9, 3517. (b) Cativiela, C.; Díaz-de-Villegas, M. D. Tetrahedron:
Asymmetry 2000, 11, 645. (c) Cativiela, C.; Díaz-de-Villegas, M. D.
Tetrahedron: Asymmetry 2007, 18, 569. (d) Cativiela, C.; Ordonez, M.
ꢀ
e
´
az-de-Villegas, M. D. Tetrahedron: Asym-
ꢀ~
(15) (a) Tsang, W. C. P.; Zheng, N.; Buchwald, S. L. J. Am. Chem.
Tetrahedron: Asymmetry 2009, 20, 1.
~
Soc. 2005, 127, 14560. (b) Muniz, K. J. Am. Chem. Soc. 2007, 129, 14542.
(20) (a) Bauer, W.; Prem, M.; Polborn, K.; Suenkel, K.; Steglich, W.;
Beck, W. Eur. J. Inorg. Chem. 1998, 485. (b) Bauer, W.; Polborn, K.; Beck,
W. J. Organomet. Chem. 1999, 579, 269. (c) Skapski, A. C.; Smart, M. L.
J. Chem. Soc., Chem. Commun. 1970, 658.
(21) (a) Roiban, D.; Serrano, E.; Soler, T.; Grosu, I.; Cativiela, C.;
Urriolabeitia, E. P. Chem. Commun. 2009, 4681. (b) Nieto, S.; Arnau, P.;
Serrano, E.; Navarro, R.; Soler, T.; Cativiela, C.; Urriolabeitia, E. P. Inorg.
Chem. 2009, 48, 11963.
(c) Wu, L.; Qiu, S.; Liu, G. Org. Lett. 2009, 11, 2707. (d) Yamashita, M.;
Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2009, 11, 2337. (e) Joyce, L. L.;
Batey, R. A. Org. Lett. 2009, 11, 2792. (f) Xiao, Q.; Wang, W.-H.; Liu, G.;
Meng, F.-K.; Chen, J.-H.; Yang, Z.; Shi, Z.-J. Chem. Eur. J. 2009, 15, 7292.
(g) Murai, M.; Miki, K.; Ohe, K. Chem. Commun. 2009, 3466.
(16) (a) Dick, A. R.; Kampf, J. W.; Sanford, M. S. J. Am. Chem. Soc.
2005, 127, 12790. (b) Racowski, J. M.; Dick, A. R.; Sanford, M. S. J. Am.
Chem. Soc. 2009, 131, 10974. (c) Hull, K. L.; Sanford, M. S. J. Am. Chem.
Soc. 2009, 131, 9651. (d) Deprez, N. R.; Sanford, M. S. J. Am. Chem. Soc.
2009, 131, 11234.
(22) (a) King, S. W.; Riordan, J. M.; Holt, E. M.; Stammer, C. H.
J. Org. Chem. 1982, 47, 3270. (b) Hamidian, H.; Tikdari, A. M. Heterocycl.
Commun. 2006, 12, 29.

1430 Organometallics, Vol. 29, No. 6, 2010
Roiban et al.
Scheme 2. Synthesis of 7a
Scheme 3.a
a Reagents and conditions: CH2Cl2 or toluene, room temperature,
24 h, Ar.
toward the most usual palladating reagents (Pd(OAc)2, Li2-
[PdCl4], etc.) under standard conditions.21a Looking for
alternative methods, we focused our attention on oxidative
addition processes,1 for which halogen-substituted (Z)-2-
aryl-4-arylidene-5(4H)-oxazolones had to be prepared
(Scheme 1, 4-6).
Compounds 4-6 were synthesized by the Erlenmeyer
reaction.23 This method involves the condensation of N-benzoyl-
glycine with a carbonyl compound, in the presence of a
cyclodehydrating agent such as acetic anhydride. While 1 is
commercially available, N-2-bromobenzoylglycine24 (2) and
N-2-iodobenzoylglycine25 (3) had to be prepared (Supporting
Information). Although two geometric isomers are possible
for 4-6, the Erlenmeyer synthesis proceeds stereoselectively,
favoring the thermodynamically more stable Z isomer, which
is easily isolated by recrystallization.26a,b Additional argu-
ments are referenced to mass spectra26c and to previous
determinations of X-ray molecular structures of related oxa-
zolones.27
a Reagents and conditions: (i) PPh2Me, CH2Cl2, room temperature;
(ii) PPh3, CHCl3, room temperature; (iii) PPh3, MeOH, Δ; (iv) PPh3,
MeOH, Δ; (v) Tl(acac), CHCl3, room temperature, 2 h.
Scheme 4.a
2. Synthesis of Six-Membered Palladacycles. The reaction
of 4 with Pd2(dba)3 CHCl328 gives the dinuclear complex 7,
3
as depicted in Scheme 2. The reaction occurs under very mild
conditions, affording high yields of 7, which is isolated as a
greenish yellow solid. The mass spectrum of 7 is in good
agreement with a dimeric structure, the most abundant
ion being the protonated molecule which loses a bromide
[M - Br]þ at m/z 788.9. The lack of solubility of 7 precludes
its characterization in solution by NMR methods, but
the evidence of its dimeric nature was obtained from its
reactivity, shown in Schemes 3 and 4.
The reaction of 7 with PPh2Me (1:2 molar ratio) failed to
give a unique reaction product. An increase in the molar
ratio 7:PPh2Me (1:4.5) gives a single compound, character-
ized as 8 (Scheme 3). The 1H NMR spectrum of 8 suggests a
monomeric structure in which the two phosphine ligands are
(23) Erlenmeyer, E. Ber. Dtsch. Chem. Ges. 1900, 33, 2036.
(24) (a) Raiford, L. C.; Buurman, C. H. J. Org. Chem. 1943, 8, 466.
(b) Novello, N. J.; Miriam, S. R.; Sherwin, C. P. J. Biol. Chem. 1926, 67, 555.
ꢀ
(25) (a) Barcelo-Oliver, M.; Terron, A.; Garcia-Raso, A.; Molins, E.
ꢀ
Polyhedron 2007, 26, 1417. (b) Barcelo-Oliver, M.; Garcia-Raso, A.; Terron,
ꢀ
ꢀ
A.; Molins, E.; Prieto, M. J.; Moreno, V.; Martinez, J.; Llado, V.; Lopez, I.;
ꢀ
Gutierrez, A.; Escriba, P. V. J. Inorg. Biochem. 2007, 101, 649. (c) Barcelo-
ꢀ
Oliver, M.; Terron, A.; Garcia-Raso, A.; Fiol, J. J.; Molins, E.; Miravitlles, C.
J. Inorg. Biochem. 2004, 98, 1703.
(26) (a) Kumar, K.; Phelps, D. J.; Careg, P. R. Can. J. Chem. 1978, 56,
232. (b) Prokofev, E. P.; Kapeiskaya, E. I. Tetrahedron Lett. 1979, 20, 737.
(c) Curcuruto, O.; Traldi, P.; Cativiela, C.; Díaz-de-Villegas, M. D.; Garcia,
J. I.; Mayoral, J. A.; Ajo, D. J. J. Heterocycl. Chem. 1990, 27, 1495.
(27) (a) Haasbroek, P. P.; Oliver, D. W.; Carpy, A. M. J. J. Mol.
Struct. 2003, 648, 61. (b) Busetti, V.; Mayoral, J. A.; Cativiela, C.; Díaz-de-
Villegas, M. D.; Ajo, D. Z. Kristallogr. 1989, 189, 65. (c) Bowden, K.;
Perjessy, A.; Benko, J.; Fabian, W. M. F.; Kolehmainen, E.; Melikian, G. S.;
Hritzova, O.; Laihia, K.; Vollarova, O.; Tapuzian, V. O.; Kiriakossian, N.;
Nissinen, M. J. Chem. Res. (S) 2002, 7, 309.
a Reagents and conditions: (i) py, CH2Cl2, room temperature; (ii) py,
MeOH, room temperature; (iii) CH3COOAg, CH2Cl2, 12 h, room
temperature; (iv) AgClO4, CH3CN.
mutually trans, since the methyl protons appear as triplets,
due to virtual coupling (JPH = 3.4 Hz), and the oxazolone is
η1-coordinated. However, the reaction of 7 with PPh3 in a 1:2
(28) Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J. J.; Ibers, J. A.
J. Organomet. Chem. 1974, 65, 253.

Article
Organometallics, Vol. 29, No. 6, 2010 1431
Figure 1. Molecular drawing of 9. Selected bond distances (A)
and angles (deg): Pd(1)-C(1), 2.007(6); Pd(1)-P(1), 2.249(5);
Pd(1)-Br(1A), 2.522(6); Pd(1)-Br(1), 2.5582(15); C(1)-
Pd(1)-P(1), 88.52(19); C(1)-Pd(1)-Br(1A), 87.72(18); P(1)-
Pd(1)-Br(1A), 175.28(5); C(1)-Pd(1)-Br(1), 173.01(17);
P(1)-Pd(1)-Br(1), 96.52(10); Br(1A)1-Pd(1)-Br(1), 87.47(8);
Pd(1A)1-Br(1)-Pd(1), 92.53(8).
Figure 2. Molecular drawing of 14. Selected bond distances (A)
and angles (deg): Pd(1)-C(1), 1.9741(16); Pd(1)-N(1), 2.0378(14);
Pd(1)-O(3), 2.0455(11); Pd(1)-O(4), 2.1268(11); C(1)-Pd(1)-
N(1), 91.71(6); C(1)-Pd(1)-O(3), 90.49(6); N(1)-Pd(1)-O(3),
177.42(5); C(1)-Pd(1)-O(4), 172.16(5); N(1)-Pd(1)-O(4),
95.54(5); O(3)-Pd(1)-O(4), 82.34(5).
found that it is stable toward the bonding of harder ligands,
such as acetylacetonate (acac), acetate, acetonitrile, and
pyridine. Therefore, 7 reacts with Tl(acac) (1:2 molar ratio)
to give the acetylacetonate 11 (Scheme 3). On the other hand,
the reaction of 7 with pyridine (1:2 molar ratio) produces
the clean cleavage of the bromide bridge affording 12
(Scheme 4). The py bonding trans to the N atom of the
oxazolone is inferred from the anisotropic shielding of the
molar ratio affords the unique soluble product 9, character-
ized by X-ray methods. A drawing of the molecular structure
and selected bond distances and angles of 9 are shown in
Figure 1. The structure shows a dimeric skeleton in which
two Pd atoms are bridged by two bromides, forming a Pd2-
(μ-Br)2 moiety. Each Pd center completes its coordination
sphere by bonding to a phosphine and to a η1-aryl ligand. The
connectivity in this structure is noteworthy, since it contains
simultaneously a bromide bridging system and a potential C,
N-chelating ligand. This means that the incoming phosphine
promotes the displacement of the N atom of the oxazolone
instead to the cleavage of the Pd(μ-Br)2Pd bridge. Conse-
quently, the stabilization by chelating effect of the palladated
oxazolone should be small, probably indicating a weak bond-
ing of the N to the Pd atom. This reactivity of ortho-palladated
dimers toward L ligands (1:2 molar ratio) is unprecedented,
since it is well established that the reaction of ortho-palladated
halide-bridged dimers [Pd(μ-X)(C∧N)]2 with neutral mono-
dentate ligands L affords mononuclear [PdX(C∧N)L] species,
through symmetrical cleavage of the bridge, where the L ligand
is trans to the N atom.29 The oxazolone ligand is normal to the
coordination plane, this fact being shown by the dihedral angle
between the best least-squares planes defined by the Pd(1)-
P(1)-Br(1) atoms and all atoms contained in the oxazolone
(89.53(15)ꢀ). Other parameters do not show deviations with
respect to reported values in similar structures.30
00
H6 signal, this only being possible if the oxazolone acts as a
chelate ligand and, therefore, lies in the molecular plane. An
additional argument in favor of the mononuclear structure
of 12 comes from a comparison of the diffusion coefficients
of 11 and 12. Diffusion ordered spectroscopy (DOSY) has
proved to be a valuable tool for the determination of relative
molecular sizes in solution.32 The D (m2 s-1) value for 11
(acac as ancillary ligand, assumed as mononuclear) is 8.94 ꢀ
10-10 (2 mM, CDCl3, 300 K, δ = 2.3 ms, Δ = 100 ms). This
value fits very well with that determined for complex 12
(8.59 ꢀ 10-10 m2 s-1), measured under the same experimen-
tal conditions, suggesting the same nuclearity in both cases. 7
reacts with excess py under harsher conditions (MeOH, Δ),
giving 13 through dimer cleavage, bonding of two pyridines
to each Pd, and opening of the oxazolone ring through
methanolysis.
The metathesis of the bromide ligands by acetate, achieved
by reaction of 7 with AgOAc (1:2 molar ratio), gives the
dimer 14, characterized by X-ray diffraction. Figure 2 shows
a molecular drawing of 14 and the most relevant bond
distances and angles. As is clear from the structure shown
in Figure 2, each Pd atom is bonded to the N(1) atom and
to the ortho benzylidenic C(1) atom of the oxazolone,
and two ortho-palladated oxazolones are connected by two
bridging acetate ligands in an “open-book” arrangement.33
The cleavage of the bromide bridge in 7, affording mono-
mer 10, occurred under harsher conditions, when excess
PPh3 was added to 7 (1:4 molar ratio) and the mixture was
refluxed in methanol for 1 h. Complex 10 can also be
obtained in two steps by further treatment of 9 with PPh3
(1:2 molar ratio) in refluxing methanol.
While the chelation of the palladated oxazolone is not
retained with the addition of soft phosphine ligands, we have
ꢀ
(31) Fornies, J.; Martı
´
nez, F.; Navarro, R.; Urriolabeitia, E. P.
J. Organomet. Chem. 1995, 495, 185.
ꢀ
(32) (a) Pregosin, P. S.; Anil Kumar, P. G.; Fernandez, I. Chem. Rev.
2005, 105, 2977. (b) Antalek, B. Concepts Magn. Reson. 2002, 14, 225.
(c) Hodge, P.; Monvisade, P.; Morris, G. A.; Preece, I. Chem. Commun.
2001, 239.
(29) Deeming, A. J.; Rothwell, I. P.; Hursthouse, M. B.; New, L.
J. Chem. Soc., Dalton Trans. 1978, 1490.
(30) (a) Orpen, A. G.; Brammer, L.; Allen, F. H.; Kennard, O.;
Watson, D. G.; Taylor, R. J. Chem. Soc., Dalton Trans. 1989, S1.
(b) Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen, A. G.;
Taylor, R. J. Chem. Soc., Perkin Trans. 2 1987, S1.
(33) Gorunova, O. N.; Keuseman, K. J.; Goebel, B. M.; Kataeva,
N. A.; Churakov, A. V.; Kuz’mina, L. G.; Dunina, V. V.; Smoliakova,
I. P. J. Organomet. Chem. 2004, 689, 2382.

1432 Organometallics, Vol. 29, No. 6, 2010
Roiban et al.
Figure 3. Molecular drawing for 15. Selected bond distances
(A) and angles (deg): Pd(1)-C(1), 1.991(3); Pd(1)-N(2),
2.000(2); Pd(1)-N(1), 2.024(2); Pd(1)-N(3), 2.120(2); C(1)-
Pd(1)-N(1), 90.27(10); C(1)-Pd(1)-N(2), 89.06(10); N(2)-
Pd(1)-N(1), 175.30(9); C(1)-Pd(1)-N(3), 173.48(9); N(2)-
Pd(1)-N(3), 87.72(9); N(1)-Pd(1)-N(3), 92.46(8).
Figure 4. Molecular drawing for 17. Selected bond distances
(A) and angles (deg): Pd(1)-C(1), 1.994(5); Pd(1)-P(1),
2.3306(13); Pd(1)-P(2), 2.3389(12); Pd(1)-I(1), 2.6682(5);
C(1)-Pd(1)-P(1), 85.51(13); C(1)-Pd(1)-P(2), 88.56(13);
P(1)-Pd(1)-I(1), 90.54(3); P(2)-Pd(1)-I(1), 94.41(3).
The relative disposition of the two palladated oxazolones is
anti, in order to minimize intramolecular interactions.
The open-book structure forces the two Pd centers to be in
close proximity, and the Pd(1)-Pd(1A) distance in 14 is
2.9357(8) A, a value shorter than the sum of the van der
Waals radii (3.26 A).34 Other parameters fall in the usual
ranges found in the literature.30
Scheme 5.a
Finally, the reaction of 7 with AgClO4 (1:2 molar ratio) in
NCMe gives the unstable bis-solvate 15, as depicted in
Scheme 4. The spectroscopic data obtained for 15 are con-
sistent with the proposed formula,35 and additional informa-
tion is provided by its X-ray structure determination. A
molecular drawing and selected bond distances and angles
for 15 are shown in Figure 3. The structure shows a mono-
nuclear complex in which the Pd atom is bonded to a C,N-
chelated oxazolone and to two acetonitriles. The oxazolone
shows a boat conformation, with a dihedral angle between
the best least-squares planes defined by N(1)-Pd(1)-C(1)
and C(6)-C(7)-C(8) of 34.71(3)ꢀ. The Pd(1)-N(2)
(2.000(2) A) and Pd(1)-N(3) bond lengths (2.120(2) A) are
quite different, due to the large trans influence of the aryl
carbon, compared with that of the iminic N(1), although
both of them are within the range reported for related
situations.30,36 Other internal parameters of the ligand are
as expected.
a Reagents and conditions: (i) Pd2(dba)3 CHCl3, PPh3, CHCl3, room
temperature, 2 h; (ii) PPh3, CHCl3, room temperature, 10 min.
3
to iodide 6 (Scheme 1). Iodide-containing substrates are the
best choice to attempt an oxidative addition, as has been
previously outlined.37 Under these conditions, 6 reacts with
Pd2dba3 and PPh3 (2:1:8 molar ratio), giving the insoluble
yellow greenish solid 16, whose plausible structure is shown
in Scheme 5. Complex 16 was insoluble in common solvents,
making its solution characterization unfeasible. Therefore,
the structure is proposed by analogy with 9 (the N atom is not
bonded in the presence of phosphines) and by subsequent
reactivity. In fact, treatment of 16 with PPh3 (1:4 molar ratio)
in CHCl3 affords soluble 17 through a typical cleavage of a
halide bridging system. The X-ray structure determination of
17 confirmed the proposal shown in Scheme 5. Figure 4 gives
a molecular drawing and collects selected bond distances
and angles. The structure shows the usual distorted-square-
planar environment for the Pd(II) center. The Pd atom is
3. Attempts To Prepare Five-Membered Palladacycles.
We have shown that the oxidative addition is an efficient
method to prepare ortho-palladated derivatives from oxa-
zolones incorporating the metal at the benzylidene ring.
Therefore, we have also attempted the preparation of five-
membered rings using the same strategy. Initial treatment of
(Z)-2-(2-bromophenyl)-4-benzylidene-5(4H)-oxazolone (5)
with [Pd2(dba)3 CHCl3] gave unreacted oxazolone and
3
black Pd. This was somewhat unexpected, since the oxidative
addition products of 4 were successfully prepared. There-
fore, we modified slightly our strategy by changing the
starting Pd source to [Pd(PPh3)4] and the starting oxazolone
(34) Bondi, A. J. Phys. Chem. 1964, 68, 441.
(35) Jensen, R. S.; Umeda, K.; Okazaki, M.; Ozawa, F.; Yoshifuji, M.
J. Organomet. Chem. 2007, 692, 286.
(36) Adrian, R. A.; Broker, G. A.; Tiekink, E. R. T.; Walmsley, J. A.
(37) (a) Roy, A. M.; Hartwig, J. F. Organometallics 2004, 23, 194.
ꢀ
Inorg. Chim. Acta 2008, 361, 1261.
(b) Alcazar-Roman, L. M.; Hartwig, J. F. Organometallics 2002, 21, 491.

Article
Organometallics, Vol. 29, No. 6, 2010 1433
bonded to the C(1) of the 2-phenyl group of the oxazolone, to
the terminal iodine I(1), and to the phosphorus P(1) and P(2)
atoms, the last two atoms being mutually trans. The dis-
tribution of the ligands is in good agreement with the
antisymbiotic effect shown by the Pd atom38 and with the
reluctance of the phosphines to be coordinated trans to
the aryl group or transphobia.39
Scheme 6.a
4. Functionalization Processes: Formation of C-C, C-O,
and C-Br Bonds. As has been described in the Introduction,
a wide prospect of synthetic tools based on ortho palladation
can be used to regioselectively functionalize organic sub-
strates. One of the most successful methods is based on
oxidative coupling processes, which have been extensively
studied. There is at the present time an exciting controversy
about the mechanism of some of these reactions, namely
halogenation, acetoxylation, and alkoxylation processes,
due to the plausible involvement of transient species of
Pd(III)5c,8e and/or Pd(IV)3h,n as active species. These studies
involve detailed mechanistic determinations,16b-d and these
processes have still not shown all their chemical potentiality.
One of the most popular oxidants used in these oxidative
couplings are iodine(III) reagents, due to their low toxicity
and milder reaction conditions in comparison with other
oxidants,40 characteristics which confer them a great potential
for the functionalization of cyclometalated complexes.3b,c,5,41
We have successfully used these reagents on the functionaliza-
tion of R-amino acids.21b
a Reagents: (i) PhI(OAc)2/AcOH; (ii) PhI(OAc)2/ROH; (iii) CO/
ROH, -Pd0.
Scheme 7. Synthesis of Compound 20
With the aim of introducing acetate groups at the ortho
position of the oxazolone, and in accord with previous
observations,5 complex 7 was reacted with excess PhI(OAc)2
in acetic acid as solvent. Surprisingly, the reaction takes a
different path and the o-bromobenzylidene compound 4
was obtained instead in 50% yield after the usual workup
(see Scheme 6). The characterization of 4 as the reaction
product was performed by comparison with an authentic
sample prepared through conventional Erlenmeyer meth-
ods.42 The formation of 4 from 7 cannot be the result of direct
reductive elimination on the Pd(II) derivative 7, since that
would mean that the reverse of oxidative addition has
occurred. This reaction is not possible on thermodynamic
grounds, since the spontaneous reaction is the formation of 7
from Pd(0). Moreover, Pd(0) should be formed and we did
not detect the presence of black palladium. Therefore, the
presence of the oxidant is critical in this process. In order to
explain the formation of 4 from 7, it is sensible to assume that
the reaction starts by oxidation of the Pd(II) center to
Pd(IV),19b-d with concomitant incoporation of the acetate
fragments (structure A; Scheme S1 in the Supporting
Information). What is important in structure A is that there
are simultaneously a bromide and at least one acetate cis to
the Pd-C bond, both ligands being able to undergo reduc-
tive elimination. The final synthesis of 4 means that C-Br
reductive elimination is favored over C-O bond formation.
Since the only source of bromine in the starting reagents
consists of the bromide bridges present in 7, we reasoned that
the simple change of bromide bridges to acetate bridges
should lead, under the same reaction conditions, to the
oxazolone being incorporated ortho to the acetate group.
In fact, reaction of 14 with excess PhI(OAc)2 in acetic acid
gives the ortho-functionalized oxazolone [C6H4-2-OAc-
CHdCNC(O)OCPh] (20) through oxidation of Pd(II)
to Pd(IV) and subsequent reductive elimination by C-O
coupling (Scheme 7). Compound 20 has been previously
reported,43 but it was not fully characterized (see the Sup-
porting Information). It is also worthy of note that the
resulting functionalized oxazolones (4 and 20) do not remain
bonded to the Pd center after the reductive coupling step, as
occurs in other substrates previously reported.21b Therefore,
the isolation of the pure free compounds is considerably
simpler. This fact could be related to the low bonding ability
of the iminic N atom, as has been stated in preceding
paragraphs (sections 2 and 3), and avoids the use of phenan-
throline to liberate the modified materials.21b
(38) (a) Pearson, R. G. Inorg. Chem. 1973, 12, 712. (b) Pearson, R. G.
J. Chem. Educ. 1968, 45, 581. (c) Davies, J. A.; Hartley, F. R. Chem. Rev.
1981, 81, 79.
(39) (a) Vicente, J.; Abad, J. A.; Frankland, A. D.; Ramırez de
´
Arellano, M. C. J. Chem. Soc., Chem. Commun. 1997, 959. (b) Vicente,
J.; Arcas, A.; Bautista, D.; Jones, P. G. Organometallics 1997, 16, 2127.
(c) Vicente, J.; Abad, J. A.; Frankland, A. D.; Ramírez de Arellano, M. C.
Chem. Eur. J. 1999, 5, 3066. (d) Vicente, J.; Abad, J. A.; Martínez-Viviente,
E.; Jones, P. G. Organometallics 2002, 21, 4454. (e) Vicente, J.; Arcas, A.;
Bautista, D.; Ramírez de Arellano, M. C. J. Organomet. Chem. 2002, 663,
ꢀ
~
164. (f) Bartolome, C.; Espinet, P.; Vicente, L.; Villafane, F.; Charmant,
J. P. H.; Orpen, A. G. Organometallics 2002, 21, 3536. (g) Vicente, J.; Arcas,
ꢀ
ꢀ
ꢀ
ꢀ
A.; Galvez-Lopez, M. D.; Julia-Hernandez, F.; Bautista, D.; Jones, P. G.
Organometallics 2008, 27, 1582.
Using the same experimental methodology, the reaction of 7
with excess PhI(OAc)2 in MeOH or EtOH gives the oxazo-
lones [C6H4-2-OR-CHdCNC(O)OCPh] (OR = OMe (18),
(40) (a) Wirth, T. Angew. Chem., Int. Ed. 2005, 44, 3656. (b) Merritt,
E. A.; Olofsson, B. Angew. Chem., Int. Ed. 2009, 48, 9052.
(41) Welbes, L. L.; Lyons, T. W.; Cychosz, K. A.; Sanford, M. S.
J. Am. Chem. Soc. 2007, 129, 5836.
(42) Mesaik,M.A.;Rahat,S.;Khan,K.M.;Zia-Ullah,C.;Muhammad,
I.; Murad, S.; Ismail, Z.; Rahman, A.; Aqeel, A. Bioorg. Med. Chem. 2004,
12, 2049.
(43) (a) Kirby, G. W.; Michael, J.; Narayanaswami, S. J. Chem. Soc.,
Perkin Trans. 1 1972, 2003. (b) Neuberger, A. Biochem. J. 1948, 43, 599.
(c) Erlenmeyer, E.; Stadlin, W. Justus Liebigs Ann. Chem. 1904, 337, 283.

1434 Organometallics, Vol. 29, No. 6, 2010
Roiban et al.
OEt (19)), respectively.44 In these cases, the expected products
derived from the incorporation of the methoxide or the
ethoxide fragments are obtained, in spite of the competing
presence of bromide and acetate groups. The lower yield of 19
(about 9%) compared with that of 18 (42%) is probably
related to the ease of formation of the methoxide anion and
its incorporation in the putative Pd(IV) intermediate, in
comparison with the ethoxide anion, due to the slightly higher
acidity of methanol. An additional proof is that 2-propanol
does not react at all with 7 and excess PhI(OAc)2 at room
temperature, and again, compound 4 is obtained due to
oxidation of the Pd(II) center in 7 and subsequent competing
reductive elimination and formation of the C-Br bond.
Once we had seen that oxazolones could be ortho-functio-
nalized by formation of new C-Br and C-O bonds, we
attempted the formation of new C-C bonds. The reaction of
7 with CO (1 atm) in the alcoholic medium ROH (methanol
or 2-propanol) results in the synthesis of [C6H4-2-CO2R-
position of the aromatic ring involves an advantageous
alternative to the direct synthesis of the oxazolone ring using
an ortho-substituted benzaldeyhde. This is due to the some-
times difficult availability of the appropriate ortho-substi-
tuted benzaldehyde and to the evident low yields in the
condensation reaction due to steric reasons. The synthesis
of the modified 5(4H)-oxazolones open the way to the
synthesis of new families of interesting compounds and, in
particular, of modified phenylalanines with a great variety of
substituents in the ortho position of the phenyl ring.
Experimental Section
Safety Note. Caution! Perchlorate salts of metal complexes
with organic ligands are potentially explosive. Only small
amounts of these materials should be prepared, and they should
be handled with great caution.46
General Methods. Details are as previously reported
(Supporting Information).21b Pd2(dba)3 CHCl3 was prepared
3
i
by following literature methods.28 The starting amides 2 and 3
were synthesized by previously described methods.24,25 Oxazo-
lone 4 was synthesized as reported,42 while 547 and 647b were
mentioned in the literature but their characterization data were
not provided.
CHdCNC(O)OCPh] (CO2R = CO2Me (21), CO2 Pr (22))
by incorporation of the CO2R functional group at the ortho
position of the oxazolone. This carbonylation process occurs
under very mild reaction conditions, avoiding the use of high
pressure or special devices, and represents an easy way to
introduce the carboxylate moiety, which is a useful synthetic
building block.7 The mechanism of this reaction is comple-
tely different from that proposed for the synthesis of 18-20,
since Pd(II)/Pd(0) species are involved in this case. It is
assumed (Supporting Information, Scheme S2) that the
initial step is the coordination of the CO ligand which, once
bonded, undergoes nucleophilic attack of the methoxide
anion, forming an acyl species. The final reductive elimina-
tion by C-C coupling gives the free modified oxazolones 21
and 22. Interestingly, the acidity of 2-propanol is enough to
promote the formation of the acyl intermediate. This fact
suggests that a broad scope of carboxylates, coming from
alcohols with similar acidity, is accessible through this
method.
Synthesis of 7. Pd2(dba)3 CHCl3 (0.300 g, 0.328 mmol) and 4
3
(0.163 g, 0.655 mmol) were suspended in toluene or CH2Cl2
(30 mL) under an Ar atmosphere, and this deep violet mixture
was stirred at 25 ꢀC for 24 h. The resulting suspension was
centrifugated, and the solid obtained was washed two times with
CH2Cl2 (20 mL) and Et2O (10 mL) to afford 7 as a green solid
(yield 0.248 g, 87%). IR: ν 1784 cm-1 vs (CdO), 1633 cm-1 vs
(CdN). MS (MALDIþ) m/z (relative intensity, %): 788.9
(100%) [M - Br]þ. Anal. Calcd for C32H20Br2N2O4Pd2: C,
44.22; H, 2.32; N, 3.22. Found C, 44.48; H, 2.65; N, 3.67.
Synthesis of 8. To a stirred suspension of 7 (0.231 g, 0.266
mmol) in CH2Cl2 (10 mL), under an Ar atmosphere, was added
PPh2Me (0.212 g, 1.058 mmol). The initial suspension gradually
dissolved. After it was stirred for 1 h at 25 ꢀC, the resulting
solution was filtered through Celite and evaporated to afford 8
1
as a yellow solid (yield 0.256 g, 76%). H NMR (400 MHz,
CDCl3) δ: 1.80 (t, J = 3.4 Hz, 6H, 2CH3), 6.60 (t, 3J = 7.3 Hz,
3
1H, H5 ), 6.75 (t, J = 7.5 Hz, 1H, H4 ), 7.09 (d, J = 6.4 Hz,
3
Conclusion
00
00
00
1H, H6 ), 7.19-7.34 (m, 12H, 4Ho-PPh Me
, 8Hm-PPh Me),
2
2
7.40-7.44 (m, 8H, Ho,Hp-PPh Me), 7.50 (t, 3J = 7.5 Hz, 2H,
A series of new ortho-metalated palladium complexes
of (Z)-2-aryl-4-arylidene-5(4H)-oxazolones were prepared
through oxidative addition. Palladation has been achieved
at both the 4-benzylidene and the 2-phenyl rings, the former
giving six-membered rings. The stability of these pallada-
cycles is strongly dependent on the neighboring ligands.
Soft ligands such as phosphines afford η1(C) bonding for
the 4-benzylidene ring, while with hard (acetate, acetyl-
acetonate) or borderline ligands (pyridine, NCMe) the
4-benzylidene group can coordinate in an stable C,N-chelat-
ing fashion. However, palladation at the 2-phenyl ring only
affords η1-aryl complexes. The reactivity of oxazolones
metalated at the 4-benzylidene ring toward soft oxidants
[PhI(OAc)2] affords the ortho-functionalized free oxazo-
lones [C6H4-2-FG-CHdCNC(O)OCPh] (FG = functional
group) under mild conditions. Different functional groups
can be introduced at the oxazolone skeleton by modification
of the solvent, the ancillary ligands at the Pd center, or the
reaction conditions. Then, the methodology presented here
allowing the introduction of the substituent at the ortho
2
3
0
0
0
00
H3 , H5 ), 7.54-7.59 (m, 1H, H4 ) 7.72 (s, 1H, H7 ), 8.10 (d, J =
7.2 Hz, 2H, H2 , H6 ), 8.18 (d, J = 8.0 Hz, 1H, H3 ). 31P NMR
3
0
0
00
(162 MHz, CDCl3) δ: 7.29 (s, 2P, 2PPh2CH3).
Synthesis of 9. Complex 9 was prepared by following the same
procedure as was reported for 8. Therefore, 7 (0.159 g, 0.183
mmol) was reacted with PPh3 (0.096 g, 0.366 mmol) in CH2Cl2
(10 mL) to give 9 as a yellow solid (yield 0.217 g, 85%). 1H NMR
00
00
(400 MHz, CDCl3) δ: 6.78-6.89 (m, 2H, H4 , H5 ), 7.10-7.39
00
(m, 6H, Hm-PPh ), 7.37-7.65 (m, 13H, 6Ho-PPh , 3Hp-PPh , H6 ,
3
3
3
3
0
0
0
0
0
H3 , H4 , H5 ), 8.12-8.16 (m, 2H, H2 , H6 ), 8.30 (d, J = 7.30 Hz,
1H, H3 ), 8.58 (s, 1H, H7 ). 31P NMR (162 MHz, CDCl3) δ:
24.04 (s, PPh3).
00
00
Synthesis of 14. To a suspension of 7 (0.258 g, 0.297 mmol) in
10 mL of CH2Cl2 was added silver acetate (0.149 g, 0.893 mmol).
The suspension changed from greenish to reddish brown. This
suspension was stirred overnight at 25 ꢀC with exclusion of light.
After the reaction time the suspension was filtered through
Celite and the reddish solution was evaporated to dryness,
(45) Nagase, S. Nippon Kagaku Zasshi 1960, 81, 309.
(46) Wolsey, W. C. J. Chem. Educ. 1973, 50, A335.
(47) (a) Grimshaw, J.; Hamilton, R.; Trocha-Grimshaw, J. J. Chem.
Soc., Perkin Trans. 1 1982, 229. (b) Palcut, M.; Benko, J.; Mueller, N.;
Hritzova, O.; Vollarova, O.; Melikian, G. S. J. Chem. Res. Synop. 2004, 10,
649.
(44) (a) Rao, I. S. J. Org. Chem. 1976, 41, 722. (b) Avenoza, A.; Busto,
J. H.; Cativiela, C.; Peregrina, J. M. Synthesis 1995, 671. (c) Buck, J. S.;
Baltzly, R.; Richard, W. S. J. Am. Chem. Soc. 1938, 60, 1789.

Article
Organometallics, Vol. 29, No. 6, 2010 1435
2
(s, 1H, H7 ), 7.40 (t, 1H, J = 8.1 Hz, H5 ), 7.48 (td, 1H, J =
3
affording 14 as a red solid (yield 0.204 g, 83%). 1H NMR
00
00
2
00 0 0
1.7 Hz, H4 ), 7.54 (t, 2H, J = 7.8 Hz, H3 , H5 ), 7.63 (tt, 1H,
(400 MHz, CDCl3) δ: 1.04 (s, 3H, CH3), 7.15-7.25 (m, 2H,
4
4
H4 , H5 ), 7.31 (dd, 3J = 7.3 Hz, J = 2.0 Hz, 1H, H6 ),
J = 1.3 Hz, H4 ), 8.18 (dd, 2H, H2 , H6 ), 8.93 (dd, 1H, H6 ).
Synthesis of 21. The synthesis of 21 has been reported
previously, but it was not fully characterized (Supporting
Information).45 A suspension of 7 (0.130 g, 0.150 mmol) in
methanol (10 mL) was stirred under a CO atmosphere for 14 h.
During this time, a clear decomposition was observed. After the
reaction time the black suspension was filtered through a plug of
Celite to remove Pd(0), and the resulting yellow solution was
evaporated to dryness. The residue was dissolved in dichloro-
methane (15 mL), the light suspension was filtered through a
pad of Celite, and the resulting yellow solution was evaporated
to dryness in vacuo to afford 21 as a pale yellow solid (yield 39.1
mg, 43.1%). 1H NMR (400 MHz, CDCl3): δ 3.47 (s, 3H, OMe),
00
00
00
0
0
0
00
3
00
0
0
00
7.38-7.45 (m, 3H, H3 , H3 , H5 ), 7.49 (s, 1H, H7 ), 7.55 (t, J =
3
7.2 Hz, 1H, H4 ), 7.85 (d, J = 7.3 Hz, 2H, H2 , H6 ).
0
0
0
Reactivity of 7 with PhI(OAc)2. Synthesis of 4. To a suspension
of 7 (0.160 g, 0.185 mmol) in AcOH (10 mL) was added
PhI(OAc)2 (0.248 g, 0.74 mmol). The resulting brown mixture
was stirred for 16 h at room temperature, affording an orange
suspension which was filtered, giving a solid and a solution
which were treated separately. The solid obtained is a mixture in
which 4 can be identified. This solid was dissolved in CH2Cl2
(3 mL), the solution was washed with H2O (5 mL), and the
organic phase was dried on anhydrous MgSO4, filtered, and
evaporated to dryness to afford 4 was as a pale yellow solid
(30.1 mg). On the other hand, the orange solution was evapo-
rated to dryness. The residue was dissolved in chloroform
(17 mL) and the solution washed with 10% Na2SO3 (4 ꢀ
10 mL) and with saturated NaCl solution (3 ꢀ 10 mL). The
organic phase was dried on anhydrous MgSO4, filtered, and
evaporated to dryness. The yellow residue was purified by silica
gel chromatography using ethyl acetate/hexane (2:8) as eluent.
The yellow band was collected and evaporated to dryness,
yielding 4 as a pale yellow solid (29.8 mg) (total yield 50%).
These solids were characterized as 4 by comparison of their
spectral data with those of an authentic sample.
Synthesis of 18. The synthesis and characterization of 18 have
been reported previously.44a,b PhI(OAc)2 (0.229 g, 0.693 mmol)
was added to a suspension of 7 (0.152 g, 0.173 mmol) in MeOH
(15 mL), and the mixture was stirred for 18 h at room tempera-
ture. After the reaction time the brown-orange solution was
evaporated to dryness. The brown-yellow residue was purified
by as described for 4 by CHCl3 solution, washing with Na2SO3
and brine, and silica gel chromatography using ethyl acetate/
hexane (1:9) as eluent. The yellow band was collected and
evaporated to dryness, giving 18 as a yellow solid (yield
41.2 mg, 42%).
0
0
0
00
7.40-7.42 (m, 3H, H4 , H3 , H5 ), 7.44 (s, 1H, H7 ), 7.61-7.68
2
(m, 3H, H2 , H6 , H5 ), 7.79 (d, 2H, J = 4.7 Hz, H4 , H3 ), 8.42
0
0
00
00
00
2
(d, 1H, J = 8.0 Hz, H6 ).
00
Synthesis of 22. Compound 22 was prepared similarly to 21,
starting from 7 (0.138 g, 0.160 mmol) and CO (1 atm) in
2-propanol (12 mL). The mixture was stirred for 16 h at room
temperature and filtered through a plug of Celite, and the
resulting orange solution was evaporated to dryness. The
residue was purified by silica gel chromatography using ethyl
acetate/hexane (3:8) as eluent. The colorless band was collected
and evaporated to dryness, affording the compound 22 as a
white solid (yield 40.1 mg, 37.4%). 1H NMR (400 MHz,
3
3
CDCl3): δ 1.24 (d, 3H, J = 6.2 Hz, CH3), 1.38 (d, 3H, J =
0
0
0
6.1 Hz CH3), 3.99 (m, CH), 7.39-7.40 (m, 3H, H4 , H3 , H5 ),
00
0
4
0
00
7.42 (s, 1H, H7 ), 7.61-7.67 (m, 3H, H2 , H6 , H5 ), 7.78 (m, 2H,
3
00
00
00
H4 , H3 ), 8.41 (dd, 1H, J = 8.0 Hz, J = 0.7 Hz, H6 ).
X-ray Crystallography. Crystals of adequate quality for X-ray
measurements were grown by slow diffusion of Et2O into
CH2Cl2 (14, 17) or CHCl3 solutions (9, 15) of the crude products
at 25 ꢀC. A single crystal of each compound (dimensions in
Table 1 in the Supporting Information) was mounted at the end
of a quartz fiber in a random orientation, covered with magic oil,
and placed under the cold stream of nitrogen. Data collection
was performed at room temperature or low temperature (150 K)
on an Oxford Diffraction Xcalibur2 diffractometer using gra-
phite-monochromated Mo KR radiation (λ = 0.710 73 A). A
hemisphere of data was collected on the basis of three ω-scan or
j-scan runs. The diffraction frames were integrated using the
program CrysAlis RED,48 and the integrated intensities were
corrected for absorption with SADABS.49 The structures were
solved and developed by Patterson and Fourier methods.50 The
structures were refined to Fo2, and all reflections were used in the
least-squares calculations.51
Synthesis of 19. The synthesis of 19 has been reported,44c but a
complete characterization was not reported (Supporting
Information). Compound 19 was prepared similarly to 18,
starting from 7 (0.152 g, 0.173 mmol) and PhI(OAc)2 (0.231 g,
0.717 mmol) in ethanol (25 mL). The orange-brown residue
was purified by silica gel chromatography using ethyl acetate/
hexane (2:8) as eluent. The yellow band was collected and
evaporated to dryness, giving compound 19 as a yellow solid
(yield 10.7 mg, 9.2%). 1H NMR (400 MHz, CDCl3): δ 1.50 (t,
3H, 3J = 7.0 Hz, CH3), 4.14 (q, 2H, OCH2), 6.92 (d, 1H, 2J =
2
4
00
8.4 Hz, H3 ), 7.09 (t, 1H, J = 8.1 Hz, H5 ), 7.42 (td, 1H, J =
00
2
1.6 Hz, H4 ), 7.54 (t, 2H, J = 7.8 Hz, H3 , H5 ), 7.68 (t, 1H, H4 ),
00
0
0
0
4
7.90 (s, 1H, H7 ), 8.17 (dd, 2H, J = 1.4 Hz, H2 , H6 ), 8.89 (dd,
00
0
0
Acknowledgment. Funding from CNCSIS 92/2004,
PNII Idei 515, and Idei 570 (Romania), the Ministerio
4
1H, J = 1.7 Hz, H6 ).
00
Synthesis of 20. The synthesis of 20 has been reported
previously, but it was not fully characterized (Supporting
Information).43 PhI(OAc)2 (0.191 g, 0.58 mmol) was added to
a suspension of 14 (0.191 g, 0.58 mmol) in AcOH (6 mL). The
resulting mixture was stirred for 18 h at room temperature, and
the brown-orange solution was evaporated to dryness. The
resulting residue was dissolved in chloroform (17 mL) and
washed with Na2SO3 10% (4 ꢀ 10 mL) and with saturated
NaCl solution (3 ꢀ 10 mL). The organic phase was dried on
anhydrous MgSO4, filtered, and evaporated to dryness. The
yellow residue was purified by silica gel chromatography using
ethyl acetate/hexane (3:8) as eluent. The yellow band was
collected and evaporated to dryness, giving 20 as a yellow solid
ꢀ
de Ciencia e Innovacion (Projects CTQ2008-01784 and
CTQ2007-62245, Spain), and Gobierno de Aragon
(PI071-09) is gratefully acknowledged.
ꢀ
Supporting Information Available: Figures and text giving a
complete experimental section with all preparative details and
tables and CIF files giving complete data collection parameters
for 9, 14, 15, and 17. This material is available free of charge via
the Internet at http://pubs.acs.org.
(48) CrysAlis RED, Version 1.171.27p8; Oxford Diffraction Ltd., 2005.
(49) Sheldrick, G. M. SADABS: Empirical Absorption Correction
€
€
Program; University of Gottingen, Gottingen, Germany, 1996.
1
(yield 50.2 mg, 56.5%). H NMR (400 MHz, CDCl3): δ 2.42
(50) Sheldrick, G. M. SHELXS-86. Acta Crystallogr. 1990, A46, 467.
(51) Sheldrick, G. M. SHELXL-97. Acta Crystallogr. 2008, A64, 112.
2
(s, 3H, CH3), 7.18 (dd, 1H, J = 8.1 Hz, J = 1.2 Hz, H3 ), 7.36
3
00