ORGANIC

LETTERS

New Methodologies for the Oxidation of 2002

Vol. 4, No. 5
Fischer Carbene Complexes: Synthesis 827-830
of Hydrazides
Dario Perdicchia,*,† Emanuela Licandro,*,† Stefano Maiorana,†
Barbara Vandoni,† and Clara Baldoli‡

Dipartimento di Chimica Organica e Industriale, UniVersità degli Studi di Milano,

Via C. Golgi, 19, I-20133 Milan, Italy, and C.N.R. Centro Studio Sintesi e
Stereochimica di Speciali Sistemi Organici, Via C. Golgi, 19, I-20133 Milan, Italy
dario.perdicchia@unimi.it

Received January 2, 2002

ABSTRACT

We report new, high-yield methodologies for oxidizing Fischer carbenes, particularly hydrazinocarbene complexes. The reagents traditionally
used to oxidize Fischer carbenes have failed because of the stability of hydrazinocarbene complexes and the easy oxidation of formed
hydrazides in the reaction conditions. The three newly developed methodologies are very mild, fast, efficient, and complementary. Differently
functionalized hydrazinocarbene complexes can be oxidized to afford new hydrazides.

Many examples of synthetic applications of Fischer-type they are suitable substrates for metathesis reactions.4 In
carbene complexes have so far been reported.1 In general, connection with the last study, we became interested in the
the synthetic strategy consists of functionalizing the com- recovery of the organic ligand as hydrazide by means of the
plexes (also in a stereoselective manner) and then converting oxidation of hydrazinocarbene complexes.
them into organic compounds. Among the reported proce- Several methods have been reported to oxidize Fischer-
dures for the recovery of the organic ligand as a stable type alkoxy and amino carbene complexes, but there are
organic molecule, oxidation is the easiest and most efficient sometimes problems in terms of low yields (e.g., using
and converts the metal-carbon into the OdC bond. DMSO,5 oxone,5 ceric ammonium nitrate (CAN),5,6 PhIO,5
We have recently developed two complementary synthetic air7) or the formation of byproducts (e.g., using pyridine
methodologies to obtain hydrazinocarbene complexes2 and N-oxide (PNO),8 silica and air,9 wet silica and air,10 CAN5,9).
studied their reactivity.3 In particular, we have shown that
(3) Licandro, E.; Maiorana, S.; Perdicchia, D.; Baldoli, C.; Graiff, C.;
* E-mail for E.L.: emanuela.licandro@unimi.it. Tiripicchio, A. J. Organomet. Chem. 2001, 617-618, 399-411.
† University of Milan. (4) Licandro, E.; Maiorana, S.; Vandoni, B.; Perdicchia, D.; Paravidino,
‡ C.N.R. P.; Baldoli, C. Synlett 2001, 757-760.
(1) For recent reviews, see: (a) Barluenga, J. Pure Appl. Chem. 1999, (5) Ezquerra, J.; Pedregal, C.; Merino, I.; Florez, J.; Barluenga, J.; Garcia-
71, 1385-1391. (b) De Meijere, A.; Schirmer, H.; Duetsch, M. Angew. Granda, S.; Llorca, M. A. J. Org. Chem. 1999, 64, 6554-6565.
Chem., Int. Ed. 2000, 39, 3964-4002. (c) Sierra, M. A. Chem. ReV. 2000, (6) Quayle, P.; Rahman, S.; Ward, E. Lucy M.; Herbert, J. Tetrahedron
100, 3591-3637. (d) Barluenga, J.; Fananas, F. J. Tetrahedron 2000, 56, Lett. 1994, 35, 3801-3804.
4597-4628. (e) Herndon, J. W. Tetrahedron 2000, 56, 1257-1280. (f) (7) Licandro, E.; Maiorana, S.; Papagni, A.; Hellier, P.; Capella, L.;
Barluenga, J.; Florez, J.; Fananas, F. J. J. Organomet. Chem. 2001, 624, Persoons, A.; Houbrechts, S. J. Organomet. Chem. 1999, 583, 111-119.
5-17. (8) Barluenga, J.; Aznar, F.; Barluenga, S.; Fernandez, M.; Martin, A.;
(2) (a) Licandro, E.; Maiorana, S.; Manzotti, R.; Papagni, A.; Perdicchia, Garcia-Granda, S.; Pinera-Nicolas, A. Chem.-Eur. J. 1998, 4, 2280-2298.
D.; Pryce, M.; Tiripicchio, A.; Lanfranchi, M. Chem. Commun. 1998, 383- (9) Neidlein, R.; Gurtler, S. Synthesis 1995, 325-329.
384. (b) Licandro, E.; Maiorana, S.; Papagni, A.; Perdicchia, D.; Manzotti, (10) Aumann, R.; Schroeder, J.; Heinen, H. Chem. Ber. 1990, 123, 1369-
R.. Chem. Commun. 1999, 925-926. 1374.

10.1021/ol025504b CCC: $22.00 © 2002 American Chemical Society

Published on Web 01/31/2002
 Tetracarbonyl chelate hydrazinocarbene complexes such
as 1a are very stable toward air (several months are needed Table 1. Oxidation of Tetracarbonyl Hydrazinocarbene
for a complete oxidation of 1a into the hydrazide 2a3, Complexes 1b-e into Hydrazides 2b-e
Scheme 1), whereas the treatment of 1a with CAN affords

Scheme 1. First Attempts to Oxidize 1a

2a in only 30% yield, and DMSO or PNO give no reaction a Reaction conditions: room temperature, water/AcOEt ) 1/1. A: 3 equiv

at all. of Ca(OCl)2, 10 equiv of NaHCO3. B: 2 equiv of Ca(OCl)2, 10 equiv of

K2HPO4, 10 equiv of KH2PO4. b For the synthesis of complexes see ref 3;
Hydrazides are also known to be very sensitive to many for complexes 1 and 4 see Supporting Information.
oxidants, such as Pb(OAc)4, SeO2, DDQ, MnO2, NaNO2,11a
and CAN,11b,c and this could explain the low yield obtained
with CAN. Another potential drawback is that hydrazides bene complexes such as those arising from aldol16 (Table 1,
are neutral bidentate chelating ligands for transition metal entry 4) or Michael addition reactions (Table 2, entry 3),
cations12 and may coordinate the Cr(III) arising from the which could epimerize in basic medium.17 Under reaction
oxidation of the complexes or the Ce(III) formed from CAN, conditions, the Cr(III) gives insoluble salts and does not
thus making it difficult to isolate the hydrazides. A similar interfere with hydrazide extraction. This method was also
problem has been reported in the case of the oxidation of successfully used to oxidize hydrazino and amino pentac-
aminocarbene complexes13 with CAN. We therefore sought arbonylcarbene complexes 3, 5, and 7 (Scheme 2).
alternative and efficient oxidation methods for both tetra- The yields reported in Table 1 and Scheme 2 were
carbonyl and pentacarbonyl hydrazinocarbene complexes. generally very high, with the exceptions of entry 4 (Table
We now report three complementary oxidation methodolo-
gies using three different reagents. The first protocol is
reported in Table 1 and uses NaOCl or KOCl as the oxidizing Table 2. Oxidation of Tetracarbonyl Hydrazinocarbene
agents, slowly generated in situ from Ca(OCl)2 (which is Complexes Using in Situ Generated Iodine
not very soluble in the reaction medium), and NaHCO3 or a
phosphate buffer (Table 1).14,15
The reactions described in Table 1 are very fast (10 min
or less) in the presence of a catalytic amount of a quaternary
ammonium salt (Bu4NHSO4); otherwise, they are very slow.
The pH of the reactions performed with NaHCO3 (condition
A) was 8-9; it was around 7 with the phosphate buffer
(condition B). The use of a phosphate buffer was expressly
investigated in order to oxidize pH-sensitive hydrazinocar-

(11) (a) De Oliveira B. M. J. V.; Barrett, A. G. M.; Barton, D. H. R.;

Girijavallubhan, M.; Jennings, R. C.; Kelly, J.; Papadimitriou, V. J.; Turner,
J. V.; Usher, N. A. J. Chem. Soc., Perkin Trans. 1 1977, 1477-1500. (b)
Parrick, J.; Ragunathan, R. J. Chem. Soc., Perkin Trans. 1 1993, 211-216.
(c) Vedejs, E.; Kruger, A. W.; Lee, N.; Sakata, S. T.; Stec, M.; Suna, E. J.
Am. Chem. Soc. 2000, 122, 4602-4607.
(12) (a) Knapp, S.; Toby, Brian H.; Sebastian, M.; Krogh-Jespersen, K.;
Potenza, Joseph A. J. Org. Chem. 1981, 46, 2490-2497. (b) David, L.;
Rusu, M.; Cozar, O.; Rusu, D.; Todica, M.; Balan, C. J. Mol. Struct. 1999,
482-483, 149-152.
a Reaction conditions: water/AcOEt ) 1/1, 10 equiv of KH PO . A:
(13) Lluch, A. M.; Jordi, L.; Sanchez-Baeza, F.; Ricart, S.; Camps, F.; 2 4
Messeguer, A.; Moreto, Josep M. Tetrahedron Lett. 1992, 33, 3021-3022. 6.7 equiv of NaBO3‚4H2O, 10 mol % of KI. B: 5 equiv of NaBO3‚4H2O,
b
3 mol % of KI. For the synthesis of starting complexes see ref 3.
(14) This methodology ensures a low concentration of oxidant (NaOCl
or KOCl) in the reaction medium.

828 Org. Lett., Vol. 4, No. 5, 2002

 perborate. Entries 1 and 3 needed 2 h of stirring, 10 mol %
Scheme 2. Oxidation of Pentacarbonyl Carbene Complexes 3, of KI, and 6.7 equiv of perborate. However, pentacarbonyl
5, and 7a complexes 3 and 5 are not oxidized by this method. These
negative results could be in line with our hypothesis of the
reaction mechanism, outlined in Scheme 3. In the first step,

Scheme 3. Hypothesis of the Oxidation Mechanism

a Reaction conditions: 10 equiv of NaHCO , water/AcOEt )

3
1/1; (a) 4 equiv of Ca(OCl)2; (b) 3 equiv of Ca(OCl)2.

1) and complex 5 (Scheme 2) because the hydrazides 1e and

6 were unstable in the oxidative condition. We were
particularly interested in solving these two problems because
complex 1e (entry 4) and compound 5 are representative of
two classes of carbenes respectively arising from the aldol iodine attacks the metal of complex 1 displacing the nitrogen
addition and metathesis reactions4 studied in our laboratories. atom; this is not possible in the case of the pentacarbonyl-
We therefore turned our attention toward alternative oxidiz- carbene complexes 11 because, in the expected intermediate
ing reagents and set up a new method that uses the iodine 12, the metal would be seven-coordinated and carbonyl
generated in situ by the oxidation of KI with sodium chromium complexes, contrary to molybdenum and tungsten
perborate at pH 7 by the addition of 10 equiv of KH2PO418 complexes, have no tendency to show such coordination21
in the biphasic water/AcOEt system (Table 2). (except for very electron-rich complexes).19b,21a The oxidation
In this way, it is possible to modulate oxidation by varying of the pentacarbonylcarbene complexes 11 cannot take place
the amount of KI. This method is very mild because of the in these conditions. On the contrary, the addition of iodine
neutral condition and the small amount of free I219 and makes to tetracarbonylcarbene complexes 1 leads to the easy
possible the oxidation of the complex 1e in high yield (entry opening of the four-membered ring to give the intermediate
2, Table 2). Using this complex, only 5 min were enough to 9. Reductive elimination of the chromium tetracarbonyl unit
complete the reaction with 3 mol % of KI20 and 5 equiv of affords 10, which are hydrolyzed to give the final hydrazides
2. Iodine is regenerated by the oxidation of iodide with
(15) General Procedure. Oxidation of Complexes by Ca(OCl)2. A sodium perborate.
solution of the carbene complex (1 equiv) in ethyl acetate (10 mL for 3.7
mmol of complex) was added to an aqueous solution of NaHCO3 (10 equiv; Compounds similar to iodide 10 have been isolated as the
pH 8-9, Scheme 2 and Table 1, condition A) or K2HPO4/KH2PO4 (10 products of oxidation of diaminocarbene complexes of
equiv each; pH 7, Table 1, condition B) and tetrabutylammonium bisulphate
(TBAB; 5 mol %) in water (10 mL for 0.37 mmol of complex). Ca(OCl)2
(2 equiv at pH 7, condition B, 3 equiv at pH 8-9, condition A, 4 equiv (19) Only a few examples of the oxidation of group VI metal carbene
with complexes 3 and 5, Scheme 2) was added by stirring. After a few complexes by iodine have been reported. These complexes have in common
minutes the reaction was quenched with a Na2SO3 saturated aqueous solution the fact that they are very electron-rich as diaminocarbenes, metal acylates,
and extracted with diethyl ether (3 × 20 mL). The organic layer was and anions. (a) Lappert, Michael F.; Pye, Peter L. J. Chem. Soc., Dalton
collected, filtered on Celite, and dried over Na2SO4, and the solvent was Trans. 1977, 1283-1291. (b) Soderberg, Bjorn C.; Bowden, Brian A.
removed in vacuo to give the hydrazide as the only product and in high Organometallics 1992, 11, 2220-2223. (c) Liu, Shiuh-Tzung; Ku, Rong-
yield (exceptions are Table 1, entry 4 and Scheme 2, complex 5). Zhi; Liu, Chung-Yuan; Kang, Fu-Mei. J. Organomet. Chem. 1997, 543,
(16) (a) Licandro E.; Maiorana S.; Papagni A.; Capella L.; Perdicchia 249-250. (d) Fuchibe, Kohei; Iwasawa, Nobuharu. Tetrahedron 2000, 56,
D. Pure Appl. Chem. 1999, 71, 1453-1461. (b) Maiorana S.; Perdicchia 4907-4915.
D.; Vandoni B. Semin. Org. Synth., Summer Sch. “A. Corbella”, 25th, 2000, (20) With 10 mol % of KI, the yield was lower and many byproducts
139-164. were formed.
(17) We have achieved high diastereoselective Michael additions, e.g., (21) (a) Lewis, J.; Nyholm, R. S.; Pande, C. S.; Sandhu, S. S.; Stiddard,
the addition of 1d to chalcone and cyclohexenone gave a de g 92%. Results M. H. B. J. Chem. Soc. 1964, 3009-3012. (b) Ganorkar, M. C.; Stiddard,
to be published. M. H. B. J. Chem. Soc. 1965, 3494-3495. (c) Stumpf, R.; Jaeger, M.;
(18) For the experimental procedure see Supporting Information. Fischer, H. Organometallics 2001, 20, 4040-4048.

Org. Lett., Vol. 4, No. 5, 2002 829

 1.1 equiv of iodine as oxidant in a biphasic water/AcOEt
Scheme 4. Oxidation of Tetracarbonyl Hydrazinocarbene system and sodium bicarbonate.18 In this way, the reaction
Complexes: Third Methoda is very fast and completed in about 5 min. On the contrary,
with the catalytic amount of iodide described in Table 2,
the oxidation is too slow. In brief, we studied the oxidative
detachment of the metal on penta- and tetracarbonylhydra-
zinocarbene complexes and have developed three new
complementary methods of oxidation that cover a wide range
of hydrazinocarbene complexes. In particular, tetracarbonyl-
carbene can be oxidized with NaOCl or KOCl, and with I2
(generated in situ by KI or added as such), and pentacarbonyl
derivatives are oxidized by NaOCl.
The examples selected in this article are representative of
new classes of hydrazinocarbene complexes obtained in our
laboratory by means of aldol addition (Table 2, entry 2),
Michael addition (Table 2, entry 3), and metathesis reactions
(complex 15). Their transformation into the corresponding
organic isolobal hydrazides allows this chemistry to be
exploited for organic synthesis. In addition, we demonstrate
that the method using Ca(OCl)2 can be useful with different
Fischer-type carbene complexes such as aminocarbenes
(Scheme 2, complex 7).

Acknowledgment. The authors gratefully acknowledge

a Reaction conditions: water/AcOEt ) 1/1, 10 equiv of NaHCO3, joint financial support from the Ministero dell Istruzione,
1.1 equiv of iodine. b For the synthesis of the starting complexes
see ref 4.
dell ’UniVersitá e della Ricerca Scientifica (MIUR), Rome,
and the UniVersity of Milan (National project “Stereoselezi-
one in Sintesi Organica. Metodologie e Applicazioni), and
chromium19c and molybdenum19a with iodine. On the basis they also acknowledge the C.N.R. of Rome.
of the above considerations, it seems that the oxidation of
Supporting Information Available: Experimental details
the pentacarbonyl complexes 11 requires their initial conver-
and characterization data for the products and the complexes.
sion into the reactive tetracarbonyl complexes 1 by heating
This material is available free of charge via the Internet at
in dichloromethane at reflux3. However, we have observed
http://pubs.acs.org.
that complexes 13 and 154 (Scheme 4), and generally the
tetracarbonyl complexes with the morpholine residue, need OL025504B

830 Org. Lett., Vol. 4, No. 5, 2002