Nitrido ruthenium porphyrins: Synthesis, characterization, and amination reactions with hydrocarbon or silyl enol ethers

Article abstract of DOI:10.1002/anie.200390111

An unprecedented synthetic strategy was used for the preparation of nitrido ruthenium(VI) porphyrins such as 1. The structure of 1 features a Ru-N (nitrido) distance of 1.656(5) A. Reactions of nitrido ruthenium(VI) porphyrins with silyl enol ethers or indan, in the presence of trifluoroacetic anhydride, afforded N-trifluoroacetyl amines in up to 84% yield.

Full text of DOI:10.1002/anie.200390111

Communications
Aminations with Ru Porphyrins
derwent NCOCF3 group transfer with cis-cyclooctene to give
an aziridine product.[8a] Subsequent works by Carreira and co-
workers demonstrate that several nitrido manganese Schiff
base complexes can be activated with TFAA and undergo
NCOCF3 group transfer with silyl enol ethers, glycols, and
styrene to afford amination or aminohydroxylation pro-
ducts.[8b e] Recently, Komatsu and co-workers reported asym-
metric aziridination of alkenes and asymmetric amination of
silyl enol ether with chiral nitrido manganese Schiff base
complexes upon (p-MeC6H4SO2)2O or TFAA activation.[8f]
Surprisingly, all the aziridination/amination reactions of
nitrido metal complexes have to date been confined to nitrido
complexes of manganese, although numerous nitrido com-
plexes of other transition metals have been reported.[9] The
amination by nitrido manganese Schiff base complexes only
Nitrido Ruthenium Porphyrins: Synthesis,
Characterization, and Amination Reactions with
Hydrocarbon or Silyl Enol Ethers**
Sarana Ka-Yan Leung, Jie-Sheng Huang, Jiang-
Lin Liang, Chi-Ming Che,* and Zhong-Yuan Zhou
Ruthenium porphyrins constitute an unmatched family of
metalloporphyrin that exhibits extraordinary versatility in
binding N-donating ligands at the axial sites.[1 A wide
5]
ꢀ
variety of ruthenium porphyrins featuring axial Ru N bonds
have been prepared, including those bearing amine,[1c,3a,3b]
d,g]
e,g,j]
amido,[3b
imido,[3a,c
imine,[3h,4] methyleneamido,[3h] ni-
occurred for unsaturated C H bonds. No nitrido metallopor-
ꢀ
trile,[1a,2] hydrazido,[3f] nitrosoarene,[1b,3i] nitrosyl,[5] and dini-
trogen[1d] axial ligands (Scheme 1, a j). This makes the lack of
phyrins have been found to undergo C-H insertion reactions
to afford amination products.
Herein we report the syntheses and amination reactions of
nitrido ruthenium(vi) porphyrins [RuVI(por)(N)(OH)] (1a:
por¼ tmp, 1b: por¼ 3,4,5-MeO-tpp; see Scheme 2).[10] These
nitrido ruthenium complexes were prepared by employing an
unprecedented synthetic strategy for nitrido metal complexes,
that is, reaction of oxo metal complexes with an imine
compound. Upon activation with TFAA, both 1a and 1b can
aminate silyl enol ethers to give N-trifluoroacetylated a-
amino ketones. Especially interesting is that the ™1a/1b þ
Ru
Ru
N
Ru
N
Ru
N
Ru N
a
d
b
c
k
N
Ru
N
Ru
N
e
f
O
N
ꢀ
TFAA∫ system can undergo C H insertion reaction with
Ru
N
N
Ru
Ru
N
O
Ru N N
indan to form N-trifluoroacetyl indan-1-ylamine. This reac-
ꢀ
tion, to our knowledge, is the first amination of saturated C
g
h
i
j
H bonds of a hydrocarbon with nitrido metal complexes.
Treatment of dioxoruthenium(vi) porphyrin [RuVI-
(por)(O)2] (por¼ tmp[11a] or 3,4,5-MeO-tpp[3b]) generated
in situ from [RuII(por)(CO)] and excess m-CPBA[10] (see
ꢀ
Scheme 1. Axial Ru N bonds in ruthenium porphyrins.
¼
isolable ruthenium porphyrins with terminal nitrido axial
ligands (Scheme 1, k) especially conspicuous.[6,7]
Scheme 2, reaction (1)) with excess HN CtBu2 in dichloro-
methane for ꢂ 40 min afforded a green solution, workup of
which gave 1a or 1b as a dark purple solid in ꢂ 85% yield
(reaction (2) in Scheme 2). Both 1a and 1b are stable to moist
air for several months in the solid state and can exist for
several hours in dichloromethane solutions exposed to the
atmosphere.
Our interest in nitrido ruthenium porphyrins stems from
ꢁ
the particular importance of nitrido metal (M N) complexes
[8]
ꢀ
in C N bond-formation reactions. In a pioneering work by
Groves and Takahashi, a nitrido manganese porphyrin, upon
activation with trifluoroacetic anhydride (TFAA) to form a
¼
trifluoroacetylimido manganese (Mn NCOCF3) species, un-
We found that reaction (2) shows surprisingly strong
dependence on the electronic properties of the porphyrin
ligand.[12] Attempts to extend reaction (2) to less electron-rich
porphyrins (such as tpp[10] and ttp[10]) and electron-deficient
porphyrins (such as tpfpp[10]) did not lead to formation of
nitrido ruthenium porphyrins; instead, m-oxo and nitrosyl
ruthenium porphyrins were obtained, respectively.
[*] Prof. Dr. C.-M. Che, S. K.-Y. Leung, Dr. J.-S. Huang, J.-L. Liang
Department of Chemistry andOpen Laboratory of Chemical Biology
of the Institute of Molecular Technology for Drug Discovery and
Synthesis
The University of Hong Kong, Pokfulam Road(Hong Kong)
Fax: (þ852)2857-1586
The reaction between [RuVI(3,4,5-MeO-tpp)(O)2] and
E-mail: cmche@hku.hk
¼
HN CtBu2 to form 1b contrasts sharply with that between
Prof. Z.-Y. Zhou
¼
the same dioxo complex and HN CPh2, the latter reaction
Department of AppliedBiology andChemical Technology
The Hong Kong Polytechnic University, Hung Hom, Kowloon (Hong
Kong)
has been reported to produce bis(methyleneamido) ruthe-
IV
¼
nium(iv) porphyrin [Ru (3,4,5-MeO-tpp)(N CPh2)2] in
ꢂ 65% yield under similar conditions.[3h]
[**] This work was supportedby The University of Hong Kong, the Hong
Kong University Foundation, the Hong Kong Research Grants
Council, andthe University Grants Committee of the Hong Kong
SAR of China (Area of Excellence Scheme, AoE/P-10/01).
Efforts were once made to prepare 1a/1b or their
analogues by employing known synthetic strategies such as
ꢀ
¼
cleavage of the N R bond in imido metal (M NR) complexes
and oxidation of coordinated ammines.[9b] However, these
synthetic strategies did not lead to isolation of pure nitrido
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
340
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Angewandte
Chemie
bands in the UV/Vis spectra appear at 485
O
CO
Ru
N
488 nm, which are substantially blue-shifted from
(1)
(2)
5]
those of other ruthenium porphyrins reported.[1
Ru
O
Ru
m-CBPA
tBu
tBu
In the electrospray mass spectra (ESI MS) of
1 3, intense cluster peaks corresponding to the
fragments [Ru(por)(N)]þ were located. The ESI
MS of 1a, 1b, and 3 also showprominent peaks
ascribable to their parent ions. Complex 2 did not
give parent-ion peaks in the ESI MS; its axial
NHTs ligand was identified on the basis of the
1H NMR spectrum. In the IR spectra, conversion
of [RuII(tmp)(CO)] into 1a and 2 led to the
appearance of a newband at 1038 cm ꢀ1, which
HN
OH
1
O
O
O
O
O
O
N
N
N
N
N
N
N
Ru
OH
Ru
N
N
[13]
ꢁ
we tentatively assigned to the Ru N group.
OH
N
O
ꢁ
Identification of the Ru N band for 1b and 3
O
was hampered by either intense signals of the
porphyrin ligand in the region of interest or
impurities in the sample.
O
O
O
O
1a
1b
The structure of 1b has been determined by X-
Scheme 2. Synthesis of the nitrido ruthenium(vi) porphyrins 1. m-CPBA¼meta-
ray crystallography (Figure 1),[14] and features a
chloroperoxybenzoic acid.
ruthenium porphyrins. For example, autodegradation of
in situ formed bis(tosylimido) ruthenium(vi) porphyrin [RuVI-
(tmp)(NTs)2][3d] in aerobic dichloromethane gave [RuVI-
(tmp)(N)(NHTs)] (2; reactions (3) and (4) in Scheme 3)
contaminated with NH2Ts; oxidation of the isolated bis(am-
mine) ruthenium(ii) porphyrin [RuII(ttp)(NH3)2] (prepared
from [RuVI(ttp)(O)2][11b] and excess NH3, reaction (5) in
Scheme 3) with 4 equivalents of NBS[10] in dichloromethane
under argon afforded [RuVI(ttp)(N)Br] (3; reaction (6))
contaminated by NBS.
The nitrido ruthenium(vi) porphyrins 1 3 are all diamag-
netic and feature ™oxidation-state marker∫ bands[3a,b] at >
1015 cmꢀ1 in their IR spectra, like dioxo, oxo(imido) or
bis(imido) ruthenium(vi) porphyrins.[3a,d] The following spec-
Figure 1. Molecular structure of 1b determined by X-ray crystallogra-
phy (hydrogen atoms are not shown). Selected bond lengths [ä] and
bondangles [ 8]: Ru-N1 2.046(6), Ru-N2 2.086(6), Ru-N3 2.001(6), Ru-
N4 2.026(7), Ru-N5 1.656(5), Ru-O13 2.086(7); N1-Ru-N2 92.7(2), N2-
Ru-N3 88.5(2), N3-Ru-N4 88.5(3), N4-Ru-N1 90.3(3), N5-Ru-O13
177.8(3).
tral features of 1 3 are distinctive. First, the signals of the
1
pyrrole protons (Hb) in the H NMR spectra are at d ¼ 9.00
(1a), 9.09 (2), 9.33 (1b), and 9.36 ppm (3), which are all
downfield from those of their dioxo,[3b,11] oxo(imido),[3a,g] or
bis(imido)[3c,d] ruthenium(vi) counterparts. Second, the b
planar porphyrin ring and a Ru N(nitrido) distance of
1.656(5) ä, slightly longer than those of nitrido ruthenium
complexes with tri- or tetradentate non-porphyrin ligands
(1.594 1.615 ä).[15] The Ru O(OH) distance of 2.086(7) ä
in 1b is longer than that in [Ru(ttp)(NO)(OH)]
(1.943(5) ä).[5g]
Ts
N
CO
Ru
N
(3)
(4)
Ru
Ru
PhI=NTs
standing
NHTs
N
Note that the above nitrido ruthenium porphyrins can
be readily converted into hexacoordinate {Ru(NO)} com-
plexes. For example, reactions of 1b with PhIO and MeOH
in dichloromethane gave [Ru(3,4,5-MeO-tpp)(NO)(OH)]
and [Ru(3,4,5-MeO-tpp)(NO)(OMe)], respectively. In an
attempt to purify 3 by chromatography on an alumina
column, the complex was converted into [Ru(ttp)(NO)Br]
(see Supporting Information).
Ts
2
O
NH3
N
(5)
(6)
Ru
O
Ru
Ru
O
NH3
NH3
Br
(NBS)
Br
N
3
O
Interestingly, treatment of 1a or 1b with silyl enol
ethers and TFAA in dichloromethane containing pyridine
under argon for ꢂ 5 h afforded respective N-trifluoroace-
Scheme 3. Formation of the nitrido ruthenium(vi) porphyrins 2 and 3 from
autodegradation of a bis(tosylimido)ruthenium(vi) porphyrin or from NBS
oxidation of a bis(ammine)ruthenium(ii) porphyrin.
Angew. Chem. Int. Ed. 2003, 42, No. 3
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341

Communications
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Table 1: Amination reaction of 1a or 1b with silyl enol ethers andindan.
Entry
Substrate
Product
Yield [%]
1
2
68 (1a)
75 (1b)
3
4
70 (1a)
84 (1b)
[4] a) C. Morice, P. Le Maux, G. Si-
monneaux, Tetrahedron Lett. 1996,
37, 6701; b) C. Morice, P. Le Maux,
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5
6
52 (1a)
63 (1b)
[5] a) A. Antipas, J. W. Buchler, M.
Gouterman, P. D. Smith, J. Am.
Chem. Soc. 1978, 100, 3015;
tylated a-amino ketones in 68 84% yields of isolated product
(entries 1 4 in Table 1). By employing indan instead of silyl
enol ethers, the same reactions gave N-trifluoroacetyl indan-
1-ylamine in 52 (1a) or 63% (1b) yield (determined by GC),
as shown in entries 5 and 6 in Table 1. These reactions are
very striking, because many non-porphyrin nitrido ruthenium
complexes have been isolated, but none of these is reported to
be reactive toward hydrocarbons or silyl enol ethers.[6,15,16]
The reaction of ™1a/1b þ TFAA∫ with indan to form N-
trifluoroacetyl indan-1-ylamine is a unique approach to N-
trifluoroacetyl amines from direct intermolecular amination
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P. Tagliatesta, P. Bianco, T. Boschi, G.-B. Yi, M. A. Khan, G. B.
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S. Bernhard, J. R. Schoonover, P. C. Ford, J. Am. Chem. Soc.
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2001, 113, 2597; Angew. Chem. Int. Ed. 2001, 40, 2529.
[7] Ruthenium porphyrins bearing a bridging nitrido ligand have
been isolated, see: W.-H. Leung, J. L. C. Chim, W. Lai, L. Lam,
W.-T. Wong, W. H. Chan, C.-H. Yeung, Inorg. Chim. Acta 1999,
290, 28. We noticed that in a previous synthesis of a terminal
nitrido complex of ruthenium(vi) porphyrin, [RuVI(4-Cl-
tpp)(N)(OH)] (H2(4-Cl-tpp) ¼ meso-tetrakis(4-chlorophenyl)-
porphyrin), from a biphasic (CH2Cl2/H2O) reaction of in situ
formed [RuVI(4-Cl-tpp)(O)2] with NH3¥H2O (see: Z.-Y. Li, C.-M.
Che, C.-K. Poon, Wuhan Univ. J. Nat. Sci. 1996, 1, 89), the
™nitrido∫ species (which was not structurally characterized)
should be reformulated as a hexacoordinate {Ru(NO)} complex,
[Ru(4-Cl-tpp)(NO)(X)], according to its UV/Vis spectral data
(Soret band: 412 nm, b band: 558 nm).
ꢀ
of hydrocarbon saturated C H bonds. Previous formation of
N-substituted amines from metal-mediated stoichiometric or
ꢀ
catalytic intermolecular amination of saturated C H bonds of
hydrocarbons was successful only for N-SO2R or N-COPh
amines.[17] We envision that the nitrido ruthenium(vi) por-
phyrin 1a or 1b, upon proper activation, might also be useful
for the synthesis of other types of N-substituted amines by
ꢀ
direct amination of saturated C H bonds; such studies,
together with the mechanisms of reaction (2) and the
NCOCF3 group-transfer reactions between ™1a/1b
TFAA∫ and indan/silyl enol ethers, are under current inves-
tigation in our laboratory.
þ
Received: September 10, 2002 [Z50138]
[1] a) N. Farrell, D. H. Dolphin, B. R. James, J. Am. Chem. Soc.
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Chem. Commun. 1996, 2343; d) M. J. Camenzind, B. R. James,
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3054.
[8] Selected examples: a) J. T. Groves, T. Takahashi, J. Am. Chem.
Soc. 1983, 105, 2073; b) J. Du Bois, J. Hong, E. M. Carreira,
M. W. Day, J. Am. Chem. Soc. 1996, 118, 915; c) J. Du Bois, C. S.
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E. M. Carreira, M. W. Day, Angew. Chem. 1997, 109, 1722;
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110, 3596; Angew. Chem. Int. Ed. 1998, 37, 3392.
[2] J.-T. Groves, K.-H. Ahn, R. Quinn, J. Am. Chem. Soc. 1988, 110,
4217.
[3] a) J.-S. Huang, C.-M. Che, C.-K. Poon, J. Chem. Soc. Chem.
Commun. 1992, 161; b) J.-S. Huang, C.-M. Che, Z.-Y. Li, C.-K.
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C. Cheng, C.-M. Che, S.-M. Peng, Chem. Commun. 1997, 1655;
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342
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Angewandte
Chemie
[10] Abbreviations: H2tmp: meso-tetrakis(2,4,6-trimethylphenyl)-
porphyrin, H2(3,4,5-MeO-tpp): meso-tetrakis(3,4,5-trimethoxy-
phenyl)porphyrin, m-CPBA: m-chloroperoxybenzoic acid,
H2tpp: meso-tetraphenylporphyrin, H2ttp: meso-tetrakis(p-tol-
yl)porphyrin, H2tpfpp: meso-tetrakis(pentafluorophenyl)por-
phyrin, NBS: N-bromosuccinimide, Ts ¼ p-toluenesulfonyl.
[11] a) J. T. Groves, R. Quinn, J. Am. Chem. Soc. 1985, 107, 5790;
b) C. Ho, W.-H. Leung, C.-M. Che, J. Chem. Soc. Dalton Trans.
1991, 2933.
Synthesis of a marine macrolide
Stereocontrolled Total Synthesis of (þ)-
Leucascandrolide A**
Ian Paterson* and Matthew Tudge
[12] As tmp is a sterically encumbered porphyrin, whereas 3,4,5-
MeO-tpp is basically a sterically unencumbered porphyrin
ligand (the latter can not prevent formation of dinuclear m-oxo
ruthenium porphyrins), yet both of them gave nitrido ruthenium
porphyrin 1 in similar yields, the steric properties of porphyrin
Leucascandrolide A (1, Scheme 1) was isolated in 1996 from
the calcareous sponge Leucascandra caveolata, collected off
the east coast of NewCaledonia, by Pietra and co-workers.
[1]
This polyoxygenated 18-membered macrolide features two
trisubstituted tetrahydropyran rings, one of which has an
unusual oxazole-bearing unsaturated side chain. To date, the
true biosynthetic origin of this unique polyketide is uncer-
tain.[2] Subsequent reisolation attempts proved unsuccessful
which indicates that leucasandrolide A may be produced by
opportunistic microbial colonization of the sponge.[2] Prelimi-
nary biological studies revealed potent cytotoxic activity
ꢁ
ligands should have a minor effect on the Ru N formation from
reaction (2).
ꢁ
[13] The frequency of this newband is comparable to the Ru
N
stretching frequency of 1023 cmꢀ1 reported for the non-porphyr-
in nitrido ruthenium(vi) complex [RuVI(N)Cl3(AsPPh3)2] (a
neutral, six-coordinate nitrido ruthenium(vi) species, like 1a
and 2). See: D. Pawson, W. P. Griffith, Inorg. Nucl. Chem. Lett.
1974, 10, 253.
against
a
range of cancer cell lines (IC50 ¼ 0.05 and
[14] CCDC-193042 (1b) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; fax: (þ 44)1223-336-033; or deposit
@ccdc.cam.ac.uk).
0.25 mgmLꢀ1 against KB oral epidermoid carcinoma and
P388 leukemia cell lines, respectively), as well as pronounced
antifungal activity. Since the natural supply of leucascandro-
lide A is unreliable, an efficient synthesis is paramount to
enable further biological studies and, furthermore, to provide
access to analogues. Consequently, leucascandrolide A has
[15] P. M. Chan, W.-Y. Yu, C.-M. Che, K.-K. Cheung, J. Chem. Soc.
Dalton Trans. 1998, 3183.
attracted considerable synthetic attention,[3 with the first
5]
[16] We treated [NnBu4][RuVI(N)Cl4] (prepared as described in W. P.
Griffith, D. Pawson, J. Chem. Soc. Dalton Trans. 1973, 1315) and
total synthesis reported by Leighton and co-workers.[3] Here-
in, we report an expedient total synthesis of (þ)-leucascan-
drolide A in which essentially complete control over all of the
stereochemistry is achieved.
[RuVI(N)(L)Cl]
(H2L ¼ 2,6-bis(2-hydroxy-2,2-diphenylethyl)-
pyridine, prepared as described in ref. [15]) with TFAA and
the silyl enol ethers shown in Table 1 under the conditions
similar to those for 1a/1b but obtained no amination products
from the reaction mixtures.
As outlined in Scheme 1, our approach relies on two
Mitsunobu reactions–the first is employed to cyclize the
seco-acid 2 and the second to append the heterocyclic side
chain 3 at C5. A double Lindlar hydrogenation should then
install the two Z-configured alkenes to provide leucascan-
drolide A directly. By exploiting the high degree of 1,3-
dioxygenation embodied within the seco-acid 2, we planned to
introduce all the oxygenated stereocenters from tetrahydro-
pyran 4 by using only substrate control. In light of the anti
configurational relationship between C7 and C11, seco-acid 2
should be accessible from the b-oxygenated ketone 4 and
aldehyde 5 by using our 1,5-anti aldol methodology.[5b,6,7]
Furthermore, the resulting C11 stereocenter could then serve,
in turn, to direct an alkylation with silyl enol ether 6 to install
the full C15 side chain.
[17] Selected examples: a) R. Breslow, S. H. Gellman, J. Chem. Soc.
Chem. Commun. 1982, 1400; b) J. P. Mahy, G. Bedi, P. Battioni,
D. Mansuy, Tetrahedron Lett. 1988, 29, 1927; c) I. N‰geli, C.
Baud, G. Bernardinelli, Y. Jacquier, M. Moran, P. M¸ller, Helv.
Chim. Acta 1997, 80, 1087; d) S.-M. Au, J.-S. Huang, C.-M. Che,
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As shown in Scheme 2, the synthesis of the trisubstituted
tetrahydropyran 4 began with a Jacobsen asymmetric hetero
[*] Prof. I. Paterson, M. Tudge
University Chemical Laboratory
Lensfield Road, Cambridge, CB2 1EW (UK)
Fax: (þ44)1223-336-362
E-mail: ip100@cus.cam.ac.uk
[**] We thank the EPSRC (studentship to M.T. and GR/N08520), the EU
(Network HPRN-CT-2000-00018), andMerck, Pfizer, andNovartis
for support.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2003, 42, No. 3
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