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Porphyrinoids
Макрюгетерюц мкл ы
http://macroheterocycles.isuct.ru
Обзор Review
Metalation of Carbaporphyrinoid Systems
Timothy D. Lash@
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160, U.S.A. @ E-mail: tdlash@ilstu.edu
Diverse carbaporphyrinoid systems have been synthesized using '3 + 1' MacDonald condensations, Lindsey-Rothemund reactions and other strategies. In common with the N-confused porphyrins (NCPs), these compounds have a CNNN core that can facilitate the generation of organometallic derivatives. Benzocarbaporphyrins and tropiporphyrins, with indene or cycloheptatriene units in place of a pyrrole ring, readily form silver(III) complexes and some gold(III) derivatives have also been prepared. On the other hand, benziporphyrins and azuliporphyrins, which have a benzene or azulene unit in place of a pyrrole moiety, are dianionic ligands that afford NiII, PdrI and Pf complexes. Stable iridium and rhodium derivatives of azuliporphyrins can also be generated. 2-Methyl or 2-phenyl NCPs act as dianionic ligands forming Nin and PdI complexes but reactions with silver(I) acetate gave the aromatic 3-oxoNCP silver(III) derivatives. A related N-phenylpyrazole-containing porphyrinoid gave nickel(II) and palladium(II) complexes but these showed little or no aromatic character. Oxybenziporphyrins, which have a semiquinone subunit, can form Pet1, Pi1, CuIII, AgIII and AuIII derivatives and can therefore act as both dianionic and a trianionic ligands. Finally, a diazuliporphyrin has been used to prepare the first example of a palladium(II) dicarbaporphyrinoid complex. These investigations demonstrate that the unique characteristics of organometallic compounds derived from carbaporphyrins and related porphyrin analogues are starting to rival the significance of the better known metal complexes of N-confused porphyrins.
Introduction
In 1994, the first examples of N-confused porphyrins (NCPs; 1, Figurel) were described.[1'2] These porphyrin isomers were formed as by-products in Rothemund-type syntheses from pyrrole and aromatic aldehydes, but were initially only generated in approximately 5% yield. Rational routes to meso-unsubstituted N-confused porphyrins were subsequently developed[3'4] using the '2 + 2' and '3 + 1' MacDonald methodologies.[5] In 1999, superior "one pot" reaction conditions were discovered by Geier et al. that used methanesulfonic acid as a catalyst, and this procedure gives meso-tetrasubstituted NCPs in up to 40% yield.[6] NCPs have attracted considerable interest due to their novel reactivity and spectroscopic properties.[7-12] The long wavelength absorptions exhibited by NCPs and related systems suggest that they may have complementary applications to true porphyrins and could potentially be used as photosensitizers in photodynamic therapy (PDT).[13] NCPs have two tautomeric forms that differ in energy by only 5 kcal/mol, and the less favorable cross-conjugated form 2 often predominates over 1 in polar aprotic solvents while the fully aromatic porphyrinoid 1 is favored in more conventional solvents such as chloroform.[14] The macro-cyclic core in NCPs has a carbon atom replacing one of the nitrogens in true porphyrins, but NCPs and related doubly N-confused porphyrins readily afford stable organometallic derivatives.[10] This aspect of NCP chemistry has been widely exploited to synthesize a wide variety of complexes involving both inner core metalation and/or coordination at the outer nitrogen. These complexes can be formally derived from both of the major tautomeric species, although the fully aromatic form is better suited to stabilize metal cations in higher oxidation states such as silver(III).[1516]
Me 4-Et
Me'
3
Benziporphyrins
Et
Et 5 Benzocarbaporphyrins
Et
Et
Et 7 Et
Me
Et
Et
4
Oxybenziporphyrins Me
Et
Azuliporphyrins Me
Me
Et R'
8
Tropiporphyrins
Carbachlorins
Figure 1. Selected examples of carbaporphyrinoid systems.
Shortly after the accidental discover of NCPs, a series of related carbaporphyrinoid systems were reported.[5'n-19] These systems share the CNNN core found in NCPs but have far greater potential for structural diversity. These variables allow for greater differences in both reactivity and spectroscopic properties, and the element of symmetry present in many of these structures also allows for a simplification in the characterization of these systems as well as facilitating greater regiochemical selectivity. Although the first synthesis of a benziporphyrin 3 (Figure 1) was reported in the same year that the earliest papers on NCPs were published,[20-22] and syntheses of oxy-benziporphyrins 4,[21'22] carbaporphyrins (e.g. 5),[23'24] azuliporphyrins 6,[25] carbachlorins 7[26] and tropiporphyrins
8[27] were reported over the next three years, until recently studies on these carbaporphyrinoid systems have fallen under the shadow of the NCPs. Nevertheless, a number of innovative synthetic routes have been developed for the synthesis of carbaporphyrinoids such as 3-8, and these systems have been shown to be capable of generating diverse organometallic complexes. These investigations have not only complemented the work conducted on NCPs but have also lead to the discovery of a significant class of novel organometallic compounds.
In this review, the methods available for synthesizing carbaporphyrinoid systems are discussed and recent developments on the metalation of these systems are described.
PT
HO2C
Et
HO2C H
1. H+
2. [O]
10 Tripyrranes a. R' = Et; b. R' = Ph; c. R' = H
Me
*V\-Et
Me
Et R'
Type A
Et R'
Type B
R
X-
OHC
f\-CHO
Et
11
a. X = R = H
b. X = OMe; R = H
Me
ft
CHO
OHC
12
Me
\
Me-^.
Me
OH
Et
Et
CHO
OHC 14
3 R'
c. X = OMe; R = Me Benziporphyrins (
C^^CH-OH OHC
17
Me '^T^-Et
hn~w
R-
OHC
CHO
.CH-OH
Et 13 Et 22-Hydroxybenziporphyrin
CHO Me
a. X = CH
b. X = NH
Et
Et R'
4 Oxybenziporphyrin 15 Oxypyriporphyrin
Et 5 R' Benzocarbaporphyrins
Me
CHO
OHC
Et Et
16 Carbaporphyrins
Carbachlorins
OHC
N-confused porphyrins
N-Confused Pyriporphyrin
Et R'
Cross-conjugated N-confused porphyrins 21 X = CH; 22 X = N
Azuliporphyrins
Et
25 Et R'
Oxynaphthiporphyrin
Me-^
Et R'
26 Tropiporphyrin
or
X
Scheme 1. Synthesis of carbaporphyrinoid systems from tripyrranes.
Synthetic Methodologies
One of the most versatile methods for porphyrin synthesis is a '3 + 1' variant on the MacDonald condensation (Scheme 1).[5] In this methodology, a dialdehyde 9 is condensed with a tripyrrolic intermediate (tripyrrane 10) in the presence of an acid catalyst.[28] Following oxidation of a dihydroporphyrinoid intermediate, the porphyrinoid system is generated.[28-31] In most cases the yields fall into a 30-50% range, although >80% yields have been noted in some cases.[28'30] When a carbocyclic dialdehyde is used, carbaporphyrinoid products of type A or
type B can be formed (Scheme 1).[17-19] In type A, a porphyrin-like conjugation pathway is retained and this allows for highly diatropic structures to be generated. However, in other cases the carbocyclic unit is cross-conjugated and the macrocycle becomes less aromatic or nonaromatic. Reaction of isophthalaldehyde (11a) with tripyrrane 10 gives the nonaromatic benziporphyrin 3a,[20-22] while related dimethoxybenzenedialdehydes 11b and 11c give dimethoxybenziporphyrins 3b and 3c, respectively.[32] Similarly, 2 -hydroxy-5 -methyl-1, 3 -benzenedicarbaldehyde (12) reacts with 10 to afford the hydroxybenziporphyrin 13, and the internal hydroxyl substituents does not appear to
Et
Et
27
OH rf\-CHO
VX
OHC 14
a. X = CH; b. X = N 1. H+ 2. [O]
Et 26
a. Y = O; b. Y = S; c. Y = NH Z = H or CO2H
Me
Me
VEt
Et
28 X = CH 29 X = N
\\J
31
R = H, tBu or Ph
AcOH Et
t-BuO2C
2 32
2
CH2OAc
Me
CO2t-Bu
TFA
CO2t-Bu
30
OHC
a. R = H; b. R = tBu; c. R = Ph
CHO
R'
R'
Me
33
a. X = NH; R' = Et; b. X = O; R' = H; c. X = S; R' = H; d. X = Se; R' = H
OH
Et
A^C^OAc R^ HO-
OH
CHO
HO-\
34 a. R = H b. R = Me
MeA\ ■ B„O>^ 35
1. p-TSA-CaCl2
2. H2-Pd/C
TV,
VX
Ph—4
Ph OH
OH
1. MsCl EtaN
Me O
39
f\
CHO
Et
Ph
41 2. Pyrrole
1. TFA
2. DDQ
HO
Et
Ч-Me
38 (R = H or Me)
a. X = NH; R' = Et
b. X = O; R' = H
c. X = S; R' = H
d. X = Se; R' = H
Ph
Ph
Et
42
Et
a. Y = N, X = Z = CH; b. Z = N, X = Y = CH ; c. X = N, Y = Z = CH
Scheme 2. Synthesis of carbaporphyrinoid systems from tripyrrane analogues.
R
O
2
significantly inhibit macrocycle formation.[33] In the early stages of these studies, we speculated that the presence of a 4-hydroxyl unit on the benzene moiety would facilitate a keto-enol tautomerization to give an aromatic type A porphyrinoid 4 rather than type B benziporphyrins obtained from dialdehydes 11 and 12.[21] This proved to be the case, as reaction of 14 (X = CH) with 10 in the presence of 5% TFA in dichloromethane, followed by oxidation with DDQ, afforded the highly diatropic system oxybenziporphyrin 4.[21,22] Oxybenziporphyrin 4 has an arrangement of core atoms than mimics tautomer 1 for NCPs, while benziporphyrins 3 more closely resemble the cross-conjugated tautomer 2.[21'22] The same trick can be applied to the synthesis of oxypyriporphyrins 15.[22,33,34] 3-Hydroxy-2,6-pyridinedicarbaldehyde (14; X = N) reacted with tripyrranes 10 under the unusual '3 + 1' conditions to give the aromatic pyridone-containing macrocycle in excellent yields.[34] Other aromatic type A systems include benzocarbaporphyrins 5,[24'35] carbaporphyrins 16[2324] and carbachlorins 7,26 all of which can be formed by reacting the necessary dialdehyde precursors with tripyrranes 10 (Scheme 1). The use of indene dialdehyde 17 in this chemistry to generate benzocarbaporphyrins 5 has been particularly successful.[24] The same strategy was applied in the synthesis of meso--unsubstituted NCPs 18 from 2,4-pyrroledicarbaldehydes 19.[36] In this work, excellent yields of NCPs could be isolated so long as ferric chloride was used as the oxidant and the products were recrystallized as the hydrochloride salts.[36] Recently, N-methyl and N-phenyl pyrrole dialdehydes 20 (X = CH) were shown to react with tripyrranes 10 to give the cross-conjugated NCPs 21.[37] In addition, pyrazole dialdehydes 20 (X = N) reacted with 10 to give the related nonaromatic 3-aza-NCPs 22. Although NCPs 21 showed some diatropic character, this property was not evident in the pyrazole-containing porphyrinoids 22.[37] Azulene dialdehydes 23 react with tripyrranes 10 to give a particularly important group of porphyrin analogues known as azuliporphyrins (6).[25'38'39] Azuliporphyrins 6 show comparable diatropic character to the cross-conjugated NCPs 21, in both cases showing the internal CH resonances in proton NMR spectra near 3 ppm, although this property is greatly enhanced upon protonation.[2539] Other systems that have been prepared using the '3 + 1' approach include N-confused pyriporphyrin 24,[40] oxynaphthiporphyrins 25[41] and tropiporphyrins 8.[27'42]
Further structural diversity can be introduced when modified tripyrrane structures are utilized in these syntheses (Scheme 2). Hence, when furan and thiophene tripyrrane analogues 26 were reacted with indene dialdehyde 17, the corresponding 23-oxacarbaporphyrins 27a and thiacarbaporphyrins 27b could be generated.[43'44] In addition, similar heteroanalogues of oxybenzi-porphyrins (28) and oxypyriporphyrins (29) could also be easily formed.[43'44] Azulene undergoes electrophilic substitution at the 1 and 3 positions, and this allows the formation of azulitripyrranes 30 when azulenes 31 are reacted with two equivalents of an acetoxymethylpyrrole 32 in the presence of acetic acid.[39'45'46] These tripyrrane analogues were generated with terminal tert-butyl ester protective groups. Following deprotection with TFA, the azulitripyrranes were condensed with pyrrole, furan, thiophene or selenophene dialdehydes to give
azuliporphyrins and their heteroanalogues 33 in good yields.[39'46] Resorcinol (34a) and 2-methylresorcinol (34b) were also shown to react with acetoxymethyl-pyrroles 35 in the presence of /-toluenesulfonic acid and calcium chloride to give tripyrrane analogues with terminal benzyl ester protective groups.[47] Following hydrogenolysis over 10% palladium-charcoal, the related dicarboxylic acids 36 were reacted with dialdehydes 37 (X = NH, O, S or Se) to give a series of rather insoluble hydroxyoxybenziporphyrins 38.[47] The macrocyclic products derived from methylresorcinol (R = Me) underwent further oxidation with PhI(OCOCF3)2 to afford the unusual but highly aromatic 3-hydroxy-2,4-diones 39.[47] Pyritripyrranes 40 were also prepared from pyridine dicarbinols 41 and these reacted with pyrrole dialdehydes to give a series of pyriporphyrins 42.[40] In 42b and 42c, a carbon atom is present in the macrocyclic core and these systems can be considered to be azabenziporphyrins.[40]
5 1 Paraformaldehyde
Ú
Florisil
31
43
' f \ 4 Ar-CHO
^N BF3 Et2O Calix[4]azulenes
H a. R = H; b. R = fBu; c. R = Me
Ar
DDQ
Ar
Ar
R = H, fBu or Ph
44 Ar
Azuliporphyrinogens Tetraarylazuliporphyrins
Ar = Ph, 4-ClC6H4, 4-BrC6H4, 4-IC6H4, 4-MeC6H4, etc.
R^ A
Ar 1. OH
Ar
Art 2
OH 2
30
N
_H_>
45
Ar'-CHO BF3.Et2O 2. DDQ
II %
Ar^
46 Ar' R = H or f-Bu OMe ph
RrV^Ph
Me^OH-
PtX 2 Ar'-CHO
P^OH 47 BF3.Et2O
2. DDQ Ar = Ph, 4-ClC6H4,
4-MeC6H4, 4-fBuC6H4
Ar
48
Ar
OH
J Ph
ÓÍoh
"30
a. R = H; b. R = Me O Ph
Ph OH 49
2 Ar-CHO BF3.Et2O 2. DDQ Ar = Ph or 4-ClCaH
Ph
6H4
Ar
Scheme 3. Rothemund-type syntheses of carbaporphyrinoids.
R
3
R
More direct routes to carbaporphyrinoid systems have also been developed (Scheme 3). Azulene favors electrophilic substitution at the 1 and 3 positions that are structurally analogous to the a-positions in pyrroles. As pyrroles cyclotetramerize to give calix[4]pyrroles or porphyrins, the possibility of generating calix[4]azulenes
43 from the reaction of azulenes 31 with paraformaldehyde was investigated.[48] Although many acid catalysts afforded low yields of 43, the macrocyclic product could not be purified by column chromatography. After attempting this reaction under numerous conditions, florisil was found to be an excellent catalyst and 43 was isolated in >70% yield.[48] The synthesis of 43 resembles a Rothemund-type porphyrin synthesis,[49] and this lead us to speculate that the same approach might be used to prepare azuliporphyrins 44.[50] Using conditions adapted from Lindsey's methods for preparing tetraaryl-porphyrins,[51'52] a 1:3:4 molar ratio of azulene, pyrrole and arylaldehydes were stirred with BF3Et2O in chloroform for 16 hours. Following oxidation with DDQ and column chromatography, the tetraarylazuliporphyrins
44 were isolated in good yields (generally 10-20%).[505354]
A similar approach to benziporphyrins was also reported.[55] Benzene dicarbinols 45 were reacted with pyrrole and aromatic aldehydes using catalytic BF3-Et2O in dichloromethane to give, following oxidation with DDQ,
A 1 1 1 Jj I I I
7 6 7 4 et 6.6 6 4
10 S S 7 6 5 4
Figure 2. 400 MHz proton NMR spectra of dimethoxybenzi-porphyrin 48a showing the presence of significant diatropic character despite the cross-conjugated nature of the benzene subunit. A - Free base in CDCl3. B - Dication in TFA-CDCl3. In the latter spectrum the internal CH shifts upfield to 3.3 ppm.
the tetraarylbenziporphyrins 46.[55] We have recently developed improved methods for the synthesis of dicarbinols 45 and this allows the introduction of novel substitution patterns on the benziporphyrin core.[56] Dimethoxybenzenedicarbinols 47 were easily prepared by reacting dilithio-derivatives with benzaldehyde and these also reacted with pyrrole in the presence of BF3-Et2O to give the dimethoxybenziporphyrins 52.[57'58] Despite the high degree of the steric congestion in 52 due to the presence of the meso-substituents, these benziporphyrins still show some diatropic character. In the proton NMR spectrum of 48a, the internal CH is shifted upfield to 5.8 ppm (Figure 2A). Although this shift is small, the chemical shift for this resonance is consistent with a degree of aromatic character being present in these benziporphyrins that results from the electron-donating effects of the methoxy substituents.[57'58] In the presence of TFA, the aromatic character of 48a is greatly increased as the protonated benziporphyrin shows this resonance further shifted upfield to 3.3 ppm (Figure 2B).[58] Even though a dication is generated, the NH resonances are still shifted upfield compared to the free base. Nevertheless, these shifts are relatively small compared to the oxybenziporphyrins.[21] However, this aromatic carbaporphyrinoid system can also be obtained by reacting the phenolic dicarbinol 49 with pyrrole and aromatic aldehydes under the Lindsey-Rothemund conditions.[59] Although the meso-tetraaryl oxybenziporphyrins 50 show smaller upfield shifts than the meso-unsubstituted oxybenziporphyrins, the internal CH is still observed upfield near -3 ppm.[59]
Benzocarbaporphyrins can also be derived from azuliporphyrins 6 (Scheme 4).[38] Azuliporphyrins are relatively polar systems that derive borderline aromatic properties from dipolar canonical forms that simultaneously give the structure carbaporphyrin and tropylium aromatic characteristics.[25] This character is limited due to the associated requirement for charge separation. However, protonation gives a dication 51 where the tropylium resonance contributor takes on greater significance because it now facilitates charge delocalization.[25] Nevertheless, the seven-membered ring of the free base azuliporphyrins is susceptible to nucleophilic attack due to its tropylium-like characteristics.[38] In the presence of nucleophiles like pyrrolidine, adducts 52 may be generated that take on fully aromatic carbaporphyrin-type spectroscopic properties.[38'39] Azuliporphyrins 6 can undergo oxidative ring contractions to afford benzocarbaporphyrins 53, and this chemistry readily occurs in the presence of tert-butyl hydroperoxide and potassium hydroxide.[38,39] Although mixtures of several carbaporphyrin products may be generated, this chemistry provides an alternative route to benzocarbaporphyrins.[38'39] Tetraarylazuliporphyrins 44 similarly react with tBuOOH and KOH to give the analogous benzocarbaporphyrins 54, and it is noteworthy that this is currently the only known route to tetraaryl benzocarbaporphyrins.[50'53] In the tetraaryl benzocarba-porphyrin series 54, the signal of the inner CH is still shifted upfield to beyond -5 ppm and the UV-vis spectra are porphyrin-like showing the presence of a strong Soret band and several Q absorptions.[5053] However, X-ray crystallography shows that the indene unit is significantly tilted from the mean plane of the macrocycle
Et
52
6
BuOOH
Et
Me-
53 Et
a. X = Y = H b. X = CHO, Y = H c. X = H, Y = CHO (minor)
44 Ar
Ar
f-BuOOH OH-
Ar
54
Ar
Ar
a. X = Y = H b. X = CHO, Y = H c. X = H, Y = CHO (minor)
Me
Et
6 R = Ph or t-Bu
jfl—Ph S
44 Ph
55 a. X = H (major)
b. X = CHO (minor when R = f-Bu)
Ph
56 Ph
a. X = H (major)
b. X = CHO (minor)
Me
f-BuOOH
OH-
Me
57
X = S or Se
Scheme 4. Synthesis of benzocarbaporphyrins from azuliporphyrins.
R
Me 58
a. X = Y = H b. X = CHO, Y = H c. X = H, Y = CHO (minor)
Me
Me R = Ph or t-Bu Me
59 60 (major)
X = S or Se
Figure 3. X-ray crystal structure of tetraphenylbenzocarb-aporphyrin 54.[53]
(Figure 3), in part due to the presence of two flanking phenyl substituents.[53] The ring contractions are believed to be triggered by an initial nucleophilic attack from the tert-butyl hydroperoxide anion at position 23 of azuli-porphyrin 6 (Scheme 5).[38] Following a Cope rearrangement,
elimination of tert-butyl alcohol would give a benzocarbaporphyrin aldehyde or a fused cyclopropanone that can extrude CO to give the benzoporphyrin 5 lacking a formyl moiety.[38'53] Attack at position 22 could give rise to an alternative aldehyde product.[38'53] Surprisingly, azuliporphyrins 6 with phenyl or tert-butyl substituents on position 23 also readily underwent ring contractions to benzocarbaporphyrins 55 (Scheme 4).[46] The results indicated that nucleophilic attack could still occur at positions 22, and to a lesser extent 21, and even the presence of a tert-butyl substituent could not block this process. Tetraphenylazuliporphyrins 44 derived from 6-phenyl or 6-tert-butylazulene also gave benzocarbaporphyrin products 56 upon treatment with KOH-tBuOOH, although not unexpectedly these appear to arise solely from nucleophilic attack at position 22 of the azuliporphyrin.[54] Heteroazuliporphyrins 57 (X = S or Se) also react under these conditions to give thia- and selenacarbaporphyrins 58,[39] and the related heteroazuliporphyrins 59 with
X
R
R
X
R
2 -phenyl or feri-butyl substituents similarly afforded heterobenzocarbaporphyrin products 60.[60]
H
Cope rearrangement
5
Scheme 5. Mechanism for the peroxide induced ring contraction of azuliporphyrins to give benzocarbaporphyrins.
Syntheses of dicarbaporphyrins and related macrocycles are less advanced, but several routes to these systems have now been reported (Scheme 6). Indane dialdehyde 61 was reported to react with diethylpyrrole in the presence of HBr, followed by oxidation with ferric chloride, to give the opp-dicarbaporphyrin 62.[61] This dicarbaporphyrin is very aromatic based upon the strongly diatropic ring current observed by proton NMR spectroscopy, and has a porphyrin-like UV-vis spectrum. However, 62 is rather unstable and this has limited further investigations.[61] Azulitripyrrane 30 has been shown to react with indene dialdehyde 17 under '3 + 1' MacDonald condensation conditions to give the 23-carbaazuliporphyrin 63.[45] Similarly, resorcinol-derived tripyrrane analogues 36 reacted with 17 to yield to the opp-carbaoxybenziporphyrins 64.[62] Unfortunately, 63 is also rather unstable and dicarbaporphyrinoids 64 have poor solubility characteristics, so these systems also have only been investigated to a limited extent. Macrocycles with two adjacent carbocyclic rings have recently been shown to be far more promising for future investigations.[63] In particular, azulene-dialdehyde 65 has been shown to react with an indene enamine 66 in the presence of dibutylboron triflate to give a fulvene dialdehyde 67. Further acid catalyzed MacDonald '2 + 2' condensation with a dipyrrylmethane dialdehyde 68 afforded the adj--dicarbaporphyrinoid system 69.[61] This 22-carbaazuliporphyrin has some diatropic character, but is quite stable and is reasonably soluble in organic
solvents.[61]
Qv
^,*CHO
ohC 61
Et
HN
1. HBr
2. FeCl
3
62
Me
CO2f-Bu TFA
CO2f-Bu
30
ho-ch^y'y
17
63
OH Et
HO
HH -o,h Et' Et
>N H N<
Et Et
69
Scheme 6. Synthesis of dicarbaporphyrinoid systems.
Metalation of Carbaporphyrins and Related Macrocycles
Our initial attempts to metalate benzocarbaporphyrins 5 or oxybenziporphyrins 4 with nickel(II), copper(II) or zinc salts were unsuccessful.[64] In the inital phases of these studies, benzocarbaporphyrin 5 was heated with excess ferric chloride in refluxing methanol-chloroform in an attempt to generate an iron complex (Scheme 7).[6465] In fact,
even at the time we considered these conditions to have little chance of working because it is difficult to insert FeIII directly into porphyrins, but we were trying out many different reaction conditions. As it worked out, the initial brown colored solution quickly turned bright green during the reflux.[64] However, the resulting product was not a metalloderivative. It turned out that ferric chloride efficiently oxidizes 5 at the internal carbon and generates a ketal product 70.[6465] This regioselective oxidation affords good yields of the polar ketal products which are isolated as hydrochloride salts. They show strong absorptions in the far red and for this reason show some potential for applications as photosensitizers in
PDT.[6465] Furthermore,
these ketals have been shown to be active against Leishmania and this property could lead to the development of a new treatment for leishmaniasis.[66] Subsequently, we noted that silver(I) acetate smoothly reacted with benzocarbaporphyrins 5 to give the silver(III) derivatives 7i.[41,67,68] These nonpolar derivatives are stable aromatic compounds and X-ray crystallography shows that the macrocycle is virtually planar. Reaction with gold(III) acetate gave a low yield of the gold(III) carbaporphyrin 72 but good yields of both the silver(III) and gold(III) derivatives 73 can be obtained by reacting the tetraarylbenzocarbaporphyrins 54 with silver(I) or gold(III) acetate.[68] Hence, this system is able to stabilize relatively high oxidation states of metals in common with NCPs 1. Oxacarbaporphyrin 27, which has two internal hydrogens, reacted with nickel(II) or palladium(II) acetate to give the nickel(II) or palladium(II) organometallic complexes 74a and 74b instead, and reactions with PtCl2 also gave low yields of the related platinum(II) complex 74c.[43'44]
Et
Et
AgOAcor -►
Au(OAc)3
Me
R'
FeCl3/ROH
Et
N N!
' ^R'
Et R'
71 M = Ag(III)
72 M = Au(III)
Et
R = Me, Et, i-Pr, CH2CH2OH, etc.
70 Et R'
Carbaporphyrin Ketals
AgOAc or Ar—--► Ar
Ar
Au(OAc)3
Ar
54
Ar
73
a. M = Ag(III) Ar
b. M = Au(III)
Et
27a
74
a. M = Ni; b. M = Pd; c. M = Pt
Scheme 7. Metalation of benzocarbaporphyrins.
Although the metalation of meso-substituted NCPs has been heavily investigated, little work has been carried out on the metalation of meso-unsubstituted N-confused porphyrins (Scheme 8). The heptaalkyl NCP 18 was
shown to react with Ni acetate in DMF to give the moderately unstable Ni11 complex 75.[36] Interestingly, if a drop of trifluoroacetic acid (TFA) is added to a solution of 75 in CDCl3, the proton NMR spectrum shows the immediate formation of an aromatic C-protonated derivative 76.[36] This protonation is reversible but if the solution is left for several hours the complex undergoes an irreversible demetalation to give protonated NCP.[36] In recent studies, the N-Me and N-Ph NCPs 21 have been shown to react with Ni(OAc)2 or Pd(OAc)2 to afford similar nickel(II) and palladium(II) complexes 77.[37] C-protonation was also observed for the nickel complexes. In addition, reaction with silver(I) acetate not only metalated the carbaporphyrinoid interior, but also gave rise to an oxidation on the inverted pyrrole ring to give the keto-NCP silver(III) derivatives 78.[37] The N-phenyl pyrazole-containing NCP 22 has also been shown to give stable nickel(II) and palladium(II) complexes 79.[37]
Me
Me
Me H
Et Me
Ni(OAc)2
Me
Et
Et Et
18
Me
\ Et
Et
/
Et
Me
H© Me
7" Et
V-V1 N.
Il \ ' {' Ni A
\ / \
psN N- \
Et
Et Et
75
76
R \
N
\\ II
R \
N
U
Me
Me
Et
Et
Et
Et Et
21 R = Me or Ph
J
M(OAc)2 Et Et
77 a. M = Ni; b. M = Pd
Et
Et
Et Et
78
Ph
Me
Ph
N II
Me
Me-^
Et
a. M = Ni; b. M = Pd
Scheme 8. Metalation of raeso-unsubstituted N-confused porphyrins.
5
Azuliporphyrins have been shown to be versatile organometallic ligands (Scheme 9).[69'70] Azuliporphyrins 6 react with Ni(OAc)2, Pd(OAc)2 or PtCl2 to give the nickel(II), palladium(II) or platinum(II) complexes 80 and these have been fully characterized by NMR, UV-vis spectroscopy, MS, electrochemistry and X-ray crystallography.[6970] In more recent investigations, 6 was shown to react with [Ir(CODCl)]2 in refluxing o-xylene to give iridium(III) complex 81, and preliminary results show that similar rhodium(III) complexes can also be generated.[71] Tetraarylazuliporphyrins 44 also readily form Nin, PdII and PtII complexes 82.[70] However, reaction with copper(II) acetate gave rise to an oxidative metalation process forming the copper(II) complex 83.[72] This system is very distorted and the X-ray crystal structure shows that the azulene subunit is tilted at an angle of 53° relative to the plane described by the three pyrrole units (Figure 4).[70] Demetalation with TFA in chloroform gave the nonaromatic ketone 84 in good yield. This unusual oxidation product can also be obtained directly by reacting 44 with silver(I) acetate.
Et
Ni(OAc)2
Pd(OAc)2 '
Me^^^Et or PtCl2
Et Et
6
R = H, Ph or f-Bu
Xylene [Ir(CODCl)]2 A
Et
Et
^-Et Et
80
M = Ni, Pd or Pt
Et
Me-V
Et Et
Ar is derived from the xylene solvent 81
R
Et
M(OAc)2 /J~Ar -► ArM = Ni, Pd or Pt
44 Ar
Tetraarylazuliporphyrins
AgOAc
ifAr
Ar
82
M = Ni, Pd or Pt
rAr
Ar
84
Figure 4. X-ray crystal structure of copper(II) complex 83.[53]
A
I) 3 0 Ï 5 r, s
j_jL_L_
J
B
ÄlliuJtl
7 7 7.6 75 7.4 73 7.2
1
C
■AILaLJUL
Ta 77 7 è 7 7> Ta T 71 77
Scheme 9. Metalation of azuliporphyrins.
Figure 5. 400 MHz proton NMR spectra of tetraphenyl-benziporphyrin derivatives in CDCl3. All three compounds show some diatropic character even though these systems cannot be planar and have a cross-conjugated benzene subunit. A -Acetoxybenziporphyrin 86. B - Nickel(II) complex 85 (M = Ni). C - Palladium(II) complex 85 (M = Pd).
R
R
MeO Ph
OMePh
M(OAc)2
/rAr
48
Ar
OMe
li
MeO' Ph
a. M = Ni; b. M = Pd OMePh
Ar
a. R = H; b. R = Me
MeO Ph
Ar
86 Ar
a. R = H; b. R = Me
Ph
Pd(OAc)2
D -^ Ph^\
Et
87
P Me
Et
Et
Et
PdCl
2
K2CO3
Et R'
4 Oxybenziporphyrin
Et
88
P Me
Et
Et
Me^^^/^v^Et
Et Et _
89
©
OH Me
R'
Et R'
91
.O Ph
Me
Et
Et
Ph
90
O Ph
Et
Ar
Ar
AgOAc Au(OAc)3 or CuCl
Ph
92
Ar
50
M = Ag(III), Au(III) or Cu(III)
Scheme 10. Metalation of benziporphyrins and oxybenzi-porphyrins.
Benziporphyrins allow for similar metalation reactions, and the tetraaryl substituted benziporphyrins have been shown to give NiII, PdII, PtII and other metallo-derivatives.[73] We have demonstrated (Scheme 10) that dimethoxybenziporphyrins 48 can also generate the nickel(II) and palladium(II) derivatives 85, although reaction with silver(I) acetate gave the corresponding acetate 86.[57'58] Interestingly, these 22-acetoxybenzi-porphyrin retain some diatropic character by NMR spectroscopy as do the NiII and PdII complexes
(Figure 5).[58] Nevertheless, the nickel(II) complex of dimethoxy-tetraphenylbenziporphyrin 48 is quite nonplanar showing a highly twisted six-membered ring by X-ray crystallography (Figure 6).[57'58] An N-confused pyriporphyrin 87, which can be considered to be a 2-azabenziporphyrin, was also shown to form a palladium(II) complex 88. Oxybenziporphyrin 4 was shown to form an anionic palladium(II) complex 89 that retains the keto-unit,[74,75] although the related platinum(II) complex appears to favor the phenolic form 90.[71] Reaction of oxybenziporphyrins 4 with silver(I) acetate gave the silver(III) derivatives 91 in high yields.[41] Hence, oxybenziporphyrins resemble NCPs in that they can act as both dianionic and trianionic ligands. Tetraphenyl-oxybenziporphyrins 50 have been shown to generate copper(III), silver(III) and gold(III) complexes 91, as well as a palladium(II) derivative.[59'60] Initial studies indicate that nickel(II) and platinum(II) complexes can be formed, but these have not been fully characterized.[60]
Figure 6. X-ray crystal structure of the nickel(II) complex of tetraphenyldimethoxybenziporphyrin 85.[58]
Et
AgOAc
25 Et R'
Oxynaphthiporphyrin
Me O
OH O
Et R'
93
OH O
Et R'
26 Tropiporphyrin
Et R'
95
Scheme 11. Silver(III) derivatives of carbaporphyrinoid systems.
Many carbaporphyrinoid systems have now been shown to form silver(III) derivatives (Scheme 11).[41] Oxynaphthiporphyrins 25 react with AgOAc to give silver(III) complexes 93,[41] the 3-hydroxydiketone 39 similarly gives Agm complex 94,[47] and tropiporphyrins 26 afford the Agm complexes 95.[44] Although these silver(III) derivatives usually form under mild conditions, the tropiporphyrin silver(III) derivatives can only be generated at elevated temperatures. X-ray crystallography for one of these tropiporphyrin complexes showed that the macrocycle is highly distorted due to the strain factors introduced by the seven-membered ring (Figure 7).[42]
Figure 7. X-ray crystal structure of silver(III) tropiporphyrin 95 showing a high degree of distortion due to the presence of the cycloheptatriene subunit.[42]
The metalation of dicarbaporphyrinoids has not been properly explored as yet, but a diazuliporphyrin 96 (Scheme 12) was recently shown to form an unusual palladium(II) complex 97.[76] This system has been characterized by X-ray crystallography and may well represent the first example of a whole series of dicarbaporphyrinoid derivatives of this type.
Conclusions
Efficient and versatile routes for the synthesis of carbaporphyrinoid systems have been developed. These porphyrin analogues range from highly aromatic systems to borderline aromatic or nonaromatic macrocycles, and the proton NMR data for these porphyrinoids provide significant insights into the nature of porphyrinoid aromaticity.[17-19] Many of these structures form stable organometallic derivatives under mild conditions. Benziporphyrins, azuliporphyrins, oxacarbaporphyrins and N-phenyl pyrazole-containing porphyrin analogues act as dianionic ligands, while benzocarbaporphyrins and tropiporphyrins are trianionic ligands that can stabilize metals in relatively high oxidation states (e.g. Agm)[41] and may find applications as catalysts. Oxybenziporphyrins can act as trianionic or dianionic ligands, as can NCPs, and this allows the synthesis of stable Pdn, Cum, Agm and Aum derivatives.[59] In addition to discovering new
organometallic systems, novel regioselective oxidation reactions have also been observed.[64] Oxidations of benzocarbaporphyrins with ferric chloride in the presence of alcohol solvents give carbaporphyrin ketals that have some promise as photosensitizers in PDT and are also being investigated as possible agents for treating leishmaniasis.[66] An initial example of a metalated dicarbaporphyrinoid system also suggests that further structural diversity in these unusual metalloporphyrin analogue systems will be possible.
Acknowledgements. This work was supported by the National Science Foundation, under Grant No. CHE-0616555, and the Petroleum Research Fund, administered by the American Chemical Society. X-ray crystallographic data were kindly provided by Professor G. M. Ferrence.
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Received 29.04.2008 Accepted 09.05.2008
