Tricarbonyl iron complexes aromatization

More recently, an environmentally benign method using air as oxidant has been developed for the oxidative cyclization of arylamine-substituted tricarbonyl-iron-cyclohexadiene complexes to carbazoles (Scheme 19). Reaction of methyl 4-aminosalicylate 45 with the complex salt 6a affords the iron complex 46, which on oxidation in acidic medium by air provides the tricarbonyliron-complexed 4a,9a-dihydrocarbazole 47. Aromatization with concomitant demetalation by treatment of the crude product with p-chloranil leads to mukonidine 48 [88]. The spectral data of this compound are in agreement with those reported by Wu[22j. 

Tricarbonyliron-coordinated cyclohexadienylium ions 569 were shown to be useful electrophiles for the electrophilic aromatic substitution of functionally diverse electron-rich arylamines 570. This reaction combined with the oxidative cyclization of the arylamine-substituted tricarbonyl(ri -cyclohexadiene)iron complexes 571, leads to a convergent total synthesis of a broad range of carbazole alkaloids. The overall transformation involves consecutive iron-mediated C-C and C-N bond formation followed by aromatization (8,10) (Schemes 5.24 and 5.25). 

Over the past 15 years, we developed three procedures for the iron-mediated carbazole synthesis, which differ in the mode of oxidative cyclization arylamine cyclization, quinone imine cyclization, and oxidative cyclization by air (8,10,557,558). The one-pot transformation of the arylamine-substituted tricarbonyl(ri -cyclohexadiene) iron complexes 571 to the 9H-carbazoles 573 proceeds via a sequence of cyclization, aromatization, and demetalation. This iron-mediated arylamine cyclization has been widely applied to the total synthesis of a broad range of 1-oxygenated, 3-oxygenated, and 3,4-dioxygenated carbazole alkaloids (Scheme 5.24). 

Using a one-pot process of oxidative cyclization in air, the arylamine 780a was transformed to the tricarbonyl(ri -4b,8a-dihydro-9H-carbazole)iron complex 792. Finally, demetalation of 792 and subsequent aromatization gave carbazomycin A (260). This synthesis provided carbazomycin A (260) in three steps and 65% overall yield based on 602 (previous route four steps and 35% yield based on 602) (610) (Scheme 5.88). 

The arylamine 794 required for the improved total synthesis of carbazomycin B (261) was prepared in quantitative yield by hydrogenation of the nitroaryl derivative 793 (see Scheme 5.85). Oxidative coupling of the iron complex salt 602 and the arylamine 794 in air afforded the tricarbonyl(ri -4b,8a-dihydro-9H-carbazole)iron complex (795). Demetalation of 795, followed by aromatization, led to O-acetylcarbazomycin B (796). 

Reaction of the iron complex salt 602 with the arylamine 921 in the presence of air led directly to the tricarbonyl(ri -4b,8a-dihydro-9H-carbazole)iron complex (923) by a one-pot C-C and C-N bond formation. Demetalation of complex 923 and subsequent aromatization by catalytic dehydrogenation afforded 3,4-dimethoxy-l-heptyl-2-methylcarbazole (924), a protected carbazoquinocin C. Finally, ether cleavage of 924 with boron tribromide followed by oxidation in air provided carbazoquinocin C (274) (640) (Scheme 5.120). 

In 1989 we reported an iron-mediated route for the construction of the tricyclic carbazole skeleton [72, 73]. This convergent method was applied to the total synthesis of the naturally occurring alkaloid carbazomycin A [72]. Key steps of our iron-mediated approach are the consecutive C C bond formation and oxidative cyclization (formation of the C N bond) between an electrophilic tricarbonyl(ri -cyclohexadienyhum)iron complex salt 30 and an arylamine 31 (Scheme 10). Subsequent oxidation and demetalation provides the aromatized carbazole 32. 

Alternatively, a mild and efficient one-pot electrophilic aromatic substitution/ oxidative cyclization without isolation of the intermediate complexes 36 has been achieved using air as oxidizing agent (mode B in Scheme 12). Thus, reaction via mode B leads to tricarbonyl(ri" -4a,9a-dihydrocarbazole)iron complexes 37, which on demetalation with trimethylamine A(-oxide and subsequent catalytic dehydrogenation provide the carbazoles 40. The naturally occurring carbazole... 

A third pathway leads via the quinone imine intermediates 38 to 3-hydro-xycarbazoles 41 (mode C in Scheme 12) [97, 98, 108, 109]. Oxidation of the complexes 36 with manganese dioxide afforded the quinone imines 38, which on treatment with very active manganese dioxide undergo oxidative cyclization to the tricarbonyl(ri" -4b,8a-dihydrocarbazol-3-one)iron complexes 39. Demetalation of 39 with trimethylamine iV-oxide and subsequent aromatization lead to the 3-hydro-xycarbazoles 41. The isomerization providing the aromatic carbazole system is a... 

The aromatic character of complex [6-19] is readily rationalized by the conventional mechanism for electrophilic substitution involving a Ti-ally-iron tricarbonyl cationic complex [6-20] shown in equation (6-35). 

Reaction of ferralactone complexes with amines provides ferralactam complexes. Aromatic amines require the addition of a Lewis acid, whereas alkyl amines react spontaneously. In the course of the reaction, the iron complex moiety moves from one end of the allyl system to the other with concomitant inversion of the configuration at Cl and C4. Reaction of a tricarbonyl(vinylketene)iron complex with electron-deficient alkenes gives (pentenediyl)iron complexes that can be oxidized to tetrasubstituted cyclopropanes. ... 

Two main classes of T -dienyliron complexes are known, namely the cationic tricarbonyliron complexes and neutral cyclopentadienyliron compounds. The cyclopentadienyl (Cp) ligand is relatively inert to a broad variety of reaction conditions. It is often introduced as a ligand to tune the properties of the iron complex, as a chiral auxiliary,or in material science in organoiron pol5miers. However, it is only rarely transformed itself into a more elaborate organic product. For this reason, the chemistry of the cyclopentadienyl ligand will not be discussed in more detail in this chapter. Tricarbonyl( n -dienylium)iron complexes, on the other hand, represent versatile electrophilic building blocks for the attachment of 1,3-butadiene, cyclohexadiene, or aromatic moieties to nucleophilic molecules. 

The reactivity sequence furan > tellurophene > selenophene > thiophene is thus the same for all three reactions and is in the reverse order of the aromaticities of the ring systems assessed by a number of different criteria. The relative rate for the trifluoroacetylation of pyrrole is 5.3 x lo . It is interesting to note that AT-methylpyrrole is approximately twice as reactive to trifluoroacetylation as pyrrole itself. The enhanced reactivity of pyrrole compared with the other monocyclic systems is also demonstrated by the relative rates of bromination of the 2-methoxycarbonyl derivatives, which gave the reactivity sequence pyrrole>furan > selenophene > thiophene, and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3] (35) with a further selection of heteroaromatic substrates (Scheme 5). The comparative rates of reaction from this substitution were 2-methylindole == AT-methylindole>indole > pyrrole > furan > thiophene (73CC540). 

In the case of tt complexes of substituted cyclopentadienones, such as the iron tricarbonyl derivatives prepared by Weiss and H libel (30), qualitative molecular-orbital theory (20) predicted a considerable reduction of the ketonic carbonyl bond order. It was observed that the ketonic carbonyl frequency dropped by as much as 65 cm-1, in agreement with theory. A similar explanation can also be provided in terms of valence bond theory (Fig. 14). It has been suggested that n complexing of arenes such as benzene results in loss of aromaticity of the ring in contrast to the dicyclopentadienyl... 

Iron tricarbonyl forms exceptionally stable complexes with 1,3-dienes. The complexes are uncharged, readily soluble species, chromatographable and, for the simpler versions, distillable. They are formed by direct reaction of the 1,3-diene with Fe(CO)5, Fc2(CO)9, or Fe3(CO)i2. These iron diene complexes are known to be reactive toward electrophiles, undergoing the analogous reaction to electrophilic aromatic substitution under Friedel-Crafts conditions. However, it is clear that the metal-ligand unit increases the polarizibility of the diene unit, and, with a sufficiently reactive nucleophile, can provide a sink for electron density. How reactive does the nucleophile need to be The other important selectivity question for 1,3-dienes concerns the regioselectivity. 

Cyclic 1,3-diene iron tricarbonyl complexes eliminate hydrogen on electron impact to give predominant odd electron ions with iron bonded to an aromatic system 57) These same molecules eliminate hydrogen and iron on photolysis to give aromatic hydrocarbon products. 

Cyclobutadiene-iron tricarbonyl is prepared through reaction of S,4-dichlorocydolmtene and diiron enneacarbonyl. In an analogous manner, one can prepare 1,2-diphenyl- 1,2,3,4-tetramethyl- and benzocyclobutadiene-iron tri-carbonyl complexes. Cyclobutadiene-iron tricarbonyl is aromatic" in the sense that it undergoes facile attack by electrophilic reagents to produce monosubstituted cydo-butadiene-iron tricarbonyl complexes. Functional groups in the substituents display many of their normal chemical reactions which can be used to prepare further types of substituted cyclobutadiene-iron tricarbonyl complexes. 

One of the most interesting properties of the complex concerns its reactions with electrophilic reagents. It is found that these reactions lead to substituted cyclobutadiene-iron tricarbonyl complexes and, in this sense, the complex is classified as aromatic just as ferrocene may be so classified. The substitution reactions which have been performed so far are summarized below. 

The mechanism of these substitution reactions can be readily rationalized in a manner which completely parallels the accepted electrophilic mechanism of benzene and other aromatic systems. The electrophile, R", adds to the cyclobutadiene ligand to produce the 7r-allyl-Fe(CO)3 cationic intermediate (XVI) loss of a proton from this intermediate generates the substituted cyclobutadiene -Fe(CO)3 complex. We have previously isolated salts of the 7r-allyl-iron tricarbonyl cation (XVII), as well... 

One final comment relating to the aromaticity of the cyclobutadiene ligand concerns the orientation effect of substituents towards introduction of a second substituent. To date, the only reaction bearing on this question which has been performed is the acetylation of methylcyclobutadiene -Fe(CO)3 (XVIII), which was prepared by reducing the chloromethyl complex (IX). Acetylation of Complex XVIII produces a mixture of 2-and 3-acetyl-1-methylcyclobutadiene-iron tricarbonyl complexes with the latter isomer (XIX) predominating ( 2 1). This is not the orientation... 

Planar chiral compounds usually (and for the purpose of this review, always) contain unsymmetrically substituted aromatic systems. Chirality arises because the otherwise enantiotopic faces of the aromatic ring are differentiated by the coordination to a metal atom - commonly iron (in the ferrocenes) or chromium (in the arenechromium tricarbonyl complexes). Withdrawal of electrons by the metal centre means that arene-metal complexes and metallocenes are more readily lithiated than their parent aromatic systems, and the stereochemical features associated with the planar chirality allow lithiation to be diastereoselective (if the starting material is chiral) or enantioselective (if only the product is chiral). 

The C NMR spectrum of cyclobutadiene-iron tricarbonyl consists of a singlet at 209.0 ppm for the carbonyl carbons and a doublet centered at 61.0 ppm, Jc-H = 191 Hz (193). The large C-H coupling constant suggests hybridization at carbon between sp and sp which is consistent with the strained cyclobutadiene ring. In a plot of C versus chemical shifts the cyclobutadiene resonances fall on the same line as resonances for aromatic molecules, their ions and their metal n complexes. 

These reactions are extremely sensitive to conditions, e.g., temperature, solvent, etc. The best one is the reaction of the palladium complex (XXXVII) with iron pentacarbonyl to give (XIII). At 80° C the yield ranges from 87% in benzene, cyclohexane, or 1,2-dichloroethane, to 17% in tetrahydro-furan-diglyme and is zero in carbon tetrachloride (77). The reaction of (XXXVII) with molybdenum hexacarbonyl only occurs in aromatic hydrocarbon solvents and since the complex (XL) is obtained in the same yield starting from either molybdenum hexacarbonyl or benzenemolyb-denum tricarbonyl, it is reasonable to assume the latter to be an intermediate in this reaction. 

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