Bacteriochlorins

Tire macrocyclic core of porphyrin systems 71 is highly conjugated and a number of effective resonance forms can be written. Tliere are nominally 22 TT-electrons but only 18 of these can be included in any one conjugative path (for a modern discussion on this topic, see references 98AGE177 and 99CEJ267). Chlorins (73, dihydroporphyrins), bacteriochlorins (74, tetra-hydroporphyrins), and isobacteriochlorins (75, tetrahydroporphyrins) also have full 18-7r delocalization available, though the number of possible resonance forms is reduced. 

Synthesis of chlorins, bacteriochlorins, isobacteriochlorins, and higher reduced porphyrins 98PHC1. 

Chlorins, e.g. 14, form adducts with osmium(VIII) oxide, which can be hydrolyzed in aqueous sodium sulfide to bacteriochlorindiols, e g. 2, or isobacteriochlorindiols, e.g. 3. Thus, similar to diimide reductions of chlorins, metal-free tetraphenylchlorin 14 (M = 2H) is selectively oxidized to a corresponding bacteriochlorin 2 whereas the zinc chlorin gives an isobac-teriochlorin 3 on oxidation with osmium(VIII) oxide.40 With less symmetrical chlorins, very complex mixtures of constitutional isomers and stereoisomers are formed by /i-bishydroxyla-tion.17... 

The extremely high sensitivity of bacteriochlorins to various reactions makes their chemistry very difficult. This might also be one reason why methods for the total synthesis of bacteriochlorins had not, until very recently, been developed.13 Total synthesis of a tolyporphin model was reported by Kishi et al.13 using an approach that is very closely related to Eschenmoser s syntheses of hexahydroporphyrins from reduced linear tetrapyrroles by cyclization (see Section 1.5.1). 

All other methods for obtaining bacteriochlorins are by partial synthesis from porphyrins, chlorins or chlorin derivatives. The bacteriochlorin is thereby produced by reactions which occur at the peripheral /J-C — C double bonds of the higher unsaturated systems. The main problem of these syntheses is the lack of regio- and stereoselectivity because three or four C —C double bonds, which are present in the starting products may be attacked, so that rcgio-and stcreoisomcric products can be formed. 

The simplest way for the preparation of bacteriochlorins is the reduction of porphyrins or chlorins with diimide or sodium in pentan-1-ol. The course of these reactions depends upon whether a metal is present in the inner core of the macrotetracycle, or not.3a h... 

The diimide reduction of nietal-free 5,10,15,20-tetraphenylporphyrin (2) or 5,10,15,20-tetraphenyl-2,3-dihydroxychlorin (3) gives the bacteriochlorins 1 in good yields. 

Oxidation of porphyrins and chlorins with osmium(VIII) oxide is an equally valuable method to produce bacteriochlorins, although it also leads to problems of regio- and stereoselectivity. 

In the case of the osmium(VIII) oxide oxidation of 5,10,15,20-tetraphenylchlorin,3b the metal-free macrocycle gives the bacteriochlorin 6, whereas the corresponding zinc derivative leads to an isobacteriochlorin. 

The bacteriochlorin 10 (65 mg, 0.11 mmol) was dissolved in coned H2S04 (18 mL) and allowed lo react at 20 C for 5 min. The mixture was poured into ice, diluted with H20 and NaOAc (7.5 g, 91 mmol) was added. The mixture was extracted several times with CHC13, the organic extractions were washed with H20 (2 x), dried (Na2S04) and evaporated. Preparative thin-layer chromatography (silica gel) gave 11 and 12 yields 10.7 mg (17%) and 44 mg (70%), respectively. 

The formation of bacteriochlorins from chlorophyll derivatives has also been studied.8 The reduction product 16 of methyl 3 -oxorhodochlorin-l 5-acetate (see Section 1.2.2.) undergoes photooxygenation with singlet oxygen to yield finally a bacteriochlorin 17. 

Transformations which alter the bacteriochlorin chromophore are quite rare. An important reaction in the structural elucidation of the bacteriochlorophylls is the dehydrogenation to chlorophyll derivatives. Thus, bacteriopyromethylpheophorbide a (1) can be smoothly dehydrogenated with 3,4,5,6-tetrachloro-l,2-benzoquinone to the corresponding chlorin 3-acetyl-pyromethylpheophorbide a (2) in high yield.1 la,b... 

Another transformation observed with a naturally occurring bacteriochlorin is the tautomer-ization of the exocyclic C — C double bond in bacleriochlorophyll b (3) in acetone which gives 7,8-dehydrobacteriochlorophyll a (4), a chlorin-type product (configurations at C7 and of the 8-ethylidene group have not been established).112,12... 

Isobacteriochlorins with two adjacent saturated pyrrole rings are the constitutional isomers of bacteriochlorins, in which two neighboring rings are partially reduced. 

Whereas in porphyrins, chlorins and bacteriochlorins the 1871-aromatic perimeter includes two nitrogens excluding their lone pairs, the.1871 perimeter of the isobacteriochlorin includes three nitrogens, one with its electron lone pair as part of the aromatic perimeter. The electron pair of the /J,/J -C —C double bond of ring D of isobacteriochlorin is not involved in the cyclic conjugation path. 

As for chlorins and bacteriochlorins, reactions at the chromophore periphery of porphyrins can be used to prepare isobacteriochlorins. The lack of regioselectivity in these reactions necessitates the use of highly symmetric porphyrins as starting materials. In some cases, intramolecular reactions have been used to solve the problems of regioselectivity. 

Isobacteriochlorins, since they are tetrahydroporphyrins, can be obtained by tetrahydrogena-tion of porphyrins and dihydrogenation of chlorins. However, alkali-metal reduction of porphyrins and metalloporphyrins always gives a mixture of chlorins, bacteriochlorins or isobacteriochlorins.14 The method of choice for the preparation of pure isobacteriochlorins, e.g. 2, is the diimide reduction of zinc(II) chlorins, e.g. l.15a,b... 

It is important to use a zinc(ll) chlorin because with the metal-free chlorin bacteriochlorins... 

Similiar problems of regioselectivity as in reduction reactions are encountered in oxidation reactions of porphyrins and chlorins. The oxidation of chlorins to isobacteriochlorins can be directed by insertion of zinc(II) or nickel(II) into the macrocycle. Again here, the metal-free chlorins give the bacteriochlorins whereas the metal chlorins, e.g. 1, give isobacteriochlorins, e.g. 3.15a,b I 7... 

Subsequently, other publications have appeared involving the DA reactions of porphyrins with other dienes. For instance, the reaction of meso-tetrakis(pentafluorophenyl)porphyrin Id with the diene generated from pyrrole-fused 3-sulfolene gave rise to the isoindole-fused chlorin derivative 8 accompanied by a mixture of stereoisomeric bacteriochlorins 9 (Scheme 2) <98CC2355>. 

When a larger excess of the azomethine ylide precursors was used and the reflux was prolonged for 40 hours, the reaction afforded isobacteriochlorin 63 as the major adduct together with a small amount of bacteriochlorin 64 (Figure 5). This result demonstrates that the attack of the second azomethine ylide species to the chlorin macrocycle occurs preferentially at the adjacent P-pyrrolic double bond, yielding the isobacteriochlorin with high site selectivity. 

Reaction of porphyrins with nitrones has also been studied and the results obtained showed that this is a versatile approach leading to the synthesis of isoxazolidine fused-chlorins (Scheme 26). For instance, chlorin 74 was successfully prepared from the reaction of the jV-methylnitrone, generated in situ from JV-methyl hydroxylamine and paraformaldehyde, with porphyrin Id . It is important to note that bis-addition also took place, yielding exclusively bacteriochlorin type derivatives 76 and 77 (Figure 6). This result contrasts with those obtained in 1,3-DC reactions with azomethinic ylides where isobacteriochlorins were obtained preferentially. 

Glycoconjugated isoxazolidine-fused chlorins and bacteriochlorins were also elegantly synthesised using a 1,3-DC approach (Scheme 26). For instance, the galactosylnitrone reacted with porphyrin Id in a small volume of toluene, at 60 °C, to yield chlorin 75, accompanied by a small amount of two related bacteriochlorins <02TL603>. 

As shown above, porphyrins can be used as dienophiles and as dipolarophiles in DA and 1,3-DC reactions with a wide range of reactive dienes and 1,3-dipoles to achieve monoadducts of the chlorin type, as the main products, or related compounds. Furthermore, under certain conditions, bis-adducts of the iso- or bacteriochlorin types can be obtained depending on the 4% species used. 

Starting from the Ni mrao-formyloctaethylporphyrin oxime complex, the meso-cyanooctaethylporphyrin N-oxide complex has been synthesized for the first time. The double addition of the nitrile oxide to 2,5-norbornadiene afford a porphyrin dimer, whose structure has been established by X-ray diffraction analysis (485). The 1,3-dipolar cycloaddition reaction of w< .so-tetraarylporphyrins with 2,6-dichlorobenzonitrile oxide yields isoxazoline-fused chlorins and stereoiso-metric bacteriochlorins. The crystal structure of one of bacteriochlorins has been characterized by X-ray diffraction (486, 487). 

More recently, Cavaleiro et al. described a new method to prepare novel glyco-dihydro- and diglycol-tetrahydroporphyrins (chlorins 116, 117, bacteriochlorins 119 and isobacteriochlorins 118), through CuCl-catalyzed cyclopropanation reactions of a-diazoacetates derived from di-acetonides of several glycosides 113bA-bD with meso-tetrakis(pentafluorophenyl)-porphyrinatozinc(n) 115 (Scheme 16).10... 

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