Sapphyrins synthesis

Sapphyrins were discovered serendipitously by Woodward33 during the course of synthetic studies directed towards the total synthesis of vitamin B, 2. The sapphyrins were the first example of expanded porphyrins in the literature. Due to sapphyrin exhibiting a deep-blue color in the crystalline state and intense green in solution. Woodward coined the expression sapphyrin with reference to the deep-blue color of sapphire stones. 

This experiment made clear that a [4 + 1] approach for the synthesis of sapphyrins is not very satisfactory. In further synthetic studies,33 Woodward demonstrated that sapphyrins could be obtained along different routes, but the yields of these methods were not at all satisfactory. 

Sandwich complexes nickel. 5, 35 Sapphyrins, 2, 888 demetallation, 2, 891 metallation, 2, 891 reactions, 2, 891 synthesis, 2, 889 Sarcoplasmic reticulum calcium/magnesium ATPase, 6, 566 skeletal muscle... 

Krai V, Davis J, Andrievsky A, Kralova J, Synytsya A, Pouckova P, Sessler JL (2002) Synthesis and biolocalization of water-soluble sapphyrins. J Med Chem 45 1073-1078. 

Sapphyrin (e.g., 2) is the most venerable of the many expanded porphyrins now known. It was first discovered serendipitously in the Woodward group more than 30 years ago during the course of studies directed toward the synthesis of vitamin Recently improved syntheses of sapphyrin have been developed by the... 

Sessler and coworkers reported a new "3+1+1" route for sapphyrins, without using a bipyrrolic moiety (01TL2447). Tripyrrane dialdehyde 133 with two equivalents of a pyrrole under acidic conditions, followed by oxidation with DDQ furnished sapphyrins 134 bearing different substituents in yields lower than by the "3+2" approach (Scheme 51), but the need of a bipyrrole synthesis could be obviated. This method (Scheme 55) allowed the synthesis of otherwise not known sapphyrins that contained various symmetric bipyrrolic subunits. 

In a later synthetic effort, a doubly N-confused sapphyrin 113 was obtained, wherein both confused rings belong to the bipyrrolic fragment of the macrocycle [255], In this system, a methoxy group is attached to one of the external a-pyrrolic positions, creating a peripheral sp3 center. This structural feature, which is presumably due to spontaneous addition of a methanol molecule during the synthesis,... 

The synthesis of this expanded porphyrin was successfully achieved using [66] a 2 + 3 MacDonald coupling similar to the one used to obtain sapphyrin [26, 66] and pentaphyrin [182, 183]. In this case, a diformyl bipyrrole 194 and a pyrrolyldipyrromethane dicarboxylic acid 225 were condensed in the prince of HBr to give the new macrocycle 226 (Scheme 39) [67]. Here, the requisite pyrrolydipyrromethanes were generated by HBr catalyzed condensations of... 

To date, the poor stability of the smaragdyrins 226, 229, and 230 has unfortunately precluded a complete study of their chemistry. However, the unique nature of these unusual aromatic materials suggests that further efforts may be warranted. Just as a leinv gation of the sapphyrin system has provided a wealth of new chemistry [157], a sinular study of the synthesis and properties of smaragdyrin and related compounds could uncover further interesting observations including, perhaps, stabilized forms of this class of expanded porphyrins. 

With the original reports of the successM synthe of the sapphyrins [26,66,152] and uranyl superphthalocyanine [112, 118, 119], interest in other expanded porphyrin systems, was kindled. The next logical step (after sapphyrin), in the expanding series of all-pyrrole systems, was the pentaphyrin macrocycle 231 which contains five pyrroles and five meso-like methine bridgra. In 1983 Gossauer et al. reported the synthesis of the first prototypical member 231 of this macrocyclic family [158, 182, 183, 185-187]. This first synthesis was achieved by a 2 + 3 MacDonald-type condensation between an oc-firee dipyrromethane 233 and a tripyrrane dialdehyde 236. More recently, the synthesis of pentaphyrin 231 has l n achieve by using a dipyrromethane 5,5 -dicarboxylic acid 235 in place of an a-firee dipyrromethane [21]. Here, as is the case in many of these kind of reactions [21,26,27,66,155], decarboxylation occurs under the reaction conditions to produce the corresponding a-free species 233 in situ. (Scheme 40) [21]. 

Synthesis and characterization of other related macrocycles, including chlorins, " isobacteriochlorins, bacteriochlorins, mono- and dioxoporphyrins, " other more highly saturated hydroporphyrins, N-alkyl- or A-arylporphyrins, some of which are chiral, porphodimethenes, thiaporphyrins, " oxaporphyrins, N-confused " and carbapor-phyrins, porphycenes " and corrphycenes, " tetraazaporphyrins, phthalocyanines, the ring-expanded sapphyrins, texaphyrins and others, and the ring-contracted corroles " and corrolazines have also been synthesized and are discussed in the indicated references. 

As implied above, the first synthesis of a sapphyrin was purely accidental and came about as the result of the reaction of the linear tetrapyrrolic precursor 5.1 with formic acid and HBr. Following oxidation with iodine, instead of obtaining the desired tetrapyrrolic corrole macrocycle, a different macrocycle was obtained (Scheme 5.1.1). This unexpected by-product was best formulated as being the deca-alkyl-substituted aromatic pentapyrrolic macrocycle 5.2. The unexpected formation... 

Although more practical than the 4 + 1 approach, the 3 + 2 route was also found early on to be limited by difficulties associated with obtaining the requisite tripyrrolic ( 3 ) and bipyrrolic ( 2 ) precursors. Thus, even though the initial reports of Woodward and Johnson served to pique the curiosity of the porphyrin community, the chemistry of sapphyrins remained undeveloped until 1991, when Sessler and coworkers introduced an improved synthesis of sapphyrins. This new synthesis is based on simple high-yielding routes to both dicarboxyl-substituted... 

Prior to developing the above synthesis, Sessler and coworkers discovered a different route to meso-axy sapphyrins. This synthetic strategy, like so many in the area of sapphyrin-related research, is based upon a reaction that was not initially intended to produce sapphyrins. Specifically, it involves the reaction between bis(pyrrolyl)bipyrrole 5,38 and diformyl dipyrrylmethane 5.39, and was found to produce, quite unexpectedly, sapphyrin 5,41 in ca. 5% yield, with none of the intended hexapyrrolic macrocycle 5,40 being detected (Scheme 5.2.3). It was thus considered that such a 4 + 2 = 5 approach might prove useful for the synthesis of we o-phenyl sapphyrins. This indeed proved to be the case. In fact, this strategy has... 

In 1995, Latos-Grazyhski and coworkers reported an efficient, albeit somewhat low-yielding, synthesis of tetraphenylsapphyrin 5.50. In this work, it was found that the acid-catalyzed, oxidative reaction of benzaldehyde (5.30) with pyrrole (5.29) in a 1 3 molar ratio gave, as expected, tetraphenylporphyrin and an isomeric N-inverted porphyrin as the main macrocyclic products (cf. discussion in Chapter 3). However, careful examination of the minor fractions revealed that one side-product of this reaction was in fact the pentapyrrolic tetraphenylsapphyrin 5.50a (Scheme 5.2.6). Unfortunately, this species could only be isolated in 1.1% yield. Nonetheless, this synthesis represented the first synthetic entry into the area of tetrakis-mc o-substituted sapphyrins. 

The methods described above for the synthesis of wc5o-arylsapphyrins are relatively new. This newness has so far limited the availability, and therefore the study, of aryl-substituted sapphyrin systems. This, however, is something that is likely to change in the near future, especially when one considers the important role that the parent me o-phenyl-substituted porphyrins have played in the development of numerous biological and materials science model systems. ... 

The synthesis of the linear trimeric oligosapphyrin 5.134 was also reported by Sessler, et alP Here, sapphyrin monoacid 5.109 was first activated (i.e., converted into any of the following forms acid chloride, acylimidazole, mixed anhydride, or activated ester) and then reacted with the bis-amino-functionalized sapphyrin 5.133. Here, too, reaction yields on the order of 50-80% were routinely achieved (Scheme 5.6.7). 

The interest and excitement aroused by the successful synthesis of sapphyrin led Grigg and Johnson to suggest that a pentapyrrolic macrocycle containing two directly linked pyrroles (e.g., 5.142, shown in its unsubstituted, free-base form Figure 5.7.1) could exist in a planar, strain-free conformation." They referred to this class of molecules as norsapphyrins since they are formally derived from sapphyrin by the removal of one me5o-carbon from its macrocyclic nucleus. Thus, the norsapphyrins (later called smaragdyrins by Woodward see below) would be expected to bear the same relation to sapphyrin as corrole does to porphyrin. 

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