Dipyrromethanes, condensation with

Monoazaporphyrins were first prepared using [2 4- 2] dipyrromethane condensation methods by Fischer et al.2 Later, Johnson et al. improved the yield to a moderate level ( 58%) by cyclization of 1,19-dibromobiladiene-a,c with NaN3.177 Syntheses of metallomonoazaporphyrins via oxophlorin intermediates have also been reported (Scheme 51),2,181... 

The synthesis of cobalt meso-diphenyl corrolates has also been reported [31]. The synthetic procedure involves the acidic condensation of 3,4-dimethyl-2-(a-hydroxybenzyl)pyrrole-5-carboxylic acid with 3,3, 4,4 -tetramethyl dipyrro-methane, followed by reaction with cobalt salts. The reaction afforded a mixture of two isomers Co(5,15-OMDPC)PPh3 and Co(5,10-OMDPC)PPh3. The formation of this latter isomer has been explained by the high tendency of self condensation of the starting pyrrole under the reaction conditions, 2-(a-hydroxybenzyl)meso-phenyl dipyrromethane can be formed. This species would afford the Co(5,10-OMDPC)PPh3 by further condensation with the dipyrromethane unit present in excess in the reaction mixture. 

Alternative approaches for substituted porphyrins have been devised in which pre-functionalized dipyrromethane derivatives 3 are condensed with similar diformyl dipyrromethanes 4 through a "2+2" condensation to form meso-tetraarylporphyrins 5 (Scheme 3). Such condensations are usually catalyzed by acids and the intermediate porphyrinogens are oxidized by air to obtain porphyrins. In a similar "3+1" synthetic approach, tripyrranes 6 are condensed with 2,5-diformylpyrroles to form etioporphyrin 5 (1996CEJ1197). 

Bampos and coworkers (10ACI3930) have reported the synthesis of a new indene expanded porphyrin also called [22]dibenzo-dicarba-hexa-phyrin (1.0.0.1.0.0) 121 (Scheme 49) by "2+2" acid-catalyzed condensation of (S-alkyl-substituted dipyrromethanes 119 with 2-ethynyl-benzaldehyde 120. 

Condensation with aldehyde mixtures of two components A and B gives six different porphyrins two parent porphyrins and four hybrid porphyrins (cis- and trans- A B, AB, and A3B). Direct access to trans-A B porphyrins is best achieved with an aldehyde reacting on a-free dipyrromethanes. Capped porphyrins can be obtained from dialdehydes and pyrroles. Even a huge w-steroidal dialdehyde yields the corresponding porphyrin in 7% yield (Scheme 6.3.2)... 

A rare example of a direct chlorin synthesis was recently reported by Bums et This approach 1,9-diformyldi-pyrromethane 124 was condensed with dipyrromethane monocarboxylic acid 125 to afford the porphodimethene 126 under controlled oxygen-free conditions. Upon metalation with Zn(II), quantitative tautomerization of 126 produced metallochlorin 127 as a single isomer (Scheme 35). 

For example, the synthesis of receptor 7, a caUxpyrrole with an isophthalate strap, is shown in Scheme This compound was synthesized by condensation of 5-hydroxy-2-pentanone with pyrrole in the presence of an acid catalyst to afford the dipyrromelhane. Isophthaloyl dichloride was made to react with 2 equivalents of Ihe dipyrromethane to afford the bis-dipyrromethane that was condensed with... 

A mild procedure which does not involve strong adds, has to be used in the synthesis of pure isomers of unsymmetrically substituted porphyrins from dipyrromethanes. The best procedure having been applied, e.g. in unequivocal syntheses of uroporphyrins II, III, and IV (see p. 251f.), is the condensation of 5,5 -diformyldipyrromethanes with 5,5 -unsubstituted dipyrromethanes in a very dilute solution of hydriodic add in acetic acid (A.H. Jackson, 1973). The electron-withdrawing formyl groups disfavor protonation of the pyrrole and therefore isomerization. The porphodimethene that is formed during short reaction times isomerizes only very slowly, since the pyrrole units are part of a dipyrromethene chromophore (see below). Furthermore, it can be oxidized immediately after its synthesis to give stable porphyrins. 

The pyridine-like nitrogen of the 2H-pyrrol-2-yiidene unit tends to withdraw electrons from the conjugated system and deactivates it in reactions with electrophiles. The add-catalyzed condensations described above for pyrroles and dipyrromethanes therefore do not occur with dipyrromethenes. Vilsmeier formylation, for example, is only successful with pyrroles and dipyrromethanes but not with dipyrromethenes. 

This reaction sequence is much less prone to difficulties with isomerizations since the pyridine-like carbons of dipyrromethenes do not add protons. Yields are often low, however, since the intermediates do not survive the high temperatures. The more reactive, faster but less reliable system is certainly provided by the dipyrromethanes, in which the reactivity of the pyrrole units is comparable to activated benzene derivatives such as phenol or aniline. The situation is comparable with that found in peptide synthesis where the slow azide method gives cleaner products than the fast DCC-promoted condensations (see p. 234). 

New electrophilic substitution reaction methods for the preparation of dipyrromethanes have been reported. The condensation of IV-methylpyrrole with benzaldehyde leading to the corresponding dipyrromethane was promoted by the addition of the organic catalyst, pyrrolidinium tetrafluoroborate <06T12375>. The reaction between pyrrole and N-tosyl imines promoted by metal triflates gave dipyrromethanes whereas tripyrromethane byproducts were not observed <06T10130>. 

The oldest methods for synthesis involve the condensation-cyclization of trifluor-omethyl or fluoroalkyl pyrroles in the presence of a metal salt. These reactions afford tetrakis(fluoroalkyl) porphyrins. The electrophilic trifluoromethylation of porphyrins is selective and leads to /I-CF3 and meso-CVT, porphyrins. While condensation of meio-trifluoromethyl-dipyrromethane with an aldehyde in acidic medium is rather difficult, it proceeds with better yields and permits a selective introduction of trifluoromethyl groups in meso The Ruppert reagent (CF3TMS) has been used to... 

Four different synthetic procedures have been examined for the preparation of the triphenyl derivative, the fourth one suggested by the synthetic conditions developed to obtain the diphenyl derivatives. In the first three procedures it has been impossible to isolate the triphenyl-dihydrobilin. Its formation has been demonstrated, however, by monitoring the electronic spectrum of the reaction mixture and the cyclization to corrole has been carried out in situ. The synthesis that gave the highest yield (20%) and that avoids tedious purification procedures is outlined in Fig. 10. It involved the acidic condensation of benzaldehyde with two equivalents of 3,3, 4,4 -tetramethyl-meso-phenyl-dipyrromethane-5,5 ... 

Pyrrolidinium tetrafluoroborate (105) serves as an organocatalyst for the reaction of benzaldehyde with A-methyl pyrrole, to give the corresponding dipyrromethanes (106) under mild conditions.301 Initial formation of an iminium ion by condensation of the aldehyde with the catalyst is proposed. 

An alternative "2+2" approach (Scheme 4) involves the acid-catalyzed condensation of a-free dipyrromethanes 3 (1994T11427,05T6614,05SC929) with aldehydes to form porphyrinogens, which are then oxidized to obtain porphyrins 7. This methodology is considerably more versatile for array formation, and is frequently higher yielding and produces more soluble products as well as allows better control over substitution at the mcso-positions. 

Scheme 4 2+2 Condensation of a-free dipyrromethanes with aldehydes.

A simple and versatile one-pot synthesis of meso-substituted trans-A2B-corroles (Scheme 7) was reported by Gryko and Jadach (01JOC4267). It affords regioisomerically pure frans-A2B-corroles 11 through the TFA-catalyzed condensation of a dipyrromethane 10 and an aldehyde followed by oxidation with DDQ. The synthesis is compatible with diverse functionalities ester, nitrile, ether, fluoro, hydroxy, etc. on the aryl group of the... 

Since meso-substituted corroles with alkyl substituents at a (l-posihon often exhibit reduced stability due to oxidative ring opening (01IC4845), attempt was made to obtain stable analogues by substituting aryl substituents at a -position, which prevented corrole oxidation. Thus, condensation of dipyrromethane 19 (Scheme 11) and appropriately substituted aldehyde 20 under the influence of TFA furnished biladiene 21, and subsequently cyclized to stable corrole 22 derivatives. 

Likewise, in a "3+2" acid-catalyzed condensation of N-confused tripyr-rane 140 and dipyrromethane-dicarbinol 14 (R1=R2=R3=Ar), the N-fused pentaphyrin 141 with all nitrogens pointing inward was obtained. Subsequent oxidation of 141 (Scheme 58) gave 142, which isomerized into doubly N-fused pentaphyrin 143, devoid of aromaticity (04ACI876). 

Chandrashekar et al. (1997TL4149, 1998JPP69) have prepared 21-oxa or 21-thia porphyrins 225 (X=0, S) by condensation of diols 222 (X=0, S) with dipyrromethanes. Likewise, mono-ol 226 (X=0, S) with benzalde-hyde and pyrrole furnished 225 (04EJOC1693,04JOC6796). 

The 21,22-dioxaporphyrin 227 was synthesized by "2+2" acid-catalyzed condensation of 5,5 -diformyldifurrylmethane and a dipyrromethane diacid (1969JCS(CC)1480). 21,22-Diheteroporphyrins 229 (X=Y=0, S X=S, Y=0) containing S and O atoms have been obtained from 228 (X=Y=0 X=Y=S and X=S, Y=0) with 5-phenyl dipyrromethane derivative, followed by oxidation with DDQ (1998BKCS314,1999TL8879). 

Condensation of dipyrromethanes with appropriate thienylpyr-romethane or furylpyrromethane diols furnished monofunctionalized 21-thia 236 (X=S) and 21-oxaporphyrins 236 (X=0). Other methods used for synthesizing these compounds have also been reported (00BKCS97, 04EJOC1693,04JOC6796,05EJOC2500). 

In 2011, Singh et al. have reported the synthesis of meso-functionalized dipyrromethanes (11SC3491) 261 (X = NH) (Scheme 101) as well as unsym-metrical bis(heterocyclyl)methanes through Grignard addition of various aliphatic and aromatic halides on pyrrole-2-carboxaldehyde, followed by BF3 OEt2-catalyzed condensation of pyrrole-2-carbinols with pyrrole, etc. 

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]. 

The octaethyl analogue of 283 was recently synthesized by Franck and coworkers [195]. Condensation of 284 with the a-free dipyrromethane 285 gave the biladiene 286 which, when reacted with formaldehyde and subsequently oxidized with DDQ, gave the vinylogous porphyrin 287 (Scheme 53) [195]. This... 

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