Dipyrromethanes, condensation with aldehydes

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)... 

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.

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... 

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. 

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. 

The inverted porphyrins (also called N-confused porphyrins) 289 were discovered accidentally as by-products of the well-known acid-catalyzed pyrrole aldehyde cyclocondensation route to porphyrins (Scheme 58) (see Chapter 14 by Latos-Grazynski). Rational multistep synthetic approaches to inverted porphyrins have t peared recently. Dolphin and coworkers. s have reported a method for the preparation of porphyrin 292 involving acid-catalyzed MacDonald-type (2 -I- 2) condensation of an a,j8-dipyrromethane 291 and a,a-dipyrromethane dialdehyde 290. Lee and coworkers have reported a (3 -I- 1) approach to porphyrin analogues with an inverted pyrrole and a thiphene, or a furan ring system 293 (Scheme 59). Pandey et reported the preparation of dibromo-a, c-... 

A more straightforward method to mew-monosubstituted, [)-unsubstituted porphyrins has been reported by Senge and co-workers in 2002 [54] and consists in the condensation of various type of aldehydes with dipyrromethane and pyrrole-2-carbaldehyde leading to dilferently substituted mew-monosubstituted porphyrins with moderate yields (2-12 %). A similar method was used to prepare (SBF)PH2 (Scheme 6) [52]. In a typical experimental procedure, dipyrromethane 2, pyrrole-2-carbaldehyde 4 and aldehyde 1 dissolved in freshly distilled dichlo-romethane were stirred with trifiuoroacetic acid, under an argon atmosphere, for 16 h. After addition of chloranil, triethylamine was added and the solvent was... 

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