The polymer-supported MacDonald-type porphyrin synthesis: Coupling of two dissimilar dipyrromethanes

Article abstract of DOI:10.1016/S0040-4039(00)01269-7

Syntheses of two completely unsymmetrical porphyrins have been achieved by MacDonald-type condensations of polymer-bound 9-formyldipyrromethanes with dissimilar solution-phase dipyrromethanes. The chemoselectivity of the process depends on the nature of t

Full text of DOI:10.1016/S0040-4039(00)01269-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 7423–7426
The polymer-supported MacDonald-type porphyrin
synthesis: coupling of two dissimilar dipyrromethanes
John M. Montierth, Alejandro G. Duran, Sam H. Leung, Kevin M. Smith and
Neil E. Schore*
Department of Chemistry, University of California, Davis, CA 95616, USA
Received 13 July 2000; accepted 26 July 2000
Abstract
Syntheses of two completely unsymmetrical porphyrins have been achieved by MacDonald-type
condensations of polymer-bound 9-formyldipyrromethanes with dissimilar solution-phase
dipyrromethanes. The chemoselectivity of the process depends on the nature of the substituents at the a
positions of the substrates. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: cyclization; dipyrromethanes; porphyrins; pyrroles; polymer support.
The MacDonald porphyrin synthesis1,2 is a useful strategy for preparing porphyrins with C2
or higher symmetry. In principle it can be applied to the synthesis of less symmetrical porphyrins
by the condensation of dissimilar dipyrromethanes, but this method is rarely used because the
components can couple in more than one way to give products which are typically difficult to
separate, e.g. Scheme 1.
Scheme 1.
* Corresponding author. Tel: 1 530 752 6263; fax: 1 530 754 7610; e-mail: neschore@ucdavis.edu
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01269-7

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By linking one of the dipyrromethanes to a solid support, however, the synthesis and
purification of single completely unsymmetrical porphyrins should be possible.3 In a very early
study by Leznoff and Svirskaya,4 a minor unsymmetrical porphyrin product was prepared on a
polymer support ( in Scheme 2) in a reaction mixture in which the major symmetrical
®
porphyrin product formed in solution and was easily washed away.
Scheme 2.
We chose to explore the potential chemoselectivity benefits of solid phase methodology on the
MacDonald process. The a-free pyrrole 15 was coupled with acetoxymethylpyrrole 26, using
Montmorillonite K10 clay as the acid catalyst, to yield dipyrromethane 3. Cleavage of the
benzyl ester gave acid 4, which was decarboxylated and then formylated (Vilsmeier) to give
formyldipyrromethane 5 (Scheme 3).
Scheme 3. (a) Montmorillonite K10 clay, CH2Cl2, 25°C; (b) H2, Et3N, THF, Pd–C, 25°C; (c) pTsOH, CH2Cl2, 25°C;
(d) POCl3, DMF, K2CO3, CH2Cl2, 0–25°C; 5, 35% from 1; 16, 46% from 6
Similarly, a-free pyrrole 67 was coupled with pyrrole 78 to give benzyl ester 8, which upon
hydrogenolysis gave protected dipyrromethane 9.
Saponification of the side-chain methyl ester of 5 yielded acid 10, whose sodium salt was
attached to Merrifield polymer as 11 in loadings as high as 0.87 meq g−1. Coupling of
polymer-supported 11 with solution-phase 9 yielded polymer-bound tetrapyrrole 12. An initial
ring closure attempt using trimethyl orthoformate failed, but treatment of 12 with TFA, pTsOH,
and benzaldehyde gave polymer-supported porphyrin 13. Saponification of 13 followed by
esterification of the crude acid 14 gave methyl ester 15 completely free of isomers, confirming the
complete chemoselectivity of the sequence (Scheme 4).

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Scheme 4. (a) LiOH, THF, H2O, 25°C, 18 h, 100%; (b) NaOH, H2O, then 2% crosslinked Merrifield’s resin, THF,
65°C, 48 h; (c) 9, pTsOH, MeOH, CH2Cl2, 65°C, 48 h; (d) PhCHO, pTsOH, CH2Cl2, 45°C, 120 h, then O2, CH2Cl2,
72 h; (e) nBu4NBr, KOH, THF, H2O, 65°C, 48 h; (f) MeOH, H2SO4, 25°C, 18 h, 2.4% from 11
As a control we then allowed the same polymer-supported formyldipyrromethane 11 to
couple with a second, solution-phase formyldipyrromethane, to determine the competition
between formation of the polymer-supported unsymmetrical porphyrin and self-condensation of
two molecules of solution-phase component. Decarboxylation of 9 followed by Vilsmeier
reaction gave an appropriate formyldipyrromethane 16 (Scheme 3). Condensation between 11
and 16 followed by hydrolysis and esterification gave rise to pure, unsymmetrical 18 (Scheme 5).
The symmetrical porphyrin 17 was readily washed away from the resin prior to liberation of 18.
Scheme 5. (a) 16, CH2Cl2, 25°C, 0.5 h; then, pTsOH, CF3CO2H, O2, 48 h, filter; (b) nBu4NBr, KOH, THF, H2O,
65°C, 48 h; (c) MeOH, H2SO4, 25°C, 18 h, 15% from 11
Although the condensation between 11 and 16 was carried out using 1, 2, and 4 equivalents
of the latter, the yield of unsymmetrical porphyrin 18 was found to vary very little, remaining
in the 15–20% range. Not surprisingly, the yield of the easily separated symmetrical porphyrin
17 was the greatest with the largest excess of 16. Thus, in addition to demonstrating the
compatibility of polymer-support strategies with the standard methodologies of pyrrole manipu-
lation and porphyrin synthesis, this system represents another case where the polymer-supported
reaction affords significant practical benefits for the preparation and isolation of a cross-coupled
product for which no inherent selectivity exists with respect to symmetrical byproduct
formation.9

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Acknowledgements
Acknowledgment is made to the National Science Foundation by N.E.S. for support of
research in polymer-supported synthesis (CHE-97-10286) and by K.M.S. for support of research
in porphyrin synthesis (CHE-99-04076). We also acknowledge a research fellowship to A.G.D.
from the MURPPS (Minority Undergraduate Research Participation in the Physical and
Mathematical Sciences) program at UC Davis.
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