Synthesis and Reaction of Unsaturated Substituents in Porphyrin Chemistry Katja Dahms and Mathias O. Senge School of Chemistry, SFI Tetrapyrrole Laboratory, University of Dublin, Trinity College Dublin, Dublin 2, Ireland (email:
[email protected])
Introduction: Porphyrins are a unique class of compounds that are ubiquitous in nature and function in a wide variety of roles ranging from oxygen transport, electron transfer, and oxidation catalysts to photosynthesis. Tetrapyrroles also play a central role in disparate areas such as photodynamic therapy, malaria, porphyrias, and unsolved medical problems such as drug-induced neuropsychiatric disorders. Due to these properties they are some of the most important fine chemicals in industry and are utilised in an ever-expanding array of applications.
Formylporphyrins have been explored extensively. However, few reactions have been reported using meso-substituted formylporphyrins for the purpose of functionalising porphyrins.[1,2] The Wittig reaction of meso-formylporphyrins offers an alternative approach to Pd-catalysed reactions for the synthesis of olefinic-substituted porphyrins. This type of reaction allows the use of milder reaction conditions, which results in similar products with yields of 61 to 81 %.[3]
O
H
N
N R
Ni
R N
R'
HO
N
Grignard
N
N R
Ni
R N
N
R' O
H
R = hexyl, phenyl R' = ethyl, phenyl, allyl N
N
Wittig
R
Ni
R
N
N
N
N R
Ni
R
N
N
R = hexyl, phenyl R' = H, cyano
R
O
N
NaH
Ni N
N
N
N
N
N Ni N
N
O P(OiPr)2 O
NaH
N
N
N Ni
Ni N
allyl
80
P(OiPr)2
73 %
H
phenyl
Also, the formyl group on the porphyrin can be converted to a secondary alcohol via Grignard reaction.[4] This methodology can be used for aryland alkyl-substituted porphyrins, giving the corresponding products in 54 to 93 % yield.
H
N
R' Yield [%] ethyl 68 ethyl 54 phenyl 93 phenyl 85
R'
Yield [%] hexyl H 61 phenyl cyano 81
O
R phenyl hexyl phenyl hexyl
N
N
A variation of the HornerWadsworth-Emmons reaction can be used for the formation R' O of allenes. As the first step, an P(OiPr)2 R'' alkenylphosphonate is prepared by the reaction of tetraisopropyl methylenediN N N N phosphonate with the R R Ni Ni R R formylporphyrin in high N N N N yield.[5] This is followed by the formation of a vinylanion by using an organolithium reagent which then can be reacted with a carbonyl compound. The resulting hydroxyalkenylphosphonates can be converted to the desired allenes by a second Horner-Wadsworth-Emmons olefination. Currently we are working on the implementation of the lithiation.
96 %
References: [1] Mathias O. Senge, Sabine S. Hatscher, Arno Wiehe, Katja Dahms, Andrea Kelling, J. Am. Chem. Soc., 2004, 126, 13634-13635. [2] Katja Dahms, Mathias O. Senge, M. Bakri Bakar, Eur. J. Org. Chem., 2007, in press. [3] Dennis P. Arnold, Richard Gaete-Holmes, Alan W. Johnson, Andrew R. P. Smith, Geoffrey A. Williams, J. Chem. Soc., Perkin Trans. 1, 1978, 1660-1670. [4] Dennis P. Arnold, Alan W. Johnson, Mailvaganam Mahendran, J. Chem. Soc., Perkin Trans. 1, 1978, 366-370. [5] Hideki Inoue, Hiroshi Tsubouchi, Yasuo Nagaoka, Kiyoshi Tomioka, Tetrahedron, 2002, 58, 83-90.
This work was generously funded by Science Foundation Ireland Professorship SFI 04/RP1/B482
