Mechanistic Studies on the Nucleophilic Reaction of Porphyrins with Organolithium Reagents

Abstract

Porphyrins react readily with organolithium reagents under substitution of free meso positions. As this method has proven to be very versatile for the preparation of a wide range of meso substituted porphyrins, a mechanistic study of the reaction was undertaken using 5,15-diaryl- and dialkyl substituted porphyrins, 2,3,7,8,12,13,17,18-octaethylporphyrin, and the respective nickel(II) complexes. A combination of deuteration experiments, electronic absorption spectroscopy of the reactive intermediates, trapping of intermediates with organic electrophiles, and reaction at different pH values showed significant differences in the reaction pathways of free base porphyrins and metalloporphyrins. In both cases the reaction proceeds initially under formation of phlorin like intermediates which are stable in water. For the Ni(II)phlorins a mesomeric carbanionic form with a highly distorted structure exists that can react as a nucleophile with electrophiles such as RI, H+, or D+. In the latter case a protonation-deprotonation equilibrium involving porphodimethen intermediates has to be assumed. Free base phlorins do not react as nucleophiles but can undergo H/D exchange reactions in strongly acidic media.

Syntheses and Functionalizations of Porphyrin Macrocycles

“…Di-, tri-, and tetra- meso -alkylated porphyrins can also be obtained via this methodology in overall yields of 20-40%, by successive one equivalent additions of alkyllithium at low temperature, followed by hydrolysis and oxidation with DDQ [249]. Alkyl- and aryl-lithium agents showed meso -regioselectivity when 5,15-disubstituted porphyrins, such as 80 were used, producing the corresponding porphyrins 116 in 56-94% yields (Scheme 42 ) [250-252]. …”

Synthesis of meso‐Substituted ABCD‐Type Porphyrins by Functionalization Reactions

“…Typically, attacking a meso position opposite to one carrying an aryl group is difficult due to steric hindrance of the mesomeric benzylic anion stabilization. [16] While the synthesis of some A 2 BCtype porphyrins by this method was successful the yields obtained of these A 2 BC-porphyrins were lower than those of A 2 BC-porphyrins formed when B was an alkyl group. For example, porphyrin 60 did not react with p-ethynylphenyllithium or n-butyllithium.…”

“…However, initially we were not too convinced, as studies with 2,3,7,8,12,13,17,18-octaethylporphyrin and other systems had shown a preference for formation of the 5,10-AB derivatives over the 5,15-AB regioisomers. [13][14][15][16] Nevertheless, we attempted some reactions of 5-substituted aryl and alkylporphyrins with LiR reagents under our standard conditions (Scheme 3).…”

“…In this context we have developed the use of organo-lithium reagents for the synthesis of various tetrapyrrole classes. [13][14][15][16] In a strategic sense the preparation of ABCD-type porphyrins by functionalization requires the use of the lesssubstituted precursors, e.g. 7, and ultimately use of unsubstituted porphyrin 8.…”

Oligoporphyrins with One-and Two-Atom Covalent Bridges: Synthesis and Reactivity, Solid-State, Solution and Electronic Structures, Spectroscopy and Applications

“…99,100 In collaboration with Wasielewski and Kim, extensive physical measurements were carried out on these and their ladder, triangular prismatic and bis(cruciform) supramolecular arrays connected through terminal 100 Lastly, the Osuka group entered this field in 2012 with an extension of their 3,7-bis(2-pyridyl)porphyrin chemistry. By treatment of substrate 80 with alkynyllithiums, two-step C-H activation by Senge-type chemistry 101 was achieved, including the preparation of the orthogonal C 2 dimer structure 81, using NiTriAP-C 2 -Li prepared in situ. 102 The chemistry of C 2 porphyrinoid dimers was extended in 2011 by Furuta and coworkers to core-modified porphyrins of the N-confused type (NCP).…”