Nucleophilic Aromatic Substitution (S_NAr) and Related Reactions of Porphyrinoids: Mechanistic and Regiochemical Aspects

Abstract

The nucleophilic substitution of aromatic moieties (SNAr) has been known for over 150 years and found wide use for the functionalization of (hetero)aromatic systems. Currently, several “types” of SNAr reactions have been established and notably the area of porphyrinoid macrocycles has seen many uses thereof. Herein, we detail the SNAr reactions of seven types of porphyrinoids with differing number and type of pyrrole units: subporphyrins, norcorroles, corroles, porphyrins, azuliporphyrins, N‐confused porphyrins, and phthalocyanines. For each we analyze the substitution dependent upon: a) the type of nucleophile and b) the site of substitution (α, β, or meso). Along with this we evaluate this route as a synthetic strategy for the generation of unsymmetrical porphyrinoids. Distinct trends can be identified for each type of porphyrinoid discussed, regardless of nucleophile. The use of nucleophilic substitution on porphyrinoids is found to often be a cost‐effective procedure with the ability to yield complex substituent patterns, which can be conducted in non‐anhydrous solvents with easily accessible simple porphyrinoids.

Nonplanar porphyrins: synthesis, properties, and unique functionalities

“…7 However, the development of facile functionalization methods has significantly improved access to such unsymmetrical compounds. A typical approach is the use of sequential S N Ar reactions, 93 developed for the preparation of dodecasubstituted ABCD-type porphyrins. 94 For example, a reaction sequence of PhLi, and NMe 2 PhLi with H 2 OEP (H 2 11 ) gave porphyrin H 2 118 in 69% yield.…”

“…Alternatively, organolithium reagents can be used as shown in Scheme 9; however, these give preferentially the 5,10-disubstitution pattern. 93…”

BODIPY‐Pt‐Porphyrins Polyads for Efficient Near‐Infrared Light‐Emitting Electrochemical Cells

“…The following two steps involved the insertion of the platinum metal center in the macrocycle core ( 7 ) and a nucleophilic aromatic substitution (SNAr) reaction for the substitution of para ‐fluorine atoms with —N 3 groups ( 8 ). [ 36 ] Finally, a copper‐catalyzed (CuI) azide–alkyne cycloaddition was performed in a THF/CH 3 CN (1:1) mixture, producing the PtBDP‐2‐8 .…”

Applications of Fluorous Porphyrinoids: An Update†

“…These results confirm that fluorinated NPs-containing porphyrinoids possess both better solubility and oxygen transport to be used for biomedical applications, but these simple systems lack site selectivity toward diseases. Fortunately, the electronegative fluorine groups present on these aromatic compounds allow multiple bio-targeting groups to be efficiently attached via nucleophilic substitution (11,34).…”

“…Several S-, N-and O-containing moieties have been conjugated to fluorinated porphyrinoids via nucleophilic aromatic substitution (10,34). Nucleophiles with electron-donating groups result in higher yields compared with those with electronwithdrawing groups when reacted with fluorinated porphyrinoids.…”