Approaches to the synthesis of chiral and amino-substituted BODIPY dyes

Abstract

Boron dipyrromethenes (BODIPYs) have attracted considerable attention due to their fluorescence properties, including high fluorescence quantum yields and absorption coefficients, good photochemical stability and narrow absorption and emission bandwidths. Because of these properties, they have found extensive use for in vivo imaging, analyte sensing, photodynamic therapy, solar cells and light harvesting arrays. This thesis is divided in two parts. Part one covers the synthesis of functionalised chiral BODIPYs whilst part two involves investigations into the synthesis and application of aminoBODIPY via metal catalysed amination reactions. Four approaches to the synthesis of novel chiral BODIPY dyes were investigated. The axially chiral BODIPY dye with C2-symmetry I was synthesised via Suzuki coupling of the corresponding 2,6-dibromoBODIPY with 2-methoxyphenyl boronic acid. The unsymmetrical axially chiral BODIPY II was synthesized via Suzuki coupling of the corresponding 2-bromoBODIPY with phenyl boronic acid. Unfortunately, attempted resolution of these chiral systems by analytical chiral HPLC was unsuccessful. The new helically chiral BODIPYs IIIa-c were synthesised. Resolution of racemic helically chiral BODIPYs IIIa and IIIb was successfully accomplished by preparative chiral HPLC. Abstract ii Electronic circular dichroism (ECD) spectra of both (M) and (P) isomers of IIIa and IIIb were measured by Prof. W. Herrebout (University of Antwerp). Comparison of the measured and computationally predicted ECD spectra allowed the absolute configuration of each of the enantiomeric samples of IIIa-b to be established. The CPL spectra of both (M) and (P) isomers of IIIa and IIIb were recorded by Prof. R. D. Peacock (University of Glasgow). The |glum| of IIIa at 637 nm is 0.0043 and IIIb at 675 nm is 0.0042, which are among the largest so far reported for a simple BODIPY fluorophore in solution. We designed and synthesized the mono-strapped BODIPY V scaffold via sequential regioselective functionalisation of the unsymmetrical BODIPY IV. Resolution of N,N,F,O-BODIPY V by analytical chiral HPLC gave two peaks confirming that single enantiomers of this compound should be accessible. The 8-anisyl-substituted BODIPY VI was synthesized using a standard synthetic route, regioselective iodination with ICl then gave the 2-iodo-substituted BODIPY VII. We unexpectedly found that copper catalysed nucleophilic substitution of the 2-iodoBODIPY VII produced the 3-amino BODIPYs VIIIa-n in good yield. The reactions occurred successfully for a range of primary and secondary alkyl and aryl amines and even with benzamide, albeit in low yield. 2-aminoBODIPYs Xa-e have been prepared successfully via Buchwald–Hartwig amination of the 2-iodoBODIPY IX (fully blocked). The presence of the nitrogen group Abstract iii in the 2-position gives a broadened red-shifted absorption maximum and quenched fluorescence. This palladium catalysed amination was used to prepare the 2-nitroaniline-substituted BODIPY XI. Reduction of the nitro group by hydrogenation gave the novel fluorescencequenched 2-aminoaniline-substituted BODIPY XII. Reaction of this compound with triphosgene gave the corresponding benzimidazolone-substituted BODIPY XIII. The bright yellow fluorescence of the triphosgene reaction product XIII can be easily visualized by the naked eye. The detection limit for phosgene was determined to be 160 nM in solution at room temperature.