Functionalization of 3,5,8-Trichlorinated BODIPY Dyes

Abstract

Catalytic hydrogenation of dibenzyl 5-dipyrroketone-2,9-dicarboxylates followed by decarboxylative iodination affords a 2,9-diiododipyrroketone which gives a 2,5,9-trichlorodipyrromethene hydrochloride after nucleophilic addition/elimination, with adventitious chloride to replace the two iodide groups. Treatment with BF3·Et2O gives a 3,5,8-trichloro-BODIPY that readily undergoes regioselective Stille coupling at the 8-position, or homo/mixed couplings at the 3,8- or 3,5- and 8-positions. Stepwise and controlled replacement of the 3,5- and 8-chlorine atoms using Stille reagents results in formation of a completely unsymmetrical trisubstituted BODIPY. Several examples of unsymmetrical BODIPYs were synthesized and characterized using this methodology. Structure features of new BODIPYs are discussed within the context of 14 new X-ray structures, and photophysical parameters of all new BODIPY compounds are reported and discussed.

Synthesis of 3,8‐Dichloro‐6‐ethyl‐1,2,5,7‐tetramethyl–BODIPY from an Asymmetric Dipyrroketone and Reactivity Studies at the 3,5,8‐Positions

“…Relative to BODIPY 1a bearing 3,8-chloro groups, slight blueshifts (1–5 nm) were observed in the absorption and emission bands of BODIPYs 7c and 14 bearing 8-phenyl groups, due to the large dihedral angles between this group and the BODIPY core (see Figures 3 and 5) as a result of 1,7-dimethyl substitution. [20] Larger blue-shifts were observed as a result from 8-phenoxy and 8-phenylamino substitution, as previously observed for 8-aryloxy and 8-arylamino-BODIPYs. [16, 29] This is in part due to the destabilization of the LUMO as a result of the electron-donating effect of these groups, which increases the HOMO–LUMO gap.…”

“…Subsequent boron complexation using excess BF 3 ·OEt 2 and N , N -diisopropylethylamine (DIEA) produced BODIPY 1a in 78% overall yield. The trans-chlorination of the 1-iododipyrroketone has been previously observed under these reaction conditions; [20] in addition, the 8-monochloro-BODIPY 1b was obtained as a minor product from the reaction, in 6% yield.…”

“…When excess phosgene was used to convert dipyrroketone 3 to the corresponding 5-chlorodipyrrin salt, the dipyrryl salt 4 was obtained instead by chlorination of the the α-methyl group of 3 , probably due to the presence of the electron-withdrawing benzyl ester. [20] Therefore, the benzyl ester was converted to an iodide by debenzylation followed by decarboxylative iodination [24] producing dipyrroketone 5 in 84% overall yield. The reaction of 5 with excess phosgene (15% in toluene) was accompanied by a color change from yellow to dark red, along with a down-field shift of the NH protons in the 1 H NMR spectrum.…”

“…However, these compounds show low fluorescence quantum yields ( Φ f <0.1), as a result of the greater freedom of rotation of the thienyl and furyl groups in comparison with phenyl, which increases the amount of energy lost to nonradiative decay to the ground state. [20, 31] The monostyryl-BODIPY 16 showed the most redshifted fluorescence emission ( λ max =617 nm) of all the BODIPYs investigated, and a high quantum yield ( Φ f =0.73). On the other hand, the significant redshift in the absorption and emission of formyl-BODIPY 17 relative to 6c is due to the conjugation of the carbonyl group with the BODIPY π-system, as indicated by the nearly co-planarity seen in the X-ray structure (Figure 6).…”

“…[20] Herein we report the synthesis of a versatile, asymmetric BODIPY 1a bearing two chloro substituents at positions 3 and 8, as well as a reactive 5-methyl group, starting from an asymmetric dipyrroketone. We show that BODIPY 1a can be regioselectively functionalized using four types of reactions, at positions 3, 5 and 8, to produce new conjugated BODIPYs.…”