Heck functionalization of an asymmetric aza-BODIPY core: synthesis of far-red infrared probes for bioimaging applications

Abstract

As part of our ongoing work on the synthesis of a new class of plant hormones named Strigolactones (SLs) and their analogues, we became interested in tracing bioactive molecules with red emitting BODIPY fluorophores in order to unravel signaling and distribution of SLs in plants. In this paper we report on an unprecedented Heck functionalization of azadipyrromethenes (aza-DIPY) which allows for the introduction of suitable functional groups to convert aza-BODIPY in bioconjugate complexes useful for untangling biological processes.

Carborane‐BODIPY Dyads: New Photoluminescent Materials through an Efficient Heck Coupling

“…Final compounds 2 – 4 , 9 – 11 and 13 were fully characterized by 1 H, 13 C{ 1 H}, 11 B{ 1 H} and 11 B NMR spectroscopy, together with ESI‐HRMS and FTIR analyses. The 1 H NMR spectral data confirmed the complete ( E )‐stereoselectivity of the Heck coupling reaction for all the compounds, as established by coupling constant analyses of the characteristic olefinic proton signals. The 1 H NMR spectra of compounds 2 – 4 , 9 – 11 and 13 feature the characteristic benzylic proton signals of the spacer in the 3.00–3.50 ppm range, whereas the 1 H NMR spectra of BODIPY derivatives 2 – 4 show the peculiar pyrrolic CH signals of the dipyrromethene core at δ 6.00 ppm.…”

“…Based on our recent results concerning the functionalization of asymmetric aza‐BODIPY derivatives using the Heck reaction, we tested our previously reported coupling procedure on carborane‐containing olefins using a simple and commercially available coupling partner. The o ‐Me‐CB and bromobenzene were thus reacted using the Pd(OAc) 2 /( o ‐Tol) 3 P (10 and 20 mol%, respectively) catalytic system, in the presence of TBAB (tetrabutyl ammonium bromide) as an additive, Bu 3 N as a base in dimethylformamide (DMF) solvent at 100 °C.…”

“…The 1,3,5,7-tetramethyl BODIPY derivative 1 hasb een synthesized by an acid-catalyzed condensation of 2,4-dimethylpyrrole with p-bromobenzaldehyde, [29] and the styrenyl-containing carborane derivatives have been successfully synthesized by lithiationo ft he parent closocarborane clusterf ollowed by the addition of 4-vinylbenzyl chloride, as described in the literature. [16d,g] Based on our recent results concerning the functionalization of asymmetric aza-BODIPY derivatives using the Heck reaction, [27] we tested our previously reported coupling procedure on carborane-containing olefinsu sing as imple and commercially available coupling partner.T he o-Me-CB andb romobenzene were thus reactedu sing the Pd(OAc) 2 /(o-Tol) 3 P( 10 and 20 mol%,r espectively)c atalytic system, in the presenceo f TBAB (tetrabutyl ammonium bromide) as an additive, Bu 3 Na s ab ase in dimethylformamide (DMF) solvent at 100 8C. Under these conditions, no reactionw as observed and the starting materialsw ere recovered unchanged.P uzzled by this unexpected result, we speculated that the peculiar reactivityo ft he carboranec age might hamper the coupling reactionb ecause the challenging step of the Heck catalytic cycleisthe coordination and transmetalation of the alkene.…”

“…The Heck reaction on BODIPY dyes is nowadays an established synthetic procedure for the post‐functionalization of the dipyrromethene core . As part of our studies aimed at tagging biological relevant compounds using fluorescent probes for live cell‐imaging applications, we exploited the excellent photo‐features of BODIPYs as optical probes and we recently reported the optimization of a Heck coupling‐reaction on an asymmetric aza‐BODIPY core . Likewise, styrene‐containing carborane derivatives have demonstrated to be excellent starting molecules to achieve different fluorescent materials through a Heck coupling reaction –.…”

“…[25] As part of our studies aimed at tagging biological relevant compounds using fluorescent probes for live cell-imaging applications, [26] we exploited the excellent photo-features of BODIPYs as opticalp robesa nd we recently reportedt he optimization of aH eck coupling-reaction on an asymmetrica za-BODIPY core. [27] Likewise, styrene-containing carborane derivativesh ave demonstrated to be excellent starting molecules to achieve different fluorescent materials through aH eck coupling reaction. [3a, 16a-d] Therefore, we envisaged that these derivativesm ight represent av ery suitable coupling partner for Heck reactions with halogenated BODIPY fluorophores and their aza-analogues.…”