Modular Access to Diverse Chemiluminescent Dioxetane‐Luminophores through Convergent Synthesis

Abstract

Adamantyl-dioxetane luminophores are an important class of chemiluminescent molecular probes for diagnostics and imaging. We have developed a new efficient synthetic route for preparation of adamantylenolether as precursors for dioxetane chemiluminescent luminophores. The synthesis is convergent, using an unusual Stille cross-coupling reaction employing a stannane-enolether, to directly afford adamantyl-enolether. In a following simple step, the dioxetane is obtained by oxidation of the enolether precursor with singlet-oxygen. The scope of this synthetic route is broad since a large number of haloaryl substrates are either commercially available or easily accessible. Such a latestage derivatization strategy simplifies the rapid exploration of novel luminogenic molecular structures in a library format and simplifies the synthesis of known dioxetane luminophores. We expect that this new synthetic strategy will be particularly useful in the design and synthesis of yet unexplored dioxetane chemiluminescent luminophores.

Exploring the Structural Space of Chemiluminescent 1,2-Dioxetanes

“…Shabat also synthesized the coumarin fluorophore linked this time to Schaap’s spiroadamantane dioxetane, which exhibited similar chemiluminescence properties . An exciting development was recently reported in a collaboration between Shabat, Baran, and co-workers to develop a convergent synthesis of luminophore dioxetanes using a Stille coupling to append a dioxetane to a fluorophore at a late stage (Figure D) . A range of dioxetane luminophores were prepared including coumarin, aminocoumarin, a luciferin analogue, a NIR cyanin, and a pyridine based scaffold, demonstrating how this strategy can be used to tune the kinetics, emission wavelengths, and quantum yields of dioxetane chemiluminophores.…”

“…79 An exciting development was recently reported in a collaboration between Shabat, Baran, and co-workers to develop a convergent synthesis of luminophore dioxetanes using a Stille coupling to append a dioxetane to a fluorophore at a late stage (Figure 6D). 80 A range of dioxetane luminophores were prepared including coumarin, aminocoumarin, a luciferin analogue, a NIR cyanin, and a pyridine based scaffold, demonstrating how this strategy can be used to tune the kinetics, emission wavelengths, and quantum yields of dioxetane chemiluminophores. Lastly, Lippert and co-workers have reported using a spiropyran photoswitch as the phenol unit of the dioxetane, furnishing Spiro-CL as a unique example of a photoswitchable chemiluminescent dioxetane (Figure 7).…”