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 adamantyl‐enolether 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 late‐stage 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.

Chemiluminescence in Combination with Organic Photosensitizers: Beyond the Light Penetration Depth Limit of Photodynamic Therapy

“…Therefore, introducing Schaap’s adamantylidene-dioxetane into PSs promises to solve the problem of selective activation of PDT. Notably, Doron Shabat’s group recently developed a new efficient synthetic route based on the Stille cross-coupling reaction for the preparation of adamantane chemiluminescents, which will greatly reduce the synthetic difficulty and expand the chemiluminescent molecular library [ 62 ].…”

Oxygen‐Sensing Chemiluminescent Iridium(III) 1,2‐Dioxetanes: Unusual Coordination and Activity

“…[2] Among the several classes of chemiluminescent probes, spiroadamantane phenoxy 1,2-dioxetanes or Schaap's 1,2-dioxetanes [3] have been in the spotlight in recent years due to their relative stability, the analyte-specific responses that can be achieved by simple alterations of the phenol caging/protecting groups and the ease of the synthetic modifications that can be carried out on the scaffold. [4] These molecules have been proposed to luminesce by a chemically initiated electron exchange luminescence (CIEEL) mechanism, [5] where removal of the analyte-specific protecting group leads to the breaking of the dioxetane ring via an electron transfer from the phenolate. The resulting biradical anion can undergo further intramolecular or intermolecular electron transfer pathways (Scheme 1A) to yield the chemiexcited benzoate species, which relaxes to the ground state via light emission.…”

Energy Transfer Chemiluminescent Spiroadamantane 1,2‐Dioxetane Probes for Bioanalyte Detection and Imaging

“…These metastable molecules can be tailored to exhibit analyte‐specific responses by judiciously choosing the reactive protecting/caging groups for the phenolic unit. Upon reacting with the analyte, this “caging group” is removed to release the phenol that can undergo spontaneous chemiluminescence decomposition Furthermore, these scaffolds can be synthetically modified with ease, offering customized designs and properties [5] . These dioxetanes exhibit chemiluminescence via the widely‐accepted chemically initiated electron exchange luminescence (CIEEL) mechanism (Scheme 1A), where an initial intramolecular electron transfer from the phenolate anion (created by removal of the protective group) to the peroxidic ring takes place.…”

“…Upon reacting with the analyte, this "caging group" is removed to release the phenol that can undergo spontaneous chemiluminescence decomposition Furthermore, these scaffolds can be synthetically modified with ease, offering customized designs and properties. [5] These dioxetanes exhibit chemiluminescence via the widely-accepted chemically initiated electron exchange luminescence (CIEEL) mechanism (Scheme 1A), where an initial intramolecular electron transfer from the phenolate anion (created by removal of the protective group) to the peroxidic ring takes place. The occurrence of this intramolecular electron transfer in induced 1,2-dioxetane decomposition has been confirmed with Hammett studies on acridinium-substituted derivatives.…”