Photochemical generation of oxa-dibenzocyclooctyne (ODIBO) for metal-free click ligations

Abstract

Oxa-dibenzocyclooctynes (ODIBO, 2a–c) are prepared by photochemical decarbonylation of corresponding cyclopropenones (photo-ODIBO, 1a–c). While photo-ODIBO does not react with azides, ODIBO is one of the most reactive cyclooctynes exhibiting rates of cycloaddition over 45 M−1s−1 in aqueous solutions. ODIBO is stable under ambient conditions and has low reactivity towards thiols. Photo-ODIBO survives heating up to 160°C and does not react with thiols.

Facile Quenching and Spatial Patterning of Cylooctynes via Strain-Promoted Alkyne–Azide Cycloaddition of Inorganic Azides

“…The reactivity of cyclooctynes 1–4 towards the azide ion and hydrazoic acid is correlated with their respective reactivity in the cycloaddition of organic azides (Table 1; Scheme 2) 9,10,13,15 . It is also interesting to note that the polarity of the alkyne seems to impact its reactivity with hydrazoic acid in comparison to azide ion.…”

“…8 The specificity and convenience of the cycloaddition reaction with an essentially limitless variety of organic azides has led to a steadily growing range of applications of SPAAC reagents in chemical synthesis and biology, usually as a selective conjugation tool. The popular SPAAC reagents ODIBO 9 , ADIBO 10,11 (a.k.a DIBAC 12 or DBCO), DIBO 13 , and BCN 14 are known to differ dramatically in their respective reaction rates with organic azides 9,10,13,15 , but little is known about their reactivity with inorganic azides. Our interest in SPAAC reactivity with inorganic azides was provoked by the intermittent failure of a cyclooctyne labeling experiment.…”

Cyclopropenone-caged Sondheimer diyne (dibenzo[a,e]cyclooctadiyne): a photoactivatable linchpin for efficient SPAAC crosslinking

“…17 We have already employed this reaction for the generation of reactive triple bonds in ynols, 18 enediynes, 19 and dibenzocyclooctynes. 20 Irradiation of bis-cyclopropenone 1 (photo-DIBOD) results in the formation of the Sondheimer diyne 2 , which, in turn reacts with two azide-functionalized substrates to create a stable covalent cross-link (Scheme 1). It is important to note that the addition of second equivalent of azide to the diyne 2a proceeds at much higher rate than the first cycloaddition.…”

Heteroatom‐embedded Medium‐Sized Cycloalkynes: Concise Synthesis, Structural Analysis, and Reactions

“…[2] In the last decade, highly reactive medium-sized cycloalkynes have attracted considerable attention as smart ligation molecules in the field of chemical biology. [3] In 2004, Bertozzi and colleagues reported the pioneering work on the catalyst-free Huisgen reaction of cyclooctyne derivatives with azides and successfully utilized this reaction in a bioimaging technique based on the bioorthogonality.…”