Substituted 5,6,11,12-Tetradehydrodibenzo[a,e]cyclooctenes: Syntheses, Properties, and DFT Studies of Substituted Sondheimer–Wong Diynes

Abstract

Highly strained cyclic acetylenes 5,6,11,12-tetradehydrodibenzo[a,e]cyclooctenes (Sondheimer-Wong diynes) having various substituents on their benzene rings were synthesized successfully by one-pot treatment of the corresponding formyl sulfones with diethyl chlorophosphate/lithium hexamethyldisilazide (LiHMDS) and then lithium diisopropylamide (LDA). When mixtures of two types of formyl sulfones bearing different substituents were subjected to this protocol, the unsymmetrically substituted Sondheimer-Wong diynes could be synthesized in a stepwise manner by isolation of the heterocoupled vinyl sulfone intermediates followed by their treatment with LDA. The UV-vis absorption spectra and cyclic voltammograms of the substituted Sondheimer-Wong diynes were recorded. The electronic effect of substituents on the diynes was investigated in their click reactions and nucleophilic and electrophilic additions.

Sequential Photochemistry of Dibenzo[a,e]dicyclopropa[c,g][8]annulene-1,6-dione: Selective Formation of Didehydrodibenzo[a,e][8]annulenes with Ultrafast SPAAC Reactivity

“…The SPAAC reactivity of the DIBOD ( k (BuN 3 ) = (6.65 ± 0.03) ×10 −2 M −1 s −1 for 2a and k (BuN 3 ) = (6.5 ± 0.02) ×10 −2 M −1 s −1 for 2b ) is surprisingly similar to that of significantly less strained dibenzo[ a, e ]cyclooctyne (DIBO), 16 and agrees well with previous estimates. 4 MC-DIBOD ( 5a ), as expected, is 3–4 fold less reactive than 2a ( k (BuN 3 ) = (1.66 ± 0.02) ×10 −2 M −1 s −1 , Figure 3). To our great surprise, mono-triazole 3a (R= Bu), generated by photo-decarbonylation of 6a- Bu, is more than 500-fold more reactive than DIBOD 2a ( k (BuN 3 ) = (34 ± 1 M −1 s −1 ).…”

“…3,4,5 Sondheimer diyne (DIBenzo[ a, e ]cycloOctaDiyne or DIBOD 2 ) is the most atom economical double-SPAAC cross-linker, as both strained triple bonds belong to the same eight-membered ring. 4 The parent dibenzocyclooctadiyne ( 2a ) has found applications in the macrocyclization of bis-azide functionalized peptides, 6 post-synthetic modification of MOF thin films, 7 protein derivatization, 4a the development of fluorescent dyes, 8 and the preparation of tetramers of HIV-related peptides. 9 The utility of the DIBOD cross-linkers ( 2 ), however, is limited by its short shelf lifetime and rapid decomposition in aqueous solutions (τ ½ ~ 10 min at pH = 7.4).…”

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

“…Sondheimer diyne), represents a unique cross-linking platform in this sense, as it contains two azide-reactive strained triple bonds within the same cyclic structure and allows for double-SPAAC click ligation of azide-tagged substrates. 12 Diyne 2a has been employed for the cross-coupling of various azide-functionalized substrates from biomolecules to metal – organic frameworks. 12,13 The utility of this method, however, is limited by the low stability of the Sondheimer diyne.…”

“…12 Diyne 2a has been employed for the cross-coupling of various azide-functionalized substrates from biomolecules to metal – organic frameworks. 12,13 The utility of this method, however, is limited by the low stability of the Sondheimer diyne. In the neat form 2a completely decomposes within two days and exhibits half lifetime of only 10 min in a neutral aqueous solution (1mM in PBS, pH 7.4, r.t.).…”

“…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. 12a …”