Mechanochemical generation of aryne

Abstract

Mechanical force is unique in promoting unusual reaction pathways and especially for the generation of reactive intermediates sometimes inaccessible to other forms of activation. The mechanochemical generation of reactive species could find application in synthetic and materials chemistry alike. However, the nature of these reactive intermediates has been mostly limited to radicals or carbenes. Here, we present a new mechanophore that generates a reactive aryne intermediate upon dissociation of a benzocyclobutene (BCB) core via a force-promoted retro [2 + 2] cycloaddition.

Fig. 1. Mechanochemical generation of aryne. (a) Mechanical activation of benzocyclobutene mechanophore 1 leads to the generation of aryne 2. Red arrows indicate the direction of the force. (b) Synthesis of chain-centered mechanophore 1. Conditions: (i) LiTMP, THF, −78 °C, 1 h, 70%. (ii) H₂, Pd/C, MeOH/AcOEt, r.t., 20 h, 60%. (iii) BiBB, Et₃N, THF, r.t., 5 h, 58%. (iv) Methyl acrylate, CuBr₂/Cu(0), Me₆TREN, DMSO, r.t., 20 min. Solid-state structure (XRD) of intermediate 5 shown (hydrogen atoms omitted for clarity). (c) Previously reported thermal and mechanical electrocyclic ring opening of the BCB core.

Fig. 2. (a) Mechanical activation of chain-centered BCB mechanophore 1. Conditions: US (20 kHz, 13.0 W cm⁻², 1 s ON/1 s OFF), furan (2000 eq.), CH₃CN, 5–10 °C, 120 min. (b) Structural and activation parameters of the sonicated polymer. Yields determined by integrating protons 2_cis and w against proton e of the intact mechanophore for 3 and 8 respectively. (c) Partial ¹H NMR (500 MHz, acetone-d₆, 298 K, 1024 scans) spectra of 1 before (i) and after (ii) sonication along with reference compounds 8_ref (iii), an independently synthesised reference of compound 8, and vinyl pivalate (iv). (d) Scope of trapping agents. Percentages indicate the yield of trapped products generated from 1.

Fig. 3. Computational investigation of the mechanochemical activation of the aryne-generating BCB mechanophore. (a) Evolution of energy upon simulated elongation (CoGEF, DFT B3LYP/6-31G*, vac.) of a model of BCB mechanophore 1. (b) Equilibrium geometries at E₀ (i), E_max1 (ii), E_max2 (iii), and after dissociation (iv). (c) Elongation of bonds a, b, and c. (d) Opening of angle α upon simulated elongation of the same model up to E_max. (e) Effect of regiochemistry on the activation of the aryne-generating BCB mechanophore.