Divergent Cyclizations of 1‑R-Ethynyl-9,10-anthraquinones: Use of Thiourea as a “S^2–” Equivalent in an “Anchor-Relay” Addition Mediated by Formal C–H Activation

Abstract

The EtONa-mediated reaction of <i>peri</i>-R-ethynyl-9,10-anthraquinones with thiourea yields 2-R-7<i>H</i>-dibenzo­[<i>de</i>,<i>h</i>]­quinolin-7-ones and 2-R-anthra­[2,1-<i>b</i>]­thiophene-6,11-diones. Although 2-R-7<i>H</i>-dibenzo­[<i>de</i>,<i>h</i>]­quinolin-7-ones were observed previously in reactions with other N-centered nucleophiles (hydrazine, guanidine, and urea), the formation of 2-R-anthra­[2,1-<i>b</i>]­thiophene-6,11-diones is a new reactivity path. DFT computations analyzed factors responsible for the switch in reactivity and the relative importance of two possible pathways: (1) the “anchor-relay” mechanism mediated by nucleophilic attack at the carbonyl and (2) direct attack at the alkyne. The two pathways converge on a vinyl sulfur anion, set up for a 5-endo-trig cyclization at the <i>ortho</i>-position. Subsequent rearomatization/oxidation provides the fused thiophene product via formal C–H activation. The calculations suggest that the latter pathway, the direct attack at the alkyne, is more likely, due to the relatively high barrier for the 8-endo-dig cyclization (pathway 1). Computational insights led to a more selective synthesis of fused thiophenes, based on the reaction of acetylenic anthraquinones with sodium sulfide. This reaction does not require prefunctionalization at the <i>ortho</i>-position since direct C–H activation is efficient. The absence of fused five-membered heterocycles in earlier work was investigated computationally. The other N-centered nucleophiles form stronger anion−π complexes with the electron-deficient quinone core, promoting carbonyl attack over direct alkyne attack