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