Divergent cyclizations of 1-R-ethynyl-9,10-anthraquinones

Use of thiourea as a "s2-" equivalent in an "anchor-relay" addition mediated by formal C-H activation

Denis S. Baranov, Brian Gold, Sergei F. Vasilevsky, Igor V. Alabugin

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The EtONa-mediated reaction of peri-R-ethynyl-9,10-anthraquinones with thiourea yields 2-R-7H-dibenzo[de,h]quinolin-7-ones and 2-R-anthra[2,1-b] thiophene-6,11-diones. Although 2-R-7H-dibenzo[de,h]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-b]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 ortho-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 ortho-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.

Original languageEnglish
Pages (from-to)2074-2082
Number of pages9
JournalJournal of Organic Chemistry
Volume78
Issue number5
DOIs
Publication statusPublished - 11 Mar 2013
Externally publishedYes

Fingerprint

Thiophenes
Thiourea
Cyclization
Anchors
Alkynes
Chemical activation
Nucleophiles
hydrazine
Anions
Anthraquinones
Guanidine
Sulfur
Discrete Fourier transforms
Urea
Switches
Oxidation
9,10-anthraquinone
Electrons
heparinized hydrophilic polymer

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Divergent cyclizations of 1-R-ethynyl-9,10-anthraquinones : Use of thiourea as a "s2-" equivalent in an "anchor-relay" addition mediated by formal C-H activation. / Baranov, Denis S.; Gold, Brian; Vasilevsky, Sergei F.; Alabugin, Igor V.

In: Journal of Organic Chemistry, Vol. 78, No. 5, 11.03.2013, p. 2074-2082.

Research output: Contribution to journalArticle

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abstract = "The EtONa-mediated reaction of peri-R-ethynyl-9,10-anthraquinones with thiourea yields 2-R-7H-dibenzo[de,h]quinolin-7-ones and 2-R-anthra[2,1-b] thiophene-6,11-diones. Although 2-R-7H-dibenzo[de,h]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-b]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 ortho-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 ortho-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.",
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