+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Theoretical Insight into the Mechansim and Origin of Ligand-Controlled Regioselectivity in Homogenous Gold-Catalyzed Intramolecular Hydroarylation of Alkynes

Theoretical Insight into the Mechansim and Origin of Ligand-Controlled Regioselectivity in Homogenous Gold-Catalyzed Intramolecular Hydroarylation of Alkynes

Journal of Organic Chemistry 83(5): 2763-2772

This work aims at understanding the mechanism and regioselectivity in ligand-controlled gold-catalyzed divergent intramolecular hydroarylation of alkynes reported by Jiang et al. ( J. Am. Chem. Soc. 2016 , 138 , 5218 - 5221 ). Focusing on a representative alkyne, N-propargyl-N-tosylaniline, we conducted a detailed computational study on the ortho- and para-position hydroarylation of the alkyne catalyzed by gold(I) catalysts with different ligands. Both the ortho- and para-position hydroarylation reactions are found to follow a similar three-stage mechanism: electrophilic cyclization, proton loss, and protiodeauration. The initial electrophilic cyclization was identified as the rate- and regiochemistry-determining step. With the flexible electron-deficient phosphite ligand, the ortho-position cyclization is identified as the energetically more favorable pathway, while with the rigid electron-abundant phosphine (Xphos) ligand, the dominant pathway turns to the para-position cyclization. The theoretical results are in good agreement with the experimental observations. The π-π interaction between alkynyl phenyl and the directing acylamino group are found to be mainly responsible for the observed ortho-selectivity, while a combination of favorable noncovalent CH···π interaction and steric repulsion between Xphos ligand and alkynyl group contributes to the observed exclusive para-selectivity. The present calculations provide deeper insight into the mechanism and origin of regioselectivity of the title reaction.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 065600605

Download citation: RISBibTeXText

PMID: 29431999

DOI: 10.1021/acs.joc.7b03213

Related references

The mechanism and regioselectivity of gold(I) or platinum(II) catalyzed intramolecular hydroarylation to pyrrolopyridinones and pyrroloazepinones. Organic and Biomolecular Chemistry 12(42): 8433-8441, 2014

Intramolecular hydroarylation of alkynes catalyzed by platinum or gold: mechanism and endo selectivity. Chemistry 11(10): 3155-3164, 2005

Mechanistic study on ligand-controlled cobalt-catalyzed regioselectivity-switchable hydroarylation of styrenes. Chemistry 19(36): 12093-12103, 2013

Pd-Catalyzed Hydroborylation of Alkynes: A Ligand Controlled Regioselectivity Switch for the Synthesis of α- or β-Vinylboronates. Organic Letters 18(3): 432-435, 2016

Anomalous ligand effect in gold(I)-catalyzed intramolecular hydroamination of alkynes. Chemical Communications 51(27): 5990-5993, 2015

Theoretical study of N-dealkylation of N-cyclopropyl-N-methylaniline catalyzed by cytochrome P450: insight into the origin of the regioselectivity. Dalton Transactions 2009(2): 291-297, 2009

Switching the regioselectivity via indium(III) and gold(I) catalysis: a post-Ugi intramolecular hydroarylation to azepino- and azocino-[c,d]indolones. Chemical Communications 49(60): 6803-6805, 2013

Rhodium-catalyzed intramolecular hydroarylation of 1-halo-1-alkynes: regioselective synthesis of semihydrogenated aromatic heterocycles. Chemistry 20(1): 317-322, 2014

Palladium-catalyzed enantioselective intramolecular hydroarylation of alkynes to form axially chiral 4-aryl 2-quinolinones. Angewandte Chemie 50(17): 3963-3967, 2011

Mechanistic insights into the gold-catalyzed cycloisomerization of bromoallenyl ketones: ligand-controlled regioselectivity. Journal of the American Chemical Society 130(22): 6940-6941, 2008

Mechanistic origin of ligand-controlled regioselectivity in Pd-catalyzed C-H activation/arylation of thiophenes. Chemistry 17(49): 13866-13876, 2011

The origin of the ligand-controlled regioselectivity in Rh-catalyzed [(2 + 2) + 2] carbocyclizations: steric vs. stereoelectronic effects. Chemical Science 6(12): 6896-6900, 2015

Gold(I)-Catalyzed Angle Strain Controlled Strategy to Furopyran Derivatives from Propargyl Vinyl Ethers: Insight into the Regioselectivity of Cycloisomerization. Organic Letters 18(4): 680-683, 2016

Synthesis of fluoranthenes by hydroarylation of alkynes catalyzed by gold(I) or gallium trichloride. Beilstein Journal of Organic Chemistry 7: 1520-1525, 2011

The Au(I)-catalyzed intramolecular hydroarylation of terminal alkynes under mild conditions: application to the synthesis of 2H-chromenes, coumarins, benzofurans, and dihydroquinolines. Journal of Organic Chemistry 74(22): 8901-8903, 2009