Intramolecular CH Activation through Gold(I)‐Catalyzed Reaction of Iodoalkynes

Abstract

The cycloisomerization reaction of 1-(iodoethynyl)-2-(1-methoxyalkyl)arenes and related 2-alkyl-substituted derivatives gives the corresponding 3-iodo-1-substituted-1H-indene under the catalytic influence of IPrAuNTf2 [IPr=1,3-bis(2,6-diisopropyl)phenylimidazol-2-ylidene; NTf2=bis(trifluoromethanesulfonyl)imidate]. The reaction takes place in 1,2-dichloroethane at 80 °C, and the addition of ttbp (2,4,6-tri-tert-butylpyrimidine) is beneficial to accomplish this new transformation in high yield. The overall reaction implies initial assembly of an intermediate gold vinylidene upon alkyne activation by gold(I) and a 1,2-iodine-shift. Deuterium labeling and crossover experiments, the magnitude of the recorded kinetic primary isotopic effect, and the results obtained from the reaction of selected stereochemical probes strongly provide support for concerted insertion of the benzylic C-H bond into gold vinylidene as the step responsible for the formation of the new carbon-carbon bond.

Recent advances in alkylidene carbene chemistry

“…In 2015, Gonz alez utilized iodoalkynes in a similar reaction, using a gold catalyst to synthesize 3-iodoindenes via 1,5 CeH insertion. 62 Zhang and Hashmi independently reported the dual activation of aromatic diynes, 63 using a gold catalyst to access the intermediate gold vinylidene via a carbocyclisation route similar to that described by Harada. 56 Zhang reported the synthesis of a range of fused polycycles from diynes employing a strategy, which utilized the activation of both alkynes (Scheme 41).…”

Construction of Halofunctionalized Indenes via a Cascade Prins‐Nazarov Cyclization Promoted by Dual Roles of BX3

“…OEt 2 (0.5-2.0 equiv.) at room temperature, 3 a was obtained in 48-65% yield (entries [3][4][5]. Elevating the temperature in refluxing dichloromethane did not increase the yield (entry 6), and changing the solvents to THF, 1,4dioxane, and acetonitrile completely shut down the reaction (entries 7-9).…”

“…[2] Owing to the importance and synthetic utility of indenes, many approaches based on intra- [3] and intermolecular [4] cyclization reactions have been reported for their synthesis. The general approaches for preparing haloindenes include gold(I)-catalyzed intramolecular cyclization of iodo-functionalized alkynes, [5] iodonium-promoted cyclization of arylethynylmalonates, [6] palladium-catalyzed tandem reaction of 2-alkenylphenylacetylenes with CuX 2 (X=Cl, Br), [7] and reactions of o-(alkynyl)styrenes with NXS (X=I, Br). [8] However, there is no report on any direct approach for the synthesis of fluorine-containing indenes on the cyclopentadiene moiety.…”

Advances and Prospects in Gold‐Catalyzed C−H Activation

“…Gonza~lez et al successfully invented a distinct protocol for gold-catalyzed intramolecular CÀ H activation involving metal vinylidenes by replacing substituent from hydrogen to iodine on the parent alkyne (Scheme 41). [39] The reaction takes place in 1,2-dichloroethane at 80°C, in the presence of 5 mol% of catalyst, and the addition of ttbp (2,4,6-tri-tert-butylpyrimidine) is beneficial to accomplish this new transformation in high yields. They have studied this reaction in the presence of different catalysts and found that the presence of ttbp gave high yields.…”