Gold-Catalyzed [3 + 2] Annulation, Carbenoid Transfer, and C–H Insertion Cascade: Elucidation of Annulation Mechanisms via Benzopyrylium Intermediates

Abstract

It has been established that a cationic gold(I)/PCy 3 complex catalyzes the intramolecular cascade reaction of enediynecarbonyls via benzopyrylium intermediates giving pentacyclic compounds, bearing five or six stereocenters with high yields and diastereoselectivity. In this cascade reaction, [3 + 2] annulation, carbenoid transfer, and C−H insertion proceed in one-pot. The DFT calculation revealed that both the [3 + 2] and [4 + 2] annulations proceed via the same gold(I) carbenoid, produced by the [3 + 2] cycloaddition, and the reaction between the gold(I) carbenoid and the additional alkyne unit promotes the present cascade reaction.

Utilizing Visible Light to Enable Contra-Thermodynamic Skeletal Rearrangement for Dearomative meta-Cycloadditions of 2-Acetonaphthalenes via Triplet Energy Transfer Cascade

“…From a synthetic perspective, this transformation will deliver highly sp 3 -rich polycyclic spiroether scaffolds, which are ubiquitous structural motifs in various bioactive compounds and drugs of natural origins. [48][49][50][51][52][53][54][55][56][57] We performed computational studies to determine the ET (∆G(T1-S0) = 53.6 kcal/mol) for substrate (Z)-1 (Table S13). It offers valuable guidance for choosing an appropriate photocatalyst among the myriad of available options.…”

Recent Advances in Gold(I)-Catalyzed Approaches to Three-Type Small-Molecule Scaffolds via Arylalkyne Activation

“…The authors found that the amine group on the right-hand benzene ring benefited 6-endo-dig cyclization via an electron-donating effect to generate naphthalenes (37) after isomerization and protodeauration. In addition, several important heterocycles (38)(39)(40)(41) were synthesized in a divergent manner from that of naphthalene derivatives (37). In 2022, Liu and colleagues reported a gold(I)-catalyzed 6-endo-dig cyclization of arylalkyne-enolethers (36) to construct 2-(naphthalen-2-yl)aniline derivatives (Scheme 10) [31].…”

Ligand-controlled chemoselectivity in gold-catalyzed cascade cyclization of 1,4-diene-tethered 2-alkynylbenzaldehydes

“…The generality of the ring formation protocol was illustrated by the applicability of a diverse range of electron-rich dipolarophiles that included vinyl ethers, alkenes, alkynes, allenes, and cyclopropenes, and heterocycles such as benzofurans and isoxazoles, as well as electron-deficient enones (Scheme 1a). [2][3][4][5][6][7][8][9][10][11][12][13][14][15] The synthetic utility of the catalytic [3 + 2] and [4 + 2] cycloaddition reaction method was also demonstrated by its application in synthetic strategies for a number of bioactive natural products and functional materials of current interest. 2c,11,12 Despite these notable advancements, the reaction chemistry of a metal-bound benzopyrylium intermediate with two or more 2π cycloaddition partners involving or initiated by a [3 + 2] cycloaddition remains conspicuously rare.…”

“…5a,10a, 18 The proposed cascade ring formations comprise a regiodivergent pathway that is unprecedented in the reaction chemistry of metal-bound benzopyrylium intermediates and adds to an increasingly important facet of gold catalysis concerning ligand-controlled product selectivity. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] The practical utility of the Au(I)-catalyzed methods were also demonstrated by their showing the late-stage modification of a series of structurally complex natural products and drug molecules.…”