Mechanistic Exploration of the Competition Relationship between a Ketone and CC, CN, or CS Bond in the Rh(III)-Catalyzed Carbocyclization Reactions

The introduction of a CO, CC, CS, or CN bond has emerged as an effective strategy for carbocycle synthesis. A computational mechanistic study of Rh­(III)-catalyzed coupling of alkynes with enaminones, sulfoxonium ylides, or α-carbonyl-nitrones was carried out. Our results uncover the roles of dual directing groups in the three substrates and confirm that the ketone acts as the role of the directing group while the CC, CN, or CS bond serves as the cyclization site. By comparing the coordination of the ketone versus the CC, CN, or CS bond, as well as the chemoselectivity concerning the six- versus five-membered formation, a competition relationship is revealed within the dual directing groups. Furthermore, after the alkyne insertion, instead of the originally proposed direct reductive elimination mechanism, the ketone enolization is found to be essential prior to the reductive elimination. The following C­(sp²)C­(sp²) reductive elimination is more favorable than the C­(sp³)C­(sp²) formation, which can be explained by the aromaticity difference in the corresponding transition states. The substituent effect on controlling the selectivity was also discussed

A Computational Mechanistic Study of Amidation of Quinoline <i>N</i>‑Oxide: The Relative Stability of Amido Insertion Intermediates Determines the Regioselectivity

The origin of site selectivity of quinoline <i>N</i>-oxide substrate in Ir­(III)-catalyzed amidation with tosyl azide was investigated computationally. The reaction proceeds exclusively at the C8 position, instead of the C2 position, which has been reported previously in many other reactions. C2-Amidation is kinetically impossible under the reaction condition according to our calculations, with high apparent activation energy up to 51.1 kcal/mol. The high energetic span is caused by the deep-lying 5-membered amido insertion intermediate, in which a strong stabilization effect was observed due to <i>n</i>_N → π*_CN delocalization. For C8-amidation, however, the 6-membered counterpart is relatively unstable, making the activation energy only about half the value of C2-amidation. Meanwhile, denitrogenation is found to be turnover-limiting in the reaction. The oxidation state changes of the Ir center during the stepwise C–N bond formation were investigated, and a considerably higher effective oxidation state was found in the Ir–nitrenoid intermediate. The ineffective Rh^III catalyst was also studied. In comparison with the results of the Ir^III catalyst, the Rh^III catalyst features higher energy profiles and higher apparent activation energies. A dual role of acetic acid additive participating both in the C–H activation and protodemetalation was also demonstrated

Tandem Synthesis of Pyrrolo[2,3‑<i>b</i>]quinolones via Cadogen-Type Reaction

A tandem [3 + 2] cycloaddition/reductive cyclization of nitrochalcones with activated methylene isocyanides for the efficient synthesis of pyrrolo­[2,3-<i>b</i>]­quinolones is reported. In this reaction, the in situ generated dihydropyrroline acts as the internal reductant to convert the nitro into an electrophilic nitroso group, which undergoes subsequent C–N bond formation. Transition-metal-free, simple experimental procedure and ready accessibility of starting materials characterize the present transformation

Tandem Synthesis of Pyrrolo[2,3‑<i>b</i>]quinolones via Cadogen-Type Reaction

A tandem [3 + 2] cycloaddition/reductive cyclization of nitrochalcones with activated methylene isocyanides for the efficient synthesis of pyrrolo­[2,3-<i>b</i>]­quinolones is reported. In this reaction, the in situ generated dihydropyrroline acts as the internal reductant to convert the nitro into an electrophilic nitroso group, which undergoes subsequent C–N bond formation. Transition-metal-free, simple experimental procedure and ready accessibility of starting materials characterize the present transformation

Solvent Mediating a Switch in the Mechanism for Rhodium(III)-Catalyzed Carboamination/Cyclopropanation Reactions between <i>N</i>‑Enoxyphthalimides and Alkenes

Recently, a new synthetic methodology of rhodium-catalyzed carboamination/cyclopropanation from the same starting materials at different reaction conditions has been reported. It provides an efficient strategy for the stereospecific formation of both carbon- and nitrogen-based functionalities across an alkene. Herein we carried out a detailed theoretical mechanistic exploration for the reactions to elucidate the switch between carboamination and cyclopropanation as well as the origin of the chemoselectivity. Instead of the experimentally proposed Rh^III–Rh^I–Rh^III catalytic mechanism, our results reveal that the Rh^III–Rh^V–Rh^III mechanism is much more favorable in the two reactions. The chemoselectivity is attributed to a combination of electronic and steric effects in the reductive elimination step. The interactions between alkene and the rhodacycle during the alkene migration insertion control the stereoselectivity in the carboamination reactions. The present results disclose a dual role of the methanol solvent in controlling the chemoselectivity

Computational Mechanistic Study of Redox-Neutral Rh(III)-Catalyzed C–H Activation Reactions of Arylnitrones with Alkynes: Role of Noncovalent Interactions in Controlling Selectivity

The mechanism of redox-neutral Rh­(III)-catalyzed coupling reactions of arylnitrones with alkynes was investigated by density functional theory (DFT) calculations. The free energy profiles associated with the catalytic cycle, involving C­(sp²)–H activation, insertion of alkyne, transfer of O atom, cyclization and protodemetalation, are presented and analyzed. An overwhelming preference for alkyne insertion into Rh–C over Rh–O is observed among all pathways, and the most favorable route is determined. The pivalate-assisted C–H activation step is turnover-limiting, and the cyclization step determines the diastereoselectivity of the reaction, with the stereoselectivity arising mainly from the difference of noncovalent interactions in key transition states. The detailed mechanism of O atom transfer, Rh^III–Rh^I–Rh^III versus Rh^III–Rh^V–Rh^III cycle, is discussed