Mechanistic Understanding of the Divergent Reactivity of Cyclopropenes in Rh(III)-Catalyzed C–H Activation/Cycloaddition Reactions of N-Phenoxyacetamide and N-Pivaloxybenzamide

Abstract

Density functional theory calculations were conducted to develop a mechanistic understanding of the Rh(III)-catalyzed C-H activation/cycloaddition reactions of N-phenoxyacetamide and N-pivaloxybenzamide with cyclopropenes, and insights into the substrate-dependent chemoselectivity were provided. The results showed that the divergence originated from the different reactivity of the seven-membered rhodacycles from the insertion of cyclopropene into the Rh-C bond. In reactions of N-pivaloxybenzamide, such an intermediate undergoes the pivalate migration to form a cyclic Rh(V)-nitrenoid intermediate in a reaction that is easier than the opening of the three-membered ring by β-carbon elimination, leading finally to a tricyclic product with retention of the cyclopropane moiety by facile reductive elimination. While similar Rh(V)-nitrenoid species could also be possibly formed in Cp*Rh(III)-catalyzed reactions of N-phenoxyacetamide, the β-carbon elimination occurs more easily from the corresponding seven-membered rhodacycle intermediate and the subsequent O-N bond cleavage gives rise to an unexpected dearomatized (E)-6-alkenylcyclohexa-2,4-dienone intermediate. The E/Z isomerization of this intermediate is required for the final cyclization to 2H-chromene, and interesting metal-ligand cooperative catalysis with Rh(III) carboxylate was disclosed in the C═C double bond rotation process.

Heptamethylindenyl (Ind*) enables diastereoselective benzamidation of cyclopropenes via Rh(iii)-catalyzed C–H activation

“…These studies together suggest that the C–H activation occurs via concerted metallation-deprotonation (CMD) mechanism and is the turnover-limiting step, as seen in several previous examples of C–H activation with Rh( iii ). 16,17 To determine if epimerization of the product occurs under the reaction conditions, we independently prepared product 3c (1 : 1 dr) and resubjected it to the reaction conditions of benzamide 1f and cyclopropene 2c . After full conversion to 3f (70% yield, 17 : 1 dr), we did not observe any change of the dr of 3c , indicating the products are not epimerized under the reaction conditions.…”

“…Based on literature precedent 17 and our mechanistic studies, the mechanism of the transformation is proposed in Scheme 2A. The Ind*Rh(OPiv) 2 species is generated in situ by an anion exchange of [Ind*RhCl 2 ] 2 and CsOPiv.…”

N‐Sulfonylcarboxamide as an Oxidizing Directing Group for Ruthenium‐Catalyzed C–H Activation/Annulation

“…[4c], [4e] However, sulfonamides have a relatively high reduction potential, which makes the pathway with intermediates 4 and 5 less plausible (Scheme ). Analogous to the proposed C–N bond formation for Rh‐catalyzed annulations,, an alternative pathway can be proposed that involves the formation of (nitrene)Ru IV intermediate 6 . Reductive elimination of the Ru atom of intermediate 6 would then lead to isoquinolone 2 .…”

Exploiting Strained Rings in Chelation Guided C−H Functionalization: Integration of C−H Activation with Ring Cleavage

“…This methodology is featured with external oxidant‐free reaction conditions and facile ring opening of cyclopropene with unique chemo‐selectivity at room temperature. Xia and co‐workers studied the mechanism of this reaction by DFT studies, wherein they concluded that β‐carbon elimination is the most favorable when the opening of the three‐membered ring occurs trans to Cp* ligand of the Rh center in order to evade steric repulsion.…”