Mechanistic Insights into the Rhodium-Catalyzed Intramolecular Ketone Hydroacylation

Abstract

[Rh((R)-DTBM-SEGPHOS)]BF(4) catalyzes the intramolecular hydroacylation of ketones to afford seven-membered lactones in large enantiomeric excess. Herein, we present a combined experimental and theoretical study to elucidate the mechanism and origin of selectivity in this C-H bond activation process. Evidence is presented for a mechanistic pathway involving three key steps: (1) rhodium(I) oxidative addition into the aldehyde C-H bond, (2) insertion of the ketone CO double bond into the rhodium hydride, and (3) C-O bond-forming reductive elimination. Kinetic isotope effects and Hammett plot studies support that ketone insertion is the turnover-limiting step. Detailed kinetic experiments were performed using both 1,3-bis(diphenylphosphino)propane (dppp) and (R)-DTBM-SEGPHOS as ligands. With dppp, the keto-aldehyde substrate assists in dissociating a dimeric precatalyst 8 and binds an active monomeric catalyst 9. With [Rh((R)-DTBM-SEGPHOS)]BF(4), there is no induction period and both substrate and product inhibition are observed. In addition, competitive decarbonylation produces a catalytically inactive rhodium carbonyl species that accumulates over the course of the reaction. Both mechanisms were modeled with a kinetics simulation program, and the models were consistent with the experimental data. Density functional theory calculations were performed to understand more elusive details of this transformation. These simulations support that the ketone insertion step has the highest energy transition state and reveal an unexpected interaction between the carbonyl-oxygen lone pair and a Rh d-orbital in this transition state structure. Finally, a model based on the calculated transition-state geometry is proposed to rationalize the absolute sense of enantioinduction observed using (R)-DTBM-SEGPHOS as the chiral ligand.

New Colours for Carotenoids – Synthesis of Pyran Polyenes

“…Nevertheless, some similarities with reported metal-catalyzed aldehyde reactions might be considered. [31][32][33][34] AlCl 3 clearly assists the reaction, C-C bond formation and hydride transfer, to intermediate II. Subsequent elimination of H 2 O leads to the transient allene III, which immediately rearranges to vinylogue α-pyranone 2.…”

Transition Metal Catalyzed Approaches to Lactones Involving CO Bond Formation

“…Arene formation by decarbonylation was a competitive pathway [85]. In order to gain insights into the mechanism of this unique asymmetric transformation, detailed experimental and theoretical studies were undertaken [89]. Hammett plot (r ¼ 0.29 with dppp) and kinetic isotope effect experiments (k H /k D ¼ 1.8 with dppp; 3.3 with (R)-DTBM-SEGPHOS) in conjunction with DFT studies suggest that ketone insertion into the RhÀH is the turnover limiting step of the catalytic cycle, contrary to previous reports of olefin hydroacylation, where reductive elimination has been shown to be turnover limiting [90].…”

Selektive gekreuzte Tischtschenko‐Reaktion – eine abfallfreie Synthese von Benzylestern

“…[20] Eine anschließende b-Hydrideliminierung führt zu einer Nickelhydridspezies, aus der das Produkt durch reduktive Eliminierung freigesetzt wird (Schema 4). [21] Insgesamt ist die Methode von Ogoshi et …”