Mechanistic Investigations of the Pd(0)-Catalyzed Enantioselective 1,1-Diarylation of Benzyl Acrylates.
ABSTRACT: A mechanistic study of the Pd-catalyzed enantioselective 1,1-diarylation of benzyl acrylates that is facilitated by a chiral anion phase transfer (CAPT) process is presented. Kinetic analysis, labeling, competition, and nonlinear effect experiments confirm the hypothesized general mechanism and reveal the role of the phosphate counterion in the CAPT catalysis. The phosphate was found to be involved in the phase transfer step and in the stereoinduction process, as expected, but also in the unproductive reaction that provides the traditional Heck byproduct. Multivariate correlations revealed the CAPT catalyst's structural features, affecting the production of this undesired byproduct, as well as weak interactions responsible for enantioselectivity. Such putative interactions include ?-stacking and a CH···O electrostatic attraction between the substrate benzyl moiety and the phosphate. Analysis of the computed density functional theory transition structures for the stereodetermining step of the reaction supports the multivariate model obtained. The presented work provides the first comprehensive study of the combined use of CAPT and transition metal catalysis, setting the foundation for future applications.
Project description:Enantioselective 1,1-diarylation of terminal alkenes enabled by the combination of Pd catalysis with a chiral anion phase transfer (CAPT) strategy is reported herein. The reaction of substituted benzyl acrylates with aryldiazonium salts and arylboronic acids gave the corresponding 3,3-diarylpropanoates in moderate to good yields with high enantioselectivies (up to 98:2 er). Substituents on the benzyl acrylate and CAPT catalyst significantly affect the enantioselectivity, and multidimensional parametrization identified correlations suggesting structural origins for the high stereocontrol.
Project description:The cross-coupling of sp(3)-hybridized organoboron reagents via photoredox/nickel dual catalysis represents a new paradigm of reactivity for engaging alkylmetallic reagents in transition-metal-catalyzed processes. Reported here is an investigation into the mechanistic details of this important transformation using density functional theory. Calculations bring to light a new reaction pathway involving an alkylnickel(I) complex generated by addition of an alkyl radical to Ni(0) that is likely to operate simultaneously with the previously proposed mechanism. Analysis of the enantioselective variant of the transformation reveals an unexpected manifold for stereoinduction involving dynamic kinetic resolution (DKR) of a Ni(III) intermediate wherein the stereodetermining step is reductive elimination. Furthermore, calculations suggest that the DKR-based stereoinduction manifold may be responsible for stereoselectivity observed in numerous other stereoconvergent Ni-catalyzed cross-couplings and reductive couplings.
Project description:Herein, we report three-component vicinal-diarylation of non-conjugated alkenes initiated by transmetalation of arylboronic acids, which provides complementary access to ?,?-diaryl carbonyl compounds. We have also screened a large number of chiral ligands for developing an enantioselective version of this reaction and obtained the preliminary results (up to 79?:?21 e.r.). Notably, the methodology developed herein represents the first three component syn-vicinal-dicarbofunctionalization of non-conjugated alkenes involving palladium catalysis.
Project description:Nickel-catalyzed coupling of benzyl acrylates with activated ketones and imines provides ?-butyrolactones and lactams, respectively. The benzyl alcohol byproduct released during the lactonization/lactamization event is relayed to the next cycle where it serves as the reductant for C-C bond formation. This strategy represents a conceptually unique approach to transfer-hydrogenative C-C bond formation, thus providing examples of reductive heterocyclizations where hydrogen embedded within an alcohol leaving group facilitates turnover.
Project description:The study of the oxidative amination of tetrahydroisoquinolines under chiral-anion phase-transfer (CAPT) catalysis by multidimensional correlation analysis (MCA) is revisited. The parameterization of the transition states (TSs) for the uncatalyzed reaction, the introduction of conformational descriptors, and the use of computed interaction energies and distances as parameters allowed access to a considerably simplified mathematical correlation of substrate and catalyst structure to enantioselectivity. The equation obtained is suggestive of key interactions occurring at the TS. Specifically, the CAPT catalyst is proposed to coordinate the intermediate iminium cation by P=O???H-O hydrogen-bonding and N???H-C electrostatic interactions. The conformational freedom of the benzyl substituent of the substrate was also found to be important in providing an efficient mode of molecular recognition.
Project description:A three-component coupling of aryl bromides, arylboron reagents, and alkenylarenes is presented. The method tolerates a variety of substitution patterns on all of the components. In particular, 1,2-disubstituted alkenylarenes are suitable and undergo highly diastereoselective diarylation.
Project description:The Cu(I)-catalyzed N,N'-diarylation of natural diamines and polyamines such as putrescine, cadaverine, spermine, spermidine and their homologues is described. Aryl iodides bearing electron-donating and electron-withdrawing groups have been employed in the study. The CuI/2-(isobutyryl)cyclohexanone/DMF catalytic system has found to be more efficient in the diarylation of diamines and spermine while the CuI/L-proline/EtCN system proved to be preferable for the diarylation of other tri- and tetraamines like spermidine, norspermidine and norspermine.
Project description:Evaluation of the scope of a Pd(II)-catalyzed oxidative 1,1-diarylation reaction of terminal olefins using aryl stannanes is reported. The reaction is shown to be tolerant of functionality commonly encountered in organic synthesis; however, the reaction outcome was found to be dependent on the nature of the aryl stannane used. A mechanistic rationale for the observation of this influence is provided.
Project description:Density functional theory calculations at IDSCRF-B3LYP/DZVP computational level were conducted on palladium-catalyzed regioselective B-H activation and diarylation of o-carboranes with aryl iodides in solution. Computational results indicate that this reaction follows a multistep mechanism and needs to get over several transition states before the final B(4,5)-diarylated o-carborane derivatives are formed. B-H activation, oxidation addition, and successive reduction of the Pd(II) catalyst involving a Pd(II)-Pd(IV)-Pd(II) catalytic cycle has been confirmed, in which AgOAc plays a crucial role. Electron-donating group on the cage carbon of o-carboranes is verified to be beneficial for its B-H activation and diarylation, while steric hindrance between the aryl and o-carboranyl groups retards it. Natural population analysis and Gibbs free energetic results predict consistent regioselectivities with experiments and manifest the pivotal role of electronic effect in controlling regioselective B-H activation of o-carboranes. These results are expected to shed some light on further improvement of experimental conditions and better controlling of regioselectivities.
Project description:A palladium-catalyzed intermolecular vicinal diarylation of terminal 1,3-dienes using aryldiazonium tetrafluoroborates and arylboronic acids is reported. Using this technology, two different arenes are regioselectively introduced in a vicinal fashion across the terminal alkene of a variety of terminal 1,3-dienes at ambient temperature. Through the action of a chiral bicyclo[2.2.2]octadienyl ligand at -20 °C, good enantioselectivity has also been achieved.