Project description:Electrochemical or photochemical single-electron oxidation of bench-stable substrates can generate radical cations that offer unique reactivities as intermediates in various bond-formation processes. Such intermediates can potentially take part in both radical and ionic bond formation; however, the mechanisms involved are complicated and not fully understood. Herein, we report electrochemical radical cation aza-Wacker cyclizations under acidic conditions, which are expected to proceed via radical cations generated by single-electron oxidation of alkenes.
Project description:The development of an intermolecular and enantioselective aza-Wacker reaction is described. Using indoles as the N-source and a selection of alkenols as the coupling partners selective β-hydride elimination toward the alcohol was achieved. This strategy preserves the newly formed stereocenter by preventing the formation of traditionally observed enamine products. Allylic and homoallylic alcohols with a variety of functional groups are compatible with the reaction in high enantioselectivity. Isotopic-labeling experiments support a syn amino-palladation mechanism for this new class of aza-Wacker reactions.
Project description:We present highly diastereoselective tethered aza-Wacker cyclization reactions of alkenyl phosphoramidates. "Arming" the phosphoramidate tether with 5-chloro-8-quinolinol was essential to achieving >20:1 diastereoselectivity in these reactions. The substrate scope with respect to alkenyl alcohols and phosphoramidate tether was extensively explored. The scalability of the oxidative cyclization was demonstrated, and the product cyclophosphoramidates were shown to be valuable synthons, including for tether removal. With chiral alkenyl precursors, enantiopure cyclic phosphoramidates were formed.
Project description:In traditional Wacker processes, Pd(II) becomes reduced to Pd(0) after C-O bond formation and β-H elimination and must be reoxidized to the electrophilic Pd(II) state via a stoichiometric oxidant like benzoquinone, CuCl(2), or O(2). We report herein a Pt-catalyzed Wacker-type process that regenerates the electrophilic Pt(2+) state by H(-) abstraction from a [Pt]-H using an oxocarbenium ion generated from an acetal or ketal under acidic conditions.
Project description:A palladium(II)-catalyzed enantioselective α-alkylation of azlactones with nonconjugated alkenes is described. The reaction employs a chiral BINOL-derived phosphoric acid as the source of stereoinduction, and a cleavable bidentate directing group appended to the alkene to control the regioselectivity and stabilize the nucleopalladated alkylpalladium(II) intermediate in the catalytic cycle. A wide range of azlactones were found to be compatible under the optimal reaction conditions to afford products bearing α,α-disubstituted α-amino-acid derivatives with high yields and high enantioselectivity.
Project description:The stereochemical course of the amidopalladation of alkenes has important implications for the development of enantioselective Pd-catalyzed "Wacker-type" oxidative amidation of alkenes. We have recently shown that the addition of base (Na2CO3) can alter the stereochemical course of amidopalladation in the (IMes)Pd(TFA)2(H2O)-catalyzed aerobic oxidative amidation of alkene. In this study, the mechanism of (IMes)Pd(TFA)2(H2O)-catalyzed oxidative heterocyclization of (Z)-4-hexenyltosylamide was investigated in the presence and absence of exogenous base Na2CO3. The results reveal two parallel pathways in the absence of base: a cis-amidopalladation pathway with turnover-limiting deprotonation of the sulfonamide nucleophile and a trans-amidopalladation pathway with turnover-limiting nucleophilic attack of sulfonamide on the coordinated alkene. The addition of base (Na2CO3) lowers the energy barrier associated with the proton transfer, leading to an overall faster turnover rate and exclusive cis-amidopalladation of alkene.
Project description:Domino reactions involving nickel-catalyzed additions of (hetero)arylboronic acids to alkynes, followed by cyclization of the alkenylnickel intermediates onto tethered acyclic ketones to give chiral tertiary-alcohol-containing products in high enantioselectivities, are described. The reversible E/Z isomerization of the alkenylnickel intermediates enables overall anti-arylmetallative cyclization to occur. The ring system of the products are substructures of certain diarylindolizidine alkaloids.
Project description:Both enantiomers of 2-methyllinalyl diphosphate (2-Me-LPP) were synthesized enantioselectively using Sharpless epoxidation as a key step and purification of enantiomerically enriched intermediates through HPLC separation on a chiral stationary phase. Their enzymatic conversion with 2-methylisoborneol synthase (2MIBS) demonstrates that (R)-2-Me-LPP is the on-pathway intermediate, while a minor formation of 2-methylisoborneol from (S)-2-Me-LPP may be explained by isomerization to 2-Me-GPP and then to (R)-2-Me-LPP.
Project description:The development of enantioselective carbon-carbon bond couplings catalyzed by nonprecious metals is highly desirable in terms of cost efficiency and sustainability. The first nickel-catalyzed enantioselective Mizoroki-Heck coupling is reported. This transformation is accomplished via mild reaction conditions, leveraging on QuinoxP* as a chiral ligand to afford oxindoles containing quaternary stereocenters. Good reactivity and selectivity are observed in the presence of various functional groups. Computational studies suggest that the oxidative addition assembles an atropisomeric intermediate responsible for the facial selectivity of the insertion step.