Project description:Allylic sulfamides undergo efficient aerobic oxidative cyclization at room temperature, mediated by a new Pd catalyst system consisting of 5% Pd(TFA)(2)/10% DMSO in THF. The synthetic utility of these reactions is enhanced by several features: (1) the sulfamide substrates are accessible in multi-gram scale from the corresponding allylic and primary amines, (2) the cyclic sulfamide products are readily converted to the corresponding 1,2-diamines upon treatment with LiAlH(4), and (3) substrates derived from chiral allylic amines cyclize with very high levels of diastereoselectivity.
Project description:A palladium-catalyzed hydroalkylation reaction of protected allylic alcohols using alkylzinc bromide reagents is reported. This account includes numerous allylic, homoallylic, and bishomoallylic alcohol derivatives, all with a uniform selectivity of >20:1 for the anti-Markovnikov product. The reaction features the ability to deliver enantiomerically enriched alcohols in unfunctionalized regions, which results from the catalyst avoiding β-hydride elimination at the allylic position.
Project description:The first two highly enantioselective palladium-catalyzed allylic alkylations with benzylic nucleophiles, activated with Cr(CO)3 , have been developed. These methods enable the enantioselective synthesis of α-2-propenyl benzyl motifs, which are important scaffolds in natural products and pharmaceuticals. A variety of cyclic and acyclic allylic carbonates are competent electrophilic partners furnishing the products in excellent enantioselectivity (up to 99 % ee and 92 % yield). This approach was employed to prepare a nonsteroidal anti-inflammatory drug analogue.
Project description:The palladium-catalyzed asymmetric allylic alkylation of a 1:1 mixture of dl- and meso-1,2-divinylethylene carbonate is reported. For the first time, both the ionization and nucleophilic addition steps of the catalytic cycle act as enantiodiscriminating steps to give a single product in high enantiomeric excess. The reactions proceed in >98% ee to efficiently generate useful chiral building blocks from acrolein. The absolute and relative configurations of iso-cladospolide B and 11-epi-iso-cladospolide B were verified by total synthesis, solving an apparent discrepancy in the literature.
Project description:The cyclization of gamma,delta-unsaturated tertiary hydroperoxides in the presence of a palladium(II) catalyst afforded 1,2-dioxanes resembling biologically active natural products. A variety of substrates were screened, and synthetic manipulations were accomplished to construct compounds with structural similarity to antimalarial targets.
Project description:A highly regio- and enantioselective synthesis of 1,2-diamine derivatives from γ-substituted allylic pivalamides using copper-catalyzed hydroamination is reported. The N-pivaloyl group is essential, in both facilitating the hydrocupration step and suppressing an unproductive β-elimination from the alkylcopper intermediate. This approach enables an efficient construction of chiral differentially protected vicinal diamines under mild conditions with broad functional group tolerance.
Project description:A series of simple heteroarylidene malonate-type bis(oxazoline) ligands 4 and 5 were applied to the palladium-catalyzed allylic alkylation reaction, and the ligand 4a bearing a phenyl group afforded excellent enantioselectivity (up to 96% ee) for the allylic alkylation product. Other substrates were also examined, giving the allylic alkylated products in high yield but with poor ee values.
Project description:A palladium(II) catalyst system has been identified for aerobic dehydrogenation of substituted cyclohexenes to the corresponding arene derivatives. Use of sodium anthraquinone-2-sulfonate (AMS) as a cocatalyst enhances the product yields. A wide range of functional groups are tolerated in the reactions, and the scope and limitations of the method are described. The catalytic dehydrogenation of cyclohexenes is showcased in an efficient route to a phthalimide-based TRPA1 activity modulator.
Project description:Palladium-catalyzed hydroalkylation of allylic amine derivatives by alkylzinc reagents is reported. This reductive cross-coupling reaction yields anti-Markovnikov products using a variety of allylic amine protecting groups. Preliminary mechanistic studies suggest that a reversible β-hydride elimination/hydride insertion process furnishes the primary Pd-alkyl intermediate, which then undergoes transmetalation followed by reductive elimination to form a new sp(3)-sp(3) carbon-carbon bond.
Project description:The synthesis of cyclic sulfamides by enantioselective Pd-catalyzed alkene carboamination reactions between N-allylsulfamides and aryl or alkenyl bromides is described. High levels of asymmetric induction (up to 95:5 e.r.) are achieved using a catalyst composed of [Pd2 (dba)3 ] and (S)-Siphos-PE. Deuterium-labelling studies indicate the reactions proceed through syn-aminopalladation of the alkene and suggest that the control of syn- versus anti-aminopalladation pathways is important for asymmetric induction.