Project description:Nitroalkenes readily undergo palladium-catalyzed [3 + 2] cycloaddition with trimethylenemethane to generate nitrocyclopentanes in excellent yield and enantioselectivity. Furthermore, the products thus formed are highly versatile synthetic intermediates and provide convenient access to both cyclopentylamines and cyclopentenones.
Project description:β,β-Disubstituted nitroalkenes readily undergo palladium-catalyzed [3 + 2] cycloaddition with trimethylenemethane to generate nitrocyclopentanes in excellent yield and enantioselectivity. The reaction provides access to heavily substituted cyclopentanes containing up to three contiguous stereocenters, and the products may be converted to both cyclopentylamines and cyclopentenones. A rare dependence of the sense of chirality of the cycloadducts was observed to be exclusively dependent on the structure of the palladium-bound trimethylenemethane intermediate.
Project description:Phenones with elongated chains are shown to be excellent substrates for ligand-promoted asymmetric Grignard synthesis of tertiary alcohols. In turn this enables the simple, short and highly enantioselective (up to 96% ee) preparation of chiral 2,2-disubstituted THFs and THPs. Thus, asymmetric addition of Grignard reagents to γ-chlorobutyrophenones and δ-chlorovalerophenones takes place in the presence of a chiral diaminocyclohexyl-derived tridentate ligand and subsequent base-promoted intramolecular cyclisation occurs with complete retention of asymmetry. As examples of the methodology, we report the shortest syntheses of gossonorol, γ-ethyl-γ-phenylbutyrolactone and δ-methyl-δ-tolylvalerolactone, the joint-shortest and flexible synthesis of boivinianin A and the shortest formal syntheses of boivinianin B and yingzhaosu C.
Project description:The Pd-catalyzed coupling of γ-hydroxyalkenes with aryl bromides affords enantiomerically enriched 2-(arylmethyl)tetrahydrofuran derivatives in good yield and up to 96:4 e.r. This transformation was achieved through the development of a new TADDOL/2-arylcyclohexanol-derived chiral phosphite ligand. The transformations are effective with an array of different aryl bromides, and can be used for the preparation of products bearing quaternary stereocenters.
Project description:A practical and enantioselective palladium-catalyzed diboration of 1,1-disubstituted allenes is developed by employing a P-chiral monophosphorus ligand, BI-DIME. A series of diboronic esters containing a chiral tertiary boronic ester moiety are formed in excellent yields and ee's with the palladium loading as low as 0.2 mol%. DFT calculations revealed a concerted mechanism of oxidative addition of bis(pinacolato)diboron and allene insertion, as well as a critical dispersion effect on the origins of the enantioselectivity. The method is successfully applied to the concise and enantioselective synthesis of brassinazole.
Project description:Oxazocines are key structural intermediates in the synthesis of natural products and pharmaceutical molecules. However, the synthesis of oxazocines especially in a highly enantioselective manner, is a long-standing formidable challenge due to unfavorable energetics involved in cyclization. Herein, a series of new PNP-Ligand P-chiral stereocenter is first designed and synthesized, called MQ-Phos, and successfully applied it in the Pd-catalyzed enantioselective higher-order formal [4+4]-cycloaddition of α, β-unsaturated imines with 2-(hydroxymethyl)-1-arylallyl carbonates. The reaction features mild conditions, excellent regio- and enantiocontrol and a broad substrate scope (54 examples). Various medium-sized rings can be afforded in moderate to excellent yields (up to 92%) and excellent enantioselectivity (up to 99% ee). The newly developed MQ-Phos is critical for synthesis of the medium-sized ring in excellent catalytic reactivity and enantioselectivity.
Project description:Chiral α-amino ketones are common structural motifs in natural products and pharmaceuticals, as well as important synthons in organic synthesis. Thus, establishing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein we disclose a new catalytic asymmetric approach for the synthesis of chiral α-amino ketones through a chiral palladium-catalyzed arylation reaction of in situ generated challenging α-keto imines from previously unreported C-acyl N-sulfonyl-N,O-aminals, with arylboronic acids. The current reaction offers a straightforward approach to the asymmetric synthesis of acyclic α-amino ketones in a practical and highly stereocontrolled manner. Meanwhile, the multiple roles of the chiral Pd(ii) complex catalyst in the reaction were also reported.
Project description:A protocol for the enantioselective [3 + 2] cycloaddition of trimethylenemethane (TMM) with imines has been developed. Central to this effort were the novel phosphoramidite ligands developed in our laboratories. The conditions developed to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of imine acceptors to provide the corresponding pyrrolidine cycloadducts with excellent yields and selectivities. Use of a bis-2-naphthyl phosphoramidite allowed the successful cycloaddition of the parent TMM with N-Boc imines, and has further permitted the reaction of substituted donors with N-tosyl aldimines and ketimines in high regio-, diastereo-, and enantioselectivity. Use of a diphenylazetidine ligand allows the complementary synthesis of the exocyclic nitrile product shown, and we demonstrate control of the regioselectivity of the product based on manipulation of the reaction parameters.
Project description:We describe a palladium-catalyzed diastereo- and enantioselective formal [3 + 2]-cycloaddition between substituted vinylcyclopropanes and electron-deficient olefins in the form of azlactone- and Meldrum's acid alkylidenes to give highly substituted cyclopentane products. By modulation of the electronic properties of the vinylcyclopropane and the electron-deficient olefin, high levels of stereoselectivity were obtained. The remote stereoinduction afforded by the catalyst, distal from the chiral pocket generated by the ligand, is proposed to be the result of a new mechanism invoking the Curtin-Hammett principle.