Construction of Chiral Tetrahydro‐β‐Carbolines: Asymmetric Pictet–Spengler Reaction of Indolyl Dihydropyridines

A highly efficient synthesis of the enantioenriched tetrahydro‐β‐carbolines was developed by using a chiral phosphoric acid catalyzed Pictet–Spengler reaction of indolyl dihydropyridines. The reaction proceeds under mild reaction conditions to afford the desired chiral tetrahydro‐β‐carbolines in good to excellent yields (up to 96 %) and high enantioselectivities (up to 99 % ee ). With this method, a formal synthesis of tangutorine and a total synthesis of deplancheine were achieved in a highly efficient manner.     

Synthesis of chiral organocatalysts derived from aziridines: application in asymmetric aldol reaction

We report the synthesis of a new series of highly efficient chiral organocatalysts derived via the regio- and stereoselective ring opening of chiral aziridines with azide anions. The catalysts have proved to be very efficient for a direct asymmetric aldol reaction, both with cyclic as well as acyclic ketones in brine with 2 mol % of catalyst loading, and afforded the products in excellent yields (up to 99%) and enantioselectivities (up to >99%). The chiral aldol adduct obtained has further been converted to a chiral azetidine ring via a convenient pathway.     

Construction of Chiral Tetrahydro-β-Carbolines: Asymmetric Pictet–Spengler Reaction of Indolyl Dihydropyridines

A highly efficient synthesis of the enantioenriched tetrahydro-β-carbolines was developed by using a chiral phosphoric acid catalyzed Pictet–Spengler reaction of indolyl dihydropyridines. The reaction proceeds under mild reaction conditions to afford the desired chiral tetrahydro-β-carbolines in good to excellent yields (up to 96 %) and high enantioselectivities (up to 99 % ee). With this method, a formal synthesis of tangutorine and a total synthesis of deplancheine were achieved in a highly efficient manner.     

Asymmetric Ring Opening/Cyclization/Retro‐Mannich Reaction of Cyclopropyl Ketones with Aryl 1,2‐Diamines for the Synthesis of Benzimidazole Derivatives

A highly efficient asymmetric ring‐opening/cyclization/retro‐Mannich reaction of cyclopropyl ketones with aryl 1,2‐diamines has been realized using a chiral N,N′‐dioxide/Sc^III catalyst. Benzimidazoles containing chiral side chains were generated under mild reaction conditions in excellent outcomes (up to 99 % yield and 97 % ee). This method also provides efficient access to chiral benzimidazole‐substituted amide and cycloheptene derivatives.     

Side-arm-promoted highly enantioselective ring-opening reactions and kinetic resolution of donor-acceptor cyclopropanes with amines

A Ni-catalyzed asymmetric ring-opening reaction of 2-substituted cyclopropane-1,1-dicarboxylates with aliphatic amines has been accomplished using the chiral indane-trisoxazoline (In-TOX) ligand. This highly enantioselective reaction provides an efficient approach to a variety of chiral γ-substituted γ-amino acid derivatives, which are readily transformed into multifunctionalized piperidines and γ-lactams. The single-crystal X-ray structure of the TOX-Ni complex is provided, and the role of the side arm in the chiral ligand is discussed.     

Room-temperature highly diastereoselective Zn-mediated allylation of chiral N-tert-butanesulfinyl imines: remarkable reaction condition controlled stereoselectivity reversal

[reaction: see text] An efficient method for the highly diastereoselective synthesis of chiral homoallylic amines by Zn-mediated allylation of chiral N-tert-butanesulfinyl imines at room temperature was developed. By simply tuning the reaction conditions, the method allows the achievement of a highly remarkable opposite stereocontrol, affording the desired stereochemical outcome in good yield and with excellent diastereoselectivity (up to 98% dr). With N-sulfinyl ketimines, the corresponding quaternary carbon-containing chiral homoallylic amines could also be produced.     

Catalytic asymmetric aza-Michael-Michael addition cascade: enantioselective synthesis of polysubstituted 4-aminobenzopyrans

A catalytic asymmetric aza-Michael-Michael addition cascade of anilines to nitroolefin enoates in the presence of chiral bifunctional thiourea catalysts has been disclosed. This reaction provides a mild and efficient approach to polysubstituted chiral 4-aminobenzopyrans bearing three consecutive stereocenters in high yields with excellent stereoselectivities.     

Phosphorus-bearing axially chiral biaryls by catalytic asymmetric cross-cyclotrimerization and a first application in asymmetric hydrosilylation

A novel and efficient, two-step route to axially chiral biaryls is demonstrated. In a direct asymmetric cross-cyclotrimerization in the presence of a chiral cobalt(I) catalyst, axially chiral biaryls bearing phosphoryl moieties have been prepared, and through indirect evidence the authors have been able to clarify the origin of the stereochemical induction and the nature of the central intermediate in the catalytic cycle. By subsequent reduction of the phosphoryl moiety to the corresponding phosphine, a very efficient and atom-economical approach to chiral systems has been developed. These chiral systems clearly have great potential use as axially chiral monodentate P- or bidentate P,O-ligands, as has been demonstrated by the employment of the novel NAPHEP as a new monodentate acting ligand in an asymmetric hydrosilylation reaction.     

Synthesis of a simple chiral auxiliary derived from levoglucosenone and its application in a Diels-Alder reaction

The synthesis of a chiral alcohol derived from levoglucosenone has been studied. The alcohol was employed as chiral template in an asymmetric Diels-Alder reaction of the corresponding acrylic ester derivative with cyclopentadiene, and was shown to be an efficient asymmetric inductor. The oxidation reaction detected during the hydrogenation of a secondary allylic alcohol intermediate with Pd/C was also investigated.     

Chiral Brønsted Acid Catalyzed Enantioconvergent Propargylic Substitution Reaction of Racemic Secondary Propargylic Alcohols with Thiols

Despite the significant progress of the enantioselective reaction using chiral catalysts, the enantioselective nucleophilic substitution reaction at the chiral sp³-hybridized carbon atom of a racemic electrophile has not been largely explored. Herein, we report the enantioconvergent propargylic substitution reaction of racemic propargylic alcohols with thiols using chiral bis-phosphoric acid as the chiral Brønsted acid catalyst. The substitution products were formed in high yields with high enantioselectivities in most cases. The cation-stabilizing effect of the sulfur functional group introduced at the alkynyl terminus is the key to achieving the efficient enantioconvergent process, in which chiral information originating from not only the racemic stereogenic center but also the formed contact ion pair is completely eliminated from the present system.     

Nickel-catalyzed enantioselective hydrovinylation of silyl-protected allylic alcohols: An efficient access to homoallylic alcohols with a chiral quaternary center

Asymmetric hydrovinylation of silyl-protected allylic alcohols catalyzed by nickel complexes of chiral spiro phosphoramidite ligands was developed. A series of homoallylic alcohols with a chiral quaternary center were produced in high yields (up to 97%) and high enantioselectivities (up to 95% ee). The reaction provides an efficient method for preparing bifunctional compounds with a chiral quaternary carbon center.     

A simple, short, and flexible synthesis of viridiofungin derivatives

Described herein is a simple, flexible, and efficient synthesis of the skeleton of the viridiofungins, a family of microbial secondary metabolites. The synthesis utilizes an asymmetric aldol reaction of a chiral oxazolidinone, a diastereoselective alkylation of a chiral 1,3-dioxolan-2-one, and a geometrically selective alkene cross-metathesis reaction as the key C-C bond-forming steps.     

A mild and efficient synthesis of a chiral pyridazinone derivative

We found a mild and efficient reaction condition for construction of a chiral 5-methyl-4,5-dihydropyridazin-3(2H)-one from a chiral β-methyl γ-ketocarboxylic acid via the corresponding acid hydrazide without racemization. Furthermore, we demonstrated that this two-step reaction can be attained by one-pot reaction. This method could be applied to various kinds of substrates because of the mild reaction conditions.     

A novel design of a levoglucosenone derived chiral auxiliary

A two-step general approach to a new chiral auxiliary starting from levoglucosenone is reported. The compound is obtained by a [4+2] cycloaddition reaction with anthracene followed by a diastereoselective reduction of the C-2 keto function in high overall yield. The auxiliary has been used as chiral template in an asymmetric Diels-Alder reaction of the corresponding acrylic ester derivative with cyclopentadiene and shown to be efficient for asymmetric induction.     

Chiral pool based synthesis of pyrrolidinium ionic liquids

Chiral ionic liquids show promising applications in various different fields. A series of pyrrolidinium-based chiral ionic liquids bearing a chiral cation, a chiral anion or both was prepared in good yields using an efficient, economic and simple pathway. The chirality was introduced using (l)-lactate and (l)-menthol derivatives. The resultant chiral compounds were characterized by both spectroscopy and polarimetry. We envision that these new chiral compounds can serve as effective reaction media and chiral catalysts for asymmetric reactions, which are presently being investigated in our lab.     

手性螺环单磷配体在不对称氢甲酰化反应中的应用

为了进一步拓展具有螺二氢茚骨架的亚磷酸酰胺酯、亚磷酸酯、亚膦酸酯等手性螺环单磷配体在不对称反应中的应用范围, 研究了手性螺环单磷配体在铑催化苯乙烯衍生物的氢甲酰化反应中的选择性.     

Catalytic, enantioselective intramolecular hydroamination of primary amines tethered to di- and trisubstituted alkenes

The in situ preparation of chiral amido alkyl ate yttrium complexes from an array of chiral N-benzyl-like-substituted binaphthyldiamines is reported. These chiral heteroleptic complexes are shown to be efficient catalysts for the enantioselective intramolecular hydroamination of primary amines tethered to sterically demanding alkenes at high reaction temperatures. Fine tuning of their chiral environment allowed up to 77% ee to be reached for the cyclization of aminoalkenes bearing 1,2-dialkyl-substituted carbon-carbon double bonds. These chiral complexes also demonstrate the ability to promote the cyclization of amine-tethered trisubstituted alkenes in up to 55% ee, as the first report of the formation of enantioenriched quaternary centers by an hydroamination reaction.     

One-pot and microwave-assisted synthesis of N-sulfonylaziridines

A novel and efficient microwave-assisted one-step reaction was developed to synthesize chiral N-sulfonylaziridines by the reaction of different chiral amino alcohols and sulfonic chlorides. The newly developed microwave synthetic method has the advantage of reducing the reaction time from 24 to 0.5 h with improved yields (84-93%) and minimizing by-products.     

Enantioselective Arylation of Benzylic C−H Bonds by Copper‐Catalyzed Radical Relay

A novel enantioselective copper‐catalyzed arylation of benzylic C?H bonds, using alkylarenes as a limiting reagent, has been developed. A chiral bisoxazoline ligand bearing an acetate ester moiety plays a key role in both the reactivity and enantioselectivity of the reaction. The reaction provides efficient access to various chiral 1,1‐diarylalkanes in good yields with good to excellent enantioselectivities, and displays excellent functional‐group tolerance.     

Enantioselective Hydroarylation of Olefins Using Palladium/Chiral Quinoline Oxazolines

Palladium-catalyzed arylation and alkenylation of olefins, known as the Heck reaction, is one of the most efficient catalytic methods for carbon-carbon bond formation in organic synthesis^[1]. During the last decade, asymmetric Heck reactions have attracted great attention, and a number of highly enantioselective chiral ligands have been developed to enhance chiral discrimination in these reactions^[2]. However, asymmetric Heck-type hydroarylations of olefins, addition of aryl halides or triflates to carbon-carbon double bonds, have not been well studied. In 1991, Brunner reported an asymmetric hydroarylation of norbornene and norbornadiene with aryl iodides using chiral bisphosphine ligands, and around 40% ee was achieved^[3]. Later on, Achiwa reached around 70% ee in the asymmetric hydroarylation of norbornene with phenyl triflate by using chiral P-N ligands^[4,5]. Herein, we wish to describe our investigations on chiral quinolinyl-oxazoline ligands that provide the first examples of efficient bisnitrogen ligands in Heck-type hydroarylation and the application of this reaction in the asymmetric synthesis of Epibatidine.