Asymmetric Hydrogenation of Unprotected Indoles Catalyzed by η⁶‑Arene/<i>N</i>‑Me-sulfonyldiamine–Ru(II) Complexes

Protecting-group-free transformation is a challenging and important issue in atom-economical organic synthesis. The η⁶-arene/<i>N</i>-Me-sulfonyldiamine–Ru­(II)–BF₄ complex-catalyzed asymmetric hydrogenation of 2-substituted unprotected indoles in weakly acidic hexafluoroisopropanol gives optically active indoline compounds with up to >99% ee. Under mild reaction media, halogen atoms and synthetically important protecting groups (e.g., silyl ether, acetal, benzyl ether, and ester) on indoles are maintained, which is advantageous for the synthesis of further complex indoline molecules

Diversity-Oriented Asymmetric Catalysis (DOAC): Stereochemically Divergent Synthesis of Thiochromanes Using an Imidazoline–Aminophenol–Nickel-Catalyzed Michael/Henry Reaction

The (<i>S</i>,<i>S</i>)-diphenylethylenediamine-derived imidazoline–aminophenol–Ni complex catalyzed tandem asymmetric Michael/Henry reaction of 2-mercaptobenzaldehydes with β-nitrostyrenes to give the corresponding (2<i>S</i>,3<i>R</i>,4<i>R</i>)-2-aryl-3-nitrothiochroman-4-ols in up to 99% diastereoselectivity with 95% ee was demonstrated in diversity-oriented asymmetric catalysis. Reduction of the nitro group of the chiral thiochromanes gave a new series of (2<i>S</i>,3<i>R</i>,4<i>R</i>)-3-amino-2-arylthiochroman-4-ols with retention of the strereoselectivity

Design and Synthesis of the First Spiro Bis(isoxazoline) Derivatives as Asymmetric Ligands

A chiral bis(isoxazoline) ligand (SPRIX) containing a rigid spiro skeleton was designed and synthesized via a double intramolecular nitrile oxide cycloaddition. The optically pure SPRIX greatly accelerated the Cu(acac)2-catalyzed asymmetric reaction of diisopropylzinc with cyclohexenone to give the Michael adduct with 49% ee. This is the first example of the use of an isoxazoline ligand for a transition metal-catalyzed reaction. The X-ray crystallographic analysis of the hexacoordinated copper complex of SPRIX confirmed the ligand character

Easy Access to Fully Functionalized Chiral Tetrahydro-β-Carboline Alkaloids

A four-step synthetic route to fully substituted chiral tetrahydro-β-carbolines (THBCs) is described. Starting from the (R,S,S)-Friedel−Crafts/Henry adduct obtained from three-component coupling of an indole, nitroalkene, and aldehyde catalyzed by imidazoline-aminophenol−CuOTf, the (1S,3S,4R)-THBCs were readily synthesized in a three-step operation including reduction of the nitro-functionality and Pictet−Spengler cyclization

Design and Synthesis of the First Spiro Bis(isoxazoline) Derivatives as Asymmetric Ligands

A chiral bis(isoxazoline) ligand (SPRIX) containing a rigid spiro skeleton was designed and synthesized via a double intramolecular nitrile oxide cycloaddition. The optically pure SPRIX greatly accelerated the Cu(acac)2-catalyzed asymmetric reaction of diisopropylzinc with cyclohexenone to give the Michael adduct with 49% ee. This is the first example of the use of an isoxazoline ligand for a transition metal-catalyzed reaction. The X-ray crystallographic analysis of the hexacoordinated copper complex of SPRIX confirmed the ligand character

Asymmetric Friedel–Crafts-Type Reaction of 2‑Vinylindoles to <i>N</i>‑Boc Imines Using a Chiral Imidazolidine-Containing NCN-Pincer Pd Catalyst

A chiral imidazolidine-containing NCN-pincer Pd-OTf complex (NCN-Pd cat) promoted the asymmetric nucleophilic addition of unprotected 2-vinylindoles to N-Boc imines in a Friedel–Crafts-type manner. The chiral (2-vinyl-1H-indol-3-yl)methanamine products become nice platforms for constructing multiple ring systems

Selective Synthesis of α,β-Unsaturated Ketones by Dibutyltin Dimethoxide-Catalyzed Condensation of Aldehydes with Alkenyl Trichloroacetates

Various α,β-unsaturated ketones were stereoselectively synthesized in high yields up to 94% by a condensation reaction between alkenyl trichloroacetates and aldehydes using dibutyltin dimethoxide as a catalyst in the presence of methanol. This process is superior to the classical Claisen−Schmidt condensation with respect to mildness of the base catalyst and product selectivity

Design and Synthesis of the First Spiro Bis(isoxazoline) Derivatives as Asymmetric Ligands

A chiral bis(isoxazoline) ligand (SPRIX) containing a rigid spiro skeleton was designed and synthesized via a double intramolecular nitrile oxide cycloaddition. The optically pure SPRIX greatly accelerated the Cu(acac)2-catalyzed asymmetric reaction of diisopropylzinc with cyclohexenone to give the Michael adduct with 49% ee. This is the first example of the use of an isoxazoline ligand for a transition metal-catalyzed reaction. The X-ray crystallographic analysis of the hexacoordinated copper complex of SPRIX confirmed the ligand character

Practical Asymmetric Henry Reaction Catalyzed by a Chiral Diamine-Cu(OAc)₂ Complex

The chiral diamine ligand 3 was designed and synthesized from (R,R)-1,2-diphenylethylenediamine, (S)-2,2‘-dibromomethyl-1,1‘-binaphthalene, and o-xylylene dibromide. The resulting 3-Cu(OAc)2 complex was a highly efficient catalyst for the Henry reaction, giving the various nitroaldols with over 90% ee (up to >99%). The reaction was performed in n-propyl alcohol at room temperature, and the Henry adducts were produced in high yield with excellent enantiomeric excess; these attributes are desirable in a catalyst for practical use

PyBidine–NiCl₂‑Catalyzed Asymmetric Addition of Alcohols and Peroxides to Isatin-Derived Ketimines

An (<i>S</i>,<i>S</i>)-diphenyldiamine-derived bis­(imidazolidine)­pyridine (PyBidine)–NiCl₂ complex catalyzed the asymmetric addition of methanol and peroxides to isatin-derived <i>N</i>-Boc-imines to form chiral quaternary <i>N</i>,<i>O</i>-acetals at the C3 position of the resulting oxiindoles in up to 99% yield with 94% ee