Development of a Chiral Bis(guanidino)iminophosphorane as an Uncharged Organosuperbase for the Enantioselective Amination of Ketones

Chiral bis­(guanidino)­imino­phosphoranes were designed and synthesized as chiral uncharged organo­superbase catalysts that facilitate activation of less-acidic pro-nucleophiles. The newly developed bis­(guanidino)­imino­phosphoranes, which possess the highest basicity among chiral organocatalysts reported to date, were proven to be a superb class of chiral organo­superbases by reaction of azodicarboxylates with 2-alkyltetralones and their analogues as the less acidic pro-nucleophiles

Copper-Catalyzed Domino [1,3]/[1,2] Rearrangement for the Efficient Synthesis of Multisubstituted <i>ortho</i>-Anisidines

Multisubstituted <i>ortho</i>-anisidines were efficiently synthesized via cationic <i>N</i>-heterocyclic carbene-Cu-catalyzed domino rearrangement of <i>N-</i>methoxyanilines that possess an electron-donating functional group, such as an alkyl or an aryl group, at the <i>ortho</i> position. The reaction proceeded first through a [1,3]-rearrangement of the methoxy group to the <i>ortho</i> position bound to the electron-donating substituent, followed by a semipinacol type [1,2]-rearrangement of the electron-donating group from the <i>ortho</i> to the <i>meta</i> position. Mechanistic studies suggest that both rearrangement reactions are promoted by a cationic Cu catalyst

Copper-Catalyzed Cascade Transformation of <i>O</i>‑Propargylic Oximes with Sulfonyl Azides to α,β-Unsaturated <i>N</i>‑Acylamidines

Copper-catalyzed cascade transformations of <i>O-</i>propargylic oximes and sulfonyl azides were carried out to efficiently afford α,β-unsaturated <i>N</i>-acylamidines. The reaction involved the intramolecular attack of the oxime group to the ketenimine moiety that was generated in situ, followed by the cleavage of the N–O bond

Kinetic Resolution of Racemic Amino Alcohols through Intermolecular Acetalization Catalyzed by a Chiral Brønsted Acid

The kinetic resolution of racemic secondary alcohols is a fundamental method for obtaining enantiomerically enriched alcohols. Compared to esterification, which is a well-established method for this purpose, kinetic resolution through enantioselective intermolecular acetalization has not been reported to date despite the fact that the formation of acetals is widely adopted to protect hydroxy groups. By taking advantage of the thermodynamics of acetalization by the addition of alcohols to enol ethers, a highly efficient kinetic resolution of racemic amino alcohols was achieved for the first time and in a practical manner using a chiral phosphoric acid catalyst

Chiral Phosphoric Acid Catalyzed Diastereo- and Enantioselective Mannich-Type Reaction between Enamides and Thiazolones

An enantioselective Mannich-type reaction between enamides, serving as aliphatic imine equivalents, and thiazolones or an azlactone, serving as α-amino acid derived pronucleophiles, was investigated using a chiral phosphoric acid catalyst. By using thiazolones, Mannich adducts with a tetrasubstituted chiral carbon center at the α-position and an aliphatic substituent at the β-position were efficiently obtained with high diastereo- and enantioselectivities

Cu-Catalyzed Skeletal Rearrangement of <i>O</i>‑Propargylic Electron-Rich Arylaldoximes into Amidodienes

<i>O</i>-Propargylic oximes that possess an electron-rich <i>p</i>-(dimethylamino)­phenyl group at the oxime moiety and an alkyl group at the propargylic position were efficiently converted in the presence of Cu­(I) catalysts to the corresponding 1-amidodienes in good to excellent yields. The reaction proceeded via a 2,3-rearrangement, followed by isomerization of the resulting <i>N</i>-allenylnitrone to the amide, presumably through the oxaziridine intermediate

Intramolecular Cyclization of Alkynyl α‑Ketoanilide Utilizing [1,2]-Phospha-Brook Rearrangement Catalyzed by Phosphazene Base

A novel catalytic cyclization reaction of alkynyl α-ketoanilide was developed by utilizing the [1,2]-phospha-Brook rearrangement. This reaction involves the generation of an amide enolate via the umpolung process, that is the addition of dialkyl phosphite to a keto moiety followed by the [1,2]-phospha-Brook rearrangement, and the subsequent intramolecular addition of the enolate to an alkyne to afford 3,4-dihydro-2-quinolone derivatives. Under high-temperature reaction conditions, further rearrangement of the allylic phosphate moiety occurs to provide 2-quinolone derivatives

Mechanistic Studies of Highly Enantio- and Diastereoselective Aza-Petasis–Ferrier Rearrangement Catalyzed by Chiral Phosphoric Acid

The precise mechanism of the highly <i>anti</i>- and enantioselective aza-Petasis–Ferrier (APF) rearrangement of hemiaminal vinyl ethers catalyzed by a chiral phosphoric acid was investigated by undertaking experimental and theoretical studies. The APF rearrangement is characterized by the following unique mechanistic features: (i) efficient optical kinetic resolution of the starting racemic hemiaminal vinyl ether, (ii) enantioconvergent process from racemic hemiaminal vinyl ethers to optically active β-amino aldehyde products, and (iii) anomalous temperature effects on the enantioselectivity (enantioselectivity increases as reaction temperature increases). The following experiments were conducted to elucidate the unique mechanistic features as well as to uncover the overall scheme of the present rearrangement: (A) X-ray crystallographic analysis of the recovered hemiaminal vinyl ether to determine its absolute configuration, (B) rearrangements of enantiomerically pure hemiaminal vinyl ethers to validate the stereochemical relationship between the hemiaminal vinyl ethers and β-amino aldehydes, (C) theoretical studies on the transition states of the C–O bond cleavage and C–C bond formation steps to gain an insight into the optical kinetic resolution of the hemiaminal vinyl ether and the origin of the stereoselectivity, as well as to elucidate the overall scheme of the present rearrangement, and (D) crossover experiments of two hemiaminal vinyl ethers having different vinyl ether and aliphatic substituents to comprehend the mechanism of the anomalous temperature effect and the enantioconvergent process. The results of experiments and theoretical studies fully support the proposed mechanism of the present <i>anti</i>- and enantioselective APF rearrangement