Rh2(II)-Catalyzed Intermolecular N-Aryl Aziridination of Olefins using Nonactivated N-Atom Precursors

The development of the first intermolecular Rh₂(II)-catalyzed aziridination of di-, tri-, or tetraubstituted olefins using aryl- or heteroaryl amines as nonactivated N-atom precursors and an iodine(III) reagent as the stoichiometric oxidant is reported. The Rh₂(II)-catalyzed N-atom transfer to the olefin is stereospecific, chemo- and diastereoselective to produce the <i>N</i>-aryl aziridine as the only amination product.

Rh2(II)-Catalyzed Intermolecular N-Aryl Aziridination of Olefins using Nonactivated N-Atom Precursors

The development of the first intermolecular Rh₂(II)-catalyzed aziridination of di-, tri-, or tetraubstituted olefins using aryl- or heteroaryl amines as nonactivated N-atom precursors and an iodine(III) reagent as the stoichiometric oxidant is reported. The Rh₂(II)-catalyzed N-atom transfer to the olefin is stereospecific, chemo- and diastereoselective to produce the <i>N</i>-aryl aziridine as the only amination product.

Non-Directed, Copper Catalyzed Benzylic C-H Amination Avoiding Substrate Excess

<div> <p>We report the development of a benzylic C-H amination protocol that addresses two common drawbacks in non-directed, intermolecular benzylic C-H aminations: (i) the need to use an excess of substrate and (ii) the limitation to only introduce one type of nitrogen source. Key to this discovery is the use of the strong oxidant <i>N</i>-fluorobenzenesulfonimide (NFSI) in combination with a Cu/diimine ligand catalyst system and an added nitrogen nucleophile. The established conditions allow to lower the C-H substrate loading to 1.0 equivalent and provide up to 95% yield of C-H amination product. Furthermore, sulfonamides and benzamides can be employed as nitrogen sources/nucleophiles, resulting in access to a diverse product scope. </p> </div>

Non-Directed, Copper Catalyzed Benzylic C-H Amination Avoiding Substrate Excess

<div> <p>We report the development of a benzylic C-H amination protocol that addresses two common drawbacks in non-directed, intermolecular benzylic C-H aminations: (i) the need to use an excess of substrate and (ii) the limitation to only introduce one type of nitrogen source. Key to this discovery is the use of the strong oxidant <i>N</i>-fluorobenzenesulfonimide (NFSI) in combination with a Cu/diimine ligand catalyst system and an added nitrogen nucleophile. The established conditions allow to lower the C-H substrate loading to 1.0 equivalent and provide up to 95% yield of C-H amination product. Furthermore, sulfonamides and benzamides can be employed as nitrogen sources/nucleophiles, resulting in access to a diverse product scope. </p> </div>

Non-Directed, Copper Catalyzed Benzylic C-H Amination Avoiding Substrate Excess

<div> <p>We report the development of a benzylic C-H amination protocol that addresses two common drawbacks in non-directed, intermolecular benzylic C-H aminations: (i) the need to use an excess of substrate and (ii) the limitation to only introduce one type of nitrogen source. Key to this discovery is the use of the strong oxidant <i>N</i>-fluorobenzenesulfonimide (NFSI) in combination with a Cu/diimine ligand catalyst system and an added nitrogen nucleophile. The established conditions allow to lower the C-H substrate loading to 1.0 equivalent and provide up to 95% yield of C-H amination product. Furthermore, sulfonamides and benzamides can be employed as nitrogen sources/nucleophiles, resulting in access to a diverse product scope. </p> </div>

Non-Directed, Copper Catalyzed Benzylic C-H Amination Avoiding Substrate Excess

<div> <p>We report the development of a benzylic C-H amination protocol that addresses two common drawbacks in non-directed, intermolecular benzylic C-H aminations: (i) the need to use an excess of substrate and (ii) the limitation to only introduce one type of nitrogen source. Key to this discovery is the use of the strong oxidant <i>N</i>-fluorobenzenesulfonimide (NFSI) in combination with a Cu/diimine ligand catalyst system and an added nitrogen nucleophile. The established conditions allow to lower the C-H substrate loading to 1.0 equivalent and provide up to 95% yield of C-H amination product. Furthermore, sulfonamides and benzamides can be employed as nitrogen sources/nucleophiles, resulting in access to a diverse product scope. </p> </div>

Asymmetric Allylic Amination of Morita–Baylis–Hillman Adducts with Simple Aromatic Amines by Nucleophilic Amine Catalysis

Asymmetric allylic amination of Morita–Baylis–Hillman (MBH) adducts with simple aromatic amines is successfully realized by nucleophilic amine catalysis. A range of substituted α-methylene-β-arylamino esters is accessed in moderate to high yields (up to 88%) and with excellent enantioselectivities (up to 97% ee). Inorganic fluorides are found to be able to improve the enantioselectivity of the allylic amination reaction. A pyrrole-2-carboxylate and a cyclic imide are also compatible with this catalytic system. A chiral 2,3-dihydroquinolin-4-one derivative is easily obtained from the allylic amination product.

Pd-catalyzed asymmetric allylic amination using easily accessible metallocenyl P,N-ligands

Pd-catalyzed asymmetric allylic aminations were carried out efficiently using both C2-symmetric and non-C2-symmetric metallocenyl P,N-ligands. A more accessible mixed ligand system of the above two was then examined, providing the amination product with high yield and excellent enantioselectivity.

Spectrometric Study of the Nitrile-Ketenimine Tautomerism

Mass spectrometry is used to evaluate the occurrence of the nitrile-ketenimine tautomerism. Mass spectra of two differently substituted nitriles, ethyl-4,4-dicyano-3-methyl-3-butenoate and diethyl-2-cyano-3-methyl-2-pentenodiate are examined looking for common mass spectral behaviors. Ion fragmentation assignments for specific tautomers allow to predict the presence of the corresponding structures. Additionally, the mass spectrum and nuclear magnetic resonance spectra of ethyl-4,4-dicyano-2,2-diethyl-3-methyl-3-butenoate and that of the corresponding amination product support the occurrence of the ketenimine tautomer in the equilibrium.

Aminolithiation of carbon-carbon double bonds as a powerful tool in organic synthesis

A conjugate amination of α,β-unsaturated carbonyl compounds with lithium amides has become a powerful method of N-C bond-forming reactions. Chiral ligand-controlled asymmetric version of the conjugate amination of enoates was developed for practical bench chemistry, giving the enantioenriched amination product with over 99 % ee. In situ diastereoselective alkylation of resulting lithium enolates allowed us to form vicinal N-C and C-C bonds in a one-pot operation. This protocol enabled us to realize a short-step asymmetric synthesis of otamixaban key intermediate. Treatment of product 3-benzylamino- and 3-allylaminoesters with tert-butyllithium gave five- or seven-membered lactams through [1,2]- or [2,3]-rearrangement of intermediate β-lactams. Isolated C-C double bonds were also found to accept intramolecular aminolithiation affording the corresponding hydroamination products. Chiral lithiophilic ligand-catalyzed reaction gave enantioenriched hydroamination products with high ee. Stereoselective intramolecular aminolithiation of allylaminoalkenes was coupled with subsequent carbolithiation to give doubly cyclized product amines.