Dihydroquinolines, Dihydronaphthyridines and Quinolones by Domino Reactions of Morita-Baylis-Hillman Acetates

An efficient synthetic route to highly substituted dihydroquinolines and dihydronaphthyridines has been developed using a domino reaction of Morita-Baylis-Hillman (MBH) acetates with primary aliphatic and aromatic amines in DMF at 50–90 °C. The MBH substrates incorporate a side chain acetate positioned adjacent to an acrylate or acrylonitrile aza-Michael acceptor as well as an aromatic ring activated toward SNAr ring closure. A control experiment established that the initial reaction was an SN2′-type displacement of the side chain acetate by the amine to generate the alkene product with the added nitrogen nucleophile positioned trans to the SNAr aromatic ring acceptor. Thus, equilibration of the initial alkene geometry is required prior to cyclization. A further double bond migration was observed for several reactions targeting dihydronaphthyridines from substrates with a side chain acrylonitrile moiety. MBH acetates incorporating a 2,5-difluorophenyl moiety were found to have dual reactivity in these annulations. In the absence of O2, the expected dihydroquinolines were formed, while in the presence of O2, quinolones were produced. All of the products were isolated in good to excellent yields (72–93%). Numerous cases (42) are reported, and mechanisms are discussed.

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>

Dehydrogenative Allylic Aminations of But-3-enoic Acid Derivatives

Two complementary Pd-catalyzed protocols enabling the γ-selective intermolecular allylic amination of but-3-enoic acid derivatives are reported. These transformations can be successfully achieved via either­ a direct Pd(II)-catalyzed protocol or by way of a one-pot Pd(II)/Pd(0)-catalyzed sequence, depending on the nature of the nitrogen nucleophile used.

Palladium-catalyzed amination of 2,3,3-trifluoroallyl esters: synthesis of trifluoromethylenamines via an intramolecular fluorine shift and CF3 group construction

The palladium-catalyzed reaction of 2,3,3-trifluoroallyl esters with amines afforded trifluoromethylenamines, which were formed by the addition of a nitrogen nucleophile at the C-2 position and the fluorine atom shift from the C-2 to C-3 position.