title: Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides.
abstract: As the complexity of targeted molecules increases in modern organic synthesis, chemoselectivity is recognized as an important factor in the development of new methodologies. Chemoselective nucleophilic addition to amide carbonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor electrophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nucleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2 ZrHCl]. The reaction took place in a highly chemoselective fashion in the presence of a variety of sensitive functional groups, such as methyl esters, which conventionally require protection prior to nucleophilic addition. The reaction will be applicable to the concise synthesis of complex natural alkaloids from readily available amide groups.
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama 223-8522 (Japan), Fax: (+81) 45-566-1551.
authors.forename: Minami
authors.initials: M
authors.lastname: Nakajima
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Oda
authors.forename: Takamasa
authors.initials: T
authors.lastname: Wada
authors.forename: Ryo
authors.initials: R
authors.lastname: Minamikawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Shirokane
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sato
authors.forename: Noritaka
authors.initials: N
authors.lastname: Chida
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D055598:Chemical Phenomena; D004952:Esters; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D000577:Amides; D000588:Amines; D004952:Esters; D009942:Organometallic Compounds; C532427:Schwartz reagent
keywords: amides; chemoselectivity; nitrogen; nucleophilic addition; sequential reactions