title: A direct and general method for the reductive alkylation of tertiary lactams/amides: application to the step economical synthesis of alkaloid (-)-morusimic acid D.
abstract: Full details of the direct and general method for the reductive alkylation of tertiary lactams and amides to give tertiary sec-alkylamines are presented. This one-pot method consists of in situ activation of a lactam or an amide with Tf2O/DTBMP, addition of a Grignard reagent, and reduction of the resulting iminium intermediates. Alkyl, benzyl, and aryl Grignard reagents and several reductants or reducing conditions (LiAlH4, NaBH4, Hantzsch ester, Bu3SnH, Pd(OH)2/C, H2) could be used effectively. Reductive alkylations of substituted lactams demonstrated good to excellent 1,3-asymmetric induction to provide the corresponding di- or trisubstituted pyrrolidine/piperidine in 6:1 (LiAlH4), 11:1 (Et3SiH), and 20:1 (catalytic hydrogenation) cis/trans diastereoselectivity, respectively. The versatility of this methodology was demonstrated by its application in the concise stereoselective synthesis of piperidine alkaloid (-)-morusimic acid.
authors.affiliation: Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, People's Republic of China.
authors.forename: Kai-Jiong
authors.initials: KJ
authors.lastname: Xiao
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Huang
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Wang
authors.forename: Pei-Qiang
authors.initials: PQ
authors.lastname: Huang
mesh_terms: D000478:Alkylation; D000577:Amides / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000577:Amides; D007769:Lactams; D010880:Piperidines