title: General one-pot reductive gem-bis-alkylation of tertiary lactams/amides: rapid construction of 1-azaspirocycles and formal total synthesis of (±)-cephalotaxine.
abstract: Amides are a class of highly stable and readily available compounds. The amide functional group constitutes a class of powerful directing/activating and protecting group for C-C bond formation. Tertiary tert-alkylamine, including 1-azaspirocycle is a key structural feature found in many bioactive natural products and pharmaceuticals. The transformation of amides into tert-alkylamines generally requires several steps. In this paper, we report the full details of the first general method for the direct transformation of tertiary lactams/amides into tert-alkylamines. The method is based on in situ activation of amide with triflic anhydride/2,6-di-tert-butyl-4-methylpyridine (DTBMP), followed by successive addition of two organometallic reagents of the same or different kinds to form two C-C bonds. Both alkyl and functionalized organometallic reagents and enolates can be used as the nucleophiles. The method displayed excellent 1,2- and good 1,3-asymmetric induction. Construction of 1-azaspirocycles from lactams required only two steps or even one-step by direct spiroannelation of lactams. The power of the method was demonstrated by a concise formal total synthesis of racemic cephalotaxine.
authors: Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (P.R. China).
authors: Kai-Jiong
authors: KJ
authors: Xiao
authors: Jie-Min
authors: JM
authors: Luo
authors: Xiao-Er
authors: XE
authors: Xia
authors: Yu
authors: Y
authors: Wang
authors: Pei-Qiang
authors: PQ
authors: Huang
keywords: CC bond formation; alkylation; lactams; reduction; synthetic methods