A general carbonyl alkylative amination for tertiary amine synthesis

doi:10.1038/s41586-020-2213-0

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2213-0
	A general carbonyl alkylative amination for tertiary amine synthesis
	Ouyang, David 1; He, Bryan 2; Ghorbani, Amirata 3; Yuan, Neal 4; Ebinger, Joseph 4; Langlotz, Curtis P.1,5; Heidenreich, Paul A.1; Harrington, Robert A.1; Liang, David H.1,3; Ashley, Euan A.1,6; Zou, James Y.2,3,6
	2020-03-25
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
文章类型	Article;Early Access
语种	英语
国家	England
英文关键词	The ubiquity of tertiary alkylamines in pharmaceutical and agrochemical agents, natural products and small-molecule biological probes(1,2) has stimulated efforts towards their streamlined synthesis(3-9). Arguably the most robust method for the synthesis of tertiary alkylamines is carbonyl reductive amination(3), which comprises two elementary steps: the condensation of a secondary alkylamine with an aliphatic aldehyde to form an all-alkyl-iminium ion, which is subsequently reduced by a hydride reagent. Direct strategies have been sought for a ' higher order' variant of this reaction via the coupling of an alkyl fragment with an alkyl-iminium ion that is generated in situ(10-14). However, despite extensive efforts, the successful realization of a ' carbonyl alkylative amination' has not yet been achieved. Here we present a practical and general synthesis of tertiary alkylamines through the addition of alkyl radicals to all-alkyl-iminium ions. The process is facilitated by visible light and a silane reducing agent, which trigger a distinct radical initiation step to establish a chain process. This operationally straightforward, metal-free and modular transformation forms tertiary amines, without structural constraint, via the coupling of aldehydes and secondary amines with alkyl halides. The structural and functional diversity of these readily available precursors provides a versatile and flexible strategy for the streamlined synthesis of complex tertiary amines. The synthesis of tertiary amines is achieved through a carbonyl alkylative amination reaction facilitated by visible light, in which an aldehyde and an amine condense to form an iminium ion that subsequently reacts with alkyl radical.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000535223300001
WOS关键词	CATALYZED HYDROAMINATION ; MULTICOMPONENT SYNTHESIS ; RADICAL-ADDITION ; CHIRAL AMINES ; IMINIUM IONS ; LITHIUM
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281077
专题	地球科学资源环境科学气候变化
作者单位	1.Stanford Univ, Dept Med, Stanford, CA 94305 USA; 2.Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA; 3.Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA; 4.Cedars Sinai Med Ctr, Smidt Heart Inst, Los Angeles, CA 90048 USA; 5.Stanford Univ, Dept Radiol, Stanford, CA 94305 USA; 6.Stanford Univ, Dept Biomed Data Sci, Stanford, CA 94305 USA
推荐引用方式 GB/T 7714	Ouyang, David,He, Bryan,Ghorbani, Amirata,et al. A general carbonyl alkylative amination for tertiary amine synthesis[J]. NATURE,2020.
APA	Ouyang, David.,He, Bryan.,Ghorbani, Amirata.,Yuan, Neal.,Ebinger, Joseph.,...&Zou, James Y..(2020).A general carbonyl alkylative amination for tertiary amine synthesis.NATURE.
MLA	Ouyang, David,et al."A general carbonyl alkylative amination for tertiary amine synthesis".NATURE (2020).