Merging of Light/Dark Palladium Catalytic Cycles Enables Multicomponent Tandem Alkyl Heck/Tsuji–Trost Homologative Amination Reaction toward Allylic Amines

Abstract

A visible light-induced palladium-catalyzed homologative three-component synthesis of allylic amines has been developed. This protocol proceeds via a unique mechanism involving two distinct cycles enabled by the same Pd(0) catalyst: a visible light-induced hybrid radical alkyl Heck reaction between 1,1-dielectrophile and styrene, followed by the "in dark" classical Tsuji−Trost-type allylic substitution reaction. This method works well with a broad range of primary and secondary amines, aryl alkenes, dielectrophiles, and in complex settings. The regiochemistry of the obtained products is primarily governed by the structure of 1,1-dielectrophile. Involvement of π-allyl palladium intermediates allowed for the control of stereoselectivity, which has been demonstrated with up to 95:5 er.

Straightforward α-allylation of carbonyl compounds with alkenes via α-carbonyl radical intermediates

“…Although the single copper catalyst finds it challenging to perform such cascade transformation in multi-step sequences, our efforts towards identifying such a catalyst system were driven by the important findings that the merger of two different catalytic cycles, such as the combination of photocatalysis with transition metal catalysis, enables diverse novel synthetic methods to be developed. 23,24 Herein, we report a Cu-catalyzed method for the α-allylation of carbonyl compounds through oxidative cross-coupling between alkenes and simple carbonyl compounds such as aryl ketones, lactones and lactams (Scheme 1c). This method uses di- tert -butyl peroxide (DTBP) as a mild oxidant to selectively convert carbonyl compounds into α-carbonyl radicals and smoothly drives the target reaction without the need for any acid or base additive, which benefits from the use of the copper–bisphosphine catalyst that could modulate the activity of the catalyst for different catalytic cycles to accelerate the necessary pathways of the target reaction and meanwhile suppress other underlying transformations of the active radical intermediates.…”

Asymmetric three-component Tsuji–Trost allylation reaction enabled by chiral aldehyde/palladium combined catalysis

“…1b ). 10 Several enantioselective instances were realized with moderate yields and moderate-to-good enantioselectivities. Thus, the development of a novel methodology to achieve a highly efficient Tsuji–Trost allylation reaction involving three or more reactants remains a pressing imperative to further enrich the domain of this seminal reaction.…”

Simplified Version of the Eschweiler–Clarke Reaction

“…Amines are vital chemical substances that play crucial roles in a large number of biological processes. Therefore, development of synthetic approaches for their preparation is still greatly important in modern organic chemistry. − Methylation of amines is often placed into separate groups on the basis of applied synthetic reagents. The value of methylation process is growing today.…”