Stereoselective and Regioselective Synthesis of Heterocycles via Copper-Catalyzed Additions of Amine Derivatives and Alcohols to Alkenes

Abstract

This Perspective describes the development of a family of copper(II)-catalyzed alkene difunctionalization reactions that enable stereoselective addition of amine derivatives and alcohols onto pendant unactivated alkenes to provide a range of valuable saturated nitrogen and oxygen heterocycles. 2-Vinylanilines and related substrates undergo alternative oxidative amination or allylic amination pathways, and these reactions will also be discussed. The involvement of both polar and radical steps in the reaction mechanisms have been implicated. Major product formation is a function of the lowest energy pathway, which in turn is a function of structural aspects of the various reaction components.

Intermolecular radical carboamination of alkenes

“…16 In addition, Pd or Cu catalyzed alkene carboamination with tethered nitrogen nucleophiles has been achieved through aza-Wacker cyclization followed by transition metal mediated or radical C-C coupling to provide substituted pyrrolidines with high stereoselectivity. [17][18][19][20] It is worth noting that transition metal catalyzed three component alkene carboamination has also been reported. [21][22][23][24][25] For instance, Rovis and co-workers disclosed a Rh-catalyzed intermolecular carboamination of alkenes by using a bifunctional reagent 21 and Engle et al used a directing group to conduct Pd-catalyzed three component alkene carboamination.…”

Pd‐Catalyzed C−C, C−N, and C−O Bond‐Forming Difunctionalization Reactions of Alkenes Bearing Tethered Aryl/Alkenyl Triflates

“…Since 2004 our group has developed and investigated a series of alkene difunctionalization reactions between aryl or alkenyl halides or triflates, and alkenes bearing tethered nucleophiles. [1,2] As shown below (Scheme 1a), these transformations affect the formation of one carbon-heteroatom bond, one carbon-carbon bond, and up to two stereocenters. The transformations afford an array of heterocyclic products, including tetrahydrofurans, [3] pyrazolidines, [4] pyrrolidines, [5] cyclic ureas [6] and cyclic guanidines, [7] in good yield and high diastereoselectivity.…”

Copper-Catalyzed Aerobic Cyclization of β,γ-Unsaturated Hydrazones with Concomitant C═C Bond Cleavage

“…The mechanistic rationale based on the literature and additional control experiments is proposed in Scheme . The reaction is initiated by the interaction of Cu catalyst with substrate 1b to generate intermediate I , which underwent reversible homolysis of the N–[Cu­(II)] bond to give N-centered hydrazonyl radical I′ . The intramolecular aminocupration of Cu­(II)-activated substrate 1b occurs to provide the alkyl-copper complex II .…”