Catalytic Intermolecular Linear Allylic C−H Amination via Heterobimetallic Catalysis

Abstract

Nitrogen functionality is prevalent in synthetic and natural small molecules with significant biological activities. 1 Current state-of-the-art methods for installing nitrogen into complex organic frameworks generally proceed through oxygen. 2 While these methods feature high selectivities and predictable reactivities, they lengthen synthetic sequences by requiring unproductive chemical manipulations to install and maintain oxygen functionality. Reactions that selectively convert C-H directly to C-N stand to significantly streamline synthetic sequences by providing obvious disconnections that avoid handling oxidized materials. 3 While significant advances have been made in developing preparatively useful intramolecular C-H aminations, 4a,5 catalytic intermolecular C-H aminations are scarce and often require excess substrate. 6,7 We report herein the first general, catalytic, intermolecular allylic C-H amination reaction. This reaction directly converts a wide range of α-olefins to linear (E)-allylic amines with good yields and outstanding regio-and stereoselectivities (>20:1) using limiting amounts of the starting olefin. Critical for achieving this catalytic reactivity is a heterobimetallic system composed of Pd/bis-sulfoxide and Cr(salen) catalysts. In addition to reactivity and regioselectivity challenges, intermolecular allylic C-H aminations face an additional chemoselectivity issue of competing reactivity with the olefin. 6d In palladium-mediated processes, addition of nitrogen nucleophiles to the olefin (aminopalladation) is the dominant reaction pathway. 8 We recently reported that bis-sulfoxide/ Pd(OAc) 2 catalyst 1 promotes intramolecular allylic C-H amination of α-olefins with a weak, tethered N-tosyl carbamate nucleophile. 4a We hypothesized that a catalytic, intermolecular allylic C-H amination would be feasible if we could identify conditions that promote functionalization without interfering with the electrophilic C-H cleavage step. Known activation approaches for Pd(0)-mediated allylic substitutions, such as adding stoichiometric

Palladium-Catalyzed Intermolecular Oxidative Amination of Alkenes with Amines, Using Molecular Oxygen as Terminal Oxidant

“…Although significant developments in aza-Wacker-type reactions have been achieved, the existing aza-Wacker process generally requires non-basic nitrogen nucleophiles such as carboxamides, carbamates, and sulfonamides as amination reagents, under relatively high oxygen pressures (4-10 atm.) or in the presence of an external oxidant source such as benzoquinone (BQ), PhBQ, PhI(OAc) 2 , or PhI(OPiv) 2 [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. In contrast, the oxidative amination of olefins using more basic, simple amines as substrates has been less explored, and is generally limited to intramolecular reactions [34][35][36][37][38], because of the strong coordination of amines to Pd, which results in catalyst deactivation.…”

“…With regard to the reaction mechanism, it is known that η 3 -allylpalladium intermediates are formed by the reaction of alkenes with Pd(II) through allylic C-H bond activation [26,27,29]. To confirm the participation of the η 3 -allylpalladium intermediate as the key in the catalytic cycle, and in order to obtain further insights into the specific role of the Pd(OCOCF 3 ) 2 catalyst in this reaction, the (η 3 -cinnamyl)palladium trifluoroacetate dimer (7) and (η  -cinnamyl)palladium acetate dimer (8) were synthesized independently as model intermediates, according to the literature methods [61,62].…”

Iron-mediated intermolecular N-group transfer chemistry with olefinic substrates

“…31 Recently, a hetero-bimetallic Pd and Cr catalytic protocol has also been developed to affect a similar amination reaction. 27 We have proposed two possible mechanistic pathways (Fig. 4).…”

A Catalytic, Brønsted Base Strategy for Intermolecular Allylic C−H Amination

“…Moreover, we have demonstrated that direct installation of nitrogen functionality from C—H bonds can have a powerful streamlining effect on synthetic routes. For example, the intermolecular C—H to C—N bond forming route to a rigidified (+)-deoxynegamycin analogue proceeded with five fewer steps, five fewer FGM, and a higher overall yield than the alternative C—O to C—N bond forming route 7. Despite this, the intermolecular allylic C—H amination reaction suffered from several limitations associated with the requirement for a Lewis acid activator [Cr(salen)Cl 2 ] to effect functionalization.…”