Associative Covalent Relay: An Oxadiazolone Strategy for Rhodium(III)‐Catalyzed Synthesis of Primary Pyridinylamines

Abstract

A relay formalism is proposed herein for categorizing the interplay among reactants, target product, and catalytic center in transition-metal catalysis, an important factor that can dictate overall catalysis viability and efficiency. In this formalism, transition-metal catalysis can proceed by dissociative relay, associative covalent relay, and associative dative relay modes. An intriguing associative covalent relay process operates in rhodium(III)-catalyzed oxadiazolone-directed alkenyl C-H coupling with alkynes and allows efficient access to primary pyridinylamines. Although the primary pyridinylamine synthesis mechanism is posteriori rationalized, the relay formalism formulated herein can provide an important mechanistic conceptual framework for future catalyst design and reaction development.

Synthesis of [5,6]‐Bicyclic Heterocycles with a Ring‐Junction Nitrogen Atom: Rhodium(III)‐Catalyzed C−H Functionalization of Alkenyl Azoles

“…Herein we describe general methods for the rhodium(III)‐catalyzed alkenyl C(sp 2 )−H functionalization of C‐alkenyl azoles for the synthesis of fused [5,6]‐bicyclic heterocycles which incorporate from two to four nitrogen atoms (Figure b,c). While previous reports have demonstrated C−H functionalization of C‐aryl azoles for the synthesis of tricyclic and higher‐order heterocycles, to the best of our knowledge, this study represents the first investigation of C‐alkenyl azole substrates . These transformations are effective for alkenyl imidazoles, pyrazoles, and triazoles incorporating a variety of substitution patterns on both the alkene and the azole.…”

Associative Covalent Relay: An Oxadiazolone Strategy for Rhodium(III)‐Catalyzed Synthesis of Primary Pyridinylamines

“…We began our investigations by evaluating synthetic conditions for ar eaction between (E)-3-styryl-1,2,4-oxadiazol-5(4H)-one (1a)a nd 1,2-diphenylacetylene (2a). Initial experiments suggest [{RhCp*Cl 2 } 2 ]asaneffective catalyst for the synthesis of 3a (structure confirmed by single-crystal X-ray analysis [10] )o nly in the presence of ab ase (KOAc, NaOAc, or CsOAc;s ee the Supporting Information). The yield is not substantially affected by ac hange of the type or amount of the base.T he reaction comes to ac omplete stop with the participation of an acid additive (HOAc).…”

“…(4)]. Further mechanistic understanding comes from the isolation of af ive-membered rhodacycle (1b-Rh;S cheme 4) and investigation of its reactivity patterns.P urification of 1b-Rh can be achieved by washing with either H 2 O/MeOH or 1,4-dioxane,t hus affording 1b-Rh-WM (containing no salt) [12] and 1b-Rh-D (containing KCl), respectively.T he use of two types of purification solvents is to ensure the acquisition of authentic reactivity information for 1b-Rh through crossreference of the behavior of 1b-Rh-WM and 1b-Rh-D,a nd consequently,e limination of incidental influence from any species (solvent or ionic). An initial surprising finding hinting at the uniqueness of the catalytic mechanism is the minimal reactivity observed between 1b-Rh and 2a [Eq.…”

Rh(III)-Catalyzed Coupling of N-Chloroimines with α-Diazo-α-Phosphonoacetates for Skeleton-Oriented Synthesis of 2H-Isoindoles

“…Transition metal-catalyzed directed C-H functionalization has recently emerged as a promising step-economic strategy for the synthesis of diverse range of structures. [3][4][5][6][7][8][9][10][11][12] Heterocycles have been the center of focus in this nascent field for their role as privileged pharmaceutical scaffolds. Forward reactivity analysis, a process of streamlining multi-step reaction steps/pathways in silico based on projected matching of reactivity between directing groups and coupling partners, can instill an element of rationality into reaction design.…”

“…Indeed, unintended appendages from the directing groups and/or coupling partners have been frequently stuck in the heterocyclic skeletons: they not only are relatively inert to designated transformations but also can completely block the inherent high reactivity of ring atoms. [3][4][5][6][7][8][9][10][11][12] Considering the thoroughly demonstrated enormous synthetic power from the heterocyclic ring atoms, a synthetically useful approach to reaction development is skeleton-oriented synthesis (SOS): SOS refers to a traceless appendage planning synthetic strategy for fabricating molecular skeletons without unintended appendages from the reactivity-assisting groups and using, subsequently, the reactivity of exposed ring atoms for attaching intended appendages.…”