Jinshuai Song

Electrochemical C−H/N−H Functionalization for the Synthesis of Highly Functionalized (Aza)indoles

Indoles and azaindoles are among the most important heterocycles because of their prevalence in nature and their broad utility in pharmaceutical industry. Reported herein is an unprecedented noble-metal- and oxidant-free electrochemical method for the coupling of (hetero)arylamines with tethered alkynes to synthesize highly functionalized indoles, as well as the more challenging azaindoles.

Amidinyl Radical Formation through Anodic N-H Bond Cleavage and Its Application in Aromatic C-H Bond Functionalization

We report herein an atom-economical and sustainable approach to access amidinyl radical intermediates through the anodic cleavage of N-H bonds. The resulting nitrogen-centered radicals undergo cyclizations with (hetero)arenes, followed by rearomatization, to afford functionalized tetracyclic benzimidazoles in a highly straightforward and efficient manner. This metal- and reagent-free C-H/N-H cross-coupling reaction exhibits a broad substrate scope and proceeds with high chemoselectivity.

Reagent‐Free C−H/N−H Cross‐Coupling: Regioselective Synthesis of N‐Heteroaromatics from Biaryl Aldehydes and NH3

An unprecedented synthesis of N-heteroaromatics from biaryl aldehydes and NH3 through reagent-free C-H/N-H cross-coupling has been developed. The electrosynthesis uses NH3 as an inexpensive and atom-economic nitrogen donor, requires no oxidizing agents, and allows efficient and regioselective access to a wide range of phenanthridines and structurally related polycyclic N-heteroaromatic products.

Copper-Catalyzed Intramolecular Oxidative Amination of Unactivated Internal Alkenes.

A copper-catalyzed oxidative amination of unactivated internal alkenes has been developed. The Wacker-type oxidative alkene amination reaction is traditionally catalyzed by a palladium through a mechanism involving aminopalladation and β-hydride elimination. Replacing the precious and scarce palladium with a cheap and abundant copper for this transformation has been challenging because of the difficulty associated with the aminocupration of internal alkenes. The combination of a simple copper salt, without additional ligand, as the catalyst and Dess-Martin periodinane as the oxidant, promotes efficiently the oxidative amination of allylic carbamates and ureas bearing di- and trisubstituted alkenes leading to oxazolidinones and imidazolidinones. Preliminary mechanistic studies suggested a hybrid radical-organometallic mechanism involving an amidyl radical cyclization to form the key C-N bond.

Electrochemical Difluoromethylarylation of Alkynes

An unprecedented radical difluoromethylarylation reaction of alkynes has been developed by discovering a new difluoromethylation reagent, CF2HSO2NHNHBoc. This air-stable and solid reagent can be prepared in one step from commercially available reagents CF2HSO2Cl and NH2NHBoc. The CF2H radical, generated through ferrocene-mediated electrochemical oxidation, participates in an unexplored alkyne addition reaction followed by a challenging 7-membered ring-forming homolytic aromatic substitution step to afford fluorinated dibenzazepines.

Electrochemical synthesis of 7-membered carbocycles through cascade 5-exo-trig/7-endo-trig radical cyclization

7-endo-trig cyclizations, especially for unhindered terminal alkenes, remain underdeveloped. We report herein an electrochemical synthesis of functionalized 7-membered carbocycles through a 5-exo-trig/7-endo-trig radical cyclization cascade. The first cyclization step of the cascade process forms a 5-membered ring with trans-disposition of the radical center and the remaining alkene. This trans configuration forces the 6-heptenyl radical to undergo regioselective 7-endo cyclization.

B-Heterocyclic Carbene Arising from Charge Shift: A Computational Verification

1-Borabicyclo[1.1.0]but-2(3)-ene (1BB) is a singlet biradical with two single electrons that can form an ionic resonance structure through a charge shift. The ionic resonance structure is a B-heterocyclic carbene (BHC), which can act as a carbene, Lewis base, or L- and Z-type ligand, to give adducts and complexes. Through a range of quantum methods, four types of stable compounds (A-D) derived from 1BB have been designed. These compounds retain the unique features of 1BB. As a consequence, the structures, stability, and Wiberg bond indices of the Lewis adducts of A-D with Lewis acids (BePh2 , BH3 , AlH3 , AlCl3 , C5 BH5 , and C13 BH9 ) and CuI , AgI , and AuI complexes have been investigated. Results show that A-D can indeed react as carbenes. Interestingly, compounds A-D, as L-type ligands, can attach to BePh2 , BH3 , AlH3 , AlCl3 , C5 BH5 , C13 BH9 , and CuCl and form compounds with planar tetracoordinate carbon (ptC), whereas Z-type ligands A-D can bind to AgCl and AuCl to provide complexes with planar tetracoordinate boron (ptB). In addition, the binuclear complexes of ClX(1BB)CuCl (X=Ag, Au) have been studied and A-D behave as both L- and Z-type ligands, in which these complexes contain both ptC and ptB. Thus, a novel method for designing compounds with ptC and ptB is presented. These rationally designed compounds involve the elements of carbene, ptC, ptB, and L- and Z-type ligands, and are expected to be unique and useful in experimental chemistry once they are synthesized.