Rhodium(III)‐Catalyzed Atroposelective Synthesis of Biaryls by C−H Activation and Intermolecular Coupling with Sterically Hindered Alkynes

Abstract

Reported herein is the atroposelective synthesis of biaryl NH isoquinolones by RhIII‐catalyzed C−H activation of benzamides and intermolecular [4+2] annulation for a broad scope of 2‐substituted 1‐alkynylnaphthalenes, as well as sterically hindered, symmetric diarylacetylenes. The axial chirality is constructed based on dynamic kinetic transformation of the alkyne in redox‐neutral annulation with benzamides, with alkyne insertion being stereodetermining. The reaction accommodates both benzamides and heteroaryl carboxamides and proceeds in excellent regioselectivity (if applicable) and enantioselectivities (average 91.8 % ee). An enantiomerically and diastereomerically pure rhodacyclic complex was prepared and offers insight into enantiomeric control of the coupling system, wherein the steric interactions between the amide directing group and the alkyne substrate dictate both the regio‐ and enantioselectivity.

Rhodium(III)‐Catalyzed Asymmetric [4+1] and [5+1] Annulation of Arenes and 1,3‐Enynes: A Distinct Mechanism of Allyl Formation and Allyl Functionalization

“…To probe the CÀHa ctivation process,achiral rhodacyclic complex 11 was prepared (Scheme 6a). [21] In the crystal structure,t he relatively bulky amide directing group stays distal to the chiral ligand, which offers important basis for stereocontrol of subsequent steps. Complex 11 proved somewhat active for the coupling of 1a and 2aat an elevated temperature,indicating relevance of CÀ Ha ctivation.…”

Chiral Cyclopentadienyl Ligands: Design, Syntheses, and Applications in Asymmetric Catalysis

“…Reviews 13214 www.angewandte.org (Scheme 35). [96] Mechanistically,t he hydroxamate cyclometalation is followed by an enantiodetermining alkyne migratory insertion. Then, an axial-to-axial chirality transfer process leads to the products 197.B oth symmetric and nonsymmetric bulky alkyne partners were successful, depending on the choice of catalyst, which gave access to abroad library of products 197 in excellent yields,r egio-and enantioselectivities.…”

Applications of Chiral Cyclopentadienyl (Cpx) Metal Complexes in Asymmetric Catalysis

“…[49] Recently, the same group used 1-alkynyl-2-naphthyl ethers 70 as coupling partners with N-OPivhydroxamate 13. [50] The reactions were performed with chiral RhCp x complex 71 and afforded the biaryl derivatives 72. Once again with a broad scope of substrates and a variety of functional groups (Scheme 16c).…”