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‐Catalyzed Atroposelective Construction of Indoles via C−H Bond Activation

“…Additionally, scale-up synthesis of 3 (1 mmol) was successful, with essentially no deterioration of enantioselectivity. Comparable efficiency and enantioselectivity (84-93 % ee) were also realized for a series of meta-substituted alkynes (11)(12)(13)(14). While ortho-substituted alkynes generally exhibited poor efficiency due to steric effect, presence of ortho F groups in the alkyne was tolerated (15).…”

“…Waldmann reported intramolecular redox-neutral [4+2] annulation of benzamides bearing a pendant alkyne using a chiral JasCpRh III catalyst, [12] and our group recently developed an intermolecular version. [13] Meanwhile, Wang disclosed Rh III -catalyzed [2+2+2] carboannulation between N-arylindolinones and alkyne. [14] Nevertheless, these very few reports [12][13][14] are limited to 6,6-biaryl synthesis due to reactivity challenge posed by employment of bulky directing group and/or coupling reagent.…”

“…[2g,h, 9, 11l] Notably, Rh III -catalyzed CÀH activation has allowed facile access to a large array of chiral products. [9,[12][13][14][15] Inspired by Fagnous pioneering oxidative indole synthesis [16] and our own racemic system in 2010, [17] we aimed to apply C À H activation of anilines for atropomeric synthesis of Nisoquinolylindolines (Scheme 1 c). Despite related racemic reports, [16][17][18] control of enantioselectivity can be challenging because this requires conformational control of the isoquinoyl directing group prior to C-N reductive elimination.…”

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‐OPiv ‐hydroxamate 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).…”

Enantioselective Synthesis of Five-Membered-Ring Atropisomers with a Chiral Rh(III) Complex

“… 11 We have described an intramolecular C–H functionalization of aromatic compounds with alkynes forming axially chiral 4-arylisoquinolones catalyzed by chiral Rh Jas Cp complexes, 12 and Li et al recently reported the use of chiral RhCp x complexes in the synthesis of axially chiral biindolyls. 13 To the best of our knowledge, there is no general enantioselective method that enables the construction of atropisomers containing a five-membered aromatic ring (furans, thiophenes, and pyrroles). Herein, we report the Rh Jas Cp-catalyzed enantioselective synthesis of these five-membered-ring atropisomers via direct C–H functionalization with 1-diazonaphthoquinones ( Scheme 1 c, bottom).…”