Ruthenium(II)‐Catalyzed Asymmetric Inert C−H Bond Activation Assisted by a Chiral Transient Directing Group

Abstract

A ruthenium(II)‐catalyzed asymmetric intramolecular hydroarylation assisted by a chiral transient directing group has been developed. A series of 2,3‐dihydrobenzofurans bearing chiral all‐carbon quaternary stereocenters have been prepared in remarkably high yields (up to 98 %) and enantioselectivities (up to >99 % ee). By this methodology, a novel asymmetric total synthesis of CB2 receptor agonist MDA7 has been successfully developed.

Transition Metal‐Catalyzed Enantioselective C−H Functionalization via Chiral Transient Directing Group Strategies

“…In view that Ru II (p-cymene) catalyst geometrically resembles CpRh III species, Wang and co-workers further expanded the cTDG strategy to Ru II -catalyzed asymmetric intramolecular hydroarylation of oxygen-tethered olefin aldehydes 20 using a-methyl chiral amine cTDG5 (Scheme 7). [19] A wide range of 2,3-dihydrobenzofurans bearing all-carbon quaternary stereocenters were formed with high yields and excellent enantioselectivities (up to > 99 % ee). However, the reactivity and enantioselectivity were significantly affected when this method was extended to a substrate with a nitrogen tether, affording the indoline 21 f in only 18 % yield with 70 % ee.…”

“…Ru II -catalyzed asymmetric CÀH activation/hydroarylation using cTDG5 to access chiral 2.3-dihydrobenzofurans (Wang et al, 2019). [19] Angewandte Chemie Minireviews including axial and planar chirality, also play important roles in asymmetric synthesis. Axial chirality, resulting from hindered rotation around a bond axis, has received a great deal of interest due to its ubiquity in natural products, materials, pharmaceuticals and asymmetric synthesis.…”

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

“…In general, the enantioselectivity of intramolecular CÀHf unctionalization reactions seems relatively easily controlled. [13,15] Thed emand for structurally diverse chiral biaryls as functional molecules and ready availability of arenes and alkynes in separate entities call for asymmetric biaryl synthesis by intermolecular CÀHa ctivation. Despite the design in Scheme 1c,t he following challenges should be properly addressed:1)the alkyne and should be judiciously selected to ensure regioselectivity of alkyne insertion;2 )the enantioselectivity of the alkyne insertion needs to be well controlled; and 3) the DG should be tightly bound to the Rh in the sevenmembered rhodacycle to ensure atropomeric stability and subsequent chirality transfer.…”

Transition Metal‐Catalyzed Enantioselective C−H Functionalization via Chiral Transient Directing Group Strategies

“…Ru II -catalyzed asymmetric CÀH activation/hydroarylation using cTDG5 to access chiral 2.3-dihydrobenzofurans (Wang et al, 2019). [19] Angewandte Chemie Kurzaufsätze 19946 www.angewandte.de including axial and planar chirality, also play important roles in asymmetric synthesis. Axial chirality, resulting from hindered rotation around a bond axis, has received a great deal of interest due to its ubiquity in natural products, materials, pharmaceuticals and asymmetric synthesis.…”