Pd-Catalyzed Dynamic Kinetic Asymmetric Cross-Coupling of Heterobiaryl Bromides with N-Tosylhydrazones

Abstract

A dynamic kinetic asymmetric Pd-catalyzed cross-coupling reaction of heterobiaryl bromides with ketone N -tosylhydrazones for the synthesis of heterobiaryl styrenes is described. The combination of Pd(dba) 2 as a precatalyst with a TADDOL-derived phosphoramidite ligand provides the corresponding coupling products in good yields and high enantioselectivities under mild conditions. Racemization-free N -oxidation and N -alkylation of the products allowed us to obtain appealing functionalized axially chiral heterobiaryl derivatives.

A Stereodivergent–Convergent Chiral Induction Mode in Atroposelective Access to Biaryls via Rhodium-Catalyzed C–H Bond Activation

“…With this mode in mind, we set out to develop an atroposelective annulation system involving an intermediate with essentially indistinguishable bonds that may give rise to initial stereodivergence. We focused on annulation between a biphenyl-2-boronic acid and a diazo reagent by virtue of dynamic kinetic transformation of the latter (Scheme c). On note, although dynamic kinetic transformation of coupling reagents has been recently reported in C–H activation, these are restricted to sterically hindered alkynes. ,, The most prominent feature of this system is the presence of a five-membered rhodafluorene intermediate containing two Rh–C bonds that are hardly distinguished by the chiral environment (Scheme c) .…”

Stereodynamic Strategies to Induce and Enrich Chirality of Atropisomers at a Late Stage

“…In 2022, Fernández, Lassaletta, and co-workers reported the dynamic kinetic cross-coupling of heterobiaryl bromides with N -tosyl hydrazones as carbene precursors for the synthesis of styrene functionalized atropisomers (Figure ). A ligand–catalyst combination of Pd­(dba) 2 and TADDOL-derived phosphoramidite ligand 90.1 with LiO t -Bu base in dioxane was able to effectively convert starting bromide ( rac )- 90.2 and tosyl hydrazone 90.3 to the coupled product ( R )- 90.4 in 86% yield and 95% ee. This reaction accommodated a number of heterobiaryl scaffolds including hindered pyridines and quinazolines, affording 90.5 (79% yield, 93%ee) and 90.6 (79% yield, 91% ee).…”

Cobalt-Catalyzed Asymmetric Reductive Alkenylation and Arylation of Heterobiaryl Tosylates: Kinetic Resolution or Dynamic Kinetic Resolution?

“…In 2013, Lassaletta, Stolz, and Virgil independently discovered palladium-catalyzed DKR of heterobiaryl (pseudo)­halides with phosphines and boroxines. Relying on this strategy, a series of nucleophiles have been applied successfully in the redox-neutral DRK of heterobiaryl (pseudo)­halides . On the other side, Murai, You, and others developed rhodium- or iridium-catalyzed DKR of racemic heterobiaryls based on directed C–H activation .…”