Palladium‐Catalzyed Atroposelective 16‐Membered Macrocyclization: Total Synthesis of Isoplagiochin D^†

Abstract

A catalytically asymmetric macrocyclization via palladium‐catalyzed intramolecular coupling between benzyl chloride and arylhydrazone was reported. This method enabled the asymmetric total synthesis of bisbibenzylis isoplagiochin D.

Catalysis and Synthesis Enabled by P-Chiral Dihydrobenzooxaphosphole Ligands

“…76 The similar strategy was applied to the total synthesis of isoplagiochin D via a palladium-catalyzed atroposelective 16-membered macrocyclization with WingPhos as the ligand by Xi and Gu (Scheme 33B). 77 The key intramolecular macrocyclic cross-coupling reaction was achieved with 93% ee.…”

“…Wu and co-workers described a palladium-catalyzed enantioselective cross-coupling between N -tosylhydrazones and phosphoryl-substituted aryl bromides using BIBOP as the ligand, providing a variety of phosphoryl-substituted atropisomeric vinyl arenes in good yields with high enantioselectivities (Scheme A) . The similar strategy was applied to the total synthesis of isoplagiochin D via a palladium-catalyzed atroposelective 16-membered macrocyclization with WingPhos as the ligand by Xi and Gu (Scheme B) . The key intramolecular macrocyclic cross-coupling reaction was achieved with 93% ee .…”

Atroposelective Synthesis of Isoriccardin C through a C−H Activated Heck Type Macrocyclization

“…More recently, Gu and Xi reported a Pd‐catalyzed macrocyclization involving a benzyl chloride and a carbene generated from a N ‐tosyl hydrazone precursor B (Scheme 2c). The ligand WingPhos together with Pd(TFA) 2 as pre‐catalyst displayed a stereoselective activity giving rise to the precursor of isoplagiochin D with up to 22 % yield and 93 % ee [17] . However, to the best of our knowledge, no atroposelective syntheses of bisbibenzyls bearing a biaryl as well as a biarylether scaffold have been reported yet.…”

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

“…Inspired by the work of Barluenga and Valdés, 15 the group of Gu reported on the use of 1-tetralone tosyl hydrazones as carbene precursors in the Pd-catalyzed coupling with substituted 1-naphthyl bromides, affording axially chiral vinyl arenes with large enantiomeric excesses ( Scheme 1 B). 16 More recently, a related Cu-catalyzed coupling of diazo compounds with isoquinoline or phthalazine N -oxides has been reported to obtain axially chiral QUINOX analogues, although in racemic form ( Scheme 1 C). 17 On the basis of the findings described above, we envisioned that the use of carbene precursors (e.g., hydrazones) as coupling partners in the DYKAT-based strategy should enable the synthesis of bifunctional heterobiaryl olefins via a palladium/carbene insertion, migration, and β-hydride elimination process ( Scheme 1 D).…”

“…On the contrary, catalytic processes initiated by formation of metal carbenoids followed by migratory insertion have rarely been applied to the synthesis of axially chiral compounds. Inspired by the work of Barluenga and Valdés, the group of Gu reported on the use of 1-tetralone tosyl hydrazones as carbene precursors in the Pd-catalyzed coupling with substituted 1-naphthyl bromides, affording axially chiral vinyl arenes with large enantiomeric excesses (Scheme B) . More recently, a related Cu-catalyzed coupling of diazo compounds with isoquinoline or phthalazine N -oxides has been reported to obtain axially chiral QUINOX analogues, although in racemic form (Scheme C) .…”