Cu(II)-Catalyzed Construction of Heterobiaryls using 1-Diazonaphthoquinones: A General Strategy for the Synthesis of QUINOX and Related P,N Ligands

Abstract

An efficient and straightforward method was developed for the synthesis of heterobiaryls using easily available N-oxides and diazonaphthoquinones under cheap Cu­(II) catalysis. The developed method offered QUINOX and related congeners in a simple manner. A wide scope of important heterobiaryls was achieved with high site selectivity. The synthesized naphthols were transformed into the privileged related P,N ligands. Suitable resolution methods can directly afford the corresponding axially chiral heterobiaryls.

Synthesis of N-Arylindoles from 2-Alkenylanilines and Diazonaphthalen-2(1H)-ones through Simultaneous Indole Construction and Aryl Introduction

“…In the meantime, metal carbenes generated from diazo compounds through extrusion of N 2 have played an important part in modern synthetic chemistry . In particular, carbenes generated from diazonaphthalen-2­(1 H )-ones (DZNPs) have been used for introducing a naphthol moiety via transition metal-catalyzed and directing group (DG)-guided inert chemical bond functionalization. , For examples, Lee et al have reported the construction of 3-naphthylindole via Rh­(II)-catalyzed arylation of indoles with DZNPs . Yang et al disclosed Ir­(III)-catalyzed direct C–H arylation of arylphosphine oxides with DZNPs .…”

Rhodium-catalyzed reaction of diazoquinones with allylboronates to synthesize allylphenols

“…In recent years, diazoquinones as carbene precursors have attracted increasing attention in transition metal catalysis due to their unusual reactivity and ready accessibility. 5–9 The conjugation of carbonyl, alkene and diazo groups in the six-membered ring scaffold makes the α-carbon of the diazo moiety flanked by two electron acceptors, which renders the corresponding quinoid carbene highly electrophilic. 6 a,e ,7 c In addition, quinoid carbenes display hydrogen atom transfer (HAT) reactivity.…”

“…6 a,e ,7 c In addition, quinoid carbenes display hydrogen atom transfer (HAT) reactivity. 6 h ,9 b Another appealing characteristic of quinoid carbene is the tendency for aromatization to form phenol, 5–9 which is prevalent in natural products and useful synthetic building blocks. 10 These unusual reactivities of diazoquinones hold great promise in organic synthesis.…”

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

“… 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). As a starting hypothesis, it was assumed that the low rotational barrier in carbenoid intermediate I increases significantly after the migratory insertion event as a result of the geometrical restrictions in the resulting intermediate II , a larger six-membered cycle with long N–Pd and Pd–C bonds.…”

“…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) . 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 D).…”