Catalytic Atroposelective Catellani Reaction Enables Construction of Axially Chiral Biaryl Monophosphine Oxides

Abstract

An unprecedented atroposelective Catellani reaction between phosphine oxide-containing aryl bromides, aryliodides, and nucleophiles for the construction of phosphine-containing biaryl atropisomers was established using an enantiopure norbornene derivative as the chiral mediator. A broad range of atropisomeric biaryl-based monophosphine oxides were obtained in good efficiency with excellent enantioselectivity. This set of three component catalytic systems successfully inhibited two-component cross-couplings and promoted the formation of an aryl-aryl chiral axis via a key atropisomeric Pd intermediate. Meanwhile, an optically active atropisomeric biaryl with two stereogenic axes was also obtained with this strategy. The synthetic utility of this methodology was illustrated through further transformations into monophosphine ligands which have been used for further applications in asymmetric catalysis. In addition, a detailed mechanism study by DFT calculation was conducted.

Diversity‐Oriented Synthesis of Flavones and Isoflavones via Palladium/Norbornene Cooperative Catalysis

“…Since the seminal work by Catellani in 1997, [ 15 ] palladium/ norbornene (Pd/NBE) cooperative catalysis (namely, the Catellani reaction) has become a powerful strategy for expeditious synthesis of highly substituted arenes. [ 16‐29 ] However, current scope of this chemistry is mainly limited to (hetero)aromatic substrates, and its application to partially aromatic or non‐aromatic scaffolds is rarely reported, [ 26‐31 ] because the vinylic C—H bonds are generally more challenging to functionalize than (hetero)aryl C—H bond. [ 35‐37 ] Owing to the efforts of Lautens, [ 30 ] Yamamoto, [ 31 ] Dong, [ 32‐33 ] and our group, [ 34 ] alkenyl Catellani reaction has emerged as a new direction of this field.…”

Tetracoordinate Boron Intermediates Enable Unconventional Transformations

“…Therefore, we designed and developed three transition metal-catalyzed reaction models with arylboronic acids: (1) palladium-catalyzed Suzuki−Miyaura coupling of thioureas or thioamides, 34 (2) copper-catalyzed atroposelective Michael-type addition to construct axially chiral biaryls, 35 and (3) catalytic atroposelective Catellani reaction to construct chiral phosphine-containing biaryls. 36 Cross-coupling reactions involving metal carbene intermediates play an important role in the construction of C−C bonds. 37 The expansion of carbene precursors from readily available materials is an ongoing challenge in organic chemistry.…”

“…The method shows excellent enantioselectivity, which is controlled by the chiral NBE (norbornene) derivative (Scheme 21). 36 A possible mechanism based on DFT calculations for this chiral Catellani reaction is shown in Scheme 21. First, Pd(0) species react with 1-iodonaphthalene 46 to afford the intermediate Int-29 via oxidative addition process, which further undergoes an intermolecular insertion with chiral NBE to obtain palladacycle complex Int-30.…”

Catalytic Synthesis of Atropisomeric o-Terphenyls with 1,2-Diaxes via Axial-to-Axial Diastereoinduction

“…35 Later on, Song and Lan disclosed a similar reaction for the construction of phosphinecontaining biaryl atropisomers. 36 Inspired by this chemistry, we envisaged a strategy for atropodiastereoselective synthesis of oterphenyls with 1,2-diaxes through axial-to-axial diastereoinduction. As shown in Figure 1B, the reaction of aryl iodide (1) with 2,6-substituted aryl bromide (2) promoted by palladium/chiral norbornene cooperative catalysis to afford the axially chiral palladium complex I has been established.…”

“…Recently, we reported a catalytic method for de novo construction of C–C axial chirality via Pd/chiral NBE* cooperative catalysis . Later on, Song and Lan disclosed a similar reaction for the construction of phosphine-containing biaryl atropisomers . Inspired by this chemistry, we envisaged a strategy for atropodiastereoselective synthesis of o -terphenyls with 1,2-diaxes through axial-to-axial diastereoinduction.…”