Diversity-oriented synthesis of P-stereogenic and axially chiral monodentate biaryl phosphines enabled by C-P bond cleavage

Abstract

Chiral monodentate biaryl phosphines (MOPs) have attracted intense attention as chiral ligands over the past decades. However, the creation of structurally diverse chiral MOPs with both P- and axial chirality is still in high demand but challenging. Here, we show a distinct strategy for diversity-oriented synthesis of structurally diverse MOPs containing both P- and axial chirality enabled by enantioselective C-P bond cleavage. The key chiral PdII intermediates, generated through the stereoselective oxidative addition of C-P bond, could be trapped by alkynes, R3Si-Bpin, diboron esters or reduced by H2O/B2pin2, leading to enantioenriched structurally diverse MOPs in excellent diastereo- and enantioselectivities. Based on the outstanding properties of the parent scaffolds, the P- and axially chiral monodentate biaryl phosphines serve as excellent catalysts in asymmetric [3 + 2] annulation of MBH carbonate affording the chiral functionalized bicyclic imide.

Catalytic Asymmetric Synthesis of Atropisomers Bearing Multiple Chiral Elements: An Emerging Field

“…In their following studies, the same group extended their protocol to the catalytic asymmetric synthesis of other biaryl atropisomers containing a P-stereogenic center with a range of coupling partners, such as alkynes 212, R 3 Si-Bpin 214, diboron esters 216, and hydride source (H 2 O/B 2 pin 2 ), affording various enantioenriched structurally diverse chiral monodentate biaryl phosphines with excellent diastereoand enantioselectivities (Scheme 48a). [96] These chiral monodentate biaryl phosphines could be directly used as chiral catalysts in asymmetric (3 + 2) annulation of MBH carbonate with N-methylmaleimide to give chiral functionalized bicyclic imide with excellent diastereo-and enantioselectivities. These results indicated the great potential of this class of chiral biaryl phosphines in the development of valuable chiral ligands and organocatalysts (Scheme 48b).…”

Palladium-Catalyzed Modular Assembly of P-Stereogenic and Axially Chiral Phosphinooxazoles (PHOX) Ligands by C–P Bond Cleavage/Intermolecular C(sp2)–H Bond Functionalization

“…On the basis of the previous studies regarding catalytic asymmetric ring opening of cationic cyclic compounds and our previous studies, we propose that our atroposelective C–P bond cleavage/intermolecular C–H bond functionalization operates through a Pd(0)/Pd­(II) cycle (Scheme ). Initially, according to the literature precedents, substrate ( Ra )- 1a and ( Sa )- 1a are in rapid equilibrium with each other via the rotation of the C aryl –C aryl single bond.…”

“…However, the asymmetric preparation of bidentate P,N-ligands from phosphonium salts can be synthetically challenging because of (1) the regioselective cleavage of C–P bonds and (2) the strong coordination ability of P,N-products, which would lead to catalyst poisoning. With the challenge in mind and on the basis of our previous findings on the asymmetric synthesis of chiral monophosphines enabled by C–P bond cleavage, herein, we report the straightforward atroposelective assembly of P-stereogenic and axially chiral PHOX ligands with synthetic and catalytic potentials via the asymmetric cleavage of C–P bond/intermolecular C­(sp 2 )–H bond functionalization (Scheme c). This protocol features a broad substrate scope and functional group tolerance.…”

Catalytic Asymmetric Synthesis of Atropisomers Bearing Multiple Chiral Elements: An Emerging Field

“…In their following studies, the same group extended their protocol to the catalytic asymmetric synthesis of other biaryl atropisomers containing a P‐stereogenic center with a range of coupling partners, such as alkynes 212 , R 3 Si‐Bpin 214 , diboron esters 216 , and hydride source (H 2 O/B 2 pin 2 ), affording various enantioenriched structurally diverse chiral monodentate biaryl phosphines with excellent diastereo‐ and enantioselectivities (Scheme 48a) [96] . These chiral monodentate biaryl phosphines could be directly used as chiral catalysts in asymmetric (3+2) annulation of MBH carbonate with N ‐methylmaleimide to give chiral functionalized bicyclic imide with excellent diastereo‐ and enantioselectivities.…”