Copper(I)‐Catalyzed Asymmetric Synthesis of P‐Chiral Aminophosphinites

Abstract

Herein, a copper(I)-catalyzed reaction of diarylphosphines and O-benzoyl hydroxylamines is developed. In the cases of symmetrical diarylphosphines, a series of aminophosphinites is prepared in high yields.In the cases of unsymmetrical diarylphosphines, an array of P-chiral aminophosphinites is synthesized in high yields with high enantioselectivity by using a copper(I)-(R,R P )-Ph-FOXAP complex as a chiral catalyst. Based on several control experiments and 31 P NMR studies, a two-electron redox mechanism involving the dynamic kinetic asymmetric transformation of unsymmetrical diarylphosphines is proposed for the copper(I)-catalyzed asymmetric reaction. Finally, one representative P-chiral phosphoric amide generated through the oxidation with H 2 O 2 is transformed to a chiral diarylphosphinate in high yield with retained enantioselectivity, which allows further transformations towards various P-chiral tertiary phosphines.

Copper-Catalyzed Asymmetric Alkylation of Secondary Phosphines via Rapid Pyramidal Inversion in P-Stereogenic Cu–Phosphido Intermediates

“…We hypothesized that any metal can mediate rapid P-inversion, which is supported by experimental data for complexes of Ti, Zr, Hf, Nb, W, Mo, Re, Fe, Ru, Ni, Pd, Pt, and Ir, with d 0 , d 2 , d 4 , d 6 , and d 8 configurations . NMR and computational studies of chiral Cu­(I) phosphido complexes , and the recent development of highly enantioselective Cu­(Taniaphos)-catalyzed asymmetric P-alkylation were also consistent with this idea, but inversion barriers in d 10 metal–phosphido complexes had not been measured, and an unusually high computed barrier of 25 kcal/mol was reported for the model complex CpZnPH 2 . Even if P-inversion in Cu–phosphido catalytic intermediates was slower than P-alkylation, enantioselection could occur by the black route in Scheme .…”

“…Although enantioselectivity was low, these results demonstrated that copper-catalyzed asymmetric P-alkylation was possible . Later, Yin and coworkers showed that a related Cu­(Taniaphos) catalyst was highly selective …”

Copper‐Phosphido Catalysis: Enantioselective Addition of Phosphines to Cyclopropenes**

“…Organophosphorous partners bearing P−H bonds with a wide range of acidities (p K a 9.0 to 22.4) [13] can be activated with transition metal catalyts [14] . For secondary phosphines, coordination followed by deprotonation results in a metal‐phosphido complex [9a,c,e–k,15] with high nucleophilicity, and recent studies have revealed impressive versatility of catalytically generated Cu‐phosphido complexes [9e,g–h,15a‐e,k‐m] . Glueck elucidated mechanistic and structural details, [15d,e] while both Glueck and Yin demonstrated catalytic transformations using Cu‐phosphidos (Figure 1B).…”

Research Progress on Catalytic Asymmetric Synthesis of P-Chiral Compounds

“…By employing O-benzoyl hydroxylamines 81 as electrophilic reaction partners, and the complex of Cu(CH 3 CN) 4 PF 6 and (R,R P )-Ph-FOXAP L14 as the catalyst, various P-chiral aminophosphinites 82 were furnished in high yields with high enantioselectivity (Scheme 24). [51] It is noteworthy that alkylarylphosphines were unsatisfactory substrates with only trace desired products obtained. This is a limitation of this strategy, so it should be overcome in the future.…”