Enantioseparation of P-Stereogenic Secondary Phosphine Oxides and Their Stereospecific Transformation to Various Tertiary Phosphine Oxides and a Thiophosphinate

Abstract

Secondary phosphine oxides incorporating various aryl and alkyl groups were synthesized in racemic form, and these products formed the library reported in this study. TADDOL derivatives were used to obtain the optical resolution of these P -stereogenic secondary phosphine oxides. The developed resolution method showed a good scope under the optimized reaction conditions, as 9 out of 14 derivatives could be prepared with an enantiomeric excess (ee) ≥ 79% and 5 of these derivatives were practically enantiopure >P(O)H compounds (ee ≥ 98%). The scalability of this resolution method was also demonstrated. Noncovalent interactions responsible for the formation of diasteromeric complexes were elucidated by single-crystal XRD measurements. ( S )-(2-Methylphenyl)phenylphosphine oxide was transformed to a variety of P -stereogenic tertiary phosphine oxides and a thiophosphinate in stereospecific Michaelis–Becker, Hirao, or Pudovik reactions.

Resolution of aryl-H-phosphinates applied in the synthesis of P-stereogenic compounds including a Brønsted acid NMR solvating agent

“…With the most suitable resolving agent [( R , R )- 2e ] in hand, solvent screening was performed and the solvents were selected based on our previous studies. 27 The results indicated that aromatic solvents in combination with hexane were the more suitable ones, and the best results were obtained in a mixture of toluene and hexane. It was also found that performing these resolutions according to the equivalent method is more beneficial than using a half equivalent of the resolving agent [( R , R )- 2e ].…”

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

“…This work also led to the synthesis of CPA 3 [38]. Alternatives to the Stec reaction to prepare chiral thiophosphorus acids have been described [41][42][43]. Once equipped with our new methods [38], the synthesis of indole-derived 2 was undertaken (Scheme 3).…”

P-Stereogenic Phosphorus Ligands in Asymmetric Catalysis

“…From 2001 to 2023, a great number of P-stereogenic phosphorus ligands with structural diversity have been designed, synthesized, and applied in numerous catalytic asymmetric reactions. This remarkable advancement is largely ascribed to the development of many efficient methods for the synthesis of P-stereogenic organophosphorus compounds including novel chiral phosphorus ligands. − ,,,,− In addition, breakthrough results obtained by the use of P-stereogenic phosphorus ligands have encouraged researchers to devote their efforts to this area.…”