Enantioselective Synthesis of P-Chirogenic Phosphorus Compounds via the Ephedrine-Borane Complex Methodology

Abstract

The stereoselective synthesis of P-chirogenic organophosphorus compounds using the versatile ephedrine-methodology is reported. The principle of the method is based on the diastereoselective preparation of 1,3,2-oxazaphospholidine borane 3 from ephedrine 2 and regio- and stereoselective ring-opening of the heterocycle leading to an aminophosphine borane 4. Finally, these ring-opening products 4 are easily transformed into P-chirogenic organophosphorus compounds, by subsequent highly stereoselective reactions involving electrophilic or nucleophilic strategies.

Keywords:

• Asymmetric synthesis
• chiral phosphines
• phosphinous derivatives
• stereoselectivity

Acknowledgments

We would like to thank more particularly the Drs C. Darcel and J. Uziel for their fruitful collaboration during the last decade and all the students concerned by this work. Thanks also to Pr. P. D. Harvey (Sherbrooke) for his help in the preparation of this manuscript.

Notes

^a Starting from racemic complex 3a.

^a The synthesis was performed starting from the (+)-ephedrine in the following references: 14b, 23, 27, 29, and 30.

^a All syntheses were performed starting from the (+)-ephedrine, except for 10b and 7af, which were prepared in racemic form.

^a All syntheses were performed starting from the (+)-ephedrine; and ^b epimeric mixture 1:1 separated by chromatography.

^a Conditions A: t-BuLi (2.7 equiv.)/ −78°C/ 1 h to 0°C.

^b Conditions B: i) LDA (1.2 equiv.)/ −78°C to −30°C; ii) TMSCl (2.4–4.8 equiv.)/ −78°C to RT°C; iii) t-BuLi (3.5-7 equiv.)/ −78°C to RT. ^c These products bear CH₂TMS as R² substituent.

^a Determined by HPLC on chiral column.