P-chiral tertiary phosphine oxides have been prepared from each of (S_p)-(-)-tert- butylphenylphosphine oxide 42 and (R_p)-(-)-tert-butylphenylphosphine oxide 43 through lithiation with lithium N,N-diisopropylamide or n-butyllithium and then by treatment with each of 2,6-bis-chloromethylpyridine, m- and p-xylyl dibromides. The corresponding bis-phosphine oxides (R_p,R_p)- and (S_p,S_p)-2,6-bis[(tert-butyl-phenyl-phosphinyl)methyl]pyridine 66 and 116, (R_p,R_p)- and (S_p,S_p)- 1,3-bis[(tert- butylphenyl-phosphinyl)methyl]benzene 67 and 117, and (S_p,S_p)- 1,4-bis-tert-butylphenylphosphinyl-methylbenzene 118 were obtained in good yields. Enantiomeric purity of the products were assessed through admixture with (R_p)- and (S_p)-tert-butylphenylphosphinothioic acids and measurement of the tert-butyl reson...[ Read more ]

P-chiral tertiary phosphine oxides have been prepared from each of (S_p)-(-)-tert- butylphenylphosphine oxide 42 and (R_p)-(-)-tert-butylphenylphosphine oxide 43 through lithiation with lithium N,N-diisopropylamide or n-butyllithium and then by treatment with each of 2,6-bis-chloromethylpyridine, m- and p-xylyl dibromides. The corresponding bis-phosphine oxides (R_p,R_p)- and (S_p,S_p)-2,6-bis[(tert-butyl-phenyl-phosphinyl)methyl]pyridine 66 and 116, (R_p,R_p)- and (S_p,S_p)- 1,3-bis[(tert- butylphenyl-phosphinyl)methyl]benzene 67 and 117, and (S_p,S_p)- 1,4-bis-tert-butylphenylphosphinyl-methylbenzene 118 were obtained in good yields. Enantiomeric purity of the products were assessed through admixture with (R_p)- and (S_p)-tert-butylphenylphosphinothioic acids and measurement of the tert-butyl resonances in the ¹H NMR spectra. A series of commercially available diphosphines were also converted by oxidation with hydrogen peroxide into the corresponding phosphine oxides.

(S_p)- and (R_p)- tert-butylphenylphosphinobromidates 63 and 64 were prepared from each of (R_p)-(-)- and (S_p)-(-)-tert-butylphenylphosphine oxide 43 and 42 and N-bromosuccinimide or bromine in dichloromethane. Enantiomeric purity of the products were assessed through admixture with (R_p)- and (S_p)-tert- butylphenyl-phosphinothioic acids and measurement of the tert-butyl resonances in the ¹H NMR spectra. The reactions are shown not to involve free radical pathways. Preparation by treatment of lithiated (S_p)-(-)-tert-butylphenylphosphine oxide 42 with bromine is shown to involve some racemization; this appears to involve reaction of free bromide with bromidate complexed with Li⁺.

Treatment of the (S_p)- and (R_p)- tert-butylphenylphosphinobromidates 63 and 64 with the amine nucleophile ethylene-l,2-diamine leads cleanly with inversion to the phosphinyl diamidate 126 whose absolute configuration was established by X-ray crystallography. Treatment of oxygen nucleophiles 2-naphthol, 1,5-dihydroxy-napthalene, (±)- 1,1'-bi-2-naphthol, (R)-(+)- 1,1'-bi-2-naphthol, resorcinol with sodium hydride followed by the bromidate gives the phosphinates 127-130 in good yields, corresponding to inversion at phosphorus. The naphthylphophine thioate 131 was also prepared from sodium hydride (44 mg, 1.1 mmol) and 2-naphthalenethiol is good yield. Absolute configuration was established by X-ray crystallography. Enantiomeric purity of all the products was assessed through admixture with (R_p)- and (S_p)-tert-butylphenylphosphinothioic acids and measurement of the tert-butyl resonances in the ¹H NMR spectra.

(S)-(-)- 1,1'-Bi-2-naphthol by treatment with sodium hydride and then phenylphosphinothioic dichloride gave bi-2-naphthyl phenylphosphonthioate 136 in good yield. Similarly, the same napthol with bi-2-naphthyl phenylphosphonate and phenylphosphonic dichloride gave bi-2-naphthyl phenylphosphonate 137 in good yield.

The diphenylpyrophosphinate 133 and the phenylpyrophosphonate 134 were prepared from (S_p)-(-)-tert-butylphenylphosphinothioic acid 46 and diphenylphosphinyl chloride and dichlorophenylphosphine oxide resepctively.

Use of the ligands in Sharpless catalytic asymmetric dihydroxylation of alkenes gave diols with enantiomeric excesses ranging to 26%. This contrasts with the much higher enantiomeric excesses reported previously by Lam for the pyridyl ligands.