Synthesis of phosphines having chiral organic groups ligated to chiral phosphorus

Abstract

3691Dimethyl oxalate was also observed when the polar material obtained from the ozonolyiiis of 4 (14 mg) was treated in a similar fashion.Reduction of the Enamides 11 and 12 with Sodium Borohydride. To 2 mg of a 1:l mixture of l l and 12 dissolved in 15 mL of ethanol was added 100 mg of sodium borohydride. The solution was stirred at room temperature for 20 h. Excess reagent was destroyed with 1 N hydrochloric acid, and the solution was concentrated and extracted with dichloromethane. The dichloromethane layer was dried over anhydrous sodium sulfate and evaporated to give a mixture of 17 and 18: 'H NMR ((C-DB)&30) 6 1.0 (m, (CHJ2CII), 1.7 (m, Leu -y-CH and P-CH2), 1.78 (s, NHAc), 1.9 (m, Val P-CH), 2.73 (dd, J = 7.5, 15.7 Hz, Trp P-CH2), 2.90 (dd, J = 6.3, 15.7, Trp P-CH,), 3.36 (s, OMe), 3.66 (m, @-CH2), 3.93 (m, Leu a-CH), 4.02 (m, Val a-CH), 4.45 (m, a-CH), 4.73 (m, a-CH), 7.09 (dd, J = 1.6, 8.7 Hz, indole H5), 7.11 (br s, CONH2), 7.13 (d, J = 2.7 Hz, indole H2), 7.54 (d, J = 1.6 Hz, indole H,), 7.56 (d, J = 8.7 Hz, indole H4), 7.80 (d, J = 8.3 Hz, NH), 7.92 (br s, CONHJ, 8.31 (s, PhH), 10.92 (br s, indole Hi).Isolation with Acetic& Anhydride. A small-scale isolation procedure (40 g, wet weight of sponge) employing acetic-d6 anhydride (10 mL, 99+ atom %; Aldrich) as the acetylating agent yielded hexaacetylcelenamide-d18 A (5,12 mg) and hexaacetylcelenamide-d18 B (6,8 mg) which proved to be identical with 3 and 4 (TLC, IR, 'H NMR), respectively, with the exception of the absence of signals in the 'H NMR spectra corresponding to phenol acetate and acetamide. Acknowledgment. We thank Michael LeBlanc (British Columbia collections) andBoth R and S phosphorus epimers of menthylmethylphenylphosphine and its phosphine oxide and of neomenthylmethylphenylphosphine and ita phosphine oxide were prepared. The menthylmethylphenylphosphine oxides were prepared from neomenthyldiphenylphosphine by a method which is potentially general for synthesis of phosphines and phosphine oxides having chiral organic groups ligated to chiral phosphorus. Thus, neomenthyldiphen ylphosphine was quaternized by methyl iodide to give neomenthylmethyldiphenylphosphonium iodide which was decomposed in boiling aqueous methanolic sodium hydroxide to give a 1:l mixture of R and S phosphorus epimers of menthylmethylphenylphosphine oxides. The pure diastereomers were obtained from the mixture by fractional crystallization and reduced to the phosphines by using hexachlorodisilane. Structures of the R phosphorus epimers of both menthyl-and neomenthylmethylphenylphosphine oxides are reported. The structure of q4-(1,5-cyclooctadiene)bis[(R)-menthylmethylphenylphosphine]rhodium(I) tetrafluoroborate is also reported.

Studies on the Efficient Generation of PhosphorusCarbon Bonds via a Rearrangement of PIII Esters Catalysed by Trimethylhalosilanes

“…Catalyst Me 3 SiBr or Me 3 SiI (20 %) was then added at room temperature by injection, and the mixture was heated at 80 8C for 5-12 h. The crude reaction mixture was allowed to cool to room temperature, and was either recrystallised or subjected to silica gel column chromatography or distillation under reduced pressure, yielding pure phosphine oxide (phosphinate or phosphonate). [26] (Table 1, [27] ( Table 1, [28] ( Table 1, P NMR date were consistent with those previously reported. [29] Allyl diphenyl phosphinoxide [30] ( Table 1, P NMR and 13 C NMR data were consistent with those previously reported.…”

Preparation of the Enantiomers of Compounds Containing Chiral Phosphorus Centers

“…The more expensive phenylsilane PhSiH 3 is a better reagent for reduction of phosphine oxides with retention at phosphorus (133) but also does not always give stereospecific reduction (188). Trichlorosilane has been used, but some phosphine oxides have been found to give racemic phosphine products.…”

“…The corresponding neomenthyl phosphines 32 and 33 were prepared following Scheme 11 (49,188). An X-ray crystal- lographic structure determination on 31 allowed chemical correlation of all the structures, 30-33 (188). Both NMR studies (204) and conformational studies (205) have also been reported for menthyl-and neomenthylmethylphenylphosphines.…”

“…R 2 R 3 P can be estimated by reoxidation with H 2 0 2 and measurement of the R 1 R 2 R 3 P=0 rotation (188). When derived from reduction of R'R 2 R 3 P=0 of known epimeric purity, the epimeric purity of R !…”

Stereogenic Phosphorus

“…Two categories of reducing agents have been exploited for use in such stereospecific reductions. Several silanes have been used for reduction of the tetracoordinated phosphine chalcogenides [35][36][37][38][39][40][41][42], and lithium aluminum hydride has been used for the reduction of phosphine chalcogenides [43][44][45], as shown in Scheme (2), as well as the cleavage of a benzyl group from quaternary phosphonium salts [23][24][25][26][27][28][29][30][31][32][33][34], shown in Scheme (3).…”