Oxides diphenylphosphine

The vitamin D3 metabolite la,25-dihydroxycholecalciferol is a lifesaving drug in treatment of defective bone formation due to renal failure. Retrosynthetic analysis (E.G. Baggjolint, 1982) revealed the obvious precursors shown below, a (2-cyclohexylideneethyl)diphenylphosphine oxide (A) and an octahydro-4f/-inden-4-one (B), to be connected in a Wittig-Homer reaction (cf. section 1.5). 

Phosphine oxides are prepared similarly[644]. Selective monophosphiny-lation of 2,2 -bis[(lrifluoromethanesulfonyl)oxy]-l,1 -binaphthyl (784) with diphenylphosphine oxide using dppb or dppp as a ligand takes place to give optically active 2-(diarylphosphino)-1,1 -binaphthyl (785). No bis-substitution is observed[645,646]. 

Phenylimino)methyl]quinoxalme (186) with dimethyl phosphonate gave 2-[a-amlmo-a-(dimethoxyphosphinyl)methyl]quinoxalme (187) (MeONa, MeOH, reflux, several hours >95%) or with diphenylphosphine oxide gave 2-[a-anilino-a-(diphenylphosphinyl)methyl)quinoxaline (188) (MeONa, EtOH, 0°C, 20 min 95%) several analogs likewise. 

An a-fluorinated phosphinyl sulfoxide derivative, prepared as a mixture of diastereomers by the treatment of lithiated (a-fluoromethyl)diphenylphosphine oxide with menthyl p-toluenesulfinate, has been used for the preparation of enan-tiomerically pure 1-fluorovinyl and 1-fluoromethyl sulfoxides [76]. (E)-Diethyl ferf-butylsulfinylmethylphosphonate 117 has been prepared by the sulfinylation... 

The preparation of diphenylphosphine oxide normally involves the controlled hydrolysis of chlorodiphenylphosphine, but the product has a significant amount of diphenylphosphinic acid impurity. This problem... 

Enamine phosphonates (172) have been prepared by the addition of amines to alkynylphosphonates and used as shown in the synthesis of ajS-unsaturated ketones. The corresponding diphenylphosphine oxides have been prepared and used in a similar manner. ... 

In closely related chemistry, Tanaka showed that Pd(PPh3)4 catalyzes addition of diphenylphosphine oxide to alkynes to give alkenyldiphenylphosphine oxides (hydrophosphinylation, Scheme 5-21). 

The anti-Markovnikov product was formed with >95% regioselectivity at 35°C. The examples in Scheme 5-21, Eq. (1) show that cyano and hydroxyl functional groups are tolerated by the catalyst, and diphenylphosphine oxide can be added to both C=C bonds in a di-alkyne. The reaction also worked for internal alkynes (Scheme 5-21, Eq. 2). Unusual Markovnikov selectivity was observed, however, for 1-ethynyl-cyclohexene (Scheme 5-21, Eq. 3) [17]. 

Similar chemistry with diphenylphosphine oxide also resulted in high yields (50-98%) and ees (75-93%) (Scheme 5-48). For this chemistry, the PrPB catalyst was the optimum choice [35]. 

As a proven technique for detecting reactive intermediates, flash pyrolysis seems to be the method of choice for direct detection or isolation of phosphenes. The result of thermal decomposition of (a-diazobenzyl)diphenylphosphine oxide (7) was nevertheless disappointing, since only triphenylmethane (75), fluorene (14), and benzophenone (75) but not the desired methyleneoxophosphorane 9 could be isolated 12). 

In complete contrast, the photolysis of (diazomethyl)diphenylphosphine oxide completely avoids the insertion (16- 18). High yields of the corresponding phos-phinic acid derivatives (19d f) are found both in water and methanol and in the presence of morpholine (see Table 1)u,14). In general, methyleneoxophosphoranes show the same reactivity towards protic nucleophiles as other heterocumulenes. 

Suitable carbonyl compounds can thus be olefmated photochemicully with (diazobenzyl)diphenylphosphine oxide (7), the oxygen function being substituted by a diphenylmethylene group 18,20). Hence irradiation of 7 for a sufficient length of time in the presence of the corresponding unsaturated ketones affords the hepta-fulvene 27 23), the trans-1,3-butadiene 28 22 and the cross-conjugated hexatriene 2922> by direct olefination with the intermediate 9. 

Like the arylmethyleneoxophosphoranes 9, the acylmethyleneoxophosphoranes 39 have so far resisted isolation as such. Flash pyrolysis12) of (diazophenacyl)-diphenylphosphine oxide (36a)27) is just as unsuccessful as that of 7 the sole product isolated is diphenylaeetylene which is presumably formed via 39 or the cyclic isomer l,2Xs-oxaphosphetane by subsequent fragmentation of 23. 

Various diphenylphosphine oxide-substituted seven-membered rings 2-200, including also hydroazulenes, were synthesized by a Michael addition of 2-198, obtained from 2-197, and 2-199 followed by a Wittig reaction as developed by Fujimoto and coworkers (Scheme 2.47) [114]. 

Mixed phosphines,113 phosphates,114,115 phosphinites (diphenylphosphine oxide) and related diphenylphosphine acids,116-119 phospholes,120 and other phosphorus ligands121-123 have been used in Pt-catalyzed hydroformylation. [PtCl2(COD)] has been used as starting material for the preparation of catalytic precursors.114,124-126... 

Due to the significant importance of dienes as monomers, absolute as well as relative rate data have been determined for the addition of initiator derived radicals. Photolysis of (2,4,6-trimethylbenzoyl)diphenylphosphine oxide (TMDPO) 5 leads to the formation of... 

Yamashita, M., Tsunekawa, K., Sugiura, M., and Oshikawa, T., Novel preparation of diphenylphosphine oxides via direct deoxygenation of 1,2-epoxy-ethyldiphenylphosphine oxides, Synthesis, 65, 1985. 

Yamakoshi, K., Harwood, S.J., Kanai, M., and Shibasaki, M., Catalytic asymmetric addition of diphenylphosphine oxide to cyclic imines, Tetrahedron Lett., 40, 2565, 1999. 

N-acylated l-aminoalkyl)diphenylphosphine oxides in good yield.137... 

Reaction of 1,2-propadienyl diphenylphosphine oxide and MX (M = Na, Li, X= Cl, Br, I) in HOAc leads to 2-halo-2-propenyl diphenylphosphine oxides in 58-75% yields. With substituent(s) in the allene moiety, the reaction is very slow. The corresponding reaction with HX gives low yields [87]. 

Further variations on the epoxyketone intermediate theme have been reported. In the first (Scheme 9A) [78], limonene oxide was prepared by Sharpless asymmetric epoxidation of commercial (S)-(-)- perillyl alcohol 65 followed by conversion of the alcohol 66 to the crystalline mesylate, recrystallization to remove stereoisomeric impurities, and reduction with LiAlH4 to give (-)-limonene oxide 59. This was converted to the key epoxyketone 60 by phase transfer catalyzed permanganate oxidation. Control of the trisubstituted alkene stereochemistry was achieved by reaction of the ketone with the anion from (4-methyl-3-pentenyl)diphenylphosphine oxide, yielding the isolable erythro adduct 67, and the trisubstituted E-alkene 52a from spontaneous elimination by the threo adduct. Treatment of the erythro adduct with NaH in DMF resulted... 

The authors did not report on trisubstituted diphenylphosphine oxides, but apparently, the results are excellent with what is usually a difficult 1,1 unsubstituted pattern about the olefin. The investigation found near perfect selectivity and yields for most of the reported compounds when using 26 as a ligand. However, a very slow reaction was noted for the E olefin 59h while hydrogenation of E configured olefin 59j preceded smoothly, indicating a delicate balance between structure and reactivity. Other anomalous behavior of the substrates 59h-j is that both E- and Z-configured olefins produce the same enantiomer. 

Table 6 Asymmetric reduction of vinyl diphenylphosphine oxides and phosphonates...

Addition of diphenylphosphine or phenylphosphine to methyl 1-cyclohexanecarboxylate under base catalysis yielded 186 and 187 [164] (Figure 17). The Pd-catalyzed Heck reaction of substituted olefins with (p-bromophenyl)diphenylphosphine oxide in dimethylformamide afforded substituted phosphine oxides which could be reduced with trichlorosilane to yiled the corresponding carboxylatedphosphines - 188, too, was prepared this way [165],... 

By using three equivalents of diphenylphosphine oxide (relative to al-kyne), the palladium-catalyzed reaction affords bisphosphine oxides in high... 

Pd bond in Me2Pd(dmpe) [dmpe=l,2-bis(dimethylphosphino)ethane] to generate phosphinate-palladium species with extrusion of a methane molecule (Scheme 40). Upon treatment the resulting palladium species with diphenylphosphine oxides, the remaining methyl-palladium bond was pro-tonated and a phosphinyl(phosphinato)palladium complex (20) was isolated. 

Diphenylphosphine oxide reacts with diethyl acetylenedicarboxylate to give a 2 1 adduct (460), and it has been suggested that in this reaction the phosphine oxide reacts in the tervalent form [Eq. (68)]. On the... 

In the presence of a catalytic amount of methanethiolate-bridged diruthenium complex (la abbreviated as met-DIRUX), reactions of propargylic alcohols (2) with a variety of heteroatom-centered nucleophiles such as alcohols, thiols, amines, amides, and diphenylphosphine oxide gave the corresponding propargylic substituted... 

Diphenylphosphine oxide can be used as a phosphorus-centered nucleophile for propargylic substitution reactions, where its tautomer (diphenylphosphinous acid) is... 

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