Phosphine oxide, trisubstituted

The initial step of olefin formation is a nucleophilic addition of the negatively polarized ylide carbon center (see the resonance structure 1 above) to the carbonyl carbon center of an aldehyde or ketone. A betain 8 is thus formed, which can cyclize to give the oxaphosphetane 9 as an intermediate. The latter decomposes to yield a trisubstituted phosphine oxide 4—e.g. triphenylphosphine oxide (with R = Ph) and an alkene 3. The driving force for that reaction is the formation of the strong double bond between phosphorus and oxygen ... 

Simple ylides are sensitive towards water as well as oxygen. By reaction with water, the ylide is hydrolyzed to give the trisubstituted phosphine oxide 4 and the hydrocarbon 10 ... 

Type III (no homodimerization) Acrylonitrile," protected 3° allylamines" Vinyl trialkoxysilanes, vinyl siloxanes 1,1-Disubstituted olefins, " non-bulky trisubstituted olefms, vinyl phosphonates, " vinyl phosphine oxides,phenyl vinyl sulfone, acrylonitrile, 4° allylic carbons (all alkyl substituents), protected 3° allylic alcohols, 7,Aolefm of 2-subst. 1.3- butadienes, 7,Aolefin of electronically deactivated 1.3- butadienes ... 

Compared to the analogous trisubstituted phosphines, the trisubstituted arsines are oxidized at slightly higher potentials (50-100mV) as expected from the decrease in electron-donating ability in the series N, P, As. However, the analogous stibines are oxidized at almost the same potentials as the arsines but dilferences in the rates of the follow-up reactions may be the cause of this apparent coincidence in irreversible potentials. Trimesitylarsine and trimesitylstibine are oxidized in diffusion-controlled, chemically reversible one-electron processesand the reversible potentials for these oxidations show (cf Table 14) that the stibine is 60 m V more difficult to oxidize than the arsine. 

The Homer reaction can be applied to the synthesis of trisubstituted alkenes. As in the case of HWE reactions, the yield obtained by adding a disubstituted phosphine oxide to an aldehyde is frequently higher than that obtained by adding an anion to a ketone. This methodology was applied to the synthesis... 

In analogy to the Peterson alkenation, the intermediate hydroxyphosphine oxidn (269) cm be prepared by addition to epoxide derivatives (268 Scheme 36). Overall yields are high for this process, and this sequence can be applied to the synthesis of phosphonate intermediates as well. Warren has studied hydroxy-directed epoxidation. Provided the allylic phosphine oxide is trisubstituted, as is (270) in equation (6S), these oxidations proceed with good selectivity. Ring opening can then be undertaken to generate the hyth-oxyphosphine oxide. 

Most recently, the immunosuppressive agent FK-S06 (416) has been the target of total synthesis. To date several approaches to the trisubstituted alkene region at C-19 and C-20 have appeared. These preliminary studies allow the comparison between the Warren phosphine oxide approach and the Julia coupling. In the first total synthesis of FK-S06, Jones and coworkers at Merck formed the the alkene deprotonadon of the phosphine oxide (418) and condensation with the aldehyde (417). The hydroxy-phosphine oxides were formed in a ratio of 1 1 in 77% yield. The less polar diastereomer was treat with base to obtain the ( )-alkene (419) in 32% overall yield from the aldehyde (equation 96). Danishefsky utilized the Julia coupling for the formation of the trisubstituted alkene region. The sulfone anion (420) was treated with isobu raldehyde as a model, followed by acetylation and reductive elimination to... 

Phosphonates (10) and phosphine oxides (11) were prepared for use in the synthesis of a series of new alk-l-enyl derivatives of adenine and thymidine (Scheme 4) via Horner reactions and Horner-Wadsworth-Emmons reactions on carbonyls. This approach, complementary to the previously reported methods for the preparation of iV-(alk-l-enyl) nucleobases, offers a novel general strategy to access trisubstituted alkenyl nucleobases. 

One of the limitations of the Warren s adaptation of Homer-Wittig olefina-tion, the failure of the (Z)-selective route when the alkene has a branched chain substituent, has now been overcome. Reduction of the p-ketophosphonates carrying a-branches, e.g. (112) and (113), with sodium borohydride and cerium chloride gives excellent a / -stereoselectivity and hence (Z)-alkene on base-induced elimination. Enantioselective synthesis of both jy -(115) and anti- ll) P-hydroxy-phosphine oxides has been achieved with up to 90% e.e. through two separate approaches. The jyn-isomer was obtained by reduction of the corresponding ketone (114), while the anti-isomer is the product of the reaction of the oxazolidine substituted aldehyde (116) with lithiated diphenylmethyl-phosphine oxide (Scheme 10). A new, highly stereoselective approach to trisubstituted alkenes has been reported. Cerium(III) chloride-promoted... 

Recently, a polymeric trisubstituted phosphine dichloride (14) was prepared by the reaction of phosgene with polymeric trisubstituted phosphine oxide (13) (Scheme 12-7) (Relies and Schluenz, 1974). This polymeric phosphine dichloride (14) was used for the preparation of acid chlorides. The by-product polymer was also regenerate. 

Ferrocenyl derivatives of 73, namely (Co3(CO)9 L (/i3-CFc)] (n = 0-3, L = phosphine or phosphite) undergo reversible reduction at the tricobalt center to detectable radical anions (n = 0), and oxidation at the iron center to give isolable cations (182). For the trisubstituted derivatives [ = 3, L = P(OMe)3 or P(OPh)3], the monocations appear to be mixed-valence species in which the two redox sites are weakly interacting low-energy absorption bands, assigned to intervalence transfer transitions, have been observed. The dications (Co3(CO)6 P(OR)3 3(/i3-CFc)] (R = Me or Ph) are also isolable, oxidation having occurred at both possible redox sites (183). 

The potentials for the chemically irreversible oxidation of trisubstituted arsines in MeCN at CP electrodes correlate roughly with the sum of the Taft cr values for the alkyl or aryl substituents (four compounds) , with a slope that is slightly larger than the corresponding correlation for the analogous phosphines. 

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