Phosphite route

Less commonly applied approaches are based on the transesterification of phosphites (Route II) [60]. This methodology has been used, for example, for the preparation of long-chain or cychc phosphites from acychc phosphites with low-boiling alcohols [61]. The reaction can be mediated by weak acids (e.g., tetrazole) [62]. In the first step, a pentavalent hydrophosphorane is formed (Scheme 2.86). The compound collapses under the elimination of alcohol to produce a mixture of the transesterification product and the starting phosphite. 

The acid process has three advantages over the alkaline process, ie, (/) higher yield of phosphine (60 vs 25%) (2) more pure gas for use in subsequent reactions (95 vs 40%) and (J) by-product phosphoric acid is relatively valuable and can be sold into a number of markets, eg, in the manufacture of fertilizers and flame retardants. There is no ready outlet for the mixture of phosphites produced via the alkaline route and additional processing by oxidative spray drying is needed to produce phosphates for sale (3). 

A convenient route to steroidal aziridines from the diaxial IN3-olefin adducts, e.g., (99), which undergo elimination with lithium aluminum hydride, was developed by Galle and Hassner. Upon treatment with trialkyl phosphite, these adducts are converted to A-phosphorylated aziridines which are reduced by lithium aluminum hydride to the free steroidal aziridine. 

Organic derivatives fall into 4 classes RP0(0H)2, HP0(0R)2, R P0(0R)2 and the phosphite esters R(OR)3 this latter class has no purely inorganic analogues, though it is, of course, closely related to PCI3. Some preparative routes have already been indicated. Reactions with alcohols depend on conditions ... 

Another chemical route is by decomposition of solid adducts of ozone with triaryl and other phosphites at subambient temperatures ... 

The deoxygeneration of nitroarenes by trivalent phosphorus compounds in the presence of amines is a useful route to 3/f-azepin-2-amines (cf. compounds 32, Section 3.1.1.4.2.2.). Subsequently, it has been shown, by carrying out the reaction in strongly basic solution, that the process can be extended to the synthesis of 1H-. 3H- and 5//-2-benzazepines from nitronaph-thalenes 43 For example, 1-nitronaphthalenes 3 with dimethyl phosphite in the presence of sodium methoxide and a primary or secondary aliphatic amine, yield the dimethyl 5//-2-ben-zazepin-3-yl phosphonates 4 accompanied, in some cases, by the isomeric 3//-2-bcnzazepin-3-yl phosphonates 5. 

Simpson and Burt have studied the same reactions in the presence of various amounts of ethanol and have plotted graphs of phosphonate (81 R = Ph) and phenyl acetylene produced against moles of alcohol added. Acetylene in the product reached a maximum (around 60%) when two moles of ethanol were added and stayed fairly constant beyond this, which suggests that the attack-on-halogen contribution to the mechanism is approximately 60%. The rest of the reaction presumably follows some other mechanism and the authors suggest the addition-elimination route (79) in view of the isolation of the phosphonate (83) from the reaction of tri(isopropyl) phosphite with the bromoacetylene (84). 

B. Electrophilic Reactions.—Transesterification followed by rearrangement is a common route from simple phosphites to more complex phos-phonates. This has now been applied to the preparation of cyclic phos-phonates (85). Both phosphites (86) and phosphoranes (87) containing phosphorus-hydrogen bonds are obtained from the cyclic biphosphite (88) and butanol. ... 

The use of an anionic reagent for addition at carbonyl carbon rather than a fully esterified form of a trivalent phosphorus acid obviates a troublesome aspect of the Abramov reaction. Specifically no dealkylation step is required. Mechanistic investigations257 258 indicate that the reaction proceeds much as a simple "aldol"-type reaction in which the anionic phosphorus site adds directly to the carbonyl center. While the initial efforts concerned with the "Pudovik reaction"259 were directed toward the use of sodium salts of the simple dialkyl phosphites, as shown in Equation 3.17,260 266 with a, 5-unsaturated carbonyl systems (vide infra) competition between sites for addition can occur. Addition at the carbonyl carbon site is the kinetically favored route.267-270... 

Finally, (3-bromoacrylate esters react with trialkyl phosphites to provide the unsaturated phosphonates (Equation 3.24), presumably through an addition-elimination route.392... 

Herzig, C. and Gasteiger, J., Reaction of 2-chlorooxiranes with phosphites and phosphanes a new route to (l-carbonylphosphonic esters and -phosphonium... 

A convenient route to j3-phosphorus nitroxides involves the 1,3-addition of trimethylsilyl phosphites (e.g., diethyl) or trimethylsilyl phosphines (e.g., diphenyl) to aldo nitrones (e.g., a-PBN, DMPO), or keto nitrones (e.g., 2-Et-DMPO or 2-Ph-DMPO), to form a-phosphityl- or a-phosphinyl-O-silylhydroxyl-amines. Acidic hydrolysis provides the corresponding hydroxylamines which are easily oxidized to p-phosphorus-nitroxides (690). 

The use of monodentate phosphoramidites in enantioselective hydrogenation was first reported in 2000, together with reports on the use of phosphites and phospho-nites [15]. Phosphoramidites are prepared in a variety of ways, but the most common route is the treatment of a diol with PC13, followed by addition of an amine [60, 61]. MonoPhos (29a), the first reported phosphoramidite used as a ligand, is prepared from BINOL and HMPT in toluene [62]. Phosphoramidites, especially... 

LLB, a so-called heterobimetallic catalyst, is believed to activate both nucleophiles and electrophiles.162 For the hydrophosphonylation of comparatively unreactive aldehydes, the activated phosphite can react with only the molecules precoordinated to lanthanum (route A). The less favored route (B) is a competing reaction between Li-activated phosphite and unactivated aldehyde, and this unfavored reaction can be minimized if aldehydes are introduced slowly to the reaction mixture, thus maximizing the ratio of activated to inactivated aldehyde present in solution. Route A regenerates the catalyst and completes the catalysis cycle (Fig. 2-9). 

In passing, it may be noted that we prepared diethyl 2-fluoroethylphosphonate (III) and diethyl benzylphosphonate (IV) by an alternative route from sodium diethyl phosphite and the corresponding halides.6... 

The reaction between dialkyl phosphorocyanatidite and acyl cyanides in dichloro-methane at 0 °C parallels that between the same phosphite and 1,2-dicarbonyl compounds, and is probably initiated by attack of tervalent phosphorus on the carbonyl group the formation of O- and V-alkyl products, (30) and (29), is an indication of the probable nature (28) of an intermediate.25 The extension of the reaction (see Organophosphorus Chemistry , Vol. 7, pp. 108, 126) to include ethyl phosphorodicyanatidite and 1-keto-esters provides a route to the 5-phosphabicyclo-[3,2,0]heptanes (31) in high yields.26... 

The general synthetic route for the preparation of bridged phosphorus cavitand is outlined in Scheme 5. From the resorc[4]arene, bearing various substituents at the lower rim, the cyclization step, which leads to the formation of the four fused eight-membered rings, was performed with three-co-ordinated and four-coordinated phosphorus reagent to give respectively tet-ra-phosphite, tetra-phosphonite, and tetra-phosphate or tetra-phosphonate derivatives. 

The intermediate phosphite employed in this synthesis was prepared by condensation of duly protected sialic acid with the nucleosidyl phospho-roamidite in the presence of N-PhIMT. Oxidation by TBHP and deprotection according to standard procedures gave the cytidine-S -monophospho-iST-ace-tylneuraminic acid. This synthetic route is claimed to have advantages over procedures published earlier [26]. The same group demonstrated the importance of 3 A and 4 A molecular sieves as moisture scavengers in the reaction of nucleoside phosphoroamidite with a nucleotide. This approach should be likely to find application in the synthesis of biophosphates outside nucleotide chemistry. 

This synthetic procedure steps a-d can be performed as a one-flask process. The simplicity of this method and its high yield observed makes this approach competitive with the most widely used method based on sulfuriza-tion of phosphite intermediate prepared on phosphoroamidite route. An analogous dithiaphospholane approach was applied earlier for the synthesis of phosphorodithioates derived from deoxyribonucleosides [105]. The oxathiophospholane strategy which allows stereoselective synthesis of P-chi-ral thioanalogues of oligonucleotides was most recently described by Guga, Okruszek and Stec [105]. 

For the synthesis of base-sensitive oxazoles (Scheme 52), /3-acyloxyvinyl azides (130) react with triethyl phosphite via an aza-Wittig-cyclization. Phosphorimidate 131 is converted to 1,3-oxazole 132 with spontaneous elimination of triethyl phosphate (89JOC431). Benzoxazoles are also available by this synthetic route (71CC1608). 

A general synthetic route has been reported for a wide range of trialkyl phosphite complexes of noble metals, including the unstable white [RhLj] [L = P(OMe)3 or P(OEt)3]. Subsequent studies have shown that the former complex reacts with NOPFg in dichloromethane to give the hydride [RhH- P(OMe)3 5](PF6)2 in high yield. 

Five years later, the same authors reported an improved total synthesis of arcyriaflavin A (345) starting from the TBS enol ether 1490 (for the synthesis see Scheme 5.252). This route involves two indolizations based on silyl enol ether nucleophilic attack and Fischer processes. Using Cadogan s procedure by heating in triethyl phosphite, the TBS enol ether 1490 was transformed into the ketone ( + )-1495, involving silyl enol ether-mediated indolization. Finally, Fischer indolization of (+ )-1495 by reacting with phenylhydrazine (524) led directly to arcyriaflavin A (345) in 57% yield (794) (Scheme 5.253). 

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