Phosphonates, deprotonation

A report from the Jorgensen laboratories detailed the enantioselective synthesis of P-phosphonic acid a-amino acid derivatives through a Cu(II)-catalyzed addition of P-keto phosphonates to an N-tosyl-a-imino ester [41]. Once again Cu(OTf)2/t-Bu-BOX (13) was found to provide the highest enantioselectivity in addition of P-keto phosphonate (141) to N-tosyl-a-imino ester (142) (Scheme 17.28). The identity of the amine base used for P-keto phosphonate deprotonation also proved critical to reaction efficiency and selectivity. Triethylamine provided the best combination of reactivity and selectivity, but it should be noted that the diastereomeric ratio was doubled when 2,6-lutidine was used as the base in the reaction. 

At present, most of the related efforts on ligand chemistry of nanociystals are focused on the development of new types of ligands [47, 48] and different passivation strategies [49] to satisfy stability requirements for certain types of applications. Typical ligands for colloidal nanociystals, such as thiolates (deprotonated products of thiols), amines, phosphonates (deprotonated products of phosphonic acids), and carbojg lates (deprotonated products of carboxylic acids), etc., are all Lewis bases. Ligand systems can consit of hexadecylamine, dodecylamine, and octylamine on one side (HD Am, DDAm, and Oct Am) and octanoic acid, oleic acid, and lauric acid on the other (OctA, OA, and LcA) [50]. The presence of a carboxylic acid is essential to obtain monodisperse isotropic nanoparticles but that the nature of the amine and acid ligands has only a very limited influence on the size of the metal particles. This is not the case in pH variation. In... 

Tlie interest in the preparation and use of dithiolium salts in connection with the synthesis of TTF derivatives led to the development of a new uses of heteroaromatic cations in organic synthesis. Based on that, a new carbonyl olefination for the synthesis of numerous heterofulvalenes was developed (77S861). For example, 2-dimethoxyphosphinyl-l,3-benzodithiole was deprotonated with butyllithium in THF at -78°C and the resulting phosphonate carbanion reacted with 9-alkyl-acridones to give the dithia-azafulvalenes of type 45 (78BCJ2674) (Scheme 15). 

The carbanionic deprotonated phosphonate thus obtained—e.g. 14—can be reacted with a carbonyl substrate 2 just like a phosphorus ylide. However... 

The reaction was carried out analogously to the general procedure for the addition of metalated ally 1 sulfoxides given in Section 1.5.2.2.3.2. BuL.i is used, in this case, for deprotonation instead of LDA. BuLi is added to a solution of 1 - 3 mmol of the phosphine oxide or phosphonate in THF until the first permanent appearance of the red color of the anion. Thereupon, 1.1 equivalents of the BuLi is added. For the phosphonates, whose anions are less intensely colored, 1.1 equivalents of BuLi are added to the solutions after the first permanent appearance of the red color of an added indicator, 2.2 -bipyridyl. 

The results presented in this review concern this metal-catalyzed mechanism. Depending on the nature, anionic or neutral, of the different nucleophiles, the result of the arylation can be a neutral substitution product or a cationic one, which most often, in the last case, undergoes an evolution, for example (starting form a phosphite) to a phosphonate or, after deprotonation, to an arylamine or to an arylether (Fig. 2). 

OS 79] ]R 17] ]no protocol] 4-Methoxybenzaldehyde and methyl diethoxyphos-phonoacetate were reacted by means of the Wittig-Horner-Emmons reaction [85] (see a more detailed description in [42]). A modified micro reaction system consisting of two mixers, for deprotonation of the phosphonates and introduction of the aldehyde, connected to an HPLC capillary of 0.8 m length and 0.25 mm diameter was employed. The micro reactor showed higher yields than laboratory batch synthesis. 

There are related reactions involving phosphonate esters or phosphines oxides. These reactions differ from the Wittig reaction in that they involve anions formed by deprotonation. In the case of the phosphonate esters, a second EWG substituent is usually present. 

An alternative procedure for effecting the condensation of phosphonoacetates is to carry out the reaction in the presence of lithium chloride and an amine such as diiso-propylethylamine. The lithium chelate of the substituted phosphonate is sufficiently acidic to be deprotonated by the amine.262... 

The zinc-pyridoxal 5 -phosphate-2-amino-3-phosphonopropionic acid system exhibits deprotonation of the coordinated phosphonate group to bind to the zinc center at increased pH but cannot be coordinated to the zinc ion below pH 8.5 when it is protonated and hydrogen bound to the phosphate group.422... 

The effects on the dynamics of photo-injected electrons where not systematically studied, despite scattered reports on the influence of amines, which induce surface deprotonation, and lower surface charge with a resulting negative shift in band edge position and an increase in the open circuit potential, Voc [103], The opposite effect is induced by Li+ ions, which intercalate in the oxide structure. Guanidinium ions increase Voc when used as counterions in place of Li+. Other adsorbing molecules that influence both Voc and short circuit current are polycar-boxylic acids, phosphonic acids, chenodeoxycholate and 4-guanidinobutyric acid. 

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

The most popular method for generation of a-thio-carbanion (migration terminus) is direct lithiation (deprotonation) with alkyllithium or lithium amide. These deprotonation methods are widely applicable to various substrates, not only benzyl or allyl sulfides , but also dithioacetals 142 which form 143 (equation 83), and a phosphonate substituted system 144 which gives 145 (equation 84). ... 

In 2006, our research group reported a novel MCR based on the reactivity of a-acidic isocyano esters (1) toward 1-azadienes (84) generated by the 3CR between phosphonates, nitriles, and aldehydes [169]. Remarkably, the dihydropyridone products (85) for this 4CR contained the intact isonitrile function at C3. The exceptional formation of the 3-isocyano dihydropyridone scaffold can be explained by the Michael-attack of the a-deprotonated isonitrile (1) to the (protonated) 1-azadiene (84), followed by lactamization via attack of the ester function by the intermediate enamine. Although in principle the isocyano functionality is not required for the formation of the dihydropyridone (85) scaffold, all attempts using differently functionalized esters (e.g., malonates, ot-nitro, and a-cyano esters) gave lower yields of the dihydropyridone analogs [170] (Fig. 26). 

Most of these reactions have been extended to ethyl bromodifluoromethyl phos-phonate (Figure 2.15). ° However, conversely to the anions of difluoroacetate, lithiated anions of diethyl difluoromethylphosphonate are easily generated through the deprotonation of ethyl difluoromethyl phosphonate. They are frequently used for the synthesis of difluorophosphonates (cf. Chapter 7)." ° ... 

Similar applications to those reported in CHEC-II(1996) have been described for more elaborate phosphonate esters 42 and 43 which undergo Horner-Emmons reactions with carbonyl compounds following deprotonation <2000EJ051, 2002CL1002>. 

Nevertheless, there is one report deahng with the addition of functionalized allylic organozinc reagents (bearing either an ester or a phosphonate moiety) to alkynes where deprotonation does not seem to operate based on the stoichiometry of the reagents and the yields. Thus, slow addition of the allylic bromide 145 to a sonicated mixture of... 

Although not strictly to be included in this section it is worth comparing the azobenzene-derived EGB s with those generated from azines. The azine-derived bases are of similar strength to the azobenzene radical-anions, as evidenced by their ability to deprotonate phosphonate esters(Table 15, p. 160). 

Derivatives of the general formula (7) in Table 6 have been successfully used as probases and their properties in this context are being further explored. In common with the azobenzenes and ethenetetracarboxylate esters, the fluoren-9-ylidene derivatives usually display two reversible one-electron peaks in cyclic voltammetric experiments. Although disproportionation is possible (cf. Scheme 12) it is the dianions which are the effective bases. It was shown early on that the radical-anions of such derivatives are long-lived in relatively acidic conditions (e.g. in DMF solution the first reduction peak of Ph C -.QCN) remains reversible in the presence of a 570-fold molar excess of acetic acid, at 0.1 V s ). Even the dianions are relatively weak bases, useful mainly for ylid formation from phosphonium and sulphonium salts (pKj s 11-15) they are not sufficiently basic to effect the Wittig-Homer reaction which involves deprotonation of phosphonate esters... 

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