Addition of Phosphorus Nucleophiles

Compared with the variety of existing carbon or nitrogen nucleophiles that were subjected to nucleophilic addition to there are few examples for phosphorus nucleophiles. Neutral trialkylphosphines turn out to be to less reactive for an effective addihon to Cjq even at elevated temperatures [114], Trialkylphosphine oxides show an increased reactivity. They form stable fullerene-substituted phosphine oxides [115] it is not yet clear if the reaction proceeds via a nucleophilic mechanism or a cycloaddition mechanism. Phosphine oxide addition takes place in refluxing toluene [115], At room temperature the charge-transfer complexes of with phosphine oxides such as tri-n-octylphosphine oxide or tri-n-butylphosphine oxide are verifiable and stable in soluhon [116], 

The synthesis of diastereomeric P-chiral fullerenyl phosphine 27a with a (-i-)-menthyl group was achieved analogously [114, 117]. No sign of epimerization upon heating 27a for 14 h at 80 °C in toluene was observed, indicating the remarkable stability of chirality at the phosphorus of 27a. 

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The conjugate addition of phosphorus nucleophiles of various oxidation states and in neutral or metallated form constitutes an efficient and well-known method for C—P bond formation [30]. In the case of phosphanes as nucleophiles especially, the corresponding phosphane-borane adducts have been used in 1,4-additions to Michael acceptors. Following the idea to use a chirally modified phosphorus nucleophile in asymmetric Michael additions to aromatic nitroalkenes, we synthesized the new enantiopure phospite 45 starting from TADDOL (44) with nearly quantitative yield. Due to the C2 symmetry, of the... 

The practicality of BINOL-Mg(ii) catalyst was further demonstrated by Ishihara et al. in a highly enantioselective addition of phosphorus nucleophiles 16 to a,p-unsaturated esters and ketones. Notably, by using water or BINOL as cocatalyst, a chiral cooperative Mg(ii) binaphtholate aqua complex was formed in the catalytic system that enabled the process to smoothly provide the corresponding adducts 17 and 18 in good to excellent yields and enantioselectivities. The authors supposed that the real active species was a cooperative 3 2 superamolecular complex of Hs-BINOLate/magnesium. Furthermore, the reaction could proceed by 1,4- or 1,2-addition by tuning the phosphorus nucleophile (Scheme 3.5). 

A review has been published on the work of Vasella s group on asymmetric induction in 1,3-dipolar cycloadditions of, and the addition of phosphorus nucleophiles to, N-glycosyl-nitrones, with the purpose of providing a general synthesis of a-aminophosphonic... 

Carbohydrates containing C-phosphorus linkages including those with phosphorus in the ring have been synthesized via addition of phosphorus nucleophiles to 6-nitro-xy/o-hex-5-enofuranose derivatives (Schemes 10 and 11). The acetyl migration of (25) to yield (26) occurred spontaneously. ... 

The asymmetric addition of phosphorus nucleophiles to imines provides direct access to phosphorus-containing chiral amines. While this chemistry is dominated by the use of phosphites and related compounds, a report by Duan outlines a successful protocol for the asymmetric addition of secondary phosphines to imines (Scheme 4.30) [81]. The reaction was catalyzed by a chiral palladium compound comprised of a palladium(II) center Ugated by a resolved pincer compound. A range of aryl and heteroaryl imines as well as several secondary phosphines were successfully used in this reaction. To aid in the isolation of the phosphines, the authors added elanental sulfur at the end of the P—C bond-fomung reaction. This chenustry provides access to a range of chiral N,P Ugands for metal centers that were previously challenging to prepare and isolate. 

Addition of Phosphorus Nucleophiles to Carbonyl Compounds Additions of dialkyl H-phosphonates (the Pudovik reaction) or trialkyl phosphites (the Abramov reaction) to carbonyl compounds constitute a convenient route to a-hydroxyphosphonates (Scheme 47.7). 

The first examples of diastereoselective additions of phosphorus nucleophiles to carbonyl compounds, applied to the synthesis of natural product analogs, involved carbohydrate-derived aldehydes and ketones. The achieved diastereoselectivity depended on the kind of sugar and protective groups used, and for the cyclic ketones usually higher diastereoselectivities were observed. In the aldose... 

During the last two decades, several methods have been developed for an asymmetric catalytic addition of phosphorus nucleophiles to carbonyl compounds. " " These reactions are mostly based on Lewis acid catalysis by metal complexes bearing chiral ligands. By using complexes of La," " Al," and Ti, ° high cc-values and a broad... 

Addition of Phosphorus Nucleophiles to Imines As the Pudovik and the Abramov reactions constitute phosphorus analogs of the aldol reaction, there is also a phosphorus equivalent for the Mannich reaction, namely, the Kabachnik-Fields reaction (see Scheme 47.7). In this process, phosphorus nucleophiles add to imines to produce a-aminophosphonate derivatives, which can be considered amino acid analogs. These compounds by themselves, or when incorporated into short peptides, find applications as enzyme inhibitors or as antibacterial and antifungal agents. However, in only a few instances were optically pure derivatives prepared for biological and pharmaceutical applications. Examples include the synthesis of antibiotic ala-fosfalin 82, penicillopepsin 83, and HIV protease... 

Along with diastereoselective reactions, an enantioselec-tive addition of phosphorus nucleophiles to imines, using chiral catalysts, has also been developed. In some cases, the same catalysts as those for the hydrophosphony-lation of a carbonyl group were used. 

Addition of Phosphorus Nucleophiles to C=C Bonds Phosphorus nucleophiles, both neutral and anionic, undergo addition to activated carbon—carbon double bonds. Such reactions constitute a phosphorus analogous of the conjugate addition, and they are often referred to as phospha-Michael addition. For hydrophosphonylation of inactivated double bonds, radical conditions are a viable option. In the last 15 years, however, an attractive alternative of a transition-metal-catalyzed hydrophosphonylation has also emerged. ... 

A stereoselective addition of phosphorus nucleophiles to C=C bonds has been employed in the synthesis of a few biologically important phosphorus-containing compounds. These were, however, confined to diastereoselective reactions, in which asymmetric elements already present in the molecule induced a sense of chirality at the newly formed stereocenters. Nevertheless, recently, significant progress has been made in the field of asymmetric catalytic hydrophosphonylation of carbon—carbon bonds with a prominent role of metal-catalyzed ° and organocatalytic reactions.One can expect that this will result in many synthetic applications of these novel and efficient reactions in the future. 

Addition of phosphorus nucleophiles to electron-poor aromatic sp carbons, followed by elimination, is a basis for the reactions in which pyridylphosphonate derivatives of dinucleotides were obtained (Schemes 47.44 and 47.45). The pyridine ring can be activated to nucleophilic attack by an appropriate substituent on the nitrogen atom. When the bulky triphenylmethyl (trityl) group was used for this... 

Metal-Catalyzed Addition of Phosphorus Nucleophiles to sp-Carhon... 

Recent developments in metal-catalysed asymmetric addition of phosphorus nucleophiles, with the formation of P-C bonds, have been reviewed the metals and electrophiles have been discussed widely. DFT study of salicylaldehyde-Al(ni)-catalysed hydrophosphonylation of benzaldehyde by diethylphosphonate (DEPH) reveals that P-H activation by the formation of Al-phosphite species is followed by rate-determining C-P bond formation, which determines the predominant (S) configuration (with 99% ee) of the a-hydroxyl phosphonate ester on regeneration of the salicylaldehyde-Al(III) complexes. Reduction of activated carbonyl groups by alkylphosphanes can proceed either through path a or path b (Scheme 35), as evidenced experimentally and theoretically. ... 

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