Organophosphorus bond formation

Several new sections have been added to this Second Edition, and the presentations of the established methods have been updated to emphasize the recent advances in their use. In addition to the survey of the approaches toward carbon-phosphorus bond formation, details of specific preparations are provided as guides for the performance of these reactions without detailed recourse to the original literature. In this way, this work is anticipated to be of particular value to the synthetic organic chemist who is skilled in the general art but not particularly experienced in organophosphorus chemistry. 

The present effort is intended to provide an update of the earlier edition, bringing to the chemist in concise form advances in the approaches to C-P bond formation previously discussed, as well as several other aspects of C-P bond formation. These latter aspects include the generation of organophosphorus compounds from elemental phosphorus (of particular industrial interest for purposes of cost containment) advances in the preparation of phosphoranes, including the use of transient oxophosphoranes as intermediates in organophosphorus compound syntheses and new approaches toward the preparation of compounds with aromatic and vinylic carbon-phosphorus bonds. 

Prior to considering synthetic approaches toward C-P bond formation, we review two areas related to the literature of organophosphorus chemistry that are of particular value to those chemists who do not focus primarily on phosphorus. 

Organophosphorus compounds. Phosphorus-carbon bond formation takes place by the reaction of various phosphorus compounds containing a P—H bond with halides or triflates. Alkylaryl- or alkenylalkylphosphinates are prepared from alkylphosphinate[638]. The optically active isopropyl alkenyl-methylphosphinate 778 is prepared from isopropyl methylphosphinate with retention[639]. The monoaryl and symmetrical and asymmetric diary lphosphi-nates 780. 781, and 782 are prepared by the reaction of the unstable methyl phosphinate 779 with different amounts of aryl iodides. Trimethyl orthoformate is added to stabilize the methyl phosphinate[640]. 

Selective Bond Formation of Organophosphorus Acids with Functional Groups of Biological Importance... 

Chiral organophosphorus compounds have been found to act as catalysts in numerous enan-tioselective reactions. This review highlights recent developments in this area and more precisely in the kinetic resolution of secondary alcohols, the enantioselective borane reduction of ketones, and in the asymmetric C-C bond formation with the introduction of asymmetric two-center catalysts. 

As for the reduction of the ketones, the amphoteric catalysts featuring acidic-basic sites have been found to be very effective for the enantioselective catalysis of C-C bond formation. Thus, Soai et al. were the first to report the enantioselective addition of dialkylzincs to aldehydes using enantiomerically pure phosphin-amides and analogues as chiral catalysts in the presence of titanium tetraiso-propoxide. Numerous chiral organophosphorus compounds have been prepared and applied in a test reaction between benzaldehyde and diethylzinc [48, 49]. An important difference in terms of enantioselectivity was observed between the behavior of P=S (47-48) and P=0 (49) groups. Thus, the enan-... 

The oxidation-reduction method, developed initially by Mukaiyama et al. [133] and related to the previously described organophosphorus methods, has permitted a variety of important solid-phase applications. The mechanism of the activation is complex and involves the oxidation of the triaryl/ alkyl-phosphine to the oxide as well as reduction of the disulfide to the mercapto derivative. However, different active species, such as 81 (Fig. 11), the 2-pyridyl thioester, or even the symmetrical anhydride, have been postulated to form. For the intermediate 81, the peptide bond formation may proceed through a (cyclic transition state. The method has been used for conventional stepwise synthesis [134], acylation of the first protected amino acid to a hydroxymethyl resin, and to achieve segment condensation on a solid support in the opposite direction (N C) [135,136]. Lastly, it has been used for efficient grafting of a polyethylene glycol (molecular weight 2000) derivative to an aminomethyl resin to prepare PEG-PS resins [137]. 

Figure 1 shows typical organophosphorus substrates, which usually act directly, or after activation at a metal center, as nucleophiles. Most include a reactive P-H bond, which, for P(V) substrates, is involved in an important tautomerization equilibrium which interconverts four- and three-coordinate compounds 1 and 2. The source of electrophilic carbon for C-P bond formation is usually unsaturated (alkynes, alkenes, aldehydes, etc), or contains a good leaving group (aryl and alkyl halides, allyl acetates). 

The previous sections have described C-P bond formation by classical organome-tallic processes, such as migratory insertion and reductive elimination. However, there is evidence in some other systems that the metal catalyst activates the organophosphorus substrate for direct nucleophilic attack on an electrophile [43]. 

Likely growth areas in future research include asymmetric catalysis for synthesis of chiral organophosphorus compounds and more detailed investigation of Cu-catalyzed phosphination, which would be much cheaper than the well-established Pd chemistry. Although some mechanistic information about metal-catalyzed C-P bond formation is available, further studies might assist the development of additional synthetically useful processes. 

The reactions belonging to this class of transformations, namely the Michaelis-Arbuzov (Arbuzov) and the Michae-lis-Becker reactions (Scheme 47.1), constitute classic methods for the C P bond formation and are widely used in the synthesis of organophosphorus natural products. ... 

The formylation of P-H bonds in mono and multiprimary phosphines, which result in the formation of hydroxymethyl phosphines, is among the facile useful reactions in organophosphorus chemistry. As shown in Scheme 9, formaldehyde in the presence of platinum catalysts transforms P-H bonds into hydroxymethyl (P-CHjOH) functionahties (Scheme 9) [52]. 

Because organophosphorus compounds are important in the chemical industry and in biology, many methods have been developed for their synthesis [1]. This chapter reviews the formation of phosphorus-carbon (P-C) bonds by the metal-catalyzed addition of phosphorus-hydrogen (P-H) bonds to unsaturated substrates, such as alkenes, alkynes, aldehydes, and imines. Section 5.2 covers reactions of P(lll) substrates (hydrophosphination), and Section 5.3 describes P(V) chemistry (hydrophosphorylation, hydrophosphinylation, hydrophosphonylation). Scheme 5-1 shows some examples of these catalytic reactions. 

The unique combination of double bonds in the molecules of those compounds, each with different reactivity along with the easy preparation, makes phosphorylated allenes useful substrates for the synthesis of different cyclic and noncyclic organophosphorus compounds. Recent investigations increase the scope of application of phosphorylated allenes as precursors in organic syntheses. Most of them are accompanied by the formation of five- or six-membered phosphorus heterocycles, which in many cases demonstrate certain biological activity. 

The existence of three equivalent bonds to each of the phosphorus atoms, which must be broken in the formation of mono-phosphorus organophosphorus compounds, might appear to be a problem at first all must be broken as new bonds are being generated to phosphorus. However, the fundamental approaches toward the use of white phosphorus accomplish this necessary action with relatively few extraneous reaction processes. 

Our radiolysis studies also indicate that phosphonates react quite slowly with the superoxide anion radical. Although our studies do not support the formation of radical cations as an initial oxidation step, we cannot rule out the possibility that radical cations are not involved in the oxidation of the C—P bond, as previously proposed [44], It is also possible that more electron-rich organphosphorus compounds or organophosphorus compounds in the adsorbed state may exhibit different redox and hydroxyl radical chemistries than what is observed under pulse radiolysis employing homogeneous conditions. 

Nb and Ta derivatives are hard acids and then-complexes with P- or As-donors are limited. Tertiary phosphines, especially PMes, have been widely used to stabilize low-valent derivatives. C-H activation reactions, promoted by the formation of thermodynamically stable Ta-H, Ta-C, and Ta=C bonds have resulted in metallacycles based on unusual anionic phosphorus donors. Nucleophilic Ta phosphinidene complexes could be stabilized by a tripodal tetradentate [NN3] amido ligand. The terminal PR ligand reacts smoothly with aldehydes, providing a general synthesis of phosphaalkenes RP=C(H)R and act thus as a phospha-Wittig reactant see Phosphorus Organophosphorus Chemistry). 

One of the subjects of our investigations involved the interaction of allenes with the P=E derivatives. This work provided some very interesting, unexpected results that may well be of use in synthetic organophosphorus chemistry. Thus, in attempting to study the (2+2)-cycloadditions of the phosphinimine and the (methylene)phosphine systems with the allenic C=C bond, we established that the reactions take a different and more interesting course — that of an ene" reaction (eq 1). In the first step of the reaction, the electrophilic phosphorus center apparently attacks the nucleophilic central carbon of the allene system. Then, instead of undergoing nucleophilic attack on the incipient carbonium ion, the anionic center (E) abstracts a proton from the terminal C-H bond, leading to the formation of a new double bond in the phosphorus-substituted 1,3-butadiene derivatives (3). 

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