Design and Development of Functionalized Water-Soluble Phosphines:  Catalytic and Biomedical Implications

Abstract

Water is an environmentally (and biologically) benign solvent, and therefore, development of chemistry in aqueous media has long been a desirable goal for chemists. In particular, chemistry of water-soluble transition metal compounds has gained considerable prominence in recent years because of their usefulness in biphasic (aqueous-organic) catalysis 1 and biomedicine. 2 High solubility of transition metal compounds in water becomes a primary requirement in the design and development of catalysts for use under biphasic media because of the need for efficient separation and recovery of expensive transition metal catalysts (in aqueous media) from organic products. Additionally, the ability of specific transition metals to exert therapeutic (and diagnostic) influence on certain diseases has provided increased impetus in the development of new water-soluble and in vivo-stable transition metal compounds. 2,3 Of the various ligands available to stabilize specific oxidation states of transition metals and to produce aqueous soluble coordination compounds, functionalized phosphines are the most attractive class of ligands because of their versatile coordination chemistry. While aqueous soluble di-or trisulfonated arylphosphines, such as P(m-C 6 H 4 SO 3 Na) 3 , have largely been employed in the development of highly active water-soluble transition metal catalysts, 1 hydrophilic alkylphosphines are being highly sought after in order to gain specific structure-activity advantages in both catalytic and biomedical applications. In this context, the formylation of PH 3 , first reported by Hoffman et al., to produce tetrakis(hydroxymethyl)phosphonium chloride (THPC) has provided one of the earliest examples for the synthesis of hydrophilic alkylphosphines (Scheme 1). 4 Water-soluble tris(hydroxymethyl)phosphine (THP) was produced upon reaction of THPC with a suitable base (e.g., triethylamine or sodium bicarbonate buffer) (Scheme 1). 5 The transition metal chemistry of THP and other functionalized phosphines, over the years, has enabled the development of a wide spectrum of water-soluble transition metal/organometallic compounds for potential use in biphasic catalysis 5,6 and biomedicine. 7,8 The ease of transformation of P-H bonds into P-C bonds (as outlined in Scheme 1) is, undoubtedly, a synthetic novelty and the (hydroxymethyl)phosphorus compounds have provided a diverse range of chemical, catalytic, biological, environmental, and biomedical applications. 5-10 Despite the potential academic interest and scope for further technological advances, formylation reactions of functionalized phosphorus hydrides and, especially, of multinuclear phosphorus hydrides (i.e., bis-, tris-, or tetraphosphines) have, surprisingly, remained largely unexplored.It must be recognized that PH 3 , in its pure form, is an extremely hazardous chemical compound. It ignites in air at about 150°C and decomposes to produce phosphoric acid. 11 In its impure form, PH 3 gas is spontaneously inflammable at room temperature and this insta-

Selective chemical reactions in supercritical carbon dioxide, water, and ionic liquids

“…Water solubility is usually reached through incorporation of strongly hydrophilic ligands bearing charges such as sulfonate (SO 3 Na) and carboxylate (CO 2 Li; Figure 3). One of the advantages of water-soluble phosphines lies in the recyclability of the catalyst that is therefore preserved in water (126,127). In 2002, Geneˆt et al (128) synthesized a new anionic water-soluble ligands based on triphenyl phosphine (Scheme 12).…”

Synthesis and Characterization of a Family of Air-Stable Ferrocene- and Ruthenocene-Containing Primary, Secondary, and Tertiary Phosphines

“…However, many phosphines, including primary and secondary examples, exhibit exceptional stability towards oxygen. 3,4 Among the most common strategies for the stabilization of phosphines through synthetic variation are the incorporation of steric bulk (e.g., 1), 4a,4b,4e the design of molecules with relatively high energy singly occupied molecular orbitals (SOMOs) for their radical cation forms (e.g., 2), 4h,4k,4l,4n and the installation of heteroatoms in close proximity to phosphorus leading to localization of the highest occupied molecular orbitals (HOMOs) away from phosphorus (e.g., 3). 4c,4d,4o Phosphines bearing ferrocene (Fc) substituents combine the desirable characteristics of phosphines and ferrocene, and often exhibit surprising stability towards air and moisture.…”

New ferrocene-derived hydroxymethylphosphines: FcP(CH2OH)2 [Fc=(η5-C5H5)Fe(η5-C5H4)] and the dppf analogue 1,1′-Fc′[P(CH2OH)2]2 [Fc′=Fe(η5-C5H4)2]

“…Hydroxymethylphosphines, containing PCH 2 OH groups, have been known for many years [1] but are attracting recent interest for their versatile reactivity [2] and ability to render metal complexes water-soluble, with uses ranging from catalysis, [2,3] metal complex immobilisation [4] and biomedical applications. [2,5] We have reported the first example of a ferrocene-derived hydroxymethylphosphine, FcCH 2 P(CH 2 OH) 2 , and some derivatives thereof.…”

“…[2,5] We have reported the first example of a ferrocene-derived hydroxymethylphosphine, FcCH 2 P(CH 2 OH) 2 , and some derivatives thereof. [6] In separate recent reports, cyclophosphazene derivatives of the phosphine sulfide FcCH 2 P(S)(CH 2 OH) 2 [7] and the methyl-substituted derivative FcCH(Me)P(CH 2 OH) 2 [8] have been studied.…”

“…[6] In separate recent reports, cyclophosphazene derivatives of the phosphine sulfide FcCH 2 P(S)(CH 2 OH) 2 [7] and the methyl-substituted derivative FcCH(Me)P(CH 2 OH) 2 [8] have been studied. In this Communication we report the synthesis of two new ferrocenyl hydroxymethylphosphines, FcP(CH 2 OH) 2 The X-ray structure determination of 1 ‡ was carried out to unambiguously confirm the formulation of the compound as the bis(hydroxymethyl)phosphine, and the molecular structure is shown in Fig. 1.…”