Bisphosphines

Much effort has been placed in the synthesis of compounds possessing a chiral center at the phosphoms atom, particularly three- and four-coordinate compounds such as tertiary phosphines, phosphine oxides, phosphonates, phosphinates, and phosphate esters (11). Some enantiomers are known to exhibit a variety of biological activities and are therefore of interest Oas agricultural chemicals, pharmaceuticals (qv), etc. Homochiral bisphosphines are commonly used in catalytic asymmetric syntheses providing good enantioselectivities (see also Nucleic acids). Excellent reviews of low coordinate (coordination numbers 1 and 2) phosphoms compounds are available (12). 

The Gabriel synthesis represents another indirect but highly valuable approach to amines. Trost has demonstrated a method for the asymmetric ring-opening of butadiene monoepoxide by use of one equivalent of phthalimide, 7t-allylpalladium chloride dimer, and the chiral bisphosphine 22 (Scheme 7.37). The dynamic kinetic asymmetric transformation proceeded through a putative achiral intermedi-... 

The coordinated silylenes in both the iron and the chromium compounds can be photolytically activated Photolysis of the complexes in the presence of triphenylphosphine gives the trans-silylene-phosphine complex, which in a second step is transformed into the trnns-bisphosphine compound by excess phosphine. If the silylenes are not trapped, polysilanes are isolated in almost quantitative... 

Biomedical and Catalytic Implications of Carboxylated Primary Bisphosphines. 136... 

This review account will summarize latest research results on the design, development and properties of functionalized primary phosphines. In particular, the focus would be centered around recent results from our laboratory on the chemical architecture of heteroatom functionahzed primary bisphosphines. We wiU also discuss synthetic protocols for the formylation reactions of functionalized primary phosphines to produce structurally diverse water-soluble hydroxymethyl phosphines. Finally, we will discuss the utility of carboxylate functionahzed primary bisphosphines for incorporation on to peptides and their potential apphcations in catalysis and biomedicine. 

Several different types of primary bisphosphines functionalized with mono-or diamides have been synthesized recently. The simplest among this series... 

The bisphosphonate - upon reduction with lithiumaluminum hydride in ether at 0°C - produced the amide functionalized primary bisphosphine (1) in good yields [45]. This reaction proceeded to reduce the amide group in 1 to produce the amine functionaUzed primary bisphosphine (2) in <5% yields. The amido bisprimary phosphine 1 is an air stable crystalline solid whereas the amine compound 2 is an oxidatively stable liquid. Separation of 1 and 2 in pure forms was achieved using coliunn chromatography. The amidic bisprimary phosphine 1 was crystallized from chloroform and exhibits remarkable stability not only in the solid state but also in solution as well. The crystal structure of the air stable primary his-phosphine 1 as shown in Fig. 1 is unprecedented to date. 

The thioether functionalized bisphosphonates, 7 and 8, upon reduction with LiAlH4 produced the corresponding S2P2 and S3P2 primary bisphosphine frameworks 9 and 10 respectively in good yields (Scheme 4) [47,48]. 

These thioether functionalized primary bisphosphines 9 and 10 showed modest oxidative stabilities and have found applications as novel precursors in the development of functionalized water-soluble phosphines via formylation reactions across P-H bonds (see below) [47]. 

The nucleophile assisted ring-opening reactions of phosphonate bearing phthahmide 13 has been utihzed in the synthesis of mixed primary phosphine-phosphonate and aromatic amide functionahzed primary bisphosphines as out-hned in Scheme 6 [50],... 

This approach makes use of bromopropyl phosphine 17 as a key synthon obtained via the reduction of 3-bromopropyl phosphonate with dichloroaluminum hydride [10]. Reaction of bromopropyl phosphine 17 with the dianion of 6,8-dithiooctanoic acid produced the -COOH functionalized P2S2-primary bisphosphine framework 18 in > 80% yields (Scheme 7) [10]. 

It is striking to note that the new generation of amide, thioether and car-boxylate functionalized primary bisphosphines, 1,10,16,18, and 19 as shown in Fig. 3, provide examples of primary bisphosphines with unprecedented oxidative inertness. 

In fact, the primary bisphosphines 1,10,16, and 19 (Fig. 3) are air stable solids demonstrating exceptional oxidative stabilities. Recently, a primary bisphosphine 20 produced by dimerization reaction of anthracenyl primary phosphine has been shown to possess good oxidative stability [29]. 

Prehminary AMI calculations carried out with the MOPAC program on 18 and related molecules suggest that there are atomic orbital contributions from the heteroatom (e.g., S in 18) to the frontier molecular orbitals. It is conceivable, therefore, that there is negative hyper conjugation involving specific orbitals of S and the P centers in 18. This electronic effect may explain the unusual stabiUty towards oxidation of 18 and other heteroatom functionaUzed primary bisphosphines as described above [51]. 

It is interesting to note that, despite drastic changes in the chemical frameworks of primary bisphosphines, there are minimal/no differences in the chemical shifts and coupling constants (Table 1). The proton coupled P NMR... 

The carboxylate functionalized primary bisphosphines P2S2COOH 18 and P2N2COOH 19 (Schemes 7 and 8) provide new opportunities for use in catalytic and biomedical motifs. The carboxylate groups in 18 and 19 can be used to conjugate these phosphine hgating units on to peptides or proteins. 

Functionally active preformed primary phosphines (e.g.,H2N(CH2)3PH2 3 or Br(CH2)3PH2 17) will provide important building blocks to functionaUze sim-ple/complex molecules with primary phosphine functionaUties. The user friendl/ nature of the air stable primary bisphosphines (e.g., 1,10,16,18-20) will open up new realms of exploratory research that utilize primary phosphines. It is also conceivable that the high oxidative stability and the ease with which primary phosphines can be incorporated on chiral backbones or peptides provide new opportunities for their appHcations in catalysis and biomedicine. 

Chapter 5 discusses recent developments in the synthesis and properties of primary phosphines. The utility of bromo and aminopropyl phosphines as well as that of carboxylate functionahzed primary bisphosphines, the latter for incorporation onto peptides and for their potential apphcations in catalysis, is under-hned by K. V. Katti, N. Pillarsetty and K. Raghuraman. 

The Wittig-Horner procedure, starting from bisphosphonate or aromatic bisphosphine oxide monomers, allows for AA/BB-coupling of the PO-activated bismethylene monomers, not only with aromatic dialdehydes but also with aromatic diketones to the corresponding PPV derivatives (76), and for the selfcondensation of AB-type aromatic starting compounds containing both alde-hyde/keto and PO-activated methylene functions [101]. 

The hydroboration of enynes yields either of 1,4-addition and 1,2-addition products, the ratio of which dramatically changes with the phosphine ligand as well as the molar ratio of the ligand to the palladium (Scheme 1-8) [46-51]. ( )-l,3-Dienyl-boronate (24) is selectively obtained in the presence of a chelating bisphosphine such as dppf and dppe. On the other hand, a combination of Pdjldba), with Ph2PC6p5 (1-2 equiv. per palladium) yields allenylboronate (23) as the major product. Thus, a double coordination of two C-C unsaturated bonds of enyne to a coordinate unsaturated catalyst affords 1,4-addition product On the other hand, a monocoordination of an acetylenic triple bond to a rhodium(I)/bisphosphine complex leads to 24. Thus, asymmetric hydroboration of l-buten-3-yne giving (R)-allenyl-boronate with 61% ee is carried out by using a chiral monophosphine (S)-(-)-MeO-MOP (MeO-MOP=2-diphenylphosphino-2 -methoxy-l,l -binaphthyl) [52]. 

Arylation of alkynes via addition of arylboronic acids to alkynes represents an attractive strategy in organic synthesis. The first addition of arylboronic acids to alkynes in aqueous media catalyzed by rhodium was reported by Hayashi et al.89 They found that rhodium catalysts associated with chelating bisphosphine ligands, such as 1,4-Ws(diphenyl-phosphino)butane (dppb) and 1,1 -/ E(diphenylphospliino)fcrroccnc... 

Riant et al. in 2006 reported an enantioselective reductive aldol reaction of acetophenone and methyl acrylate mediated by PhSiH3 (140 mol %) and catalyzed by a complex generated in situ from [CuF(Ph3P)3]2MeOH (1-3 mol %) and a chiral bisphosphine (1-3 mol %) [57]. According to Mori s... 

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