Phosphines bisphosphines

A number of structural studies of iminophosphoranes have been reported. These include the product obtained from the reaction of phosphine (bisphosphine sulphide) (31) with p-tolyl azide which on the basis of its iH and iP n.m.r. exists in the C-ylide form (32) rather than as an iminophosphorane.16 Treatment of (32) with base gave the relatively stable iminophosphorane anion (33) which was isolated as a Rh(l) complex. The molecular structures of the iminophosphoranes (34),17 (35),1 and (36)19 have been determined by X-ray crystallography and their structural parameters compared with those determined for l,8-bis(dimethylamino)-... 

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 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... 

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. 

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. 

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]. 

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]. 

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 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]. 

The best phosphines found so far are bisphosphines of the general formula R2P(CH2) PR2, where n = 2 or 3 and R = aryl groups. Examples of some very good ligands are 1,2-bis(diphenylphosphino)ethane (32) and 1,2-bis(diphenylphosphino)propane (33) ... 

The number of phosphine ligands on the active catalyst system is also subject to speculation. In Scheme 9 Hata postulated an active complex consists of only one chelating phosphine. However, he (66) and others (70, 71, 83) also observed that 2 moles of the bisphosphine 32 per mole of Co are needed for best selectivity. Sarafidis (55) suggested that a more desired structure might consist of two bisphosphines, with one of the Co—P bonds having the ability to dissociate to provide coordination sites for incoming monomers (see structure 34). 

A number of chiral phosphine ligands has also been reported (Figure 4). Zhang and co-workers described binaphthalene phosphine 44 with a pyridine moiety to afford the addition product with up to 92% ee.50,50a With chiral bisphosphine 45, Imamoto et al. got only moderate enantioselectivity for the addition of cyclohexenone,... 

The asymmetric hydrosilylation that has been most extensively studied so far is the palladium-catalyzed hydrosilylation of styrene derivatives with trichlorosilane. This is mainly due to the easy manipulation of this reaction, which usually proceeds with perfect regioselectivity in giving benzylic silanes, 1-aryl-1-silylethanes. This regioselectivity is ascribed to the formation of stable 7t-benzylpalladium intermediates (Scheme 3).1,S Sa It is known that bisphosphine-palladium complexes are catalytically much less active than monophosphine-palladium complexes, and, hence, asymmetric synthesis has been attempted by use of chiral monodentate phosphine ligands. In the first report published in 1972, menthyldiphenylphosphine 4a and neomenthyldiphenylphosphine 4b have been used for the palladium-catalyzed reaction of styrene 1 with trichlorosilane. The reactions gave l-(trichlorosilyl)-l-phenylethane 2 with 34% and 22% ee, respectively (entries 1 and 2 in Table l).22 23... 

In contrast to the free-radical polymerizations, there have been relatively few studies on transition metal catalysed polymerization reactions in water. This is largely due to the fact that the early transition metal catalysts used commercially for the polymerization of olefins tend to be very water-sensitive. However, with the development of late transition metal catalysts for olefin polymerizations, water is beginning to be exploited as a medium for this type of polymerization reaction. For example, cationic Pd(II)-bisphosphine complexes have been found to be active catalysts for olefin-CO copolymerization [21]. Solubility of the catalyst in water is achieved by using a sulfonated phosphine ligand (Figure 10.5) as described in Chapter 5. 

Hydroxy-phosphines undergo benzoylation with o-sulfobenzoic anhydride in the presence of bases (Na2C03 or BuLi) affording sulfobenzoylated phosphine products. In such a way several mono- and dihydroxy phosphines could be made soluble in water, exemplified by the chiral bisphosphines 53. It should be noted, that this general method allows the preparation of water-soluble sulfonated derivatives of acid-sensitive phosphines, such as DIOP, too, which are not accessible via direct sulfonation [56]. 

The sulfonated atropisomeric bisphosphine MeOBIPHEP (48) was prepared in a Grignard reaction of the appropriate bisphosphonic dichloride and p-indolylsulfonamido-bromobenzene followed by reduction of the phosphine oxide with HSiCU [52]. The indolylsulfonyl protecting group was... 

Palladium catalyzed P-C ctoss coupling [58] between primary or secondary phosphines and appropriate aryl iodides made possible the preparation of several aminophenyl-phosphines with the general formula 70 and also the bisphosphine 71. 

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