Phosphine oxides bisphosphine

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 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... 

Phosphine oxides are similar excellent orf/zo-directors which have seen only limited use so far. The iodide 123, for example—a precursor of a new class of bisphosphine ligands—can be made by cooperatively-directed ortholithiation of the phosphine oxide 122, itself derived by halogen-metal exchange from 121 (Scheme 53) . 

Bidentate oxygen-donor extractants include the neutral diamide compounds, such as the malonamides used in the French DIAMEX and DIAMEX-SANEX processes, RR N(C=0)-CHR"-(C=0)NRR the bisphosphine oxides, RR (P=0)- CIIR"-(P=0) RR the carbamoyl-(methyl)-phosphinates, R0R 0(P=0)-(CI I On o 0rr(C=0)NRR or the more efficient carbamoyl-methyl-phosphine oxides, RR (P=0)-CHR"-(C=0)... 

A chiral bisphosphine containing two ferrocene moleeules has been prepared using Ugi s lithiation as a key step (Scheme 2-9) [20]. Thus, the diphenylphosphinyl group is introduced at the ferrocenylmethyl position of the iodide obtained from lithiated ferrocene 2. Oxidative coupling of the iodoferrocene followed by reduction of the phosphine oxide gives the bisferrocene-bisphosphine 15. The bisphosphine is unique in that a tra j-chelate is formed on its coordination to a metal. 

A chiral bisphosphine that is analogous to BINAP but that contains a biferrocenyl backbone has been obtained by optical resolution of the corresponding phosphine oxide [22]. 

Miscellaneous Systems Many systems have been mentioned [li,m,2i] acyloxy and acylsilyl phosphine oxides, phosphine sulfides, cyclic compounds, benzoyloxa-ziridine derivatives, dibenzoylmethane derivatives, triazene and pentaazadiene moiety containing compounds. New developments include benzyl benzoin benzyl ethers [112], dithiocarbamates [113], ketoamides [114], phosphonates [115], bromo-acetylpyrene [116], alkylimides [117], aryloxy naphthalene [118], oligosilanes [119], bisphosphine sulfides [120], sulfamic esters of benzoin ethers [121], sulfur [122], or carbohydrate [123] containing compounds. 

Enantiomerically pure Norphos derivatives were synthesized and used as chiral bisphosphine ligands for the catalyst system Pd(dba)3 CHCI3/ PhC02H in the intramolecular hydroamination of aminoalkynes. The synthetic approach to the racemic bis(phosphine oxide) precursor of Methyl Norphos is shown in Scheme 7. ... 

Close attention has been devoted in recent years to the homogeneous catalytic reduction of N-acylaminoacrylic acids with the aid of chiral Rh-complexes. In some cases exceptionally high optical yields have been achieved in these reactions. Phosphine-Rh catalysts of the DIOP type, i. e. with chiral carbon skeleton, have been used 108, 109, 133,142,145, 146, 172, 193, 194, 234), as have catalysts with phosphine oxide ligands 409), ferrocenyl-phosphine-Rh complexes 171), bisphosphine-Rh complexes with a chiral pyrrolidine ring 3, 4), systems with chiral phosphines 216—221) and bisphosphines (222), or with a chiral P- and C-skeleton 130). 

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]. 

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]. 

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. 

In the case of phosphine, the active catalyst is presumably either bisphosphine dicarbonyl or the phosphine tricarbonyl complex. Kinet-ically the bis-phosphine nickel complex cannot be the predominant species. However, in the presence of very high phosphine concentration it may have an important role in the catalyst cycle. After ligand loss and methyl iodide oxidative addition, both complexes presumably give the same 5 coordinate alkyl species. 

Strengthening of the Ni-C bond by electron charge donation of a trans phosphine ligand in the bisphosphine complex (equation 18) retards the elimination of CO prior to the oxidative step (30, 31). This is not the case for the phosphine nickel tricarbonyl (equation 19) where carbon monoxide is easier to eliminate (32). 

The chromium carbonyl linkers 1.40 (98) and 1.41 (99) were prepared from commercial triphenylphospine resin and respectively from pre-formed p-arene chromium carbenes and Fischer chromium amino carbenes. Their SP elaboration is followed by cleavage with pyridine at reflux for 2 h (1.40) and with iodine in DCM for 1 h at rt (1.41) both linkers produce the desired compounds in good yields. A similar cobalt carbonyl linker 1.42 (100) was prepared as a mixmre of mono- (1.42a) and bis- (1.42b) phosphine complex, either from pre-formed alkyne complexes on triphenylphosphine resin or by direct alkyne loading on the bisphosphine cobalt complex traceless cleavage was obtained after SP transformations by aerial oxidation (DCM, O2, hp, 72 h, rt) and modified alkynes were released with good yields and... 

For the case of tri(o-tolyl)phosphine-ligated catalysts, the upper pathway appears to predominate. Oxidative addition occurs first via loss of a ligand from the bisphosphine precursor to form the oxidative adduct, which exists as a dimer bridged through the halogen atoms (equation 33). This dimer is broken up by amine, the coordination of which to palladium renders its proton acidic. Subsequent deprotonation by base leads to the amido complex, which can then reductively eliminate to form the product. When tert-butoxide is used as the base, the rate is limited by formation of and reductive elimination from the amido complex, while for the stronger hexamethyldisilazide, the rate-determining step appears to be oxidative addition. ... 

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