The phenyl ring in the crown ether, 13-phenyl-1,4,7,10-tetraoxa-13-azacyclopentadecane (I), was used a site for functionalizing the compound. Electrophilic bromination of the ring with tribromide ion gave a 95% yield of the product substituted in the para position. This product underwent lithium-bromine exchange when reacted with n-butyllithium. The resulting anion was used to prepare PhZPX and PhPX2 derivatives, X p-C6H4NCH2(CH2OCH2)4&12 The oxide of PhZPX was completely characterized by an x-ray diffraction study which showed, in general, that the phosphorus was tetrahedral, the nitrogen planar, and the crown ether ring organized with the oxygen atoms endodentate. Several attemps were made to nitrate or nitrosate the phenyl ring in the parent crown ether. Spectroscopic evidence obtained from the products indicate that the reaction led to mixtures of mono and disubstituted products. / Department of Chemistry

This study has resulted in a crown ether functionalized with both phosphine and phenol groups, 5-diphenylphosphino-1,3-xylyl-18-crown-5. The target molecule was obtained from a six step synthesis. 4-Bromophenol was treated in sequence with formaldehyde, dimethylsulfate, and phosphorus tribromide producing 4-bromo-2,6-bis(bromomethyl)anisole. The main intermediate, 5-diphenylphosphino-1,3-xylyl-18-crown-5, was obtained by treating 4-bromo-2,6-bis(bromomethyl)anisole in sequence with tetraethylene glycol, lithium iodide, and methyldiphenyl phosphonite. The lithium iodide cleaved the anisole-to-methyl group bond, and the methyldiphenyl phosphonite provided the phosphine group for the crown ether following a lithium bromine exchange reaction. The 31P NMR of the phosphine crown ether showed a single signal at 6 -5.9, showing consistency of a single product. The IH NMR of the phosphine crown ether in deuterated chloroform showed signals at 6 3.55-3.7 (crown CH2), 6 4.6 (benzylic CH2), 6 7.1 (d, J = 7.o Hz, crown aromatic CH2), and 6 7.2-7.4 (noncrown aromatic CH2). / Department of Chemistry

The phosphine(III) crown ethers, [4'-(N-phenylaza-15crown-5)]3P (1), [4'-(N-phenylaza-l8-crown-6)]3P (2), [4'-(Naza-18-crown-6)]2-Ph-P (3), and [4'-(benzo-15-crown-5)]3P (4) were synthesized by using an electrophilic bromination of the crown phenyl ring (with a tribromide ion) followed by the preparation of a lithium salt and subsequent reaction of the resulting lithiocrowns with P(III) reagents. The oxide of compound 1 was completely characterized by an X-ray diffraction study, which showed that structurally there is not a significant difference in P-O bond distances and OPC bond angles with [4'-(N-phenylaza-15-crown-5)]-Ph2-P=O. Thespectroscopic data of compound 1 and 2 were compared. It appears that 1 and 2 are similar in P environment; also they are more air sensitive than 3 and 4. In addition, a discussion about compounds 1-4, and a literature review of the preparation of phosphines are included. / Department of Chemistry

The ortho metallation of some aromatic ring systems has been investigated in regard to the influence of several types of phosphorus-centred directing groups upon the reactivity, regioselectivity, and utility in later synthetic elaboration. The metallation step allows derivatisation in several useful ways, offering several routes to the synthesis of novel chiral ditertiary phosphines. Thus, an ortho lithiation of N,N,N',N'-tetramethyl-P-phenylphosphonic diamide (10) led to the interesting primary phosphine, 2-(diphenylphosphino)phenylphosphine (14), after elaboration of the phosphonic diamide directing group. This primary phosphine undergoes an unprecedented facile phenyl group exchange process between its two phosphorus atoms, upon di-lithiation of the primary phosphorus centre. The primary phosphorus centre of (14) has been elaborated in several ways to yield new ditertiary phosphines. The alkylation of this centre in the copper(I) chelate complex has been investigated in several directions. In another direction, (14) has been chemically elaborated to give a new hybrid chiral ditertiary phosphine ligand, &quotSemiPHOS&quot, containing both a chiral phospholane ring and an adjacent diphenylphosphino group. SemiPHOS has been obtained in optically pure forms by a stereoselective synthesis and, independently, by a resolution procedure on its racemate. The molecular design of SemiPHOS was devised such that, when chelated to a metal atom, a subtle steric interaction appears to allow the chirality of the phospholane ring to influence the neighbouring diphenylphosphino group to adopt a complementary chiral conformation. This idea was tested and evaluated by applying SemiPHOS in catalytic asymmetric hydrogenations of (Z)-a-(Nacylamino) acrylate substrates to produce the R-amino acid precursors. Aryl species lithiated ortho to phosphorus-centred directing groups were coupled oxidatively by a convenient in situ method, to yield biaryl species that could then be elaborated to give biaryl ditertiary phosphine ligands. This method was used to make several atropisomeric chiral ditertiary phosphines.

The ortho metallation of some aromatic ring systems has been investigated in regard to the influence of several types of phosphorus-centred directing groups upon the reactivity, regioselectivity, and utility in later synthetic elaboration. The metallation step allows derivatisation in several useful ways, offering several routes to the synthesis of novel chiral ditertiary phosphines. Thus, an ortho lithiation of N,N,N',N'-tetramethyl-P-phenylphosphonic diamide (10) led to the interesting primary phosphine, 2-(diphenylphosphino)phenylphosphine (14), after elaboration of the phosphonic diamide directing group. This primary phosphine undergoes an unprecedented facile phenyl group exchange process between its two phosphorus atoms, upon di-lithiation of the primary phosphorus centre. The primary phosphorus centre of (14) has been elaborated in several ways to yield new ditertiary phosphines. The alkylation of this centre in the copper(I) chelate complex has been investigated in several directions. In another direction, (14) has been chemically elaborated to give a new hybrid chiral ditertiary phosphine ligand, &quotSemiPHOS&quot, containing both a chiral phospholane ring and an adjacent diphenylphosphino group. SemiPHOS has been obtained in optically pure forms by a stereoselective synthesis and, independently, by a resolution procedure on its racemate. The molecular design of SemiPHOS was devised such that, when chelated to a metal atom, a subtle steric interaction appears to allow the chirality of the phospholane ring to influence the neighbouring diphenylphosphino group to adopt a complementary chiral conformation. This idea was tested and evaluated by applying SemiPHOS in catalytic asymmetric hydrogenations of (Z)-a-(Nacylamino) acrylate substrates to produce the R-amino acid precursors. Aryl species lithiated ortho to phosphorus-centred directing groups were coupled oxidatively by a convenient in situ method, to yield biaryl species that could then be elaborated to give biaryl ditertiary phosphine ligands. This method was used to make several atropisomeric chiral ditertiary phosphines.

The ortho metallation of some aromatic ring systems has been investigated in regard to the influence of several types of phosphorus-centred directing groups upon the reactivity, regioselectivity, and utility in later synthetic elaboration. The metallation step allows derivatisation in several useful ways, offering several routes to the synthesis of novel chiral ditertiary phosphines. Thus, an ortho lithiation of N,N,N',N'-tetramethyl-P-phenylphosphonic diamide (10) led to the interesting primary phosphine, 2-(diphenylphosphino)phenylphosphine (14), after elaboration of the phosphonic diamide directing group. This primary phosphine undergoes an unprecedented facile phenyl group exchange process between its two phosphorus atoms, upon di-lithiation of the primary phosphorus centre. The primary phosphorus centre of (14) has been elaborated in several ways to yield new ditertiary phosphines. The alkylation of this centre in the copper(I) chelate complex has been investigated in several directions. In another direction, (14) has been chemically elaborated to give a new hybrid chiral ditertiary phosphine ligand, &quotSemiPHOS&quot, containing both a chiral phospholane ring and an adjacent diphenylphosphino group. SemiPHOS has been obtained in optically pure forms by a stereoselective synthesis and, independently, by a resolution procedure on its racemate. The molecular design of SemiPHOS was devised such that, when chelated to a metal atom, a subtle steric interaction appears to allow the chirality of the phospholane ring to influence the neighbouring diphenylphosphino group to adopt a complementary chiral conformation. This idea was tested and evaluated by applying SemiPHOS in catalytic asymmetric hydrogenations of (Z)-a-(Nacylamino) acrylate substrates to produce the R-amino acid precursors. Aryl species lithiated ortho to phosphorus-centred directing groups were coupled oxidatively by a convenient in situ method, to yield biaryl species that could then be elaborated to give biaryl ditertiary phosphine ligands. This method was used to make several atropisomeric chiral ditertiary phosphines.

Palladium complexes of bis(di-tert-butylphosphinomethyl)benzene (DTBPMB) show remarkably high activity as alkene methoxycarbonylation catalysts, in addition to numerous other catalytic conversions, and are currently being commercialised by Lucite in ethene methoxycarbonylation to methyl propanoate. Any large-scale exploitation of this catalyst system for heavier products, however, is likely to be hindered by catalyst-product separation problems common to homogeneous catalysts; hence modification of this catalyst system to allow facile product separation was investigated. Tethering of DTBPMB residues onto polystyrene via Suzuki-type coupling of suitable precursors onto bromopolystyrene and boronic acid functionalised polystyrene resins was investigated and the phosphine was successfully immobilised. Phosphination of the resins was not complete however and as such there is concern that other phosphine residues may be present which do not exhibit a bidentate binding motif. The synthesis of a potassium sulfonate derivative of DTBPMB (KBPMBS) was successful and immobilisation of this onto ion exchange resins was also investigated. Some preliminary results from studies into 1-octene methoxycarbonylation using palladium complexes of these resins were obtained. Supporting of this diphosphine onto silica via a sol-gel co-condensation methodology was also investigated; the synthesis of a suitably functionalised precursor containing a sulfonamide linkage was successful via protection of the diphosphine using borane. Although formation of the silica support was successful, attempts to deprotect the phosphine-borane resulted in cleavage of the ligand from the support. An alternative route to this supported ligand was attempted and others discussed. Synthesis of a suitable sol-gel precursor via alkene hydrosilation was also attempted and is discussed. Supporting of the sulfonated phosphine, KBPMBS onto silica functionalised with imidazolium tethered residues was also investigated, although complete leaching of the phosphine from the support by methanol washing was observed. Immobilisation of the synthesised KBPMBS ligand in an ionic liquid (IL) phase was investigated. Complex formation and catalytic activity were demonstrated and a positive effect on conversion was observed upon addition of carbon dioxide to the system; possibly due to the increased CO solubility within the IL phase. Efficient product separation from the IL-immobilised catalyst system was demonstrated, both by organic extraction and using supercritical carbon dioxide flow. However, poor catalyst stability under these conditions appears to present a barrier to recycling this system, with loss of conversion observed on catalyst recycling. Other attempts to immobilise the DTBPMB ligand are discussed and reduction of the sulfide derivative of DTBPMB was demonstrated using hexachlorodisilane, which could be used as a general synthetic strategy for protecting highly electron rich phosphines. It is possible that increasing the bulk of the DTBPMB ligand may increase catalyst stability and result in catalyst systems with higher turnover numbers. Therefore syntheses of bulky ligands based on the DTBPMB backbone were investigated. 1,2,4,5-tetrakis(di(tert-butyl)phosphinomethyl)benzene was successfully synthesised although palladium complexes of this showed no activity in catalytic methoxycarbonylation. Attempts to synthesise a related biphenyl-based tetraphosphine is also discussed, although isolation of this in a pure form was not achieved. Routes toward tetraphenyl and dimethyl-diphenyl functionalised derivatives of DTBPMB have also been explored, although only a monophosphine was isolated due to difficulties in obtaining an intermediate di(chloromethyl) precursor in both synthetic pathways, although this now appears to have been overcome.

This thesis describes the development of the [RuCl₂(P N N)L] catalytic system for asymmetric hydrogenation. It has been demonstrated that the current system is efficient in preparing a range of bulky chiral alcohols in good enantioselectivity, many of which are likely to be inaccessible using the more classic [RuCl₂(P P)N N)] system developed by Noyori and coworkers. It has been shown that the current system is tolerant of a range of substrate electronic effects as well as the presence of heteroaromatic functionality, thus showing its applicability in synthesis. This has been extended to prepare a number of bulky derivatives of synthetically important molecules. The demonstration of this is significant as in drug design, for example, studies that aim to extend lipophilicity or steric bulk make the ability to prepare alcohols across the full range of steric properties important. We have shown that chiral alcohols with adjacent gem-dimethyl groups can be prepared in high enantioselectivity and their conversion into other valuable molecules, such as chiral lactones has been demonstrated. Detailed mechanistic studies have been undertaken for the present system in order to aid rational design of new, more active and selective catalysts. A number of achiral variants of the original system have been prepared and the key features of ligand structure for efficient catalysis have been identified. This was accomplished by rigorous kinetic analysis of each complex, using specialist gas-uptake monitoring equipment. The key features of catalyst structure and optimal reaction conditions for efficient asymmetric hydrogenation have been identified. Our greater understanding of the present system allowed us to rationally design new catalysts of for enantioselective hydrogenation. Our aim was to be able to tune the catalyst structure to carry out hydrogenation of a greater variety of ketone substrate with high activity and selectivity. We have successfully prepared second generation catalysts that show enhanced enantioselectivity for a variety of substrates, many of which were problematic with the Noyori system.