xviii, 724 p. : ill. (some col.) / Structural trends applicable to crystal engineering were studied in three classes of thiourea-based compounds. The aim of the study was to identify, predict, and ultimately design reliable single-molecule structural features, which could then be used to engineer crystals with desirable properties. In one class of compounds, this goal was achieved: N-alkyl and N-aryl derivatives of N,N'-bis(3-thioureidopropyl)piperazine adopted an identical conformation in the solid state, which resulted in near-identical crystal packing. A second class of closely related compounds, N-substituted tris(2-thioureidoethyl)amines, showed no such reliability in the solid state, likely because the parent structure lacked hydrogen-bonding functionalities sufficient to control intramolecular structure. In the third class of compounds that we studied, 1-benzoyl-3-(2-pyridyl)thioureas, substitution patterns were often predictive of molecular conformation; however, these intramolecular trends did not lead to recognizable crystal packing motifs. Nevertheless, certain physical properties observed in this last class of compounds--color, solubility, and often crystallinity--were conformer-specific, interestingly without any apparent relevance to crystal lattice structure. Solution-state and solid-state conformational trends in these 1-benzoyl-3-(2-pyridyl)thioureas have been documented, and speculations as to the source of color in one of the two observed conformations have been noted. / Committee in charge: Shih-Yuan Liu, Chairperson; Kenneth M. Doxsee, Advisor; Michael M. Haley, Member; Catherine J. Page, Member; Paul J. Wallace, Outside Member

Thesis (MSc)--Stellenbosch University, 2003. / ENGLISH ABSTRACT: In this study, a number of mono- and di-substituted acyl(aroyl)thioureas were investigated for potential application as specific carriers (ionophores) for the transport and extraction of Ag(l) from a mixture of Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Pb(lI) ions. The experimental arrangement for the transport experiments employed a liquid membrane set up involving a 3-phase system - 2 aqueous phases (source and receiving phase) separated by a chloroform membrane incorporating the ligand. Competitive metal ion transport experiments were conducted using the liquid membrane set up. The aqueous source and receiving phases were analyzed using Atomic Absorption Spectroscopy (AAS) and results were confirmed by Inductively Coupled Plasma-Optical Emission Spectroscopy (ICPOES). The transport results show that the N,N-dialkyl-substituted-N'-acyl(aroyl) (HL) thioureas studied, with the exception of the N,N-di-(2-hydroxyethyl)-N'-benzoylthiourea (HL3 ) and N-piperidyl-N'-4-nitrobenzoylthiourea (HL9 ), were efficient and selective for Ag(I). HL9 was also selective for Ag(l) but not efficient. HL3 was selective for Cu(II). Under the experimental conditions employed, 13% Cu(lI) was transported by HL3 . Among the N,Ndialkyl- N'-aroylthioureas, maximum Ag(l) transport was obtained by using N,N-diethyl-N'-4- chlorobenzoylthiourea (HL5 ) and N,N-di-n-butyl-N'-benzoylthiourea (HL \ Under the experimental conditions employed, the percentages of Ag(l) transported by HL5 and HL 1 were 48% and 42% respectively. The transport selectivity and efficiency of 3,3,3' ,3'-tetraethyl-1 ,1'-isophthaloylbisthiourea (H2L12 ) and N,N-diethyl-N'-camphanoylthiourea (HL13)for Ag(l) were also studied. We were particularly interested, in comparing the Ag(l) transport and extraction efficiency of these ligands with that of the HL and H2L ligands. The experimental results reveal that, of all the ligands we investigated in this study, HL 13 was the most efficient and selective carrier for Ag(l) transport. The interesting result is that, depending on the ligand concentration used, HL 13 transported 71-81% of Ag(I). Competitive two-phase metal ion solvent extraction experiments were also performed under conditions similar to the transport studies. The results show that by varying the ligand concentration in the membrane phase, up to 100% Ag(l) can be selectively and efficiently extracted from the mixture of the seven metal ions. Finally, the N,N-di-(n)-butyl-N'-benzoylthiourea (HL1) ligand and its complex with Ag(l) were synthesized. Single crystals of the complex were grown for X-ray crystallography and the crystal and molecular structure of the complex was determined. The crystal structure showed that Ag(l) is bonded to the deprotonated ligand through the S,O atoms forming interesting cluster [Ag (L - S, 0)] 4 in the solid state. This structure is monoclinic and crystallizes in the space group P21!c with a = 17.805 (4) A, b = 21.759 (4) A, c = 36.438 (7) A, f3= 96.34(3)°, Z = 8 and a final R-factor of 5.4%. / AFRIKAANSE OPSOMMING: In hierdie proefskrif is 'n aantal mono- en di-gesubstitueerde asiel(ariel) tioureums ondersoek vir moontlike gebruik as ionofore (spesifieke draers) vir die transportasie en ekstraksie van Ag(l) vanuit 'n mengsel van Co(ll), Ni(II), Cu(II), Zn(II), Cd(II), Ag(l) en Pb(lI) ione. 'n Drie-fase selsisteem is gebruik vir die transportasie eksperimente, twee waterige fases (bron- en ontvang-fase) wat geskei is met die chloroform membraan fase wat die ligande bevat. Kompeterende metaalioon transportasie eksperimente is uitgevoer met behulp van hierdie vloeistof membraan stelsel. Die twee waterige fases is deur middel van Atoomabsorpsie Spektroskopie (AAS) ge-analiseer en resultate is bevestig met gebruik van Induktief-gekoppelde Plasma-Optiese Emissie Spektroskopie (IGP-OES). Die resultate het getoon dat elkeen van die N,N-dialkiel-gesubstitueerde-N'-asiel(ariel) (HL) tioureums, met uitsondering van N,N-di(2-hidroksie-etiel)-N'-benzieltioureum(HL 3) en Npiperidiel- N'-4-nitrobenzieltioureum(HL9 ), doeltreffend en selektief was vir Ag(l) transportasie. HL9 was selektief vir Ag(I), maar die transportasie waarde was nie hoog nie, dws. dit was nie doeltreffend nie. HL3 was selektief vir Cu(II). Met gebruik van ons eksperimentele kondisies is 13% Cu(lI) getransporteer deur HL 3. Van die N,N-dialkiel-N'- ariel tioureums, is maksimum transportasie van Ag(l) verkry met gebruik van N,N-dietiel- N'-4-chlorobenzieltioureum (HL5) en N,N-di-n-butiel-N'-benzieltioureum (HL1). Met gebruik van ons eksperimentele kondisies was die persentasie transportasie van Ag(l) deur HL5 en HL 1 48% en 42% onderskeidelik. Die selektiwiteit en doeltreffendheid van 3,3,3' ,3'-tetra-etiel-1 ,t-isoftaltelblstioureumtl+L 12) en N,N-di-etiel-N'-kamfonieltioureum (HL13) vir Ag(l) transportasie is ook onderneem. Ons was besonder ge-interesseerd om die Ag(l) transportasie en ekstraksie van hierdie ligande te vergelyk met dié van die HL en H2L tipe ligande. Die eksperimentele resultate het getoon dat van al die ligande wat bestudeer is, HL 13 die doeltreffendste en mees selektiewe ionofoor was. Van besondere, belang was dat, afhangend van die ligand konsentrasie wat gebruik is, HL13 71-81% Ag(l) getransporteer het. Kompeterende twee-fase metaalioon vloeistof-vloeistof ekstraksie eksperimente is ook uitgevoer onder toestande soortgelyk aan dié van die transportasie eksperimente. Die resultate toon dat met varierende ligand konsentrasie, tot soveel as 100% Ag(l) selektief en doeltreffend geëkstrakeer word vanuit 'n mengsel van die sewe metaal ione. N,N-di-n-butiel-N'-benzieltioureum (HL1 ) ligande en die kompleks daarvan met Ag(l) is ook gesintetiseer. Enkel-kristalle van die kompleks is verkry en X-straal kristallografiese analiese is onderneem. Die kristalstruktuur toon hoedat Ag(l) gebind is aan die gedeprotoneerde ligand deur die S en Q atome en toon ook interessante [Ag(L-S,Q)]4 groepe in die vaste toestand. Hierdie struktuur is monoklinies en kristaliseer in die ruimtegroep P21!c met a = 17.805(4) Á, b = 21.759(4)Á, c = 36.438(7)Á, P = 96.34(3t, z = 8 en 'n finale R-faktor van 5.4%.

published_or_final_version / Chemistry / Master / Master of Philosophy

Small molecule synthesis has become a valuable tool in the study of biological systems. Biologically active compounds can be designed based on well-characterized endogenous systems or they can be found through the screening of large libraries of small molecules. This work involves the development of a small library of cyclic thiourea-based small molecules by use of an unreported synthetic pathway. Briefly, parent thioureas were cyclized by reaction with bromoacetyl bromide, and one or two isomeric heterocycles were found to form. Further studies indicated that the reaction could be easily manipulated by temperature or solvent to effectively control the product distribution. These iminothiozolidinones were characterized by single crystal x-ray analysis. The new reaction was explored in an effort to uncover the factors influencing the control of the isomer formation. Furthermore, these iminothiozolidinones underwent a novel decyclization reaction that resulted in the loss of the parent thiourea connectivity and incorporation of an external nucleophile to yield an aminooxoethylcarbamothionate. The reaction proceeds through a termolecular mechanism. These reactions can be combined to a one-pot reaction series. These compounds share similarities with a class of compounds reported to be known HIV-1 reverse transcriptase inhibitors94. In addition to these new synthetic reactions, work was conducted with a previously developed cyclen thiourea receptor for the anionic dye HPTS and its derivatives50-52. This system was used to develop a cell labeling assay that led to the amplification of fluorescent labeling of target cells through the use of liposomes. Briefly, a dye-ligand conjugate for the glycine receptor was synthesized. Liposomes functionalized with the cyclen receptor were prepared encapsulating Rhodamine B. Confocal microscopy studies demonstrated the binding of the HPTS-ligand to the cell membranes. Addition of the liposomes resulted in quenching of the green fluorescence, indicating binding of the cyclen to HPTS. Subsequent excitation of Rhodamine B showed red fluorescence associated with the cells. The intensity of the red signal was demonstrably higher than for the signal resulting from the binding of the ligand-dye to the receptor. Together, these projects increase the synthetic usefulness of thiourea based small molecules and demonstrate the potential biological applications of related compounds.

"October, 2005" / Coursework / Bibliography: leaves 97-105. / xvi, 136 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (D.Clin.Dent.)--University of Adelaide, Dental School (Endodontics), 2005

Submitted by Marcos Akio Ono (dr.marcosono@gmail.com) on 2018-08-22T19:44:11Z No. of bitstreams: 1 Dissertação para impressão.pdf: 1029289 bytes, checksum: a1d633fffa89289013b2b320e32ecbeb (MD5) / Approved for entry into archive by Silvana Alvarez null (silvana@ict.unesp.br) on 2018-08-24T13:48:01Z (GMT) No. of bitstreams: 1 ono_ma_me_sjc.pdf: 1029289 bytes, checksum: a1d633fffa89289013b2b320e32ecbeb (MD5) / Made available in DSpace on 2018-08-24T13:48:01Z (GMT). No. of bitstreams: 1 ono_ma_me_sjc.pdf: 1029289 bytes, checksum: a1d633fffa89289013b2b320e32ecbeb (MD5) Previous issue date: 2018-06-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo desse estudo foi avaliar o efeito da tiouréia (T) como um catalisador químico na eficiência clareadora do peróxido de hidrogênio. Para tal, foram misturados dentro de um frasco Becker uma associação de cromógenos (vinho tinto, tabaco e café), peróxido de hidrogênio em quantidade suficiente para que se obtivesse uma concentração final de 35%, solução de hidróxido de sódio para o ajuste de pH e concentrações variadas de tiouréia como catalisador químico. Foram testadas cinco diferentes concentrações de tiouréia (0,05%, 0,125%, 0,25%, 0,375% e 0,425%), sendo pH inicial de todas as associações ajustado para 7. Um grupo controle sem catalisador também foi avaliado. Após a mistura, a cor inicial das soluções e a concentração de peróxido foram avaliados empregando, respectivamente, espectrofotômetro colorimétrico e um titulador automático. As leituras foram repetidas após 30 minutos. A mudança na variação de cor (∆E) e o percentual de queda na concentração de peróxido após a reação foram analisados estatisticamente, assim como a correlação entre as duas variáveis foi avaliada. Os dados foram analisados utilizando os testes de ANOVA a um fator e Tukey. Diferenças significavas foram observadas para a variação de cor (p=0,0001) e para a concentração de H2O2 (p=0,0001). Os resultados do teste de Tukey para o ∆E foram: Controle (20,68 ± 2,14)a, T 0,05% (25,24±3,71)a, T 0,125% (56,23 ± 5,92)e, T 0,25% (50,01±5,04)d, T 0,375% (43,29± 3,24)c, T 0,425% (37,65± 3,28)b. Os resultados do teste de Tukey para o percentual de redução da concentração foram: Controle (0,59±0,53)a, T 0,05% (0,70±0,56)a, T 0,125% (4,76±1,28)c, T 0,25% (4,26±1,57)c, T 0,375% (2,50±0,72)b, T 0,425% (1,51±0,81)a. Concluiu-se que o uso da tiouréia aumentou significativamente o efeito clareador e o consumo do peróxido de hidrogênio durante a reação, com uma forte correlação positiva entre eles, tendo o máximo efeito sido constatado em a uma concentração 0,125% de tiouréia. / The aim of this study was to evaluate thiourea (T) effectiveness as a chemical catalyst on hydrogen peroxide bleaching efficiency. For that, an association of chromogens (red wine, tobacco and coffee) were mixed in a Becker bottle with hydrogen peroxide in sufficient amount to obtain a final concentration of 35%, sodium hydroxide solution for pH adjustment and a range of different concentrations of thiourea as a chemical catalyst. Five different concentrations of thiourea were tested (0.05%, 0.125%, 0.25%, 0.375% and 0.425%), with the pH adjusted to 7. A control group without a catalyst was also evaluated. After mixing, the baseline color of the solutions and the peroxide concentration were evaluated using a colorimetric spectrophotometer and an automatic titrator. The readings were repeated after 30 minutes. The color change (ΔE) and the percentage of peroxide concentration reduction after the reaction were statistically analyzed, as well as the correlation between the two variables. Data were analyzed using one-way ANOVA and Tukey´s test. Significant differences were observed for the color change (p = 0.0001) and for the H2O2 concentration (p = 0.0001). The results of the Tukey´s test for ΔE were: Control (20.68 ± 2.14)a, T 0.05% (25.24 ± 3.71)a, T 0.125% (56.23 ± 5,92)e, T 0.25% (50.01 ± 5.04)d, T 0.375% (43.29 ± 3.24)c and T 0.425% (37.65 ± 3.28)b. The results of the Tukey´s test for the percentage of peroxide reduction were: Control (0.59 ± 0.53)a, T 0.05% (0.70 ± 0.56)a, T 0.125% (4.76 ± 1.28)c, T 0.25% (4.26 ± 1.57)c, T 0.375% (2.50 ± 0.72)b, T 0.425% (1.51 ± 0.81)a. It was concluded that thiourea significantly increased the bleaching effect and the consumption of hydrogen peroxide during the reaction, with a strong positive correlation between them, with a maximum effect when 0.125% of thiourea was used. / CAPES / Demanda Social 02/2016 a 08/2017

Orientador: Carlos Rocha Gomes Torres / Banca: Taciana Marco Ferraz Caneppele / Banca: Andréa Anido Anido / Resumo: O objetivo desse estudo foi avaliar o efeito da tiouréia (T) como um catalisador químico na eficiência clareadora do peróxido de hidrogênio. Para tal, foram misturados dentro de um frasco Becker uma associação de cromógenos (vinho tinto, tabaco e café), peróxido de hidrogênio em quantidade suficiente para que se obtivesse uma concentração final de 35%, solução de hidróxido de sódio para o ajuste de pH e concentrações variadas de tiouréia como catalisador químico. Foram testadas cinco diferentes concentrações de tiouréia (0,05%, 0,125%, 0,25%, 0,375% e 0,425%), sendo pH inicial de todas as associações ajustado para 7. Um grupo controle sem catalisador também foi avaliado. Após a mistura, a cor inicial das soluções e a concentração de peróxido foram avaliados empregando, respectivamente, espectrofotômetro colorimétrico e um titulador automático. As leituras foram repetidas após 30 minutos. A mudança na variação de cor (∆E) e o percentual de queda na concentração de peróxido após a reação foram analisados estatisticamente, assim como a correlação entre as duas variáveis foi avaliada. Os dados foram analisados utilizando os testes de ANOVA a um fator e Tukey. Diferenças significavas foram observadas para a variação de cor (p=0,0001) e para a concentração de H2O2 (p=0,0001). Os resultados do teste de Tukey para o ∆E foram: Controle (20,68 ± 2,14)a, T 0,05% (25,24±3,71)a, T 0,125% (56,23 ± 5,92)e, T 0,25% (50,01±5,04)d, T 0,375% (43,29± 3,24)c, T 0,425% (37,65± 3,28)b. Os resultado... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of this study was to evaluate thiourea (T) effectiveness as a chemical catalyst on hydrogen peroxide bleaching efficiency. For that, an association of chromogens (red wine, tobacco and coffee) were mixed in a Becker bottle with hydrogen peroxide in sufficient amount to obtain a final concentration of 35%, sodium hydroxide solution for pH adjustment and a range of different concentrations of thiourea as a chemical catalyst. Five different concentrations of thiourea were tested (0.05%, 0.125%, 0.25%, 0.375% and 0.425%), with the pH adjusted to 7. A control group without a catalyst was also evaluated. After mixing, the baseline color of the solutions and the peroxide concentration were evaluated using a colorimetric spectrophotometer and an automatic titrator. The readings were repeated after 30 minutes. The color change (ΔE) and the percentage of peroxide concentration reduction after the reaction were statistically analyzed, as well as the correlation between the two variables. Data were analyzed using one-way ANOVA and Tukey's test. Significant differences were observed for the color change (p = 0.0001) and for the H2O2 concentration (p = 0.0001). The results of the Tukey's test for ΔE were: Control (20.68 ± 2.14)a, T 0.05% (25.24 ± 3.71)a, T 0.125% (56.23 ± 5,92)e, T 0.25% (50.01 ± 5.04)d, T 0.375% (43.29 ± 3.24)c and T 0.425% (37.65 ± 3.28)b. The results of the Tukey's test for the percentage of peroxide reduction were: Control (0.59 ± 0.53)a, T 0.05% (0.70 ± 0.56)a... (Complete abstract click electronic access below) / Mestre

Pleiomaltinine is an alkaloid-pyrone natural product that was the first of its kind to be isolated in nature. Synthesis of this compound from pleiocarpamine and a reactive quinone methide-like pyrone is described. Furthermore, model compounds have been made that will allow for full testing of this new heterocycle’s biological properties. This process has also been rendered enantioselective using asymmetric organocatalysis with thioureas. Additionally, work has been conducted towards the total synthesis of vinylallene-derived natural products. Progress towards the syntheses of chloropupukeananin, chloropestolide A, pestalofone C, iso-A82775c, and maldoxin isolated from Pestalotiopsis fici are described. All of these compounds are complex and possess biological activities including anti-cancer and anti-HIV. The strategies applied to develop a selective synthesis of reactive vinylallenes are discussed and plans designed to overcome this synthetic challenge are shown in detail. New methodologies are presented along with literature precedent in these areas of research.

Onychomycosis is fungal infection of toe nails or fingernails caused by a fungal microbe that invades the nail bed. It is the most common disease of the nails and constitutes about a half of all nail abnormalities and may affect toenails or fingernails, but toenail infections are particularly common. It occurs in about 10 percent of the adult population. The most common symptoms of fungal nail infection are thickening and discoloration of the nail. Treatment of onychomycosis is challenging because the infection is embedded in the nail making it difficult for the drug to diffuse to the site of infection. Onychomycosis is an opportunistic infection in people with compromised immune function and in those with diabetes, psoriasis, HIV/AIDS etc. Onychomycosis affects patients’ physical and psychological health and has a negative impact on overall quality of life. Oral administration of antifungal agents has been the mainstay in treatment of onychomycosis such as griseofulvin, terbinafine and itraconazole, but has limitations of systemic adverse events and drug interactions, whereas several drugs have been approved for topical administration but their efficacy is limited by the low permeability of the nail plate. This study evaluated the preformulation transungual permeability of econazole nitrate and formulation development of a transungual topical patch utilizing penetration enhancers in combination with econazole nitrate to optimize the delivery and penetration through the nail. The objectives of this project were to: 1) determine the critical factors for the in vitro transungual delivery of econazole nitrate, 2) design and develop a transungual formulation containing econazole nitrate and selection of the penetration enhancers, and 3) characterize the physical characteristics and functional properties of a novel transungual formulation. There were ten penetration enhancers being screened in this project according to the enhancement for saturation solubility, in vitro nail penetration and in vitro skin permeation and penetration of the antifungal drug econazole nitrate. Unlike transdermal drug delivery, the selection requirements for skin penetration enhancer were to increase drug accumulation in the epidermis and decrease the amount in the dermis to avoid unnecessary systermic absorption (Palliyil, et al. 2013). Thiourea (TU) improved the solubility and nail penetration of econazole nitrate. It also produced enhancement in the transungual diffusion of the drug. It was selected as the nail permeation enhancer and skin penetration enhancer for econazole nitrate. In the pH study, pH 5 ammonium phosphate buffer was the most effective pH for both enhancing the amount of drug in the nail and decreasing keratin binding. This resulted in increased accumulated of free drug in the target nail. In the formulation screening study, pressure sensitive adhesives (PSA), polyisobutylene, polysiloxane and polyacrylate classes of adhesives, were screened to develop a monolithic drug-in-adhesive type nail patch. Increasing the concentration of TU from 1% to 2.5% resulted in drug crystallization in the dry patch, therefore the concentration of 1% (w/w) TU was selected for all further screening. The concentration of econazole nitrate, propylene glycol and triethyl citrate were screened at 2.5%, 10% and 10% accordingly to ensure high drug release rate with no drug crystallization. The in vitro drug release rate of EN from the patch was improved with propylene glycol and hydrophobic plasticizer triethyl citrate. Polyvinylpyrrolidone was added to the patch formulation to lower the pH of the patch. This resulted in a greater concentration of ionized EN. The nail permeation and penetration of EN were studied in vitro using human cadaver toenails mounted in Franz diffusion cells. Thiourea, when formulated in the novel nail patch, was shown to deliver higher amount of EN into target tissues with a shorter permeation lag time compared to formulations which did not utilize thiourea. / Pharmaceutical Sciences

This thesis is divided into three main results chapters that reflect the path my research took. In the first results chapter, the first organocatalyst for the carbonyl-ene reaction was discovered and found to give high conversion using 1,3-bis(3,5-bis(trifluoromethyl)phenyl)thiourea. Various carbonyl and alkene precursors were examined in the ene reaction in both catalysed and uncatalysed reactions. It was found that ene reactions using fluoral and ethyl trifluoropyruvate give higher rates of reaction when compared to other carbonyl compounds. A novel enantiopure thiourea was synthesised and the ene reaction was catalysed enantioselectively to 33% e.e. In an attempt to catalyse the reaction to a further extent a new thiourea bonded to a P(=S)R2 group was developed. However, the intramolecular hydrogen bonding of this catalyst was thought to be so strong that this it did not catalyse the reaction. The synthesis of a chiral phosphoric acid was achieved but this was an unsuccessful catalyst in the ene reaction. Two component achiral thiourea and chiral acids were also examined in the ene and Mannich-type reaction. The new easily synthesised thiourea for this reaction has an interesting intermolecular hydrogen bonding coordination in the solid state. Asymmetric fluorination of ketoesters using palladium is a dynamic kinetic resolution. In the 2nd chapter cationic palladium complexes were synthesised and used to determine the optimum parameters for bidentate ligands in this reaction. Four carbon chain phosphines were found to give the highest conversion for this reaction among those ligands tested such as 1,4-bisdiphenylphosphinobutane (bite angle 99º). A new bis-phosphinous amide chiral ligand was developed with a bite angle of 96.7º. The dichloropalladium complex of this phosphine was isolated and structurally characterised. The use of the palladium complex in asymmetric fluorination was attempted however this was found to be unsuccessful. Mechanistic studies reveal that the formation of the desired cationic catalyst did not occur under conditions shown to work well for other palladium phosphine complexes. The ligand was investigated further in hydrogenation reactions. The phosphinous amide was protected as its borane and was used in the rhodium catalysed hydrogenation of alkenes to give high conversion and up to 93% e.e. The borane protected phosphinous amide was also found to catalyse the hydrogenation of acetophenone using copper complexes with up to 84% e.e for the hydrogenation of acetophenone, although conversion was quite low.