Terence P. Kee

CHIRAL ALUMINIUM COMPLEXES AS PHOSPHO-TRANSFER CATALYSTS

Abstract Readily accessible, chiral complexes of aluminium are effective and enantioselective catalysts for the phospho-aldol reaction under aerobic conditions.

Multiplication of microbes below 0.690 water activity : implications for terrestrial and extraterrestrial life

Since a key requirement of known life forms is available water (water activity; aw ), recent searches for signatures of past life in terrestrial and extraterrestrial environments have targeted places known to have contained significant quantities of biologically available water. However, early life on Earth inhabited high-salt environments, suggesting an ability to withstand low water-activity. The lower limit of water activity that enables cell division appears to be ∼ 0.605 which, until now, was only known to be exhibited by a single eukaryote, the sugar-tolerant, fungal xerophile Xeromyces bisporus. The first forms of life on Earth were, though, prokaryotic. Recent evidence now indicates that some halophilic Archaea and Bacteria have water-activity limits more or less equal to those of X. bisporus. We discuss water activity in relation to the limits of Earths present-day biosphere; the possibility of microbial multiplication by utilizing water from thin, aqueous films or non-liquid sources; whether prokaryotes were the first organisms able to multiply close to the 0.605-aw limit; and whether extraterrestrial aqueous milieux of ≥ 0.605 aw can resemble fertile microbial habitats found on Earth.

New chiral catalysts for phospho-transfer

Chiral salcyan complexes of aluminium are effective air and water tolerant enantioselective catalysts for the hydrophosphonylation of carbonyls. Complexes of the form [(R,R)-salcyan]AlX (X=OH, OR) result in product enantioselectivity changes (Δee) of ca. 100% compared to those returned in the presence of related complexes [(R,R)-salcyen]AlX even though they both possess a chiral ligand framework with the same absolute stereochemistry.

Phospho-transfer catalysis: On the asymmetric hydrophosphonylation of aldehydes

Abstract We report here a precise, in situ 31 P{ 1 H}-NMR method of assaying enantiopurity of α-hydroxyphosphonate esters, the products of the carbonyl hydrophosphonylation (Pudovik) reaction. This method is based upon a diazaphospholidine chiral derivatising agent (CDA) which satisfies all of the criteria for a precise assay; (i) derivatisation of α-hydroxyphosphonate esters is both rapid and clean, (ii) kinetic resolution is absent and (iii) 31 P{ 1 H} chemical shift dispersions are excellent (>5ppm). Calibration of this assay has been achieved by cross-referencing the 31 P{ 1 H}-NMR signals obtained for the CDA-derivatised ester of (MeO) 2 P(O)CHPh(OH) to optical rotation measurements from scalemic material obtained upon lipase catalysed hydrolysis (F–AP 15, Rhizopus oryzae ) of (MeO) 2 P(O)CHPh(OAc). Analysis of NMR chemical shift and coupling parameters for a closely related series of derivatised α-hydroxyphosphonate esters support further configuration assignments on the basis of inference. We report also on the configurational stability of α-hydroxyphosphonate esters in the presence of acids, organonitrogen bases and metal salts. 2 H-labelling and carbonyl crossover experiments reveal that low levels of epimerisation ( α ) of α-hydroxyphosphonate esters is possible under certain conditions of catalysis and within certain limits. A design strategy for the construction of catalyst systems in the Pudovik reaction is outlined based upon a combination of Lewis acidic ( E ) and Lewis basic ( N ) sites. Four types of catalyst are outlined, members of two distinct Classes I and II according to the nature of the acid and base sites, along with our investigations of representative examples of each Class. A variety of Class I.1 systems based on β-amino alcohols (one hydrogen bonding E site and one organonitrogen N site), have been assayed in the model reaction between (MeO) 2 P(O)H and PhCHO. Results suggest that catalysis of the Pudovik reaction is clean and efficient in certain cases but that catalytic activity is strongly dependent upon the nature of the basic ( N ) nitrogen centre. Moreover, only low levels ( E and/or N sites) have been examined to model carbonyl and H-phosphonate binding; an amphoteric receptor based on a pyridine dicarboxamide scaffold has been synthesised and shown to bind benzaldehyde >50% more strongly ( K 11 0.53 mol −1 dm 3 ) than dimethyl-H-phosphonate ( K 11 0.34 mol −1 dm 3 , 298 K) and to catalyse the hydrophosphonylation reaction between these two substrates with a second order rate constant comparable to that of triethylamine (both k 2 5.9×10 −2 mol −1 dm 3 h −1 , 293 K). However, one of the major limitations of this model is that competitive product inhibition dominates after some 15 turnovers (75% completion). Model studies reveal that hydrophosphonylation catalysis via a nitrogen Lewis base is accelerated up to 10-fold upon the introduction of [Zn(OSO 2 CF 3 ) 2 ] as co-catalyst. Consequently, Class II.1 systems employ metal salts [Zn(OSO 2 CF 3 ) 2 ] as Lewis acidic E sites and chiral co-catalysts capable of binding to the metal and also acting as Lewis basic N sites. Such systems catalyse the addition of (MeO) 2 P(O)H to PhCHO cleanly with modest turnover numbers ( E and N sites with more basic N functions and consequently are far more active as catalysts than the other classes. This increased catalytic activity is exemplified by one of the simplest achiral members, diethylzinc which catalyses the 100% chemo- and regioselective addition of (MeO) 2 P(O)H to PhCHO to afford (MeO) 2 P(O)CHPh(OH) with an average turnover rate (over a 1 h reaction time at 298 K) of 115 h −1 compared to ca. 1 h −1 for NEt 3 under analogous conditions. Chiral variants are proposed.

New, improved syntheses of the group 6 oxyhalides, W(O)Cl4, W(O)2Cl2 and Mo(O)2Cl2

Abstract Hexamethyldisiloxane is a useful reagent for the convenient, high yield preparation of oxyhalide derivatives of molybdenum and tungsten.

The use of silylethers and silylthioethers in syntheses of oxohalide and thiohalide compounds of molybdenum and tungsten

Abstract Convenient procedures for the preparation of molybdenum and tungsten oxo- and thiohalides are described which exploit reactions between transition metal halides and bis(silyl)ether and -thioether reagents, according to the general equation: MCI x +(Me 3 Si) 2 Y (Y = O,S)→M(Y)Cl x−2 +2Me 3 SiCl. W(O)Cl 4 ( 1 ) and Mo(O)Cl 3 ( 5 ) are formed in high yield by room temperature treatment of WCl 6 and MoCl 5 with (Me 3 Si) 2 O in CH 2 Cl 2 solvent. Mo(O) 2 Cl 2 ( 6 ) may be obtained from Mo(O)Cl 4 by an analogous room temperature procedure; efficient generation of W(O) 2 Cl 2 ( 2 ) requires warming of W(O)Cl 4 with (Me 3 Si) 2 O at 80°C in octane. In acetonitrile solvent, W(O)Cl 4 reacts with one equivalent of (Me 3 Si) 2 O to give W(O) 2 Cl 2 (CH 3 CN) 2 ( 3 ) in 70% yield. Treatment of W(O)Cl 4 with two equivalents of (Me 3 Si) 2 O in CH 2 Cl 2 leads to blue crystalline W(O) 2 Cl(OSiMe 3 ) ( 4 ), which is stable to elimination of Me 3 SiCl to 1OO°C. W(S)Cl 4 ( 7 ), W(S) 2 Cl 2 ( 8 ) and Mo(S)Cl 3 ( 9 ) are obtained by low temperature treatment of WCl 6 , W(S)Cl 4 and MoCl 5 , respectively, with one equivalent of (Me 3 Si) 2 S in CH 2 Cl 2 solvent. The mixed oxothiohalide compounds W(O)(S)Cl 2 ( 10 ) and Mo(O)(S)Cl 2 ( 11 ) may be isolated in good yield through the reaction of W(O)Cl 4 or Mo(O)Cl 4 with (Me 3 Si) 2 S in CH 2 Cl 2 at low temperature.

Direct evidence for the availability of reactive, water soluble phosphorus on the early Earth. H-Phosphinic acid from the Nantan meteorite

Anoxic irradiation of a type IIICD iron meteorite known to contain the phosphide mineral schreibersite (Fe,Ni)3P in the presence of ethanol/water affords the reactive oxyacid H-phosphinic acid (H3PO2) as the dominant phosphorus product.

CHIRAL PHOSPHORUS(III) TRIFLATES. ON THE NATURE OF THE PHOSPHORUS-OXYGEN INTERACTION

Abstract Reaction of chiral phosphorodiamidites with trimethylsilyltriflate affords chiral phophorus(III) triflate species, such as 1-trifluoromethylsulfonato-2,9-(dibenzyl)diaza-1-phospha[4.0.3]bicyclononane 4, which has been examined by a combination of solution and solid state analytical techniques. Arguably the most important feature of this molecule is the nature of the interaction between phosphorus and triflate oxygen atoms. Single crystal X-ray diffraction analysis reveals that the phosphorus atom interacts principally with two oxygen atoms from two different triflate groups in the solid state, implying overall four-coordination at phosphorus. At distances of 2.841 and 2.755 A, these interactions are well within the van der Waals distance for a phosphorus–oxygen [P–O] interaction (ca. 3.35 A) but are nevertheless over 1 A longer than expected for a single [P–O] covalent bond. Investigations in solution via a combination of 31P, 19F, 13C, variable concentration, variable temperature NMR spectroscopy and solution conductivity provide support for a phosphorus–oxygen interaction which is intermediate between ‘ionic’ (two-coordinate phosphorus) and ‘covalent’ (three-coordinate phosphorus) and which possesses dynamic character in solution. Indeed, it has proved possible to calculate a relative equilibrium constant between ‘ionic’ and ‘covalent’ forms of 4 using empirical NMR data (13C and 19F; CH2Cl2 solvent; 300 K). These calculations return an equilibrium constant of ca. 3 (2.8 using 13C-NMR data and 3.3 using 19F-NMR data) in favour of the ionic form, a result commensurate with those suggested from variable temperature 19F-NMR and solution conductivity studies. Indeed, that the triflate group in 4 is capable of being displaced readily has been demonstrated by reaction with two-electron nitrogen, oxygen and phosphorus donor molecules. We have found 13C{1H}-NMR spectroscopy to be an extremely valuable probe of the ionic character of the triflate group in such systems providing a quantitative measure of the relative strength of interaction (relative basicity Br) between donor molecule and phosphorus atom of 4; the stronger the interaction, the more ionic the character of the triflate group and the lower the value of Br. Indeed, Br values for various ligands correlate well with steric and electronic properties of the latter and 31P-NMR resonances of the adducts themselves. As expected, the relative basicity of a given ligand correlates to the equilibrium constants K for adduct formation, which range from 39 M−1 for the weakest binding ligand studied (1,4-dioxane) to 5.4×104 M−1 for the strongest binding ligand (4-Me2N–NC5H4).

Asymmetric Silylphosphite Esters: Synthesis and Reactivity of (rac-O,O-Binaphtholato)POSiR3 (R3 = Ph3, tBuMe2, Et3)

Abstract The new, silylphosphite compounds, (rac-O,O-binaphtholato)POSiR3 (R3 = Ph3, tBuMe2, Et3) have been synthesised by the reactions of (rac-O,O-binaphtholato)PC1 and R3SiOH. The abilities of these silylphosphite esters to act as phosphonylating agents towards benzaldehyde have been investigated.

Accurate in situ 31P{1H} assay of enantiopurity in α-hydroxyphosphonate esters using a diazaphospholidine derivatizing agent

Abstract A rapid, convenient and efficient in situ assay of enantiomeric excess in α-hydroxyphosphonate esters is reported exploiting 31 P{ 1 H} NMR analysis of the diastereoisomers formed upon condensation with a phosphorochloridite reagent containing a chiral diazaphospholidine ring. Use of this chiral framework affords chemical shift dispersions > 5 ppm between diastereoisomers. Accurate integrations are thus possible once account is taken of differential n.O.e. effects and spin lattice T 1 relaxation times of the phosphorus nuclei.