Riesgos regulatorios en la gestión de contrataciones

NMR spectra were recorded at 400 MHz on a Varian VXR-400 instrum ent or, unless stated, at 200 MHz on a Varian XL-200 instrument. NMR spectra were recorded at 100.6 MHz on a Varian VXR-400 instrument. Residual protic solvent was taken as internal standard, with CDCI3

as solvent unless otherwise stated, stored over 4Â m olecular sieves and filtered through a pad of basic alum ina prior to use. Infrared were recorded as thin film s on sodium chloride plates or as potassium chloride disks on a Perkin-Elm er FT-IR 1605 instrument. All peaks quoted are medium, unless otherwise stated. Mass spectra measurements were recorded by electron im pact (El) studies with an Autospec Q, VG 7070 or VG 7070B instrument, unless fast atom bom bardm ent (FAB) is stated, in which case a ZAB-SE instrument was used. Analytical gas chrom atography was performed on a Hewlett Packard HP5890 machine fitted with a SGE BPX5 capillary (50m x 0.32mm i.d., polyimide coated fused silica column) and flam e ionisation detector. Split injection was used with hydrogen as the carrier gas. Melting points were taken on a Reichert hot stage and are uncorrected. Optical rotations were taken with a ‘POLAAR 2000’ instrum ent by Optical Activity Ltd. and are given in the units 10‘Meg.cm^.g'V

Petrol refers to light petroleum boiling in the range 40-60°C which was distilled prior to use as a chrom atography eluent. Ether refers to diethyl ether, used as received fo r this purpose, as were ethyl acetate, methanol and DCM. For use as reaction solvents ether, tetrahydrofuran and benzene were freshly re-distilled under dry nitrogen from sodium benzophenone-ketyl and toluene from molten sodium, Dichloromethane was freshly re-distilled from phosphorous (V) oxide. Chlorobenzene and 1,2-dichloroethane were re-distilled from phosphorous (V) oxide and stored over 4Â molecular sieves. Methanol was distilled from magnesium turnings and stored over 4Â m olecular sieves. Unless otherwise stated 'ethanol' refers to absolute ethanol (>99.7%) -and was used as received. Dimethyl sulfoxide and fEj-A/,A/-diethylgeranylamine were distilled under reduced pressure and stored over 4Â m olecular sieves. Trim ethylsilyl chloride was freshly re-distilled from calcium hydride. Triethylam ine, diisopropylamine and pyridine were distilled from and stored over potassium hydroxide. Acetic anhydride was distilled under reduced pressure from magnesium powder and flushed through phosphorous (V) oxide prior to use. Commercially, avaiiable allylic alcohols were treated with potassium carbonate and distilled onto 4Â m olecular sieves before use as substrates. Benzaldehyde and methyl iodide were purified by accepted procedures prior to distillation.^^^

Analytical thin layer chromatography was performed on pre-coated glass backed plates (Merck Kieselgel 60 F254) and visualised with ultraviolet light (254nm), iodine, potassium permanganate [add 62.5g NagCOg in water (1.25 litre) to 12.5g KMn0 4 in water (1.25 litre)], acidic am m onium molybdate (IV) [conc. H2SO4 (250ml), am m onium molybdate tetrahydrate, w ater (250ml)], or vanillin [vanillin (2.4g), conc. H2SO4 (2.5ml), ethanol (100ml), stored in the dark] as appropriate. Preparative column chromatography was performed at low positive pressure on Merck Kieselgel

178 Experim ental

60. HPLC was carried out on a Gilson M303 instrument with a 25cm x 5mm normal phase Lichrosorb silica gel column, using a Bischoff Rl 8110 refractive detector. Solvents used were HPLC grade and were degassed prior to use.

All isom érisations reactions were performed using Schlenk-line techniques and glassware (oven or flam e d r i e d ) . S o l u t i o n s were prepared using standard air-sensitive handling procedures and twice degassed prior to mixing. ‘Degassed’ refers to one freeze-thaw cycle as described below. The Schlenk-line was served by a two stage rotary oil pump and an on-line vacuum m aintained at between 0.01 and 0.05 mbar. Argon was dried and deoxygenated by passage through a colum n of chrom ium (II) on activated silica:

To a mechanically stirred solution of chromium (VI) oxide (60g) in distilled water (2 I) was slowly

added silica gel (1.5Kg, ca. 100 mesh). The resulting bright orange slurry was recovered by

Büchner filtration and dried first at the pump (12 hours) and then on several large crystallisation dishes in an oven at 100°C (48 hours). The orange powder was placed in a large sintered glass chromatography column, in a cylindrical furnace, and dehydrated in a stream of oxygen at

250°C (3-4 hours). After heating at 500°C (1 hour), and in a stream of dry nitrogen (30

minutes), a supply of carbon monoxide was attached and slow passage of the gas continued at >400°C until the transition through green to blue had run the length of the column (1 -2 hours). A flow of nitrogen was then maintained for several hours until the column had cooled to room temperature.

Absorption of oxygen was characterised by a gradual change in colour to orange-brown m oving in a distinct front in the direction of argon flow. The column was sufficient fo r several cylinders of gas and may be regenerated by the above procedure.

'C om m ercially obtained solutions of n-BuLi were regularly quantified by the ‘double-quench and titration’ procedure - subtraction of background base (hydroxide by reaotion with 1,2- dichloroethane and then water) from total base (n-BuLi and hydroxide by reaction with water); or by direct titration with N-pivaloyl-O-toluidene - the end point being reached when the colourless solution turns yellow.^®®

The catalysts NiCl2(DIPH0S),^®® NiOl2(Cy3P)2/"® NiCl2(Ph3P)2,^°° NiCl2Py2/ ° ' [Rh(C0D)DIPH0 S]CI0 4,‘'^° [Rh(G0D)('S;-(-)-BINAP]GI0 4^^® and PhgPGuGI^®® were prepared by published procedures and stored under argon in air-tight bottles. Ni(G0D)2^^^ was also prepared by published procedure and was stored at -40°G under argon in a fully equipped glove box. [Rh(G0D)('R X+)-BIN AP]G I0 4 and [Rh(GOD)GI]2 were purchased from Aldrich and were stored under argon in air-tight bottles. Note that [Rh(G0D)GI]2 was used to prepare [Rh(G O D)(Sj-(-)- BINAP]GI04.

179 Experim ental