Diethyl titanocene

Cyclisations initiated by zirconocene 1-butene are incompatible with ester functionality, a limitation which has been overcome by the use of a diethyl titanocene reagent which gives titanocycles exemplified by 23 (Scheme 5.8). 

To a solution of the titanocene(II) reagent 29 in THF (42 mL) in a 300-mL round-bottomed flask, prepared from titanocene dichloride (6.54 g, 26.3 mmol), magnesium turnings (0.766 g, 31.5 mmol), triethyl phosphite (8.96 mL, 52.5 mmol), and finely powdered 4 A molecular sieves (1.31 g) according to the procedure described above, was added a solution of l,l-bis(phenylthio)cyclobutane (63 2.29 g, 8.40 mmol) in THF (14 mL). The reaction mixture was stirred for 15 min. and then a solution of (S)-isopropyl 3-phenylpro-panethioate (91 1.46 g, 7.00 mmol) in THF (21 mL) was injected dropwise over a period of 10 min. The reaction mixture was refluxed for 1 h, then cooled, whereupon 1 m aq. NaOH solution (150 mL) was added. The insoluble materials produced were removed by filtration through Celite and washed with diethyl ether. The aqueous layer was separated and extracted with diethyl ether. The combined ethereal extracts were dried (Na2S04), filtered, and concentrated. The residual liquid was purified by column chromatography (silica gel, hexane) to afford 1.33 g (77%) of (l-isopropylthio-3-phenylpropan-1 -ylidene) cyclobutane (92). 

Trimethylaluminum (20 mL of a 2 M solution in toluene, 40 mmol) is added to titanocene dichloride (5.0 g, 20 mmol) under inert gas. The resulting mixture is stirred at room temperature for 3 d with evolution of methane. The mixture is then cooled to 0 °C and a solution of phenyl benzoate (4.0 g, 20 mmol) in THE (20 mL) is added over 5 min. The resulting mixture is left to warm to room temperature within 45 min and is then diluted with anhydrous diethyl ether (50 mL). Approximately 50 drops of a 1 M aqueous sodium hydroxide solution are carefully added over 10-20 min. When gas evolution has ceased anhydrous sodium sulfate is added and the slurry is filtered through a pad of Celite. After rinsing with diethyl ether the combined filtrates are concentrated and the product is purified by column chromatography (150 g basic alumina, pentane/diethyl ether 9 1). 2.8 g (70%) of the title compound is obtained. NMR (250 MHz, CDCI3) 5 4.45 (d, 2.3 Hz, IH), 5.05 (d, 2.3 Hz, IH), 7.06-7.11 (m, 3H), 7.29-7.38 (m, 5H), 7.66-7.70 (m, 2H). 

Finally, carbohydrate ligands of enantioselective catalysts have been described for a limited number of reactions. Bis-phosphites of carbohydrates have been reported as ligands of efficient catalysts in enantioselective hydrogenations [182] and hydrocyanations [183], and a bifunctional dihydroglucal-based catalyst was recently found to effect asymmetric cyanosilylations of ketones [184]. Carbohydrate-derived titanocenes have been used in the enantioselective catalysis of reactions of diethyl zinc with carbonyl compounds [113]. Oxazolinones of amino sugars have been shown to be efficient catalysts in enantioselective palladium(0)-catalyzed allylation reactions of C-nucleophiles [185]. 

Examples of p-aminoalkylphosphonates prepared include the analogues (277) and (278) of the docetaxel C-13 side-chain (276). The diethyl esters have been synthesised previously but the authors claim that there are advantages in using the methyl esters in syntheses. Air-stable titanocene(IV) salt complexes, e.g. (279), have been prepared by the reaction of titanocene dichloride with phosphorus and sulfur p-amino acid analogues. ... 

Virieux et al. have reported a radical phosphonylation of alkenes (509) and a double phosphonylation of nitriles (507) with diethyl phosphite (508) to form alkylphosphonates (510) and aminobisphosphonates (506), respectively, using phosphorus-centered radicals induced by titanocene dichloride (Cp2TiCl2) (Scheme 126). ... 

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