4-phenylpyridine A-oxide

To a solution of m-ethyl cinnamate (44, 352 mg, 85% pure, 1.70 mmol) and 4-phenylpyridine-A-oxide (85.5 mg, 29 mol%) in 1,2-dichloromethane (4.0 mL) was added catalyst 12 (38.0 mg, 3.5 mol%). The resulting brown solution was cooled to 4°C and then combined with 4.0 mL (8.9 mmol) of pre-cooled bleach solution. The two-phase mixture was stirred for 12 h at 4°C. The reaction mixture was diluted with methyl-t-butyl ether (40 mL) and the organic phase separated, washed with water (2 x 40 mL), brine (40 mL), and then dried over Na2S04. The drying agent was removed by filtration the mother liquors concentrated under reduce pressure. The resulting residue was purified by flash chromatography (silica gel, pet ether/ether = 87 13 v/v) to afford a fraction enriched in cis-epoxide (45, cis/trans . 96 4, 215 mg) and a fraction enriched in trans-epoxide cis/trans 13 87, 54 mg). The combined yield of pure epoxides was 83%. ee of the cis-epoxide was determined to be 92% and the trans-epoxide to be 65%. 

Af-methylmorpholine A-oxide or 4-phenylpyridine A-oxide as cocatalysts. The yields and enantioselectivities obtained with HgOg or urea hydrogen peroxide were comparable, with slightly better yields for the epoxidation with HgOg (73% versus 68% for the epoxide of 1,2-dihydronaphthalene in the presence of NH4OAC). 

These catalysts, 11-13, show good enantioselectivity ranging from 80 to 95% ee in the epoxidation of conjugated cfs-di- and tri-substituted olefins. Epoxidation of "good substrates such as 2,2-dimethylchromene derivatives proceeds with excellent enantioselectivity (>95% ee). Since the results obtained with these first-generation Mn-salen catalysts have been reviewed [21,33], only typical examples are shown in Table 6B.1. These reactions are usually carried out in the presence of donor ligand [34] such as 4-phenylpyridine A -oxide with terminal oxidants such as iodosylbenzene and sodium hypochlorite as described above. However, the use of some other terminal oxidants under well-optimized conditions expands the scope of the Mn-salen-... 

Abbreviations AD, asymmetric dihydroxylation BPY, 2,2 -bipyridine DMTACN, 1,4-dimethyl-l,4,7-triazacyclonane EBHP, ethylbenzene hydroperoxide ee, enantiomeric excess HAP, hydroxyapatite LDH, layered double hydroxide or hydrotalcite-type structure mCPBA, meta-chloroperbenzoic acid MTO, methyltrioxorhenium NMO, A-methylmorpholine-A-oxide OMS, octahedral molecular sieve Pc, phthalocyanine phen, 1,10-phenantroline PILC, pillared clay PBI, polybenzimidazole PI, polyimide Por, porphyrin PPNO, 4-phenylpyridine-A-oxide PS, polystyrene PVP, polyvinylpyridine SLPC, supported liquid-phase catalysis f-BuOOH, tertiary butylhydroperoxide TEMPO, 2,2,6,6-tetramethyl-l-piperdinyloxy TEOS, tetraethoxysilane TS-1, titanium silicalite 1 XPS, X-ray photoelectron spectroscopy. 

The synthesis of the tetrasubstituted dihydroquinoline portion of siomycin Di, which belongs to the thiostrepton family of peptide antibiotics, was achieved in the laboratory of K. Hashimoto. The Jacobsen epoxidation was utilized to introduce the epoxide enantioselectively at the C7-C8 position. The olefin was treated with 5 mol% of Jacobsen s manganese(lll)-salen complex (R =f-Bu) and 4% aqueous NaOCI solution in dichloromethane. To enhance the catalyst turnover, 50 mol% of 4-phenylpyridine-A/-oxide was added to the reaction mixture. The desired epoxide was obtained in 43% yield and with 91% ee. 

PPNO 4-phenylpyridine A-oxide RDC residual dipolar coupling... 

One of the most significant developmental advances in the Jacobsen-Katsuki epoxidation reaction was the discovery that certain additives can have a profound and often beneficial effect on the reaction. Katsuki first discovered that iV-oxides were particularly beneficial additives. Since then it has become clear that the addition of iV-oxides such as 4-phenylpyridine-iV-oxide (4-PPNO) often increases catalyst turnovers, improves enantioselectivity, diastereoselectivity, and epoxides yields. Other additives that have been found to be especially beneficial under certain conditions are imidazole and cinchona alkaloid derived salts vide infra). 

Conditions (a) 1-5 mol% catalyst, w-CPBA/NMO, -78°C, CH2CI2. (b) 1-5 mol% catalyst, NaOCl, 4-phenylpyridine iV-oxide, 0°C, CH2CI2. (c) 1-5 mol% catalyst, NaOCl, pyridine iV-oxide, 0°C, CH2CI2. (d) Solvent = diethyl ether... 

A 100 mL flask, was filled with (Z)-ethyl cinnamate, (666 mg of the mixture containing 75 % of (Z)-ethyl cinnamate), 4-phenylpyridine N-oxide (116 mg) and dichloromethane (6mL). Jacobsen s catalyst (108 mg) was then added. 

Resolution of a racemic mixture is still a valuable method involving fractional crystallization [113], chiral stationary phase column chromatography [114] and kinetic resolutions. Katsuki and co-workers demonstrated the kinetic resolution of racemic allenes by way of enantiomer-differentiating catalytic oxidation (Scheme 4.73) [115]. Treatment of racemic allenes 283 with 1 equiv. of PhIO and 2 mol% of a chiral (sale-n)manganese(III) complex 284 in the presence of 4-phenylpyridine N-oxide resulted... 

Over the years further tuning of the ligand by varying the substituents in the aromatic ring has led to >90% ee for a number of olefins [278]. Improvements were also achieved by adding amine-N-oxides such as 4-phenylpyridine-N-oxide... 

Phenylpyridine N-oxide was purchased from Aldrich Chemical Company, Inc., and used as received. Other pyridine N-oxide derivatives have been used with success in the epoxidation reaction. The choice of the pyridine N-oxide derivative has been demonstrated to have a small yet measurable impact on both the rate of reaction and the enantiomeric excess of the product epoxide. ... 

---