Rep:Mod:experiment1clabreport
Title
Comprehensive enantioselective epoxidation of alkenes mediated by Jacobsen's catalyst and Shi's catalyst.
Abstract
Catalytic asymmetrical epoxidation of alkenes furnish valuable alcohol-containing molecules in high enantiomeric purity.
These transformations, however, require high catalyst loadings (20–30 mol%) and long reaction times (2–5 days).
Here, we report that a counterintuitive strategy involving the use of an achiral co-catalyst structurally similar to the chiral catalyst provides an effective solution to this problem.
A combination of seemingly competitive Lewis basic molecules can function in concert such that one serves as an achiral nucleophilic promoter and the other performs as a chiral Brønsted base.
On the addition of 7.5–20 mol% of a commercially available N-heterocycle (5-ethylthiotetrazole), reactions typically proceed within one hour, and deliver the desired products in high yields and enantiomeric ratios. In some instances, there is no reaction in the absence of the achiral base, yet the presence of the achiral co-catalyst gives rise to facile formation of products in high enantiomeric purity.
Introduction
Asymmetric epoxidation of alkenes is a powerful method for the synthesis of chiral intermediates in the pharmaceutical and agrochemical fields. (R.A. Sheldon, J.K. Kochi, Metal-Catalysed Oxidation of Organic Compounds, Academic Press, New York, 1981.) In chemical synthesis, epoxidation of an alkene would generate up to two stereochemical outcomes. (Faveri, G.D., Ilyashenko, G. and Watkinson, M., Chem. Soc. Rev., 2011, 40, 1722-1760.) Thus, asymmetrical epoxidation (AE) of complex molecules containing the prochiral olefins is a great challenge to synthetic chemist. Synthesizing enantiomerically pure epoxides are vital as epoxides occur widely in natural products. (???) Besides that, epoxides are synthetically useful as a crucial synthetic strategy in construction of a molecule as the strained epoxide ring is extremely reactive, and easily ring opens to relieve the ring strain imposed on the three-membered epoxide ring, can be an important synthetic intermediates which is widely employed in organic synthesis.
The year 2001 marked a great recognition in the importance of catalytic asymmetrical epoxidation (AE) research. The Nobel Prize in Chemistry 2001 was awarded to Professor Sharpless "for his work on chirally catalysed oxidation reactions", specifically involving his seminal work on titanium-catalyzed asymmetric epoxidation (AE) of allylic alcohol (up to 90% e.e.!) (Katsuki, T., and Sharpless, K.B., J. Am. Chem. Soc., 1980, 102, 5974-5976.) ( Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 2002, 41, 2024.) Despite this being an excellent means of synthesizing high enantioselective epoxides, epoxidation of unfunctionalized alkenes would not gain any enantioselectivity benefit from it, due to lack of pendant functional group. In fact, Jacobsen (McGarrigle, E.M. and Gilheany, D.G., Chem. Rev., 2005, 105, 1563-1602)and Shi (Wong, O.A. and Shi, Y., Chem. Rev., 2008, 108, 3958-3987.) independantly came out with chiral catalysts that complements each other for different unfuntionalized alkenes to carry out a comprehensive AE of non-functionalized olefins.
Jacobsen's catalyst is a manganese (III) complex, coordinated with a salen ligand [salen= N,N'-bis(salicylidene)-ethylenediaminato] at the equatorial and a chloride at the axial, forming slight distorted square pyrammidal structure. Epoxidation of unfunctionalized olefin using achiral salen complexes as catalyst and PhIO as the stoichiometric oxidant emerged when Kochi reported his findings in 1985. (Sames, E.G., Srinivasan, K., Kochi, J.K., J. Am. Chem. Soc., 1985, 107, 7606.) Jacobsen soon recognized the potential of salen complexes in catalytic AE of unfuntionalized alkenes and improvized on the idea. Mn(salen)-catalyzed AEs of unfunctionalized olefins was soon reported by Jacobsen in 1990 using iodosylarenes (ArIO) as stoichiometric oxidants. ( Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1990, 112, 2801). Manganese was unsurprisingly chosen as an ideal candidate catalytic metal in epoxidation chiefly due to its low toxicity, commercially availability and most crucially, the role it played in numerous biochemical redox processes. To exemplify, peroxidases, catalases and in photosystem II (PSII) where it is involved in the oxidation of water to dioxygen. (Faveri, G.D., Ilyashenko, G. and Watkinson, M., Chem. Soc. Rev., 2011, 40, 1722-1760.). Therefore, conveniently, it was the prime focusTypically, asymmetric epoxidation of various unfunctionalized disubstituted, tri- and tetrasubstituted alkenes.
On the other hand, Shi's catalyst is a fructose-derived chiral ketone, reacting with oxone (potassium peroxomonosulfate) to form dioxiranes (Montgomery, R. E. J. Am. Chem. Soc. 1974, 96, 7820) which acts as an oxidant in the epoxidation.(Narsaiah, A. V. Synlett 2002, 7, 1178). The first chiral ketone-catalyzed asymmetrical epoxidation was reported by Curci, dated back in 1984. (Curci, R., Fiorentino, M., Serio and M.R., J.Chem., Soc., Chem. Commun., 1984, 155.)However, the AE reported by Curci suffered from long reaction time but with merely maximum of 12.5% e.e. Yet, it demonstrated that chiral ketones could be utilized in obatining chiral epoxides. Shi built on the idea and came out with the fructose-derived chiral ketone which showed high enantioselectivities (up to 97% ee) in the AE of unfuntionalized olefins. (Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J.-R.; Shi, Y. J. Am Chem. Soc. 1997, 119, 11224)
In the current investigation, studies on the stereoselectivity of Jacobsen and Shi catalyst on different unfunctionalized alkenes. Herein the results of the investigtion was reported.
The present study describes the This development work included Several oxidants were investigated
cornerstone: an important quality or feature on which a particular thing depends or is based.
(http://www.ch.ic.ac.uk/local/organic/tutorial/asymsynth2.pdf)
(http://pubs.rsc.org/en/content/articlepdf/2011/cs/c0cs00077a)
(http://pubs.acs.org/doi/pdf/10.1021/cr0306945) The present study describes the This development work included Several oxidants were investigated
(http://pubs.acs.org/doi/pdf/10.1021/jo0491004)
(http://pubs.acs.org/doi/pdf/10.1021/cr068367v)
The symmetrical Mn(III)-salen complexes, two novel non-C2-
symmetric Mn(III)-Schiff-base complexes containing salicylaldehyde and 1-(2- hydroxyphenyl)ketone units were synthesized using a stepwise procedure. One of the two complexes was catalytically active in asymmetric epoxidation of various alkenes and showed moderate-to-good enantioselectivity, although it was lower than that obtained for analogous C2-symmetric salen-based catalysts. Possible reasons for the differences in reactivity and selectivity between these two types of catalysts are briefly discussed.
Experimental
General Information
1H and 13C NMR spectra were recorded in CDCl3 (unless otherwise stated) on Bruker AVANCE machines operating at 400 MHz, respectively. Chemical shifts are reported in δ (ppm), referenced to TMS. Multiplicity is abbreviated to s (singlet), d (doublet), t (triplet), q (quartet), and m (multiplet).
Melting points were recorded using an Stanford Research System MPA100 Optimelt automated melting point apparatus, and were uncorrected.
Solid state IR spectra were recorded on a Perkin Elmer Paragon 1000 series FT-IR Spectrometer, fitted with a beam-condensing ATR accessory while IR spectra were recorded on a Perkin Elmer Paragon 1000 series FT-IR Spectrometer.
The enantiomeric excesses of the products were elucidated via GC which was performed on Perkin Elmer Clarus 480, each equipped with variable wavelength UV detectors, using chiral HPLC columns (250 × 4.6 mm).
Magnetic susceptibility was executed using Sherwood Scientific Ltd MK 1 Magnetic Susceptibility Balance.
Optical rotation measurements were performed using Bellingham & Stanley ADP410 Polarimeter.
Column chromatography was carried out using silica gel (200–300 mesh)
Unless otherwise stated, all chemical reagents and precursors were procured from commercial sources (i.e. Alfa Aesar, Sigma Aldrich and Acros) and used without purification.
The following compounds were prepared by following literature procedures: 2- (benzyloxy)ethanol (8a),12 2-(2,2-dimethyl-1,1-diphenylpropoxy) ethanol (8b),13 benzyl (10a) and methyl (10b) 2-(diethoxyphosphoryl) acetylcarbamates.10
The Jacobsen's and Shi's catalysts were prepared following the reported procedures.
Larrow, J.F., Jacobsen, E.N., Org. Synth., 1999, 75, 1. (http://www.orgsyn.org/Content/pdfs/procedures/V75P0001.pdf
)
Tu, Y., Frohn, Z.-X., Wang, Shi, Y., Org Synth., 2003, 80, 1.(http://www.orgsyn.org/Content/pdfs/procedures/v80p0001.pdf
)
Jacobsens catalyst
Synthesis of (R,R)-1,2-Diammoniumcyclohexane mono-(+)-tartrate.
L-(+)-Tartaric acid (0.80 g, 5.33 mmol) is added into 20 mL of distilled water with 1.02 mL (10.66 mmol, 2.0 eq) of racemic trans-1,2-diaminocyclohexane added. A slurry is formed initially but complete dissolution is observed once addition is complete.
Glacial acetic acid (5 mL) is then added in one portion. Product begins to precipitate during the addition, and continues to precipitate while the reaction mixture is allowed to cool from 90°C to 5°C, with stirring, over 3 to 4 hr. The temperature is maintained at 5°C for an additional hour and the product is isolated by filtration. The filter cake is washed with 50 mL of cold (0°C) water followed by 4 × 20-mL portions of ambient temperature methanol (Note 5). The enantiomeric excess of the derivatized diamine is determined by sampling the top and bottom of the filter cake using the procedure below. The product is dried at 40-45°C under reduced pressure to give 1.27 g (Yield 90%) of the (R,R)-1,2-diammoniumcyclohexane mono-(+)-tartrate salt as a white powder. (R,R)-1,2-Diaminocyclohexane obtained from this salt exhibits >98.0% enantiomeric excess.
Synthesis of (R,R)-N,N'-Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine.
1.13 g of (R,R)-1,2-diammoniumcyclohexane mono-(+)-tartrate salt (4.27 mmol),1.18 g of potassium carbonate (0.225 mol, 2 eq), and 10 mL of water. The mixture is stirred until dissolution is achieved, and 30 mL of ethanol is added. The cloudy mixture is heated to reflux and a solution of 2.0 g (8.53 mmol, 2.0 eq) of 3,5-di-tert-butylsalicylaldehyde in 15 mL of ethanol is then added in a slow stream over 15 min. The reaction mixture is heated reflux for 2 hr before heating is discontinued. Water, 10 mL, is added and the stirred mixture is cooled to ≤5°C over 0.5 hr. and maintained at that temperature for another hour. The yellow solid is collected by vacuum filtration and washed with 10 mL of ethanol .
After the solid is air dried, it is dissolved in 250 mL of methylene chloride . The organic solution is
washed with 2 × 30 mL of water, followed by 30 mL of saturated aqueous sodium chloride . The
organic layer is dried over sodium sulfate , and filtered to remove the drying agent. The solvent is
removed by rotary evaporation to yield the product as a yellow solid, mp 205.3-206.1°C. Yield 94.6% (2.20g)
Synthesis of (R,R)-N,N'-Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino manganese(III) chloride.
2.70 g (11.0 mmol; 3 eq) of manganese acetate tetrahydrate (Mn(OAc)2·4H2O) and 25 mL of ethanol . Reaction mixture is heated to reflux (75-80°C). A solution of 2.00 g (3.67 mol, 1 eq) of (R,R)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine in 20 mL of toluene is added in a slow stream over 45 min. The reaction mixture is stirred at reflux for 2 hr. Then air is bubbled through the refluxing reaction mixture for 1 hr, and the reaction is monitored for complete ligand consumption by thin layer chromatography. When ligand consumption is complete, heating and air addition are discontinued and 25 mL of saturated aqueous sodium chloride is added. The reaction mixture is cooled to room temperature then transferred to a 2-L separatory funnel. The flask is rinsed into the funnel with 20 mL of toluene and the organic solution is washed with 3 × 50-mL portions of water followed by 50 mL of saturated aqueous sodium chloride . The organic layer is dried over anhydrous sodium sulfate and followed by rotary evaporation. The dark brown solid is dissolved in 20 mL of methylene chloride. Heptane (20 mL) is added, and the methylene chloride is removed by rotary evaporation. The brown slurry is stirred for 1 hr at ≤5°C in an ice bath. The brown solid is collected by filtration and air dry to yield the product, mp 315.0-315.3°C. (Yield 2.1 g, 90%)
The epoxides for Jacobsen's catalyst were prepared from the following procedures
Zhang, W., Jacobsen, E.N., J. Org. Chem., 1991, 56(7), 2296.
(R)-Phenylethylene oxide
(S)-Phenylethylene oxide
(2R,3R)-2-methyl-3-phenyl oxirane
(2S,3S)-2-methyl-3-phenyl oxirane
(1S,2R)-1,2-Epoxy-3,4-dihydronaphthalene
(1R,2S)-1,2-Epoxy-3,4-dihydronaphthalene
(2R,3R)-2,3-di(phenyl)oxirane
(2S,3S)-2,3-di(phenyl)oxirane
Results and Discussion
Short description of reaction performed
-Any interesting/unusual observations
Interpretation of spectral data to support compound identity and purity
Analysis of catalytic turnover and selectivity
-Any deviation from expected values? If so, why?
The catalytic turnover number is defined by the number of moles of product per mole of catalyst used.
b For consistency, the total turnover number is determined as the total concentration of oxidation products divided by the initial catalyst concentration at t = 180 min which is the point where no significant catalyst activity can be observed. In the case of styrene, TON was calculated with the inclusion of phenylacetaldehyde as an oxidation product. c ee were determined by GC (Supelco βDex column (30 m ×0.25 mm, 0.25m film)) (http://chemgroups.northwestern.edu/hupp/Publications/172.pdf)
Brief presentation of mechanism(s) and stereoselectivity
Mechanism and stereoselectivity of Jacobsens catalyst
)
Path A : Radical pathway
Path B: Involving metallaoxetane
Path A is favoured beause the reaction is enhanced by the addition of N-oxides which supports the replacement of the chloride by these ligands and subsequent activation of the metal.
For Path B, it would be extremely crowded at the metal center with a coordinated N-oxide.
Also, recent computational studies found that the metallooxetane structure to be too high in energy to be a reasonable intermediate.
In homogeneous solution, linear Erying plots are found for styrene, indene, and cyclooctadiene.
This supports PAth A and argues against a mechanism with an equilibrium formation of a metallooxetane prior to rate-determining epoxide of formation (as in Path B) One might expect radical rearrangements in PAth A but they are not observed. In the epoxidation reaction (C), which incorporates the very rapid 'phenylcyclopropyl clock", no ring-opened products were observe, implying no free radical involvement.
Mechanism and stereoselectivity of Shi's catalyst
Reference
-use 'and' in author -RSC format
solvent (http://www.sas.upenn.edu/~marisa/documents/OrganoMetSolv.pdf)