Allyl alcohols molecular sieves

The emergence of the powerful Sharpless asymmetric epoxida-tion (SAE) reaction in the 1980s has stimulated major advances in both academic and industrial organic synthesis.14 Through the action of an enantiomerically pure titanium/tartrate complex, a myriad of achiral and chiral allylic alcohols can be epoxidized with exceptional stereoselectivities (see Chapter 19 for a more detailed discussion). Interest in the SAE as a tool for industrial organic synthesis grew substantially after Sharpless et al. discovered that the asymmetric epoxidation process can be conducted with catalytic amounts of the enantiomerically pure titanium/tartrate complex simply by adding molecular sieves to the epoxidation reaction mix-... 

Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves, or with peroxy acids. Epoxidation of allylic alcohols can also be done with high enantioselectivity. In the Sharpless asymmetric epoxidation,allylic alcohols are converted to optically active epoxides in better than 90% ee, by treatment with r-BuOOH, titanium tetraisopropoxide and optically active diethyl tartrate. The Ti(OCHMe2)4 and diethyl tartrate can be present in catalytic amounts (15-lOmol %) if molecular sieves are present. Polymer-supported catalysts have also been reported. Since both (-t-) and ( —) diethyl tartrate are readily available, and the reaction is stereospecific, either enantiomer of the product can be prepared. The method has been successful for a wide range of primary allylic alcohols, where the double bond is mono-, di-, tri-, and tetrasubstituted. This procedure, in which an optically active catalyst is used to induce asymmetry, has proved to be one of the most important methods of asymmetric synthesis, and has been used to prepare a large number of optically active natural products and other compounds. The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound formed from the titanium alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the r-BuOOH. ... 

Sharpless and co-workers have shown how, with a catalyst developed by Sharpless, the rate and selectivity in a,symmetric epoxidation of allylic alcohols can be improved substantially by using molecular sieve 3 A / 4 A (Gao et al., 1987). In some ca.ses, the use of molecular sieves has allowed asymmetric epoxidation, which was not possible with the original catalyst. 

Liquid allylic alcohols ((E)-2-methyl-3-phenyl-2-propenol and (E)-2-hexen-l-ol) were stored over preactivated 3 A molecular sieves. 

These results should be interpreted in terms of the different accessibility of the organic molecule to the active sites and of differences in the metal size. However, it is worth noting that using Ru supported on these molecular sieves, it is possible to reach a 100% diastereomeric excess in the (1 IS, 15R) form for about 80% selectivity to allyl alcohol. These results also indicated the fact that the reaction is very sensible to the solvent nature. Methanol was found to enhance the reaction rate compared with THF or ethanol. 

More recently, Hartwig and coworkers reported iridium-catalyzed, asymmetric aminations of allylic alcohols in the presence of Lewis acid activators [103]. The addition of molecular sieves and Nb(OEt)5 or catalytic amounts of BPh3 activated the allylic alcohol sufficiently to allow allylic amination reactions to occur in high yield, branched-to-linear selectivity, and enantioselectivity (Scheme 29). Without the activators, only trace amounts of product were observed. 

This method has proven to be an extremely useful means of synthesizing enantiomerically enriched compounds. Various improvements in the methods for carrying out the Sharpless oxidation have been developed.48 The reaction can be done with catalytic amounts of titanium isopropoxide and the tartrate ester.49 This procedure uses molecular sieves to sequester water, which has a deleterious effect on both the rate and enantioselectivity of the reaction. Scheme 12.9 gives some examples of enantioselective epoxidation of allylic alcohols. 

Sheldon and coworkers have developed chromium-substituted molecular sieves (CrAPO-5) as recyclable solid catalysts for several selective oxidations, among them also the allylic" and benzylic ° " ° " ° oxidations using TBHP or O2 as the terminal oxidants (equation 63), which yielded the corresponding benzylic ketones in moderate yield (conv. 13-70%) and moderate to good selectivity (41%, 65-97%). The benzylic alcohols were formed as side products. Allylic oxidation also proceeded with good conversions, while selectivities were lower and both possible products, the allylic ketone (31-77% selectivity) and the allylic alcohol (0-47% selectivity), were formed. Chromium sUicalite showed activity for selective benzylic oxidation in the presence of TBHP as well as giving mainly the allylic ketone (2-cyclohexen-l-one with 74% selectivity) and the allylic alcohol as minor product (2-cyclohexen-l-ol with 26% selectivity) -. ... 

In 1980, Katsuki and Sharpless described the first really efficient asymmetric epoxidation of allylic alcohols with very high enantioselectivities (ee 90-95%), employing a combination of Ti(OPr-/)4-diethyl tartrate (DET) as chiral catalyst and TBHP as oxidant Stoichiometric conditions were originally described for this system, however the addition of molecular sieves (which trap water traces) to the reaction allows the epoxidation to proceed under catalytic conditions. The stereochemical course of the reaction may be predicted by the empirical rule shown in equations 40 and 41. With (—)-DET, the oxidant approaches the allylic alcohol from the top side of the plane, whereas the bottom side is open for the (-l-)-DET based reagent, giving rise to the opposite optically active epoxide. Various aspects of this reaction including the mechanism, theoretical investigations and synthetic applications of the epoxy alcohol products have been reviewed and details may be found in the specific literature . 

This transformation has been applied to several chiral production processes, the first being the synthesis of a pheromone (Disparlure) intermediate (S) albeit with low turnover numbers and only 91 % ee. Another industrial product is the epoxide of allyl alcohol as developed by PPG-Sipsy, to give a process where catalyst loading was decreased by molecular sieve addition and the safety factors involving peroxide contamination were overcome. These examples are shown in Figure 1.46. 

Propylene carbonate [108-32-7] M 102.1, b 110°/0.5-lmm, 238-239°/760mm, d 1.204, n 1.423. Manufactured by reaction of 1,2-propylene oxide with CO2 in the presence of a catalyst (quaternary ammonium halide). Contaminants include propylene oxide, carbon dioxide, 1,2- and 1,3-propanediols, allyl alcohol and ethylene carbonate. It can be purified by percolation through molecular sieves (Linde 5A, dried at 350° for 14h under a stream of argon), followed by distn under vac. [Jasinski and Kirkland AC 39 163 1967], It can be stored over molecular sieves under an inert gas atmosphere. When purified in this way it contains less... 

Activated manganese dioxide, which is generally used for the selective oxidation of allylic alcohols, permitted the synthesis of an unsaturated (3-keto-arabino-hexopyranosyl)pyridine.13 New oxidative systems for alcohols, involving molecular sieve-assisted... 

To a solution of the allylic alcohol 150 (16.7 g, 49.7 mmol) [Eq. (28)] in 500 mL of toluene, under argon, was added AfAf-dimethylacetamide dimethyl acetal (33.117 g, 249 mmol). The reaction mixture was heated at reflux for 10 h, with continuous removal of methanol by molecular sieve (4 A) trap. The reaction mixture was then cooled to room temperature and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (EtOAc) to afford compound 151 (13.6 g, 68%) as a white foam. The corresponding acetate was obtained in 27% yield and quantitatively transformed into 151 a]D +2.7° (c 1.1, CHClj). 

The Sharpless epoxidation is sensitive to preexisting chirality in selected substrate positions, so epoxidation in the absence or presence of molecular sieves allows easy kinetic resolution of open-chain, flexible allylic alcohols (Scheme 26) (52, 61). The relative rates, kf/ks, range from 16 to 700. The lower side-chain units of prostaglandins can be prepared in high ee and in reasonable yields (62). A doubly allylic alcohol with a meso structure can be converted to highly enantiomerically pure monoepoxy alcohol by using double asymmetric induction in the kinetic resolution (Scheme 26) (63). A mathematical model has been proposed to estimate the degree of the selectivity enhancement. 

Titanium-pillared montmorillonite may be used as a heterogeneous catalyst for the Sharpless asymmetric epoxidation of allylic alcohols (Scheme 20) (46). The enantiomeric purities of the epoxy products are comparable with those achieved using homogeneous Ti isopropoxide with molecular sieves as water scavengers (Chapter 4). Since basal spacing of the recovered catalyst after the reaction is unaltered, the catalyst can be recycled. 

Catalytic asymmetric epoxidation.1 Addition of heat-activated, powdered 3-5 A molecular sieves to the asymmetric epoxidation of allylic alcohols increases the rate and, more importantly, permits use of catalytic amounts of titanium reagent and the tartrate ester. However, it is still important to use at least a 10% excess of the tartrate ester over Ti(0-i-Pr)4 a 20% excess is usually advisable. In general, 5% of Ti(0-i-Pr)4 and 7.5% of the tartrate ester is used for the catalytic epoxidation. 

H202, cat chloroperoxidase (enantioselcctive) i-Bu02H, molecular sieves (allylic alcohols) /-Bu02H, Al(0-r-Bu)j (allylic alcohols) /-Bu02H, Si02... 

An important improvement in the asymmetric epoxidation process is the finding, reported in 1986, that by adding molecular sieves to the reaction medium virtually all reactions can be performed with a catalytic amount (5-10 mol %) of the Ti-tartrate complex [3]. Previously, only a few structural classes of allylic alcohols were efficiently epoxidized by less than stoichiometric amounts of the complex, and most reactions were routinely performed with stoichiometric quantities of the reagent. 

The addition of activated molecular sieves (zeolites) to the asymmetric epoxidation milieu has the beneficial effect of permitting virtually all reactions to be earned out with only 5-10 mol % of the Ti-tartrate catalyst [3,4]. Without molecular sieves, only a few of the more reactive allylic alcohols are epoxidized efficiently with less than an equivalent of the catalyst. The role of the molecular sieves is thought to be protection of the catalyst from (a) adventitious water and (b) water that may be generated in small amounts by side reactions during the epoxidation process. 

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