Catalysts diethyl tartrate

This chemical bond between the metal and the hydroxyl group of ahyl alcohol has an important effect on stereoselectivity. Asymmetric epoxidation is weU-known. The most stereoselective catalyst is Ti(OR) which is one of the early transition metal compounds and has no 0x0 group (28). Epoxidation of isopropylvinylcarbinol [4798-45-2] (1-isopropylaHyl alcohol) using a combined chiral catalyst of Ti(OR)4 and L-(+)-diethyl tartrate and (CH2)3COOH as the oxidant, stops at 50% conversion, and the erythro threo ratio of the product is 97 3. The reason for the reaction stopping at 50% conversion is that only one enantiomer can react and the unreacted enantiomer is recovered in optically pure form (28). 

N-Acetyl-(R)-phanylalanlna (6). The rhodium catalyst was obtained by adding (-) dlop 5 (from diethyl tartrate) to a benzene solution of [RhCi(cyclooctene)2]2 under Ar, and stirring for tS mn A solution of the Rh catalyst (1 mM in EtOH PhH 4 1) was introduced under Hj to a solution of a-N acetylamino- phenytacrylic acid 4 (molar ratio Rh 4 1.540) The solvent was evaporated, the residue dissolved In 0 5 N NaOH, the catalyst was filtered and the solution acidified and concentrated to dryness to give 6 (81% ee) in 90 95% yield... 

In 1980, Katsuki and Sharpless communicated that the epoxidation of a variety of allylic alcohols was achieved in exceptionally high enantioselectivity with a catalyst derived from titanium(IV) isopropoxide and chiral diethyl tartrate. This seminal contribution described an asymmetric catalytic system that not only provided the product epoxide in remarkable enantioselectivity, but showed the immediate generality of the reaction by examining 5 of the 8 possible substitution patterns of allylic alcohols all of which were epoxidized in >90% ee. Shortly thereafter. Sharpless and others began to illustrate the... 

A number of reaction variables or parameters have been examined. Catalyst solutions should not be prepared and stored since the resting catalyst is not stable to long term storage. However, the catalyst solution must be aged prior to the addition of allylic alcohol or TBHP. Diethyl tartrate and diisopropyl tartrate are the ligands of choice for most allylic alcohols. TBHP and cumene hydroperoxide are the most commonly used terminal oxidant and are both extremely effective. Methylene chloride is the solvent of choice and Ti(i-OPr)4 is the titanium precatalyst of choice. Titanium (IV) t-butoxide is recommended for those reactions in which the product epoxide is particularly sensitive to ring opening from alkoxide nucleophiles. ... 

In light of the previous discussions, it would be instructive to compare the behavior of enantiomerically pure allylic alcohol 12 in epoxidation reactions without and with the asymmetric titanium-tartrate catalyst (see Scheme 2). When 12 is exposed to the combined action of titanium tetraisopropoxide and tert-butyl hydroperoxide in the absence of the enantiomerically pure tartrate ligand, a 2.3 1 mixture of a- and /(-epoxy alcohol diastereoisomers is produced in favor of a-13. This ratio reflects the inherent diasteieo-facial preference of 12 (substrate-control) for a-attack. In a different experiment, it was found that SAE of achiral allylic alcohol 15 with the (+)-diethyl tartrate [(+)-DET] ligand produces a 99 1 mixture of /(- and a-epoxy alcohol enantiomers in favor of / -16 (98% ee). 

A closely related asymmetric synthesis of chiral sulphoxides, which involves a direct oxidation of the parent sulphides by t-butylhydroperoxide in the presence of metal catalyst and diethyl tartrate, was also reported by Modena and Di Furia and their coworkers-28-7,288 jjje effect 0f the reaction parameters such as metal catalyst, chiral tartrate and solvent on the optical yield does not follow a simple pattern. Generally, the highest optical purities (up to 88%) were observed when reactions were carried out using Ti(OPr-i)4 as a metal catalyst in 1,2-dichloroethane. 

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. ... 

Along another line of work in our group (S,S)-l,4-bis(dimethylamino)-2,3-dimethoxy butane (DDB), which had been used as cosolvent in asymmetric synthesis [113], was tested as a core moiety for a dendritic amine catalyst. The conformationally flexible DDB-core, which has been synthesized in five steps from diethyl tartrate was coupled with different branches to give dendritically expanded diamines 90-92 (molecular weight 3800 Da) [114] (Fig. 32). 

Since its discovery in 1980,7 the Sharpless expoxidation of allylic alcohols has become a benchmark classic method in asymmetric synthesis. A wide variety of primary allylic alcohols have been epoxidized with over 90% optical yield and 70-90% chemical yield using TBHP (r-BuOOH) as the oxygen donor and titanium isopropoxide-diethyl tartrate (DET, the most frequently used dialkyl tartrate) as the catalyst. One factor that simplifies the standard epoxidation reaction is that the active chiral catalyst is generated in situ, which means that the pre-preparation of the active catalyst is not required. 

An alternative method for the epoxidation of enones was developed by Jackson and coworkers in 1997 , who utilized metal peroxides that are modified by chiral ligands such as diethyl tartrate (DET), (5,5)-diphenylethanediol, (—)-ephedrine, ( )-N-methylephedrine and various simple chiral alcohols. The best results were achieved with DET as chiral inductor in toluene. In the stoichiometric version, DET and lithium tert-butyl peroxide, which was generated in situ from TBHP and n-butyllithium, were used as catalyst for the epoxidation of enones. Use of 1.1 equivalent of (-l-)-DET in toluene as solvent afforded (2/f,35 )-chalcone epoxide in 71-75% yield and 62% ee. In the substo-ichiometric method n-butyllithium was replaced by dibutylmagnesium. With this system (10 mol% Bu2Mg and 11 mol% DET), a variety of chalcone-type enones could be oxidized in moderate to good yields (36-61%) and high asymmetric induction (81-94%), giving exactly the other enantiomeric epoxide than obtained with the stoichiometric system (equation 37). 

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 . 

The Sharpless reagent, i.e. Ti(OPr-i)4/TBHP/diethyl tartrate, has been tested in the asymmetric BV oxidation of mono and bicyclic butanones . Conversions are low in all cases and ee values range from moderate to good. The best result has been obtained with the most bulky bicyclic ketone of the series, oxidized to the corresponding lactone with ee values up to 75%, using (+)-diethyl tartrate as ligand (equation 79). The use of a modified Sharpless reagent, based on Ti-TADDOL catalyst , increased the reaction rates, but decreased the enantiomeric excesses . ... 

Both the ally lie alcohol and tert-hutyX hydroperoxide are achiral, but the product epoxide is formed in high optical purity. This is possible because the catalyst, titanium tetraiso-propoxide, forms a chiral (possibly dimeric [36]) complex with resolved diethyl tartrate [(+)-DET] which binds the two achiral reagents together in the reactive complex. The two enantiotopic faces of the allylic double bond become diastereotopic in the chiral complex and react at different rates with the tert-butyl hydroperoxide. Many other examples may be found in recent reviews [31, 37-39]. 

The oxidation of sulfides to sulfoxides by TBHP in the presence of Mo and V catalysts has been extensively studied.230,256 A modified Sharpless reagent,243 i.e. Ti(OPr )4/2 diethyl tartrate/1 H20, was used for the asymmetric oxidation of prochiral sulfides to sulfoxides with enantiomeric excess greater than 90% (equation 82).160,257... 

Uemura et al. [49] found that (R)-1,1 -binaphthol could replace (7 ,7 )-diethyl tartrate in the water-modified catalyst, giving good results (up to 73% ee) in the oxidation of methyl p-tolyl sulfoxide with f-BuOOH (at -20°C in toluene). The chemical yield was close to 90% with the use of a catalytic amount (10 mol %) of the titanium complex (Ti(0-i-Pr)4/(/ )-binaphthol/H20 = 1 2 20). They studied the effect of added water and found that high enantioselectivity was obtained when using 0.5-3.0 equivalents of water with respect to the sulfide. In the absence of water, enantioselectivity was very low. The beneficial effect of water is clearly established here, but the amount of water needed is much higher than that in the case of the catalyst with diethyl tartrate. They assumed that a mononuclear titanium complex with two binaphthol ligands was involved, in which water affects the structure of the titanium complex and its rate of formation. 

The second-generation synthesis of (S,S)-TaDiAS 1 is summarized in Scheme 6.1 [16], This process requires only common and inexpensive reagents under operationally simple reaction conditions. When using the first-generation synthesis (a five-step process from diethyl tartrate) [4a] or the second-generation synthesis (a four-step process from tartaric acid), a variety of catalysts with versatility on the acetal moieties (R1 and R2) and aromatic parts (Ar) were synthesized (over 100 derivatives) [18]. A large-scale reaction (>20g) can also be performed with the same efficiency. 

A number of stereospecific non-enzyme catalysts have been developed that convert achiral substrates into chiral products. These catalysts are usually either complex organic (Figure 10.8(a)) or organometallic compounds (Figure 10.8(b)). The organometallic catalysts are usually optically active complexes whose structures usually contain one or more chiral ligands. An exception is the Sharpless-Katsuki epoxidation, which uses a mixture of an achiral titanium complex and an enantiomer of diethyl tartrate (Figure 10.8(c)). 

The enantiomers of thiochroman 1-oxide have been obtained by oxidation of thiochroman in the presence of (R,R)-l,2-diphenylethane-l,2-diol (DPED) or L-diethyl tartrate. In the case of the enantioselective oxidation of thiochroman-4-one, (R,R)-DPED and (V,V)-DPED were used as the chiral inducers <2002CH400>. Fligh yields of both (—)-(R)-thiochroman 1-oxide and (—)-(R)-thiochroman-4-one 1-oxide and with enantioselectivities of 98% and 96%, respectively result from the reaction of H202 with the heterocycles when significant amounts of chloroperox-idase are used as catalyst <1998CH246>. 

The typical protocol of the catalytic Sharpless epoxidation requires 5-10 mol% of Ti(OiPr)4, which is chelated in situ by an equimolar amount of enantiomerically pure dimethyl or diethyl tartrate (15). The reaction proceeds in anhydrous CH2CI2, and a 4A zeolite is added to make the reaction catalytic. An early attempt by Farrall et al. (30) to anchor the catalyst was carried out with a tartrate monomer covalently attached to a cross-linked polystyrene resin. The enantiomeric excess (ee) values obtained (about 60%) were significantly lower than in the homogeneous reaction, for which values greater than 90% ee have been regularly achieved. 

Hie first of Sharpless s reactions is an oxidation of alkenes by asymmetric epoxidation. You met vanadium as a transition-metal catalyst for epoxidation with r-butyl hydroperoxide in Chapter 33, and this new reaction makes use of titanium, as titanium tetraisopropoxide, Ti(OiPr)4, to do the same thing. Sharpless surmised that, by adding a chiral ligand to the titanium catalyst, he might be able to make the reaction asymmetric. The ligand that works best is diethyl tartrate, and the reaction shown below is just one of many that demonstrate that this is a remarkably good reaction. 

The Intermediate In this synthesis of disparlure, (Z)-2-tridecenol, Is obtained by hydrogenation of 2-trldecynol In the presence of a palladium catalyst poisoned with barium sulfate and quinoline. Oxidation of (Z)-2-tridecenol with tert-butyl hydroperoxlde/tItanium tetralsopropoxlde/D (-)-diethyl tartrate gives (2R, 3S)-epoxytrldecanol In enantiomeric excess reported to be as much as 98 percent after recrystalllzatlon. 

The SAE is arguably one of the most important reactions discovered in the last 30 years. The SAE converts the double bond of allyl alcohols into epoxides with high enantioselective purity using a titanium tetraisopropoxide catalyst, Ti(0-iPr)4, chiral additive, either L-(+)-diethyl tartrate [(+)-DET, 7.45] or D-(—)-diethyl tartrate [(—)-DET, 7.46], and tert-butyl peroxide (t-BuOOH, TBHP (f-butylhydroperoxide)) as the source of the oxidant in stoichiometric amounts (see section 1.5, references 28-30 of Chapter 1). 

Hydrogen peroxide or t-butyl hydroperoxide may be used in the presence of a catalyst such as sodium tungstate(VI) or vanadyl acetylaceto-nate [ MeC0CH=C(0 )Me 2V0] for the epoxidation of allylic alcohols. The stereochemistry of the hydroxyl group has a profound effect on the stereochemistry of epoxidation. A system which has been applied to allylic alcohols, to make optically active epoxides, utilizes titanium(rV) isopropoxide, t-butyl hydroperoxide and either of the enantiomeric forms of diethyl tartrate. This system forms chiral epoxides of predictable stereochemistry. When the reactivity of epoxides is combined with the... 

The Sharpless reagent consists of three components rcrr-butyl hydroperoxide, (CHgjgCOOH a titanium catalyst—usually titanium(IV) isopropoxide, Ti[OCH(CH3)2l4 and diethyl tartrate (DET). There are two different chiral diethyl tartrate isomers, labeled as (+)-DET or (-)-DET to indicate the direction in which they rotate polarized light. 

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