Diethyl tartrate chiral reagent

An achiral reagent cannot distinguish between these two faces. In a complex with a chiral reagent, however, the two (phantom ligand) electron pairs are in different (enantiotopic) environments. The two complexes are therefore diastereomeric and are formed and react at different rates. Two reaction systems that have been used successfully for enantioselective formation of sulfoxides are illustrated below. In the first example, the Ti(0-i-Pr)4-f-BuOOH-diethyl tartrate reagent is chiral by virtue of the presence of the chiral tartrate ester in the reactive complex. With simple aryl methyl sulfides, up to 90% enantiomeric purity of the product is obtained. 

With this epoxidation procedure it is possible to convert the achiral starting material—i.e. the allylic alcohol—with the aim of a chiral reagent, into a chiral, non-racemic product in many cases an enantiomerically highly-enriched product is obtained. The desired enantiomer of the product epoxy alcohol can be obtained by using either the (-1-)- or (-)- enantiomer of diethyl tartrate as chiral auxiliary ... 

Seebach and Daum (75) investigated the properties of a chiral acyclic diol, 1,4-bis(dimethylamino)-(2S,35)- and (2K,3/ )-butane-2,3-diol (52) as a chiral auxiliary reagent for complexing with LAH. The diol is readily available from diethyl tartrate by conversion to the dimethylamide and reduction with LAH. The diol 52 could be converted to a 1 1 complex (53) with LAH (eq. [18]), which was used for the reduction of aldehydes and ketones in optical yields up to 75%. Since both enantiomers of 53 are available, dextro- or levorotatory products may be prepared. The chiral diol is readily recoverable without loss of optical activity. The (- )-52-LAH complex reduced dialkyl and aryl alkyl ketones to products enriched in the (S)-carbinol, whereas (+ )-52-LAH gives the opposite result. The highest optical yield of 75% was obtained in the reduction of 2,4,6-... 

Although it was also Henbest who reported as early as 1965 the first asymmetric epoxidation by using a chiral peracid, without doubt, one of the methods of enantioselective synthesis most frequently used in the past few years has been the "asymmetric epoxidation" reported in 1980 by K.B. Sharpless [3] which meets almost all the requirements for being an "ideal" reaction. That is to say, complete stereofacial selectivities are achieved under catalytic conditions and working at the multigram scale. The method, which is summarised in Fig. 10.1, involves the titanium (IV)-catalysed epoxidation of allylic alcohols in the presence of tartaric esters as chiral ligands. The reagents for this asyimnetric epoxidation of primary allylic alcohols are L-(+)- or D-(-)-diethyl (DET) or diisopropyl (DIPT) tartrate,27 titanium tetraisopropoxide and water free solutions of fert-butyl hydroperoxide. The natural and unnatural diethyl tartrates, as well as titanium tetraisopropoxide are commercially available, and the required water-free solution of tert-bnty hydroperoxide is easily prepared from the commercially available isooctane solutions. 

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 . 

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]. 

Preparative Methods the title reagent can be prepared from commercially available (1,2-benzenedithiol and 1,3-dichloroacetone. After condensation of these reagents in the presence of DMAP, the resulting l,5-benzodithepan-3-one is enantioselectively oxidized to the (/f)-monosulfoxide by modified Sharpless oxidation [cumene hydroperoxide, Ti(0-t-Pr)4] in the presence of (-F)-diethyl tartrate as a chiral ligand. - Subsequent dry ozonation" of the (/f)-monosulfoxide affords (lf ,5f )-bis-sulfoxide 1, having >98% optical purity. Alternative use of (—)-diethyl tartrate in the modified Shaipless oxidation makes possible convenient access to enantiomeric (15,5S)-1. ... 

Preparative Methods chiral titanates are usually prepared by mixing dichlorodiisopropoxytitanium and a chiral 1,4-diol in toluene. Other solvents such as ether and dichloromethane can also be employed. The alcohol exchange reaction takes place immediately at rt. Wherever necessary, liberated isopropyl alcohol is removed by azeotropic removal with toluene. The chiral 1,4-diols are prepared from dimethyl (or diethyl) tartrate by a two-step procedure comprising acetalization followed by the addition of an aryl Grignard reagent. ... 

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. 

A modified Sharpless reagent has been developed by Kagan [503, 814], Modena [502, 814] and their coworkers. This new catalyst is formed by mixing water, Ti(0/-Pr)4, and diethyltartrate in a ratio of 1/1/2. The modified catalyst promotes enantioselecfrve oxidation of arylalkylsulfides by fert-BuOOH, and chiral sulfoxides are produced with excellent enantiomeric excesses (> 90%). Lower selectivities are observed from dialkylsulfides. From (R,R) or (5 S)-diethyl tartrate, either sulfoxide enantiomer can be obtained. The use of cumene hydroperoxide as the oxidant may improve the enantioselectivity. Uemura and coworkers obtained similar results by replacing the tartrates in these complexes with binaph-thols [815],... 

The Sharpless epoxidation of allylic alcohols by hydroperoxides uses as mediator [45] or as catalyst [46] a chiral titanium complex obtained from the combination Ti(OPr )4/diethyl tartrate (DET) in 1 1 ratio. Kinetic resolution of P-hydroxysulfides was also observed, but without diastereoselectivity for the product P-hydroxysulfoxides [47]. We found that the Sharpless reagent deactivated by 1 equivalent of water allows the enantioselective oxidation of aryl methyl sulfides into sulfoxides to be performed with ee s up to 90% [4S-50]. The best reagent combination proved to be Ti(0Pr )4/DET/H20 = 1 2 1. Independently, Modena et al. obtained similar enantioselectivities with the combination Ti(OPr )4/DET in 1 4 ratio [51]. These two combinations are sometimes referred to as the Kagan reagent and the Modena reagent, respectively. They will be considered successively. 

One of the most useful organic reactions discovered in the last several decades is the titanium-catalyzed asymmetric epoxidation of primary aUyUc alcohols developed by Professor Barry Sharpless, then at Stanford University. The reagent consists of tert-butyl hydroperoxide, titanium tetraisopropoxide [Ti(0-iPr)J, and diethyl tartrate. Recall from Section 3.4B that tartaric add has two chiral centers and exists as three stereoisomers a pair of enantiomers and a meso compound. The form of tartaric add used in the Sharpless epoxidation is either pure (+)-diethyl tartrate or its enantiomer, (-)-diethyl tartrate. The fert-butyl hydroperoxide is the oxidizing agent and must be present in molar... 

Most applications of sulfide oxidations by alkyl hydroperoxides have involved titanium catalysis together with chiral ligands for enantioselective transformations. The groups of Kagan in Orsay [61] and Modena in Padova [62] reported independently on the use of chiral titanium complexes for the asymmetric sulfoxidation by the use of BuOOH as the oxidant. A modification of the Sharpless reagent with the use of Ti(0 Pr)4 and (J ,J )-diethyl tartrate (J ,J )-DET) afforded chiral sulfoxides with up to 90% ee (Eq. (8.17)). 

Among the thousands of enantioselective reactions now known, one of the most general is the so-called Sharpless epoxidation, in which an allylic alcohol, such as geraniol, is treated with tert-butyl hydroperoxide, (CHajaC—OOH, in the presence of titanium tetraisopro-poxide and diethyl tartrate (DET) as a chiral auxiliary reagent. When the (R,R) tartrate is used, geraniol is converted into its 2R,3S epoxide with 98% selectivity. 

With optically active tartrate esters present in the reaction system, titanium alkoxides catalyze a very stereoselective oxidation of allylic alcohols. This method must depend on specific interactions in the transition state by which the hydroxyl group controls the relationship between the double bond and approaching reagent and the tartrate establishes a chiral environment at the metal atom. The (+) and (-) enantiomers of diethyl tartrate give enantiomeric epoxides, each in >90% yield." ... 

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