Tartrates chiral

Polavarapu PL, Petrovic AG, Zhang P. Kramers-Kronig transformation of experimental electronic circular dichroism application to the analysis of optical rotatory dispersion in dimethyl-L-tartrate. Chirality 2006 18(9) 723-732. 

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

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). 

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. 

The reaction of diethyl tartrate with sulfur tetrafluonde at 25 °C results in replacement of one hydroxyl group, whereas at 100 °C, both hydroxyl groups are replaced by fluonne to form a,a -difluorosuccinate [762] The stereochemical outcome of the fluonnation of tartrate esters is retention of configuration at one of the chiral carbon atoms and inversion of configuration at the second chiral center [163,164, 165] Thus, treatment ofdimethyl(+)-L-tartrate with sulfur tetrafluonde gives dimethyl meso-a,a difluorosuccinate as the final product [163, 164], whereas dimethyl meso tartrate is converted into a racemic mixture of D- and L-a,a -difluorosuccmates [765] (equation 80)... 

TMSCN, (—)-DIPT [diisopropyl L-tartrate], Ti(/-PrO)4, CH2CI2, 0°, 6 h, rt, 12 h, 95% yield. These conditions afford chiral cyanohydrins. ... 

The Sharpless-Katsuki asymmetric epoxidation reaction (most commonly referred by the discovering scientists as the AE reaction) is an efficient and highly selective method for the preparation of a wide variety of chiral epoxy alcohols. The AE reaction is comprised of four key components the substrate allylic alcohol, the titanium isopropoxide precatalyst, the chiral ligand diethyl tartrate, and the terminal oxidant tert-butyl hydroperoxide. The reaction protocol is straightforward and does not require any special handling techniques. The only requirement is that the reacting olefin contains an allylic alcohol. 

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... 

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 ... 

A model for the catalytically active species in the Sharpless epoxidation reaction is formulated as a dimer 3, where two titanium centers are linked by two chiral tartrate bridges. At each titanium center two isopropoxide groups of the original tetraisopropoxytitanium-(IV) have been replaced by the chiral tartrate ligand ... 

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-... 

Excellent double diastereoselection has also been realized in the reactions of (7 )-2,3-[isopro-pylidenebis(oxy)]propanal and chiral 2-butenylboron reagents (Table 8). The best selectivity for the (3R,4R)- and (SS /Q-diastereomers was obtained by using the tartrate ( )- and (Z)-2-butenylboronates. (S.S -D and (R,R)-D, respectively69,81, while (E)- and (Z)-2-butenyl-2,5-dimethylborolane reagents (R,R)-C and (S,S) C provided the greatest selectivity for the (3S, 45)- and (3y ,4S )-diastereomers< 9. Comparative diastereoselectivity data for reactions with the achiral (E)- and (Z)-2-butenyl-4,4,5,5-tetramethyl-l,3,2-dioxaborolanes have also been provided in the table. 

Results of the asymmetric 2-propenylborations of several chiral a- and /i-alkoxy aldehydes are presented in Table 11 74a-82 84. These data show that diisopinocampheyl(2-propenyl)borane A and l,3-bis(4-methylphenylsulfonyl)-4,5-diphenyl-2-propenyl-l,3,2-diazaborolidine C exhibit excellent diastereoselectivity in reactions with chiral aldehydes. These results are in complete agreement with the enantioselectivity of these reagents in reactions with achiral aldehydes (Section 1.3.3.3.3.1.4.). In contrast, however, the enantioselectivity of reactions of the tartrate 2-propenylboronate B (and to a lesser extent the tartrate (/i)-2-butenylhoronate)53b is highly... 

The matched double asymmetric reactions with (7 )-l and (a.R,S,S)-2 provide the (S,Z)-diastereomer with 94% and 96% selectivity, while in the mismatched reactions [(S)-l and (aS,R,R)-2] the (S.Z)-diastereomer is obtained with 77% and 92% selectivity, respectively. Interestingly, the selectivity of the reactions of (/ )-2,3-[isopropylidenebis(oxy)]propanal and 2 is comparable to that obtained in reactions of (7 )-2,3-[isopropylidenebis(oxy)]propanal and the much more easily prepared tartrate ester modified allylboronates (see Table 7 in Section 1.3.3.3.3.1.5.)41. However, 2 significantly outperforms the tartrate ester allylboronates in reactions with (5)-2-benzyloxypropanal (Section 1.3.3.3.3.1.5.), but not the chiral reagents developed by Brown and Corey42-43. 

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. 

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