Tartrate, diisopropyl epoxidation

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... 

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. ... 

Epoxidation of the simplest allylic alcohol, allyl alcohol 7, is achieved in 88-92% ee with yields of 50-60% using diisopropyl tartrate as ligand. In situ derivatization of the product glycidol 8 via esterification, sulfonylation, or ring opening with nucleophile is an attractive alternative to isolating glycidol. 

DIPT diisopropyl tartrate SAE Sharpless Asymmetric Epoxidation... 

The tartrate (either diethyl or diisopropyl ester) stereoisomer that is chosen depends on the specific enantiomer of the epoxide desired. 

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. 

The real breakthrough in the field of enantioselective epoxidation was reached by Sharpless and Katsuki with the development of the catalytic system consisting of titanium tetraisopropoxide and optically active diethyl- or diisopropyl tartrate (DET or DIPT) and water-free TBHP as oxygen donor (Scheme This milestone in synthetic organic... 

Diisopropyl tartrate (DIPT), aUyhc alcohol epoxidation, 395... 

The Sharpless epoxidation of allylic alcohols with lert-butyl hydroperoxide/titanium tetraiso-propoxide/diisopropyl tartrate (DIPT) is a highly enantioface-selective reaction and follows the topicity shown51. 

Optically active tartrate esters are the source of chirality for the asymmetric epoxidation process. With a few subtle exceptions, the esters used conventionally—dimethyl (DMT), diethyl (DET), and diisopropyl tartrate (DIPT)—are equally effective at inducing asymmetry during the crucial epoxidation event. The minor exceptions that have been noted include (a) a slight improvement... 

Within limits, an increase in the steric bulk at the olefin terminus of allylic alcohols of the type R1 CH(OH)CH=CHR2 causes an increase in the rate of epoxidation of the more-reactive enantiomer, and a decrease in the rate for the less-reactive enantiomer, resulting in enhanced kinetic resolution334. However, complexes of diisopropyl tartrate and titanium tetra-terf-butoxide catalyse the kinetic resolution of racemic secondary allylic alcohols with low efficiency335. Double kinetic resolution techniques can show significant advantages over the simple Sharpless epoxidation techniques336. 

Kinetic resolution of chiral aUylic alcohols.7 Partial (at least 60% conversion) asymmetric epoxidation can be used for kinetic resolution of chiral allylic alcohols, particularly of secondary allylic alcohols in which chirality resides at the carbinol carbon such as 1, drawn in accordance with the usual enantioface selection rule (Scheme I). (S)-l undergoes asymmetric epoxidation with L-diisopropyl tartrate (DIPT) 104 times faster than (R)-l. The optical purity of the recovered allylic alcohol after kinetic resolution carried to 60% conversion is often > 90%. In theory, any degree of enantiomeric purity is attainable by use of higher conversions. Secondary allylic alcohols generally conform to the reactivity pattern of 1 the (Z)-allylic alcohols are less satisfactory substrates, particularly those substituted at the /1-vinyl position by a bulky substituent. 

Thus, the reaction is very predictable. When a ( )-tartratc ligand such as (-)-DET (diethyl tartrate) or (-)-DIPT (diisopropyl tartrate) is used, the oxygen atom is delivered to the top face of the olefin when the allylic alcohol is depicted as in 31. The (+)-tartrate ligand, on the other hand, allows the bottom face to be epoxidized. 

Further examples of molybdenum-catalyzed asymmetric epoxidations of simple alkenes have been reported by Otsuka and co-workers21 who described a reagent derived from tert-butyl hydroperoxide, chelated with molybdenum oxide and (-f)-diisopropyl tartrate. 

The structure of the tartrate ester has only a minor effect on enantioselection and is not considered an important reaction variable42. Both diethyl and diisopropyl tartrate are commonly used in asymmetric epoxidations. 

The procedure for catalytic asymmetric epoxidation of allyl alcohol coupled with in situ derivatization involves the same methodology detailed above for ( )-2-octenol. On a 1.0 mol scale using ( + )-diisopropyl L-tartrate the reaction was complete in 6 hours at — 5°C. 

To test the power of the Sharpless asymmetric epoxidation process, epoxidation of 32 with (-)-(iS, S)-diisopropyl tartrate (DIPT) was also performed and did indeed give the epoxide in the C-20 section. 

In conclusion, a Sharpless asymmetric epoxidation reaction may be used to achieve regioselectivity in a complex molecule containing two allylic alcohol moieties with opposite topicity. Thus, 32 could be alternatively converted into laulimalide (1) and its C-20 regioisomer simply by switching the chiral additive from +)- R,R)- to -)- S,S)-diisopropyl tartrate (DIPT). Biological tests have shown that the natural compound 1 is by far the most active one compared to other derivatives such as the C-20 regioisomer. 

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