Diisopropyl tartrate , allylic alcohol

TPOUnd s nicely illustrative of this reaction (and often cited) is allylic alcohol17 it L-(+)-diisopropyl tartrate this alcohol has a fast-reacting (S) and a slow-reacting (R) enantiomer but what is not addressed in the above diagram is that, in principle, both enantiomers cou give two different diastereomers 25 and 26. 

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. 

It has recently been found that Et2Zn promotes the 1,3-dipolar cycloaddition of nitrile oxides to allyl alcohol in the presence of catalytic amounts of diisopropyl tartrate (DIPT). By this method, 2-isoxazlines are obtained in good yields and up to 96% ee (Eq. 8.73).124a A positive nonlinear effect (amplification of ee of the product) has been observed in this reaction. There is an excellent review on positive and negative nonlinear effects in asymmetric induction.124b... 

The asymmetric 1,3-dipolar cycloaddition of nitrones (515), possessing an electron-withdrawing group, to allylic alcohols was achieved by using diisopropyl (/ ,/ )-tartrate [(R,R-DIPT)] as a chiral auxiliary. The isoxazolidines (516) and... 

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 use of other metal cations such as those derived from zinc, lithium, or aluminium proved less effective (136). Treatment of allyl alcohol with diethyl zinc in the presence of a catalytic amount of diisopropyl (/ ,/ )-(+ )-tartrate (DIPT) in 1,4-dioxane, however, afforded the corresponding (5/f)-2-isoxazolines with excellent selectivity er >92 8) (178). Addition of dioxane was necessary in order to avoid precipitation of the complex of zinc salts containing the DIPT moiety. Without this solvent, lower stereoselectivity was found, probably due to the precipitation mentioned above, which prevents the favorable catalytic cycle proposed (Scheme 6.32) (178). 

Ukaji and co-workers (379-381) described the first, and so far only, metal-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrile oxides with alkenes. Upon treatment of allyl alcohol with diethylzinc and (7 ,/ )-diisopropyl tartrate followed by the addition of diethylzinc and substimted hydroximoyl chlorides 274, the isoxazoli-dines 275 are formed with enantioselectivities of up to 96% ee (Scheme 12.87). 

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. 

A chiral zinc(II) complex derived from Et2Zn and diisopropyl (/ ,/ )-tartrate as a chiral auxiliary is applied to the asymmetric 1,3-dipolar cycloaddition of nitrile oxides to an achiral allylic alcohol, giving the corresponding (R)-2-isoxazolines with high enantioselectivity. Addition of a small amount of ethereal compounds such as DME and 1,4-dioxane is crucial for achieving the high asymmetric induction in a reproducible manner [71] (Eq. 8A.47). 

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. 

Brown and co-workers developed a novel homoallenyl boronate reagent 169 based on diisopropyl tartrate for the stereoselective homoallenylation of aldehydes 170. The reagent 169 was prepared via homologation of the corresponding allenyl boronate or the alkylation of halomethyl boronate with allenyl Grignard similar to those reported in Scheme 26. The allyl boronate 169 upon reaction with aldehydes furnished the dienyl alcohols 172 with high ee (Scheme 28) <1996JOC100>. 

A catalytic asymmetric 1,3-DC of nitrone 99 with y-substituted allylic alcohols was achieved by using diisopropyl tartrate as chiral ligand. Isoxazolidines 100 were formed with high ee <02CL302>. 

PhCMe202H, cat Ti(0-i-Pr)4, cat diisopropyl tartrate, molecular sieves (allylic alcohols, enantioselective)... 

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. 

Preparative Methods the title reagent (1) is obtained in 40% overall yield by the zeolite-modified Sharpless asymmetric epoxi-dation of allyl alcohol, using D-(-)-diisopropyl tartrate (DIPT) to obtain (S)-(l) and l-(+)-DIPT to obtain (R)-(l), followed by in situ low-temperature tosylation of glycidol. Alternatively, (R)- and (S)-(l) can be prepared by direct sulfonylation of commercially available chiral Glycidol, Note that the relative configuration of (R)-glycidyl tosylate is the same as that of (5)-glycidol. 

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. 

Roush, W. R., Grover, P. T. Diisopropyl tartrate (E)-Y-(dimethylphenylsilyl)allylboronate, a chiral allylic alcohol 3-carbanion equivalent for the enantioselective synthesis of 2-butene-1,4-diols from aldehydes. Tetrahedron Lett. 1990, 31,7567-7570. 

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