Allylic alcohol Sharpless epoxidation

An effective deoxygenation using enantiomerically pure epoxides from primary allylic alcohols ( Sharpless epoxides ) [44] to give enantiomerically pure secondary allylic alcohols was described by Yadav [45]. This approach circumvented a kinetic resolution of secondary allylic alcohols that implies a maximum yield of 50% ( Scheme 5). 

ASYMMETRIC EPOXIDATION OF ALLYLIC ALCOHOLS SHARPLESS EPOXIDATION... 

Chiral Ligand for Asymmetric Catalysis. Dimethyl l-tartrate is a demonstrated chiral ligand for the Ti -catalyzed asymmetric epoxidation of allylic alcohols (Sharpless epoxidation), and the Zn -mediated asymmetric cyclo-propanation of allylic alcohols (Simmons-Smith reaction), see lodomethylzinc Iodide Enantioselectivities in these reactions... 

DIBAH reduction of 4 at -78 °C provides the corresponding trans-allylic alcohol. Successive epoxidation with meto-chloroperbenzoic acid (MCPBA) yields a single syn epoxide 5. The stereochemical assignment is proven by a second experiment using the asymmetric Sharpless epoxidation protocol. Both MCPBA and the Sharpless protocol using (-)-diethyl D-tartrate provided 5. 

The ability of the Sharpless epoxidation catalyst to differentiate between the two enantiomers of an asymmetric allyl alcohol affords a powerful synthetic tool to obtain optically pure materials through kinetic resolution.43 Because the procedure relies on one enantiomer of a secondary allyl alcohol undergoing epoxidation at a much faster rate than its antipode, reactions are usually run to 50-55% completion.22 In this way, resolution can often be impressive.18 25 26 44-46 An increase in steric bulk at the olefin terminus increases the rate of reaction.46 47... 

Sharpless asymmetric epoxidation of allylic alcohols, asymmetric epoxidation of conjugated ketones, asymmetric sulfoxidations catalyzed, or mediated, by chiral titanium complexes, and allylic oxidations are the main classes of oxidation where asymmetric amplification effects have been discovered. The various references are listed in Table 4 with the maximum amplification index observed. 

Chiral epoxides are important intermediates in organic synthesis. A benchmark classic in the area of asymmetric catalytic oxidation is the Sharpless epoxidation of allylic alcohols in which a complex of titanium and tartrate salt is the active catalyst [273]. Its success is due to its ease of execution and the ready availability of reagents. A wide variety of primary allylic alcohols are epoxidized in >90% optical yield and 70-90% chemical yield using tert-butyl hydroperoxide as the oxygen donor and titanium-isopropoxide-diethyltartrate (DET) as the catalyst (Fig. 4.97). In order for this reaction to be catalytic, the exclusion of water is absolutely essential. This is achieved by adding 3 A or 4 A molecular sieves. The catalytic cycle is identical to that for titanium epoxidations discussed above (see Fig. 4.20) and the actual catalytic species is believed to be a 2 2 titanium(IV) tartrate dimer (see Fig. 4.98). The key step is the preferential transfer of oxygen from a coordinated alkylperoxo moiety to one enantioface of a coordinated allylic alcohol. For further information the reader is referred to the many reviews that have been written on this reaction [274, 275]. 

Enantioselectivity. In 1980, T. Katsuki and K. B. Sharpless (Nobel Prize, 2001) reported a method whereby prochiral allylic alcohols are epoxidized in the presence of r-BuOOH, Ti(/-OPr)4, and (-h)-or (-)-diethyl tartrate (DET) with high regio- and stereoselectivity to produce the corresponding optically active epoxides." ... 

The enantioselective total synthesis of the annonacenous acetogenin (+)-parviflorin was accomplished by T.R. Hoye and co-workers." The b/s-tetrahydrofuran backbone of the natural product was constructed using a sequential double Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylation. The bis allylic alcohol was epoxidized using L-(+)-DET to give the essentially enantiopure bis epoxide in 87% yield. 

T. Hori, K. B. Sharpless, Synthetic applications of arylselenenic and arylseleninic acids. Conversion of olefins to allylic alcohols and epoxides, J. Org. Chem. 43, 1689-1697 (1978). 

Enantioselective Epoxidation of Allylic Alcohols (Sharpless Reaction). . 69... 

The original report on the titanium-catalysed asymmetric epoxidation of allylic alcohols (Sharpless system) prescribed stoichiometric amounts of the titanium tartrate catalyst in the general procedure and many applications of this asymmetric epoxidation have been carried out using stoichiometric or near-stoichiometric amounts of the catalyst. Sharpless has reported the first general procedure for the asymmetric epoxidation of allylic alcohols using catalytic ( <10 %) amounts of titanium(IV) isopropoxide and diethyl tartrate. 

Sharpless epoxidation of allyl alcohols (Sharpless, 1985, 1988 Pfenninger, 1986 Rossiter, 1985 Woodard et al., 1991 Finn and Sharpless, 1991 Corey, I990a,b), an example of which is included in Table 9.6, is perhaps the most recent and one of the most remarkable applications of asymmetric catalysis. The reaction is normally performed at low temperatures (-30 to 0°C) in methylene chloride with a titanium complex consisting of a chiral component [diethyl tartrate (DET) or diisopropyl tartrate (DIPT)] and a titanium salt (titanium tetraisopropoxide) as the catalyst. The beauty of the synthesis is that both enantiomers of the tartrate are available so that either form of the product can be prepared in more than 90% ee. 

Unlike the Sharpless epoxidation, which gives ehiral epoxides fix)m allylic alcohols, asymmetric epoxidation of unfimctionalized alkenes achieved by Jacobsen et al. [74],by using chiral salen-metal catalysts. Salen-Mn catalysts are preferred since manganese itself is relatively a low eost and nontoxic metal, primarily because of fewer side reaetions over other metal eomplexes. Variety of simple oxidants, such as PhlO, NaClO, and oxone are employed as reoxidants and best possible enantioselectivity for a given substrate could be achieved by choosing the proper metal-salen catalyst and reaction conditions [81], The catalyst can be Irne-tuned for required steric and electronic properties by making a variety of chiral salen ligands fi om various chiral diamines with salicylaldehyde derivates [82]. 

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... 

Sharpless epoxidations can also be used to separate enantiomers of chiral allylic alcohols by kinetic resolution (V.S. Martin, 1981 K.B. Sharpless, 1983 B). In this procedure the epoxidation of the allylic alcohol is stopped at 50% conversion, and the desired alcohol is either enriched in the epoxide fraction or in the non-reacted allylic alcohol fraction. Examples are given in section 4.8.3. 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

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... 

The AE reaction has been applied to a large number of diverse allylic alcohols. Illustration of the synthetic utility of substrates with a primary alcohol is presented by substitution pattern on the olefin and will follow the format used in previous reviews by Sharpless but with more current examples. Epoxidation of substrates bearing a chiral secondary alcohol is presented in the context of a kinetic resolution or a match versus mismatch with the chiral ligand. Epoxidation of substrates bearing a tertiary alcohol is not presented, as this class of substrate reacts extremely slowly. 

The asymmetric epoxidation of an allylic alcohol 1 to yield a 2,3-epoxy alcohol 2 with high enantiomeric excess, has been developed by Sharpless and Katsuki. This enantioselective reaction is carried out in the presence of tetraisopropoxyti-tanium and an enantiomerically pure dialkyl tartrate—e.g. (-1-)- or (-)-diethyl tartrate (DET)—using tcrt-butyl hydroperoxide as the oxidizing agent. 

The Sharpless epoxidation is one of the most important of the newer organic reactions. Although limited to allylic alcohols, it has found wide application in natural product synthesis. 

The essential features of the Masamune-Sharpless hexose synthesis strategy are outlined in a general way in Scheme 4. The strategy is based on the reiterative- application of a two-carbon extension cycle. One cycle comprises the following four key transformations (I) homologation of an aldehyde to an allylic alcohol (II) Sharpless asymmetric epoxidation of the allylic alcohol ... 

A careful analysis of this problem led to the identification of an exceedingly simple solution (see Scheme 10). The Masamune-Sharpless solution to the threo 2,3-diol problem actually takes advantage of the ready availability of the erythro 2,3-diol diastereoisomer. As we have seen in Scheme 9, erythro 2,3-diols such as 20 can be conveniently assembled from trans allylic alcohols via sequential SAE and Payne rearrangement/epoxide opening reac-... 

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-... 

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