Sharpless-Katsuki asymmetric

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. 

The Sharpless-Katsuki asymmetric epoxidation (AE) procedure for the enantiose-lective formation of epoxides from allylic alcohols is a milestone in asymmetric catalysis [9]. This classical asymmetric transformation uses TBHP as the terminal oxidant, and the reaction has been widely used in various synthetic applications. There are several excellent reviews covering the scope and utility of the AE reaction... 

Nucleophilic reduction by telluride ion of oxirane tosylates provides allylic alcohols, presumably via telluriranes as shown in Equation (12) and Table 7 <1997T12131>. When used in conjunction with the Sharpless-Katsuki asymmetric epoxidation, optically active transposed allylic alcohols can be made in high enantiomeric excess <1993JOC718, 1994JOC4311, 1994JOG4760>. 

Equation 12.16 is an example of the Sharpless-Katsuki asymmetric epoxi-dation of allylic alcohols, which is catalyzed by a Ti complex bound to a chiral tartrate ligand.38 A Mn-salen39 complex serves as catalyst for asymmetric epoxi-dation (Jacobsen-Katsuki reaction) of a wide variety of unfunctionalized alkenes, shown in equation 12.17.40 0s04 complexed with chiral alkaloids, such as quinine derivatives (equation 12.18), catalyzes asymmetric 1,2-dihydroxylation of alkenes (known as the Sharpless asymmetric dihydroxylation).41 The key step of all these transformations is the transfer of metal-bound oxygen, either as a single atom or as a pair, to one face of the alkene. 

Efaroxan, an a2 adrenoreceptor antagonist, could be used for the treatment of neurodegenerative diseases (Alzheimer and Parkinson), migraine and type II diabetes. Therefore, the total syntheses of ( + )-efaroxan and their derivatives have drawn much attention.The chiral 2,3-dihydrobenzofuran carboxylic acid 135, the direct precursor of (+ )-efaroxan, was obtained mainly from the resolution of racemic 135. Coelho el al. have reported a straightforward enantioselective synthesis of i -( + )-2-ethyl-2,3-dihydrofuran-2-carboxylic acid (135) achieved by a Sharpless-Katsuki asymmetric epoxidation reaction (Scheme 5.22). The dihydrobenzofuran acid 135 was obtained in seven steps from MBH adduct 136 in an overall yield of 17%. 

Preparation of (2S,3S)-3-propyloxiranemethanol. Catalytic Sharpless-Katsuki asymmetric epoxidation (AE) (Scheme 1.1)... 

The past thirty years have witnessed great advances in the selective synthesis of epoxides, and numerous regio-, chemo-, enantio-, and diastereoselective methods have been developed. Discovered in 1980, the Katsuki-Sharpless catalytic asymmetric epoxidation of allylic alcohols, in which a catalyst for the first time demonstrated both high selectivity and substrate promiscuity, was the first practical entry into the world of chiral 2,3-epoxy alcohols [10, 11]. Asymmetric catalysis of the epoxidation of unfunctionalized olefins through the use of Jacobsen s chiral [(sale-i i) Mi iln] [12] or Shi s chiral ketones [13] as oxidants is also well established. Catalytic asymmetric epoxidations have been comprehensively reviewed [14, 15]. 

Reviews on asymmetric epoxidation326, with particular emphasis on the Sharpless-Katsuki procedure327,328, have appeared. 

Permanganate oxidation of 1,5-dienes to prepare f r-2,5-disubstituted tetrahydrofurans is a well-known procedure (Equation 80). The introduction of asymmetric oxidation methodology has revived interest in this area. Sharpless-Katsuki epoxidation has found widespread application in the catalytic enantioselective synthesis of optically active tetrahydrofurans and the desymmetrization of w ro-tetrahydrofurans <2001COR663>. A general stereoselective route for the synthesis of f-tetrahydrofurans from 1,5-dienes has been developed which uses catalytic amounts of osmium tetroxide and trimethyl amine oxide as a stoichiometric oxidant in the presence of camphorsulfonic acid <2003AGE948>. 

The mechanism of the asymmetric epoxidation of allylic alcohols with the Sharpless-Katsuki catalyst is assumed to be very similar to the one described for the Halcon-ARCO process in Section 2.5. The key point is that the chiral tartrate creates an asymmetric environment about the titanium center (Figure 18). When the allylic alcohol and the t-butyl hydroperoxide bind through displacement of alkoxy groups from the metal, they are disposed in such a way as to direct oxygen transfer to a specific face of the C=C double bond. This point is crucial to maximize enantioselectivity. 

The most famous asymmetric oxidation catalyst, Sharpless-Katsuki complex [Ti(0-iPr)4, t-BuOOH and ester of tartaric acid], used for the asymmetric epoxidation of allylic alcohols can also oxidize prochiral and racemic cyclobutanones 7.25 and 7.27 to enan-tiomerically enriched lactones 7.26 and 7.28, respectively. 

Katsuki and Sharpless s ° asymmetric epoxidation of 727 gave 728 only if the... 

Important chemical reactions which are applied for asymmetric synthesis are the Sharpless-Katsuki epoxidation and, more recently, the Sharpless dihydroxylation. These reactions have been applied with great success, e,g. in the synthesis of (35,5R,65,3 5,5 R,6 5)-violaxanthin (259) by the school of Eugster. 

Rossiter BE, Katsuki T, Sharpless KB. Asymmetric epoxidation provides shortest routes to four chiral epoxy alcohols which are key intermediates in syntheses of methymycin, erythromycin, leukotriene C-1, and disparlure. J. Am. Chem. Soc. 1981 102(2) 464-465. 

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... 

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 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. 

Jacobsen epoxidation 359 -, Katsuki epoxidation 361 -, Mukaiyama-aldol reaction 367 f. -, oxime ether reduction 363 -, Sharpless asymmetric dihydroxyla-tion 361... 

Ten years after Sharpless s discovery of the asymmetric epoxidation of allylic alcohols, Jacobsen and Katsuki independently reported asymmetric epoxidations of unfunctionalized olefins by use of chiral Mn-salen catalysts such as 9 (Scheme 9.3) [14, 15]. The reaction works best on (Z)-disubstituted alkenes, although several tri-and tetrasubstituted olefins have been successfully epoxidized [16]. The reaction often requires ligand optimization for each substrate for high enantioselectivity to be achieved. 

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