Katsuki-Sharpless oxidation

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]. 

An important breakthrough in asymmetric epoxidation has been the Katsuki-Sharpless invention [1], The reaction uses a chiral Ti(IV) catalyst, t-butylhydroperoxide as the oxidant and it works only for allylic alcohols as the substrate. In the first report titanium is applied in a stoichiometric amount. The chirality is introduced in the catalyst by reacting titanium tetra-isopropoxide... 

In this chapter, the ligand design for the catalytic enantioselective oxidations developed after the Katsuki-Sharpless epoxidation and the Sharpless AD will be discussed. 

Both chemical and enzymatic synthetic methods for the asymmetric oxidation of the carbon-carbon double bond have been developed [46], but the area of carbon-carbon double bond oxidations has been shaped by the breakthrough discovery of asymmetric epoxidation of allylic alcohols with the Katsuki-Sharpless method [47]. Catalytic asymmetric synthesis of epoxides from alkenes by Jacobsen... 

The Katsuki-Sharpless asymmetric epoxidation of ( )-allylic alcohols is the key-step in the total synthesis of all tetroses and hexoses developed by Sharpless and Masamune [259,260] and that are summarized in O Scheme 57 for the L-series. The epoxide obtained by oxidation of... 

The Katsuki-Sharpless asymmetric epoxidation is one of the first predictably enantioselective oxidations. For reviews see (a) Katsuki, T. Martin, V. Org. React. 1996, 48, 1-299. (b) Pfenniger, D. S. Synthesis 1986, 89-116. 

The process is called the Sharpless oxidation, after Sharpless, K. B., Professor, Massachusetts Institute of Technology (MIT). The first descriptons of the process appeared in 1980 (Katsuki.T. Sharpless, K. B. J. Am. Chem. Soa, 1980,102,5974). 

Scheme 8.19. A cartoon representation of the process by which stereospeciflc introduction of an oxygen (as an oxirane) is accomplished in the Sharpless oxidation. Diethyl (2R,3R)-2,3-dihydroxybutane-l,4-dicarboxylate [L-(+)-diethyl tartrate],Et = CHjCHj forms a complex with titanium(IV) Mopropoxide,TiL4, where l = OCH(CHj)2. In the process, the two hydroxyl groups at C2 and C3 of the tartrate displace (replace) two of the four isopropoxy groups originally attached to titanium (see Katsuki,T. Sharpless, K. B. /. Am. Chem. 5oc., 1980,102, 5974).

Miscellaneous. Racemic ketones have been resolved by condensation with (R,R)- or (S,5)-2,3-butanedithiol, then reduced as above to give resolved deoxy compounds (eq 6). Oxidation of prochiral 1,3-dithiolanes under modified Katsuki-Sharpless conditions yields monosulfoxides of high ee. In peptide synthesis, (1) is frequently used as a cation scavenger during deprotection.Transition metal cations are strongly chelated by (1), as exemplified by demetalation of Cu and Ni metalloporphyiins. ... 

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... 

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 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-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... 

Indeed, several interesting procedures based on three families of active catalysts organometallic complexes, phase-transfer compounds and titanium silicalite (TS-1), and peroxides have been settled and used also in industrial processes in the last decades of the 20th century. The most impressive breakthrough in this field was achieved by Katsuki and Sharpless, who obtained the enantioselective oxidation of prochiral allylic alcohols with alkyl hydroperoxides catalyzed by titanium tetra-alkoxides in the presence of chiral nonracemic tartrates. In fact Sharpless was awarded the Nobel Prize in 2001. 

Interestingly, solution studies on the namre of the active catalyst, carried out in the case of Ti(IV)-tartrate catalysts proposed by Katsuki and Sharpless for the enantioselective oxidation of allylic alcohols, opened routes to enantioselective oxidations of thioethers . ... 

In 1980, Katsuki and Sharpless described the first really efficient asymmetric epoxidation of allylic alcohols with very high enantioselectivities (ee 90-95%), employing a combination of Ti(OPr-/)4-diethyl tartrate (DET) as chiral catalyst and TBHP as oxidant Stoichiometric conditions were originally described for this system, however the addition of molecular sieves (which trap water traces) to the reaction allows the epoxidation to proceed under catalytic conditions. The stereochemical course of the reaction may be predicted by the empirical rule shown in equations 40 and 41. With (—)-DET, the oxidant approaches the allylic alcohol from the top side of the plane, whereas the bottom side is open for the (-l-)-DET based reagent, giving rise to the opposite optically active epoxide. Various aspects of this reaction including the mechanism, theoretical investigations and synthetic applications of the epoxy alcohol products have been reviewed and details may be found in the specific literature . 

Angert, K. B. Sharpless, Angew. Chem. Int. Ed. Engl. 1996,35,2813 (c) H. C. Kolb, K. B. Sharpless, Asymmetric Aminohydroxylation in Transition Metals for Organic Synthesis, Vol. 2 M. Beller, C. Bolm (Eds.) WILEY-VCH, Weinheim, 1998,243 - 260 (d) G. Schlingloff, K. B. Sharpless, Asymmetric Aminohydroxylation in Asymmetric Oxidation Reactions A Practical Approach T. Katsuki (Ed.) Oxford University Press, Oxford, in press. 

Schlingloff G, Sharpless KB (2001) Asymmetric aminohydroxylation. In Katsuki T (ed) Asymmetric oxidation reactions. Oxford UP, Oxford, p 104... 

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