Allylic alcohols Sharpless-Katsuki asymmetric epoxidation

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>. 

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]. 

T. Katsuki, V S. Martin, Asymmetric Epoxidation of Allylic Alcohols The Katsuki-Sharpless Epoxidation Reaction, Org. React. 1996, 48, 1-299. 

Asymmetric Epoxidation of Allylic Alcohols The Katsuki-Sharpless Epoxidation Reaction... 

Katsuki T, Martin VS. Asymmetric epoxidation of allylic alcohols the Katsuki-Sharpless epoxidation reaction. Org. Reactions 1996 48 1. 

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. 

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. 

The scope of metal-mediated asymmetric epoxidation of allylic alcohols was remarkably enhanced by a new titanium system introduced by Katsuki and Sharpless epoxidation of allylic alcohols using a titanium(IV) isopropoxide, dialkyl tartrate (DAT), and TBHP (TBHP = tert-butyl-hydroperoxide) proceeds with high enantioselectivity and good chemical yield, regardless of... 

The asymmetric dihydroxylation protocol was the second massive contribution by Professor Barry Sharpless to synthetic organic chemistry. The first procedure, introduced with Katsuki, involves the catalytic asymmetric epoxida-tion of allylic alcohols. A typical example is shown in Scheme 17, wherein ( )-allylic alcohol (23) is epoxidized with tert-b utyl hyd roperox ide, in the presence of titanium tetra-isopropoxide and optically active diethyl tartrate to give the... 

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 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 . 

Asymmetric Epoxidation. Asymmetric epoxidation of nonfunctionalized alkenes manifests a great synthetic challenge. The most successful method of asymmetric epoxidation, developed by Katsuki and Sharpless,332 employs a Ti(IV) alkoxide [usually Ti(OisoPr)4], an optically active dialkyl tartrate, and tert-BuOOH. This procedure, however, was designed to convert allylic alcohols to epoxy alcohols, and the hydroxyl group plays a decisive role in attaining high degree of enantiofa-cial selectivity.333,334 Without such function, the asymmetric epoxidation of simple olefins has been only moderately successful 335... 

APTMS-modified MCM-41 surface. In a last step, titanium tetra-wo-propoxide reacted with the chiral organic-inorganic hybrid material, to give the heterogeneous variant of the asymmetric epoxidation catalyst of allylic alcohols, proposed by Katsuki and Sharpless.312... 

Catalytic, asymmetric epoxidations are one of the most important asymmetric processes. In 1980 Katsuki and Sharpless reported a stoichiometric asymmetric epoxidation of allylic alcohols, a method that was later improved to become a catalytic process.9 Moreover, catalytic asymmetric epoxidations of unfunctionalized olefins using salen-manganese complexes have been reported independently by several groups.10-12 In striking contrast to these successful achievements, an efficient catalytic asymmetric epoxidation of enones with broad generality has not been developed.13-22... 

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. 

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 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. 

A simple, divergent, asymmetric synthesis of the four stereoisomers of the 3-amino-2,3,6-trideoxy-L-hexose family was proposed by Dai and coworkers [222], which is based on the Katsuki-Sharpless asymmetric epoxidation of allylic alcohols (Scheme 13.115). Recently, A-trifluoroacetyl-L-daunosamine, A-trifluoroacetyl-L-acosamine, A-benzoyl-D-acosamine and A-benzoyl-D-nistosamine were derived from methyl sorbate via the methyl 4,5-epoxy-( -hex-2-enoates obtained via a chemoenzymatic method [223]. 

The first practical asymmetric epoxidation of primary and secondary allylic alcohols was realized by Sharpless and Katsuki in 1980. They discovered that the use of titanium(IV) tetraisopropoxide, tert-butylhydroperoxide (TBHP), and an enantiopure chiral auxiliary (such as diethyl tartrate (6)) accomplishes the epoxidation of allylic alcohols with excellent stereoselectivity ee > 90 %) to give chiral 2,3-epoxy alcohols, which represent valuable building blocks. In acknowledgement of the discovery and of his outstanding contributions to the development of this reaction. Sharpless was awarded one half of the Nobel Prize in Chemistry in 2001. ... 

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 synthetic utility of the oxirane technology was further extended by the development by Sharpless and Katsuki [33, 34] of the titanium(lV) tartrate catalyst for the asymmetric epoxidation of allylic alcohols with TBHP (eq. (16)). 

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