Asymmetric synthesis Sharpless-Katsuki epoxidation

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>. 

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. 

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]. 

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... 

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]. 

Katsuki-Sharpless asymmetric epoxidation. Since its introduction in 1980 [10], the Katsuki-Sharpless asymmetric epoxidation (AE) reaction of allylic alcohols has been one of the most popular methods in asymmetric synthesis ([11-14]). In this work, the metal-catalyzed epoxidation of allylic alcohols described in the previous section was rendered asymmetric by switching from vanadium catalysts to titanium ones and by the addition of various tartrate esters as chiral ligands. Although subject to some technical improvements (most notably the addition of molecular sieves, which allowed the use of catalytic amounts of the titanium-tartrate complex), this recipe has persisted to this writing. 

In recent years the discovery of novel methods of asymmetric synthesis has greatly increased the ability of organic chemists to synthesize optically active sugars. For example, the asymmetric epoxidation reaction discovered by Katsuki and Sharpless [142] was recently used as the key step in a synthesis of D-oleandrose 118 from divinyl carbinol 119 by Hatakeyama et al. [143]. An alternative approach to asymmetric synthesis of oleandrose was taken by Danishefsky et al. [144,32] in their synthesis of avermectin which is the first, and currently the only, reported total synthesis of an avermectin. The key step of this synthesis was a cyclocondensation reaction of optically active diene 121 with acetaldehyde catalyzed by the optically active Lewis acid (-h)-Eu(hfc)3 [145]. The resulting chiral pyrone was then elaborated to methyl-L-oleandroside 113. This was further converted to the disaccharide glycal 122 by a 4 step sequence in which glycoside formation was accomplished by iV-iodosuccinimide mediated addition of the alcohol to a glycal followed by tributyltin hydride... 

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%. 

The Katsuki-Sharpless epoxidation of allylic alcohols constitutes one of the most important developments in asymmetric synthesis [189, 190], but there are some limitations in this approach. For instance, they are not generally applicable to substrates other than allylic alcohols and the products have to be purified from significant amounts of catalyst residues. A useful alternative is in the lipase-catalyzed resolution (Scheme 3.10) [191, 192]. 

A particular class of modified electrodes consists of those containing a layer of asymmetric compounds, and such electrodes are termed chiral. If one uses these electrodes in organic synthesis, the compound produced may also be asymmetric and optically active. One of the better-known examples of such phenomena is called the Sharpless process (Finn and Sharpless, 1986 Katsuki, 1996). In such processes, the electrode is modified by asymmetric compounds that lead to epoxidation and dihy-droxylation of olefenic compounds, but in an asymmetric form. An example is shown in Fig. 11.5, in which the hydroxylation occurs either on the top or the bottom of the enantiomorphic surface. 

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. 

Since the advent of asymmetric epoxidation by Sharpless and Katsuki in 1980, numerous asymmetric reactions have been invented, and some of them are selective and efficient enough to be employed in pheromone synthesis.6,11 Examples will be given later in this chapter. 

Sharpless and Katsuki described a very general method for the asymmetric epoxidation ofallylic alcohols (Scheme 9) [53]. The titanium alcoholate was initially used in stoichiometric amounts, though it was subsequently found it was possible to run the reaction catalytically in the presence of molecular sieves [54]. This method soon became a routine reaction in synthesis, because of its gener-... 

Since the first report by Katsuki and Sharpless in 1980 [21], the asymmetric epoxidation of allylic alcohols has been widely applied to the synthesis of various compounds [22]. Among several asymmetric epoxidations developed, the Sharpless asymmetric epoxidation (AE) is undoubtedly the most popular and versatile method, which has greatly contributed to the progress of natural product synthesis. 

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