Epoxides, asymmetric synthesis

In addition, NaOMe, and NaNH2, have also been employed. Applieation of phase-transfer conditions with tetra-n-butylammonium iodide showed marked improvement for the epoxide formation. Furthermore, many complex substituted sulfur ylides have been synthesized and utilized. For instance, stabilized ylide 20 was prepared and treated with a-D-a/lo-pyranoside 19 to furnish a-D-cyclopropanyl-pyranoside 21. Other examples of substituted sulfur ylides include 22-25, among which aminosulfoxonium ylide 25, sometimes known as Johnson s ylide, belongs to another category. The aminosulfoxonium ylides possess the configurational stability and thermal stability not enjoyed by the sulfonium and sulfoxonium ylides, thereby are more suitable for asymmetric synthesis. 

The Best results are obtained with cA-alkenes however, the epoxidation of tri-and tetra-substituted double bonds is also possible. Because of its versatility, the Jacobsen-Katsuki epoxidation is an important method in asymmetric synthesis. 

Asymmetric Synthesis of Epoxides and Aziridines from Aldehydes and I mines... 

Of course, the key limitation of the ylide-mediated methods discussed so far is the use of stoichiometric amounts of the chiral reagent. Building on their success with catalytic asymmetric ylide-mediated epoxidation (see Section 1.2.1.2), Aggarwal and co-workers have reported an aza version that provides a highly efficient catalytic asymmetric synthesis of trans-aziridines from imines and diazo compounds or the corresponding tosylhydrazone salts (Scheme 1.43) [68-70]. 

To extend the scope of asymmetric transannular C-H insertions, more highly functionalized medium-sized cyclic epoxides have been investigated. A triad of cydooctene oxides 34, 36, and 38, possessing protected diol units, gave the expected alcohols 35, 37, and 39 (Scheme 5.10) [17, 18] an asymmetric synthesis of (-)-xialenon A has been achieved starting from alcohol 39 [19]. In comparison,... 

Hodgson et al. showed that a series of bis- and tris-homoallylic terminal epoxides underwent intramolecular cydopropanation to give a range of bicydic alcohols. A short asymmetric synthesis of sabina ketone based on this chemistry was demonstrated (Scheme 5.20). A practical advantage with this process is that the volatile epoxides can be replaced with readily available chlorohydrins, an extra... 

When n-BuLi is used instead of t-BuLi, the byproduct after desulfinylation (n-BuS(O)Ph) possesses an acidic proton, which is abstracted by the metalated epoxide. Hence, overall, a stereoselective protodesulfmylation is achieved. This can be used for the asymmetric synthesis of epoxides, such as that of (-)-disparlure from enantiopure sulfoxide 222 (Scheme 5.53) [78]. 

Without question, the most significant advance in the use of sulfur-centered nucleophiles was made by Shibasaki, who discovered that 10 mol% of a novel gallium-lithium-bis(binaphthoxide) complex 5 could catalyze the addition of tert-butylthiol to various cyclic and acyclic meso-epoxides with excellent enantioselectiv-ities and in good yields (Scheme 7.11) [21], This work builds on Shibasaki s broader studies of heterobimetallic complexes, in which dual activation of both the electrophile and the nucleophile is invoked [22]. This method has been applied to an efficient asymmetric synthesis of the prostaglandin core through an oxidation/ elimination sequence (Scheme 7.12). 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

Asymmetric epoxidations of alkenes have been intensively studied since Sharpless initial report on asymmetric epoxidation of allylic alcohols in 1980. This reaction, discussed in Section 9.1.3, has become one of the most widely employed reactions in asymmetric synthesis, due to its reliability and high enantioselectivity [2],... 

The development of Sharpless asymmetric epoxidation (SAE) of allylic alcohols in 1980 constitutes a breakthrough in asymmetric synthesis, and to date this method remains the most widely applied asymmetric epoxidation technique [34, 44]. A wide range of substrates can be used in the reaction ( ) -allylic alcohols generally give high enantioselectivity, whereas the reaction is more substrate-dependent with (Z)-allylic alcohols [34]. 

Racemic 5-methyl-5 -(sodiomethyl)-A-(4-methylphenylsulfonyl)sulfoximine reacts with ketones to give an initial methylene transfer which produces an intermediate epoxide that is ring expanded to the oxctanc56. Application to 4-rerf-butylcyclohexanonc affords a single oxetane in 69% yield. While only achiral alkylidcne transfer reagents were utilized, in principle this reaction is amenable to the asymmetric synthesis of oxetanes. 

Chiral epoxides and their corresponding vicinal diols are very important intermediates in asymmetric synthesis [163]. Chiral nonracemic epoxides can be obtained through asymmetric epoxidation using either chemical catalysts [164] or enzymes [165-167]. Biocatalytic epoxidations require sophisticated techniques and have thus far found limited application. An alternative approach is the asymmetric hydrolysis of racemic or meso-epoxides using transition-metal catalysts [168] or biocatalysts [169-174]. Epoxide hydrolases (EHs) (EC 3.3.2.3) catalyze the conversion of epoxides to their corresponding vicinal diols. EHs are cofactor-independent enzymes that are almost ubiquitous in nature. They are usually employed as whole cells or crude... 

Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves, or with peroxy acids. Epoxidation of allylic alcohols can also be done with high enantioselectivity. In the Sharpless asymmetric epoxidation,allylic alcohols are converted to optically active epoxides in better than 90% ee, by treatment with r-BuOOH, titanium tetraisopropoxide and optically active diethyl tartrate. The Ti(OCHMe2)4 and diethyl tartrate can be present in catalytic amounts (15-lOmol %) if molecular sieves are present. Polymer-supported catalysts have also been reported. Since both (-t-) and ( —) diethyl tartrate are readily available, and the reaction is stereospecific, either enantiomer of the product can be prepared. The method has been successful for a wide range of primary allylic alcohols, where the double bond is mono-, di-, tri-, and tetrasubstituted. This procedure, in which an optically active catalyst is used to induce asymmetry, has proved to be one of the most important methods of asymmetric synthesis, and has been used to prepare a large number of optically active natural products and other compounds. The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound formed from the titanium alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the r-BuOOH. ... 

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