Nonracemic chiral epoxides

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... 

The hydrolysis of epoxides is a well-known reaction which can be exploited for various synthetically useful outcomes. Chiral nonracemic epoxides can be prepared from their racemates through the salen-mediated hydrolytic kinetic resolution (HKR). Racemic epichlorohydrin 53 was resolved in the presence of catalyst 52 and a slight excess of water under solvent-free conditions. The catalyst counterion exerts a significant effect on the course of the reaction, presumably due to competitive addition onto the epoxide, an effect which is evident in apparent reaction rates, but not enantioselectivities. Less nucleophilic counterions, such as tosylate, lead to more rapid resolution and lower catalyst loading requirements <04JA1360>. 

The mixture of isomeric acetates is converted to the corresponding mixture of alcohols and that mixture subjected to Sharpless asymmetric epoxidation. From this reaction, the chiral nonracemic epoxide 87 is isolated in 60% yield (>94% ee). Compound 87 is converted by standard transformations to 88 and 89, ultimately affording the leukotriene methyl ester LTAt-Me (90) (Scheme 27). A number of other leukotrienes (e.g., LTC4, LTD4,... 

Development of chiral, nonracemic dioxiranes for the catalytic enantioselective epoxidation of alkenes 99SL847. 

In recent years, enantioselective variants of the above transannular C-H insertions have been extensively stiidied. The enantiodetermining step involves discrimination between the enantiotopic protons of a meso-epoxide by a homochiral base, typically an organolithium in combination with a chiral diamine ligand, to generate a chiral nonracemic lithiated epoxide (e.g., 26 Scheme 5.8). Hodgson... 

Preparation of nonracemic epoxides has been extensively studied in recent years since these compounds represent useful building blocks in stereoselective synthesis, and the epoxide functionality constitutes the essential framework of various namrally occurring and biologically active compounds. The enantiomericaUy enriched a-fluorotropinone was anchored onto amorphous KG-60 silica (Figure 6.6) this supported chiral catalyst (KG-60-FT ) promoted the stereoselective epoxidation of several trans- and trisubstituted alkenes with ees up to 80% and was perfectly reusable with the same performance for at least three catalytic cycles. 

A chiral, nonracemic oxirane, (3 )-2-[(R)-fluoro(phenyl)methyl]oxirane, can react with (chiral) amines under the influence of lithium perchlorate using either heat or microwave irradiation. This reaction sequence provides a material from which the ee of chiral a-branched amines can be determined <2005OL3829>. Guanidines serve as a useful nitrogen nucleophile for the direct conversion of epoxides to aziridines <2004JOC8504>. 

The enantioselective cleavage of strained ethers (epoxides and oxetanes) by organolithiums, mediated by chiral, nonracemic ligands (as well as additions to aldehydes and ketones), has been reviewed by Goldfuss <2005S2271>. 

Denmark, S. E. Wu, Z. The Development of Chiral, Nonracemic Dioxiranes for the Catalytic Enantioselective Epoxidation of Alkenes, Synlett 1999, 847-859. 

Highly acid sensitive a-siloxy epoxides (108 R1 = R2 = Me) are available in good to excellent yields through the epoxidation of silyl enols ethers (107) with jV-sulfonyloxaziridine (63b) <87JOC954>. Hydrolysis of (108) gave the a-hydroxy carbonyl compound (109) in good-to-excellent yield (55-95%) and represents an alternative to peracids usually used to effect this transformation known as the Rubottom reaction. With chiral nonracemic TV-sulfonyloxaziridines the ees of (109) were low (7-11% ee) because of the poor facial discrimination between the re and si faces of the silyl enol ether (Scheme 20). 

Chiral nonracemic a-hydoxylated ketones are commonly accessed by asymmetric epoxidation or dihydroxylation of enol ethers and this methodology is discussed in the relevant sections of this book. Another general method for the enantioselective a-oxygenation of ketones and aldehydes is by reaction of an electrophilic source of oxygen with chiral nonracemic enamines or enolates or in the presence of Lewis acids. 

Likewise, this procedure provides a route for the reduction of a,/3-epoxy ketones and a, -epoxy esters to generate the corresponding /3-hydroxy carbonyl compounds (eqs 7 and 8). The epoxy ketone substrates may be derived from Sharpless asymmetric epoxidation. Consequently, this procedure provides a means to prepare a variety of chiral, nonracemic 8-hydroxy carbonyl compounds that are difficult to acquire by more traditional procedures. 

One of the most elegant methods for the selective formation of C—O bonds is the catalytic Jacobsen-Katsuki epoxidation, the enantioselective synthesis of optically active epoxides by oxygen-transfer reactions with chiral, nonracemic manganese 0x0 salen complexes. These complexes have been suggested as the catalytically active species in epoxidations catalyzed by metal-salen and porphyrin complexes [78]. One of these complexes was for the first time isolated and characterized by Feichtinger and Planner through ESI-MS studies [79]. 

A related synthesis used chiral, nonracemic epoxy-alcohol 6.90, and involved oxidation of the alcohol moiety to an acid moiety (to give 6.91). Opening the epoxide with ammonia led to a 66% overall yield of R-GABOB (49%ec). It is noted that allyl oxirane was recently converted to R-GABOB in two steps. ... 

Sulfonium ylides in synthesis of optically active epoxides 93PS(74)215. Syntheses and reactions of chiral acetylenic oxiranes 92BSB415. Syntheses of nonracemic glycidol and related 2,3-epoxy alcohols 91 CRV437. 

The nonracemic chiral seven-membered ring siloxanes 160 were employed to prepare numerous difficult-to-attain tertiary alcohols. Thus, on treatment with MeLi in THF at 22 °C, tertiary alcohol 290 was obtained (93% ee). Subjection of the siloxane 160 to w-chloroperbenzoic acid (MCPBA) led to the diastereoselective formation of epoxide 291, which reacts further with tetrabutylammonium fluoride (Bun4NF = TBAF) to give 1,3-tertiary diol 292 (Scheme 50) <2002JA2868>. 

Few studies have been conducted on chiral POPs in humans, for obvious reasons. The handful of measurements made has been on breast milk, blood, feces, or tissues that can be obtained ethically. The chlordane metabolites heptachlor epoxide and oxychlordane were found in nonracemic proportions in human adipose tissue in early studies [116,217], with an... 

The presence of a functional group in the vicinity of the epoxide can lead to interesting results. Such is the case for the epoxy-2,3 alcohols 2.23, which can be obtained in a nonracemic form by asymmetric epoxidation of the corresponding allylic alcohols [KS3]. The action of LAH in THF or better yet of Red-Al in the same solvent [MM2, VI] or preferably in DME [GS4] selectively leads to the 1,3-diols 2.24, while DIBAH [FKl] or LiBH4-(i-PrO)4Ti in [DLl] gives access to the 1,2-diols 2.25 (Figure 2.15). The hydride attack is stereospecific, and in the nonracemic chiral molecule 2.26, the reaction proceeds with inversion [FKl] (Figure 2.15). If the alcohol residue is transformed into a methyl ether, Red-Al does not promote any reduction [FKl]. 

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