Epoxides interesting examples

Considerable attention has been directed to the epoxidation of alkenes on account of interest in the epoxides as industrial intermediates. The wide metabolic capability of MMO, which has already been noted, has been applied to the epoxidation of C2, C3, and C4 alkenes (Patel et al. 1982). A large number of propane-utilizing bacteria are also effective in carrying out the epoxidation of alkenes (Hou et al. 1983). Especially valuable is the possibility of using microorganisms for resolving racemic mixtures of epoxides. For example, this has been realized for cis- and tra 5 -2,3-epoxypentanes... 

The enzyme catalysed epoxidation of alpha-olefins like 1-octene with oxygen to the optically active epoxide provides an interesting example of a four-phase system (de Bont et al., 1983). The hold-up of the organic phase may be 2-4 % and the presence of biosurface active agents leads to the creation of a large liquid-liquid interfacial area the liquid droplet size becomes smaller than the gas-liquid diffusion film thickness. 

In addition, new some epoxide hydrolases have also shown a great utility for the desymmetrization of meso-epoxides. An interesting example is the synthesis of nelfinavir-the active pharmaceutical ingredient (API) of the anti-human immunodeficiency virus drug Viracept-where the (R,R)-diol obtained by opening the meso-epoxide is a suitable starting material. Scheme 10.6 shows a synthetic route to nehinavir [14]. 

An interesting example exists of variation of diastereoselectivity, due both to the nature and sense of chirality of the electrophile, and to the configuration of the 2-pyrrolidinemethanol auxiliary6. Thus, the use of epoxide 16 as electrophile leads to an unexpected reversal of the diastereoselectivity relative to that observed when the corresponding O-protected iodohydrin 10 is employed. Both of the electrophiles are chiral and therefore reaction of each with the enantiomers of 1-(l-oxopropyl)-2-pyrrolidinemethanol leads to different diastereoselectivities due to the fact that there is a matched and a mismatched pair of reactions. 

The remaining chapters deal with a variety of catalysts for effecting oxidation reactions. Chapter 5 describes three simple protocols for the controlled oxidation of primary or secondary alcohols. The importance of stereocontrolled epoxidation and hydroxylation reactions is reflected by the fact that Chapter 6, directed at this field, is one of the most extensive sections of the book. An interesting example of an enantioselective Baeyer-Villiger reaction is featured in Chapter 7, together with an industrially important ketone to enone conversion. Oxidative carbon-carbon... 

Epoxides can also be formed from the oxidation of alkenes by molecular oxygen via in situ generation of hydroperoxides by autoxidation.251,252 An interesting example is the direct stereoselective oxidation of cyclohexene by 02 to syn-l,2-epoxycyclohexan-3-ol catalyzed by CpV(CO)4 with a 65% yield and 99% stereoselectivity (equation 78).253... 

Cyclization of allylic alcohols to form epoxides has been particularly problematical, and the reactions have been more of mechanistic than of synthetic interest. For reactions conducted under basic conditions, it is possible that epoxide formation involves initial halogen addition followed by nucleophilic displacement to form the epoxide. Early examples of direct formation of epoxides from allylic alcohols with sodium hypobromite," bromine and 1.5 M NaOH,12 and r-butyl hypochlorite13 have been reviewed previously.fr Recently it has been shown that allylic alcohols can be cyclized effectively with bis(jym-collidine)iodine(I) perchlorate (equation 3).14 An unusual example of epoxide formation competing with other cyclization types is shown in equation (4).15 In this case, an allylic benzyl ether competes effectively with a -/-hydroxyl group as the nucleophile. 

Because of their high refractive index, these materials possess desirable optical and thermal properties, in addition to being impervious to a variety of chemicals [5]. Analogous reactions involving carbon disulfide and epoxides have provided extremely interesting examples of atom-exchange polymerization processes. 

This result, caused by the proximity effect between peripheral catalytic sites, can translate into higher or lower catalytic activity of the metallodendrimer in homogeneous catalysis, and is commonly termed the dendritic effect. In the above case, a negative dendritic effect is observed. An interesting example of a positive dendritic effect on catalyst activity was reported by Jacobsen et al. in the hydrolytic kinetic resolution of terminal epoxides by peripherally Co(salen)-substituted PAMAM dendrimers [39]. 

Another interesting example taken from the synthesis of natural products is reported in equation 6. Epoxidation of 13 with cpba affords a mixture of 14a and 14b, which can be directly desilylated with tetrabutylammonium fluoride to give fi ,Z-isospongiadiol (15). ... 

Another interesting example of the preparation of unsaturated O- and C-glycosides 36 was presented recently [44]. This was based on the Sn2 attack of the nucleophile on unsaturated epoxide 35. Substitution at C-1 proceeded with simultaneous migration of the double bond and opening of the three-member ring providing 2,3-unsaturated derivative 36 (O Scheme 20). Conversion of 4-deoxy-2,3-unsaturated sugars into 3,4-unsaturated ones reported by Banaszek and Zamojski already in 1972 [3] was one of the key-steps in total s)mthesis of monosaccharides by a hetero Diels-Alder approach. 

A further interesting example is the use of l,l-di(phenylthio)med)yllithium to open an epoxide followed by a Grob fragmentation process as shown in Scheme 56 (entry b). The reaction of 1,1-di-(thio)methyllithium with epoxides has also been used - in the one-pot synthesis of l,l-di(thio)cyclopropanes involving an intramolecular cyclization of the 7-tosyloxydi(phenylthio)alkylli-thium. This intramolecular alkylation reaction proceeds even more efficiently than its intermolecular version, and allows the synthesis of a large variety of l,l-di(thio)cyclopTDpanes from 3-chloro- and 3-phenylthio-l,l-di(thio)alkanes and n-butyllithium in THF (Scheme 57 and Scheme 58). 

Remote double bonds often participate in epoxide openings, sometimes with extensive skeletal changes. ejco-Norbomadiene oxide (15 equation 6) provides an interesting example. Meinwald et alP found that this very acid-sensitive material rearranged simply on standing to give the endo-aldehyde (17), presumably via the intermediate nortricyclanol ion (16). 

On the other hand, no epoxide has been reported to be immune to reaction with BF3, although an interesting example of inertness was noted by Crandall and Machleder. Allene epoxides are usually too sensitive to acids to be isolable from peroxy acid epoxidations, but the bulky r-butyl groups on (70 equation 30) make it exceptionally unreactive. Several hours of reflux with BF3 in ether were required to effect the conversion to (71). 

Rearrangement of epoxides. An interesting example reported by House is as follows. A benzene solution of the glycidic ester (1) is saturated with BF3 and allowed to stand at room temperature for 30 min. workup alfords the a-keto ester (2) in high yield. 

Biological enzymes are well known to carry out epoxidation. For example, MMO is an efficient and selective catalyst for epoxidation of small terminal olefins such as ethylene, propylene, and 1-butene [246,247]. Lipases have been used to generate peroxoacids which in turn are used for epoxidation reactions [248,249]. The subject has been reviewed [250]. Biocatalytic systems are of interest not only because they can carry out enantioselective epoxidation of substrates, but also because they offer the exciting possibility of being engineered for specific transformations of nonnatural reagents. 

Although the conditions of catalysis have not yet been optimized, the results are interesting in the sense that these heterogeneous molecular catalysts all show properties different from their molecular counterparts, in terms of either activity (epoxidation of olefins, MPVO reactions, silane activation) or selectivities (epoxidation for example). These features need to be further investigated, by varying the number of solid ligands in the coordination sphere of Zr preliminary experiments with epoxidation of olefins show that this parameter is important for the activity of Zr. 

Ziiumennan and coworkers have described an interesting example of an acid-catalyzed participation of a urethano group. The epoxide (177)... 

Interesting examples of optical resolutions include the use of dicarbonyl-rhodium(i) 3-trifluoroacetyl-(li )-camphorate for g.l.c. separation of chiral olefins and of dimeric nickel(ll) bis-(3-trifluoroacetyl-li -camphorate) for an improved separation of chiral epoxides (cf. Vol. 8, p. 8). The resolution of (i /5)-pantoic acid with chiral amines derived from a- and jS-pinene (Vol. 7, p. 43, ref. 420) may signal their more widespread use. 1,3-Dithian 1-oxide has been resolved. ... 

The benzylic oxidation depicted in the second step of Scheme 8.28b is actually a formal group-selective differentiation of diastereotopic C-H bonds, since asymmetric epoxidation occurs prior to hydroxylation [125]. However, the reaction is an interesting example of a kinetic resolution that depends on the fact that the catalyst used reacts with the two epoxides at different rates, apparently because the chiral catalyst system ... 

Entry 5 is an interesting example that entails both enzymatic and hydrolytic epoxide conversion. In the first step, an enzymatic hydrolysis proceeds with retention of the configuration at the tertiary center. This reaction is selective for the 5-epoxide. The remaining 7 -epoxide is then subjected to acid-catalyzed hydrolysis, which proceeds with inversion at the center of chirality (see p. 186). The combined reactions give an overall product yield of 94%, having 94% e.e. ... 

An interesting example of selective epoxidation involves the oxidation of a-... 

Based on knowledge of a biosynthetic pathway one can select certain steps which could be of interest for bioconversion of (a) readily available precursor(s). This could, for example, be stereospecific reactions, like the reduction of quinidinone in quinine or quinidine and the epoxidation of atropine to scopolamine. For the bioconversion one can consider using plant cells [e.g., the production of L-dopa from tyrosine by immobilized cells of Mucuna pruriens (10)] or isolated enzymes from the plant itself. An interesting example of the latter is the (5)-tetrahydroprotoberberine oxidase (STOX) enzyme, which oxidizes (5)-reticuline but not its stereoisomer (11). This feature can be used in the production of (i )-reticuline from a racemic mixture (see below). Immobilized strictosidine synthase has been successfully used to couple secologanin and tryptamine. The gene for this enzyme has been isolated from Rauvolfia (6) and cloned in Escherichia coli, in which it is expressed, resulting in the biosynthesis of active enzyme (7). The cultured bacteria produced 20 times more enzyme... 

Epoxidation of olefinic compounds with metachloroperbenzoic acid. An interesting example (Brandstrom, 1983) is the epoxidation of olefinic... 

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