Vinylepoxides

Scheme 2.14 Synthesis of vinylaziridines by aminolysis of vinylepoxides by liquid ammonia.

Cycloadditions of isocyanates and their derivatives with vinyiaziridines were first reported by Alper and coworkers. From their previous studies of cydoadditions to vinylepoxides or alkylaziridines, they investigated cydoadditions to vinyiaziridines and found that such reactions with isocyanates, carbodiimides, or isothiocyanates in the presence of catalytic amounts of Pd(OAc)2 (2 mol%) and PPh3 (10 mol%) at room temperature afforded five-membered ring products 249 in 34—97% yields (Scheme 2.61) [91]. When an aziridine 247 possessing an alkyl substituent at the... 

Vinylepoxides can be obtained by various strategies, all with their inherent limitations. Racemic epoxidation of olefins is a straightforward route to epoxides, as pure trans- or cis-epoxides can be obtained from ( )- or (Z)-alkenes, respectively. Various oxidants - such as mCPBA and other peracids, H2O2, or VO(acac)2/TBHP - can all be employed in this transformation [1],... 

Enantioselective epoxidation of unfunctionalized alkenes was until recently limited to certain ds-alkenes, but most types of alkenes can now be successfully epoxi-dized with sugar-derived dioxiranes (see Section 9.1.1.1) [2]. Selective monoepox-idation of dienes has thus become a fast route to vinylepoxides. Functionalized dienes, such as dienones, can be epoxidized with excellent enantioselectivities (see Section 9.1.2). 

The major problem associated with the synthesis of vinylepoxides is the instability of reaction intermediates and/or products. High crude yields can be obtained by... 

The catalytic system was subsequently applied to the monoepoxidation of dienes. This was potentially a difficult task, as there was a need to address the issues not only of enantioselectivity, but also of regioselectivity and monoepoxidation versus bisepoxidation. Fortunately, a wide range of dienes could be efficiently monoepoxidized by ketone 1, which meant that a straightforward route to vinylepoxides had been developed (Table 9.1) [9]. 

Conjugated dienes can be epoxidized to provide vinylepoxides. Cyclic substrates react with Katsuki s catalyst to give vinylepoxides with high ees and moderate yields [17], whereas Jacobsen s catalyst gives good yields but moderate enantiose-lectivities [18]. Acyclic substrates were found to isomerize upon epoxidation (Z, )-conjugated dienes reacted selectively at the (Z)-alkene to give trans-vinylepoxides (Scheme 9.4a) [19]. This feature was utilized in the formal synthesis of leuko-triene A4 methyl ester (Scheme 9.4b) [19]. 

This strategy can be applied to the synthesis of vinylepoxides, since high enantioselectivity and good regioselectivity can often be obtained in asymmetric dihydroxylation of dienes, resulting in vinylic diols [24, 25], Transformation of the diols into epoxides thus represents an alternative route to vinylepoxides. This strategy was recently employed in the synthesis of (+)-posticlure (Scheme 9.6) [26]. 

Vinylepoxides from Functionalized Dienes 9.1.2.1 From Dienones or Unsaturated Amides... 

The asymmetric epoxidation of enones with polyleucine as catalyst is called the Julia-Colonna epoxidation [27]. Although the reaction was originally performed in a triphasic solvent system [27], phase-transfer catalysis [28] or nonaqueous conditions [29] were found to increase the reaction rates considerably. The reaction can be applied to dienones, thus affording vinylepoxides with high regio- and enantio-selectivity (Scheme 9.7a) [29]. 

A one-pot procedure from aldehydes, through Wittig olefmation and a subsequent epoxidation, was also reported. Aldehydes could be converted into a,P,y,8-unsaturated N-acyl pyrroles, which were epoxidized in the same pot to give N-acyl pyrrole-substituted vinylepoxides [32]. 

Scheme 9.10 Vinylepoxide synthesis from divinyl carbinol.

The epoxidation of divinyl carbinol constitutes a special case of a dienol epoxida-tion, as the starting diene is not conjugated (Scheme 9.10). Desymmetrization by SAE, followed by a Payne rearrangement, furnishes the vinylepoxide in high yield and with excellent enantioselectivity (compare Table 9.2, Entry 1) [43]. 

In our work with aminolysis of vinylepoxides (see Section 9.2.1.1), the substrates were routinely synthesized by SAE followed by Swern/Wittig reactions (Table 9.3, Entries 1-4) [48, 49]. This procedure is well suited for terminal olefins, but dis-ubstituted olefins can seldom be obtained with useful (E Z) selectivities. Nakata recently synthesized some advanced intermediates towards natural products in this manner (Entries 5, 6) [50, 51]. 

Aliphatic, aromatic and vinylic aldehydes can be employed in this reaction with similar yields and enantioselectivities. When chiral aldehydes are utilized, excellent diastereoselectivity is obtained for matched cases, whereas mismatched cases yield products with moderate to good diastereoselectivity (Scheme 9.13a) [67]. The limitation of the methodology is that only terminal vinylepoxides can be obtained. 

Winssinger later utilized syn-a-vinylchlorohydrin 16 for the generation of both cis- and trans-vinylepoxides 17 and 18 (Scheme 9.14) [69], ris-Epoxide 17 was... 

When ot, 3-unsaturated aldehydes were employed, vinylepoxides were obtained with excellent transxis ratios but in poor yields. When benzaldehyde was treated with a, 3-unsaturated tosylhydrazone salts, the yields of vinylepoxides were improved but the transxis ratios dropped. When chiral sulfides were utilized, the ees were high with a, 3-unsaturated aldehydes, whereas unsaturated, chiral sulfur ylides gave moderate ees, poor yields, and modest transxis ratios. 

An alternative process for the synthesis of vinylepoxides was clearly needed, so reactions with stoichiometric amounts of chiral sulfide were investigated (Scheme 9.16a) [74]. Indeed, when benzyl sulfonium salt 20 was treated with unsaturated aldehydes, the ees and des were high in all cases, whereas the yields [75] were highly substrate-dependent. The same products could be formed by treatment of an unsaturated sulfonium salt with benzaldehyde, but the yields and se-lectivities were generally slightly lower. 

Chiral sulfonium salts derived from oxathianes have been developed for stoichiometric epoxidation reactions. The sulfonium salts were deprotonated and allowed to react with a, 3-unsaturated aldehydes to give trons-vinylepoxides with excellent ees and transxis ratios (Scheme 9.16b) [76]. The yields were generally high [75], and the best results were obtained with Ar = 4-OMePh. 

Metzner and co-workers reported a one-pot epoxidation reaction in which a chiral sulfide, an allyl halide, and an aromatic aldehyde were allowed to react to give a trons-vinylepoxide (Scheme 9.16c) [77]. This is an efficient approach, as the sulfonium salt is formed in situ and deprotonated to afford the corresponding ylide, and then reacts with the aldehyde. The sulfide was still required in stoichiometric amounts, however, as the catalytic process was too slow for synthetic purposes. The yields were good and the transxis ratios were high when Ri H, but the enantioselectivities were lower than with the sulfur ylides discussed above. 

The major limitation of asymmetric sulfur ylide epoxidations is that only aromatic vinylepoxides can be formed efficiently and with high selectivity. When an aliphatic aldehyde is allowed to react with a semistabilized or nonstabilized sulfur ylide, poor diastereoselectivities and yields are observed, due to problems in controlling the ylide conformation and competing ylide rearrangement reactions [71]. However, some racemic, aliphatic vinylepoxides have been successfully formed by sulfur ylide epoxidations, although varying diastereoselectivities were observed [78-80],... 

Vinylepoxides from Other Substrates 9.1.5.1 From Allenes... 

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