Alkene epoxidation with ketone

Styrenes [103], conjugated aT-dienes [107], and aT-enynes [108] are also epoxidized with ketones 57 in high ees (Table 5, entries 9-14). No isomerization of the epoxides was observed therefore only c/x-epoxides were obtained from cis-olefins. Alkenes and alkynes appear to be effective directing groups to favor the desired transition states T and V (Fig. 19). 

Trifluoromethyl ketones that are frequently used for mediating alkene epoxidation with dioxiranes are subject to degradation. A stabilized form is made by covalent anchoring to silica. ... 

Ketones 43 and 46 (Scheme 3.7), obtained by replacing the fused ketal of 42 with more electron-withdrawing diacetates and an oxazolidinone respectively, show significantly enhanced reactivity. Only 1-5 mol% of ketone 46 is required to achieve good conversions for the epoxidation of a variety of trans and trisubstituted alkenes with high ees [28]. A variety of a, 3-unsaturated esters can be epoxidized with ketone 43... 

Epothilone is a highly potent anticancer agent. In their synthesis of highly potent epothilone analogs [51], Altmaim and coworkers reported that alkene precursor 61 was stereoselectively epoxidized with ketone ent-42 to give compounds 62a,b (Scheme 3.22). It appears that the epoxidation is compatible with several functional groups such as the benzimidazole in 61, and the existing ketone in the macrocycle did not appear to interfere with the epoxidation [51, 52]. 

In their synthesis of pladienolide B (65) (potent antitumor agent) (Scheme 3.23), Kotake and coworkers recently reported that sulfone 63 was epoxidized with ketone 42 in 71% yield and >99% de after recrystallization, and the resulting epoxide was then attached to the macrocylic ring via Julia-Kocienski alkenation [53]. 

Marshall and coworkers reported that the internal trisubstituted alkene of 69 was stereoselectively epoxidized with ketone 42 in 80% yield, and the resulting epoxide (70) was transformed into the bistetrahydrofuran C17-C32 segment (72) of antibiotic ionomycin (Scheme 3.25) [55]. 

In their synthesis of various isomers of annonaceous bis-TH F acetogenins, Sinha and coworkers reported that compound 91 containing two trans double bonds can be selectively epoxidized at alkene a with ketone 42 to provide mono-THF lactone 93 in 54% overall yield after cyclization with CSA (Scheme 3.31) [66]. 

Epoxidation with ketone 42 was also carried out on pilot-plant scale at DSM Pharma Chemicals. Crude alkene 127, prepared from 4-pentynoic acid by hydro-boration and Suzuki coupling with 3-fluorobenzyl chloride, was epoxidized with ketone 42 to give lactone 128 (59 lb) in around 63% overall yield and 88% ee after cyclization, without need for isolation of any intermediates during the entire process (Scheme 3.41) [81]. 

As illustrated by the above examples and others [82], the epoxidation with ketone 42 has been utilized in various syntheses. The reaction can be applied to rather complex substrates with various functional groups. When more than one alkene is present, certain alkenes can often be selectively epoxidized with carefully controlled reaction... 

In a formal synthesis of fasicularin, the critical spirocyclic ketone intermediate 183 was obtained by use of the rearrangement reaction of the silyloxy epoxide 182, derived from the unsaturated alcohol 180. Alkene 180 was epoxidized with DMDO to produce epoxy alcohol 181 as a single diastereoisomer, which was transformed into the trimethyl silyl ether derivative 182. Treatment of 182 with HCU resulted in smooth ring-expansion to produce spiro compound 183, which was subsequently elaborated to the desired natural product (Scheme 8.46) [88]. 

As a, (3-unsaturated ketones are electron-poor alkenes, they do not generally give epoxides when treated with peracids. They can be epoxidized with hydrogen peroxide which involves nucleophilic attack by HOO- to give the epoxy ketone (Figure 4.1). 

The dioxirane epoxidation of a prochrral alkene will produce an epoxide with either one new chirality center for terminal alkenes, or two for internal aUcenes. When an optically active dioxirane is nsed as the oxidant, expectedly, prochiral alkenes should be epoxi-dized asymmetrically. This attractive idea for preparative purposes was initially explored by Curci and coworkers in the very beginning of dioxirane chemistry. The optically active chiral ketones 1 and 2 were employed as the dioxirane precursors, but quite disappointing enantioselectivities were obtained. Subsequently, the glucose-derived ketone 3 was used, but unfortunately, this oxidatively labile dioxirane precursor was quickly consumed without any conversion of the aUcene . After a long pause (11 years) of activity in this challenging area, the Curci group reported work on the much more reactive ketone... 

FIGURE 10.6 Transition states for the epoxidation of cw-alkenes with ketone 1. 

Recently, comprehensive World Wide Web (Internet) databases have been established on insect pheromones and semiochemicals The Pherolist , a database of chemicals identified from sex pheromone glands of female lepidopteran insects and other chemicals attractive to male moths (Am et al., 1999) and The Pherobase , a database of pheromones and semiochemicals for Lepidoptera and other insect orders (El-Sayed, 2006). These large databases on behavior modifying chemicals have extensive cross-linkages for animal taxa, indexes of compounds and source (reference) indexes. The indexes include those compounds cited in this chapter and many more with pheromone and semiochemical function acetate esters, diols, epoxides, ethers, ketones and secondary alcohols. For example, The Pherolist reports approximately 90 epoxy derivatives of C17-C23 of n-alkancs, mono-alkenes and di-alkenes as insect semiochemicals. 

If alkene epoxidation cannot be avoided, protection as a dibromide prior to oxidation may be necessary. Baeyer-Villiger oxidations with and without V-oxide formation have been reported. Only heteroatom oxidations of a-thiophenyl and a-selenenylphenyl ketones have been reported with MCPBA. 

---