Cis-Stilbene oxide

Threo-2-Azldo-1,2-dlphenylethanol (2). A mixture ot cis-stilbene oxide 1 (3 92 g, 20 mmol) and NaNa (4 46 g, 70 mmol) in 50% aqueous acetone (60 mL) was relKixed lor 3h The solvent was removed in vacuum and the resxlue extracted with CHCI3 The organic solution was washed with water, dned (MgS04) and concentrated. Distillation of the resxlue afforded 3 70 g of 2 (77%) as a pale yellow oil, tsp 122°C/0 IS mm... 

The effect of substrate structure on product profile is further illustrated by the reactions of cis- and trons-stilbene oxides 79 and 83 with lithium diethylamide (Scheme 5.17) [32]. Lithiated cis-stilbene oxide 80 rearranges to enolate 81, which gives ketone 82 after protic workup, whereas with lithiated trans-stilbene oxide 84, phenyl group migration results in enolate 85 and hence aldehyde 86 on workup. Triphenylethylene oxide 87 underwent efficient isomerization to ketone 90 [32]. 

Mn impregnated into MCM-4i, a silicalite containing uniform mesopores of approximately 22 A, catalyzes TBHP epoxidation of alkenes.88 Over Mn-MCM-41, both cis- and trans-stilbene yield trans-stilbene oxide, which the authors conclude signals a radical mechanism.88 In contrast, over Ti—MCM-41, trans-stilbene cannot be oxidized, only cis-stilbene is epoxidized to the cis-stilbene oxide, which suggest a radical-free mechanism.89 Finally, emphasizing the shape selectivity possibilities, only trans-stilbene (not cis-stilbene) can be epoxidized over Mn-ZSM-5, a zeolite with relatively small pores of 5.1 x 5.4 A (Fig. 6.14).88... 

Resistance to hydration was elucidated with tricyclic model compounds that lack the side chain and, hence, pharmacological activity. In this context, a useful comparison has been made between two meso compounds, namely 5W-dibenz.oja, dIcycloheplene 10,11-oxide (10.130, X = CH2) and d.v-slilbcnc oxide (10.7) [195]. The former compound proved to be a very poor substrate for rabbit liver microsomal EH, with a Km value comparable to that of cis-stilbene oxide, but Emax ca. 100-fold lower. This indicates that the two compounds have a comparable affinity for the enzyme, but that nucleophilic attack in the catalytic step is much less efficient for dibcnzo[ // cycloheplcnc 10,11-oxide than for d.v-slilbcnc oxide. This implies that the former compound acts better as an inhibitor than as a substrate of microsomal EH. Furthermore, there was also a fundamental steric difference in the reaction course of the two substrates, since the predominant stereoisomer formed from dibenzo //]cyclohep(ene 10,11-oxide had the (I OS, 11. -configuration,... 

For epoxidations, electron-rich alkenes react more readily, in case of p-substituted styrenes, with a concomitant increase in the amount of aldehyde by-product, suggesting formation of an unsymmetric intermediate. However, cw-stilbene is converted to cis-stilbene oxide in 82% yield, and the intermediate, if any, must be short-lived. Under the same conditions, the reaction of trans-stilbene is slow. A close parallel approach of the double bond to the active heme site seems to be essential for epoxidation. 

The process development for this efficient Aggarwal-type sulfur-ylide epoxidation has recently been summarized in review [226], Several detailed studies of the reaction mechanism have also recently been reported [227-230]. In particular, a comprehensive experimental and computational investigation of the reaction mechanism has been performed by the Aggarwal group [227, 228]. The two dia-stereoselective pathways for synthesis of trans- and cis-stilbene oxides, as representative examples, are shown in Scheme 6.103 [228]. The initial step is addition of the sulfur ylide to the C=0 double bond of the aldehyde with formation of the cor-... 

Denmark et al. employed the chiral phosphoramide 74 (Scheme 13.37) as nucleophilic activator [75]. As summarized in Scheme 13.37, the best enantiomeric excess was observed for cis-stilbene oxide (87%). The study revealed that enantioselectivity was highly dependent on the ring size (cyclohexene oxide cyclopentene oxide > cyclooctene oxide). 

Building on an earlier conclusion, epoxidations of various olefins by this manganese catalyst revealed at least two mechanisms but not the oxygen rebound mechanism. To extend these studies, the epoxidation of cis-stilbene was performed with 2% H2O2 under an atmosphere of 2 (Schemes 3.8 and 3.10). The deviation in the content from 100% in case of cis-stilbene oxide approximates... 

Thus it takes less than a minute for traits stilbene to react with the oxidizer at 0 °C producing trans stilbene oxide in higher than 90% yield. The physical constants of the oxide show a full retention of the starting material configuration. Similar results were observed with cis stilbene, which was converted to cis stilbene oxide without any trace of the trans isomer. Substituted stilbenes react as well, as evidenced by the transformation of trans 4-chlorostilbene and trans 4,4 -dinitrostilbene to the corresponding epoxides in 90% and 70% yield respectively (figure 9). 

Thiiranes Oxiranes react with this reagent and TFA in CH2CI2 at 0° to give thiiranes, usually in quantitative yields. The reaction is stereospecific cis-stilbene oxide is converted exclusively into cir-stilbene episulfide. 

Fig. 31.27 Marker substrates- of EH. (1) cis-stilbene oxide (2) butadiene monoxide (3) benzo[a]pyrene-4,5-oxide (4) trans-stilbene oxide (5) 11,12-epoxyeicosatrienoic acid.

In addition, this class of chiral phosphoramides could catalyze the enantioselective ring opening of epoxides with siUcon tetrachloride (SiCLt) [4], For instance, the reaction of cis-stilbene oxide with SiCb proceeded smoothly in the presence of 1 to afford the desired chlorohydrin in an enantiomerically enriched form (Scheme 7.3). The reactive ion pair shown in the scheme was proposed to be generated through the activation of SiCLj by the coordination of one phosphoramide 1, serving to activate the epoxide it was confirmed that bis-phosphoramide 2 was far less selective in this reaction. 

Formation.—A convenient and rapid synthesis of thiirans (yields 35— 90%) consists of treatment of epoxides with triphenyl- or tri-n-butyl-phosphine sulphide in the presence of acid. cis-Stilbene oxide gave exclusively cis-stilbene sulphide. (S)-(-)-Methylphenyl-n-propylphosphine sulphide gave, with a twofold excess of cyclohexene oxide, the (S)-(-)-oxide, indicating that this reaction proceeds with retention of configuration at phosphorus. " A mechanism involving two inversions was suggested for the conversion of 2a,3a-epoxycholestane into the 2, 3 3-epithio-isomer, as shown in Scheme 1. Epithiochlorohydrin is obtained by treatment of epichlorohydrin with di-(0-ethyl)dithiophosphoric acid and triethylamine. "... 

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