Stilbene oxides

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]. 

The observation that addition of imidazoles and carboxylic acids significantly improved the epoxidation reaction resulted in the development of Mn-porphyrin complexes containing these groups covalently linked to the porphyrin platform as attached pendant arms (11) [63]. When these catalysts were employed in the epoxidation of simple olefins with hydrogen peroxide, enhanced oxidation rates were obtained in combination with perfect product selectivity (Table 6.6, Entry 3). In contrast with epoxidations catalyzed by other metals, the Mn-porphyrin system yields products with scrambled stereochemistry the epoxidation of cis-stilbene with Mn(TPP)Cl (TPP = tetraphenylporphyrin) and iodosylbenzene, for example, generated cis- and trans-stilbene oxide in a ratio of 35 65. The low stereospecificity was improved by use of heterocyclic additives such as pyridines or imidazoles. The epoxidation system, with hydrogen peroxide as terminal oxidant, was reported to be stereospecific for ris-olefins, whereas trans-olefins are poor substrates with these catalysts. 

Asymmetric epoxidation of olefins with ruthenium catalysts based either on chiral porphyrins or on pyridine-2,6-bisoxazoline (pybox) ligands has been reported (Scheme 6.21). Berkessel et al. reported that catalysts 27 and 28 were efficient catalysts for the enantioselective epoxidation of aryl-substituted olefins (Table 6.10) [139]. Enantioselectivities of up to 83% were obtained in the epoxidation of 1,2-dihydronaphthalene with catalyst 28 and 2,6-DCPNO. Simple olefins such as oct-l-ene reacted poorly and gave epoxides with low enantioselectivity. The use of pybox ligands in ruthenium-catalyzed asymmetric epoxidations was first reported by Nishiyama et al., who used catalyst 30 in combination with iodosyl benzene, bisacetoxyiodo benzene [PhI(OAc)2], or TBHP for the oxidation of trons-stilbene [140], In their best result, with PhI(OAc)2 as oxidant, they obtained trons-stilbene oxide in 80% yield and with 63% ee. More recently, Beller and coworkers have reexamined this catalytic system, finding that asymmetric epoxidations could be perfonned with ruthenium catalysts 29 and 30 and 30% aqueous hydrogen peroxide (Table 6.11) [141]. Development of the pybox ligand provided ruthenium complex 31, which turned out to be the most efficient catalyst for asymmetric... 

Nakajima reported the use of a chiral bipyridine N,N -dioxide 18 in the desym-metrization of acyclic meso epoxides (Figure 7.3). Although the enantioselectivity was not as high as in the method developed by Fu for meso-stilbene oxide (90% ee vs. 94% ee), it was higher for the same aliphatic epoxide (74% ee vs. 50% ee) [57]. Nakajima showed that mono-N-oxide derivatives 19 and 20 were much less effective than 18 in tenns of both yield and enantioselectivity, and accordingly proposed a unique mechanism for 18 involving a hexacoordinate silicon intermediate coordinated to both N-oxides of the catalyst. 

Silyl enol ethers, 23, 77, 99-117,128 Silyl enolates, 77 Silyl peroxides, 57 Silyl triflate, 94 Silyl vinyl lithium, 11 (E)-l -Silylalk-1 -enes, 8 Silylalumimum, 8 Silylation, 94 reductive, 26 a-C-Silylation, 113 O-Silylation.99,100 / -SilyIketone, 54 non-cydic, 55 Silylmagnesium, 8 Silyloxydienes, 112 Sodium hexamethyldisilazide, 89 Sodium thiosulphate pentahydrate, 59 Stannylation, see Hydrostannylation Stannylethene, 11 (Z)-Stilbene, 70 (E)-Stilbene oxide, 70 /3-Styryltrimethylsilane, 141 Swern oxidation. 84,88... 

Apart from monooxygenases, other enzymes concerned wih xenobiotic metabolism may also be induced. Some examples are given in Table 2.5. Induction of glucuronyl transferases is a common response and is associated with phenobarbital-type induction of CYP family 2. Glutathione transferase induction is also associated with this. A variety of compounds, including epoxides such as stilbene oxide and... 

Phenobarbital, trans stilbene oxide, 2-acetyl aminofluorene Various, including phenobarbital... 

Reactions of 1 with epoxides involve some cycloaddition products, and thus will be treated here. Such reactions are quite complicated and have been studied in some depth.84,92 With cyclohexene oxide, 1 yields the disilaoxirane 48, cyclohexene, and the silyl enol ether 56 (Eq. 29). With ( )- and (Z)-stilbene oxides (Eq. 30) the products include 48, ( > and (Z)-stilbenes, the E- and Z-isomers of silyl enol ether 57, and only one (trans) stereoisomer of the five-membered ring compound 58. The products have been rationalized in terms of the mechanism detailed in Scheme 14, involving a ring-opened zwitterionic intermediate, allowing for carbon-carbon bond rotation and the observed stereochemistry. 

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... 

Preparation of all four diastereomers of /3-hydroxydiphenylethyl spirophosphoranes 72 via deprotonation of hydrospirophosphoranes 70 (R = H) with BuLi facilitated a subsequent mechanistic study on stereospecific alkene formation <1997TL7753, 2002CL170>. Three of the diasteromers could be formed by reacting 70 (R = H) with BuLi, followed by treatment with cis or /ra/w-stilbene oxide at room temperature (Scheme 12). 

Interestingly, Jacobsen et al. have also reported that addition of a /3-hydroxy ammonium salt to the reaction medium accelerates the isomerization in the presence of an /V-benzylated quinine salt epoxidation of cw-stilbene with (27) gives Zrarax-stilbene oxide with 90% ee as the major product (trans cis= >96 4).109 In 2000, Adam et al. reported that the isomerization ratio was related to the triplet-quintet energy gap of the radical intermediate which was affected by the... 

Rearrangement of trans-Stilbene Oxide to Diphenylacetaldehyde with Catalytic Methylaluminum Bis(4-bromo-2,6-di-tert-butylphenoxide). 

Figure 7.14 Structural similarity between a biaryl derivative and nematic phase K15, and between Irans-stilbene oxide and the nematic MBBA.

The crude material was purified by flash chromatography on silica gel (60 g), buffered with 1 % of triethylamine, using w-hexane-diethyl ether (95 5) to afford (R,R)-( )-stilbene oxide as a colourless oil (123 mg, 0.62 mmol, 62%). 

Reactions.—Nucleophilic Attack at Carbon. (/) Carbonyls. Methyl arylglyoxylates react with trisdimethylaminophosphine (TDAP) to form m-a/S-dimethoxycarbonyl-stilbene oxides.63 The initially formed zwitterion (61) reacts with a second molecule of the ester to form a fra/ -diphenyl-1,4,2-dioxaphospholan intermediate, which undergoes a concerted symmetry-allowed retrograde n2s + 4 cycloaddition to give a carbonyl ylide, conrotatory cyclization of which leads to the cw-oxirans (62) (Scheme 3). 

The reaction of cis- and frans-stilbene oxides with phenylphosphonothioic dichloride in the presence of magnesium gives cis- and fra/ts-stilbene and (7).13 Phenylphosphinidene sulphide is postulated as being an intermediate. The zwitterion (8) bears a remarkable similarity to the controversial perepoxides which are thought to be intermediates in the reaction of singlet oxygen with alkenes. 

The checkers report that GLC analysis (Note 13) at this point shows that the product is contaminated with ca. 4% of trans-stilbene oxide and <1% of the Tischenko product (Note 14). 

Gas chromatography conditions are as follows Supelco fused silica capillary SPB-1 column (30 m, 0.32-mm ID, 0.25 micrometers df), 100°C initial temperature, 280°C final temperature, 10°C/min. The following retention times were obtained diphenylacetaldehyde (6.7 min), trans-stilbene oxide (7.4 min), Tischenko product (18.2 min). 

S)-(-)-CITRONELLOL from geraniol. An asymmetrically catalyzed Diels-Alder reaction is used to prepare (1 R)-1,3,4-TRIMETHYL-3-C YCLOHEXENE-1 -CARBOXALDEHYDE with an (acyloxy)borane complex derived from L-(+)-tartaric acid as the catalyst. A high-yield procedure for the rearrangement of epoxides to carbonyl compounds catalyzed by METHYLALUMINUM BIS(4-BROMO-2,6-DI-tert-BUTYLPHENOXIDE) is demonstrated with a preparation of DIPHENYL-ACETALDEHYDE from stilbene oxide. A palladium/copper catalyst system is used to prepare (Z)-2-BROMO-5-(TRIMETHYLSILYL)-2-PENTEN-4-YNOIC ACID ETHYL ESTER. The coupling of vinyl and aryl halides with acetylenes is a powerful carbon-carbon bond-forming reaction, particularly valuable for the construction of such enyne systems. 

T. Ooi, K. Maruoka, and H. Yamamoto 95 REARRANGEMENT OF trans-STILBENE OXIDE TO DIPHENYL-ACETALDEHYDE WITH CATALYTIC METHYLALUMINUM BIS(4-BROMO-2,6-DI-tert-BUTYLPHENOXIDE)... 

Figure 2.10 Chromatograms of ( + )-trans-stilbene oxide. Conditions column, Chiralpak OP( + ), 25 cm x 4.6 mm i.d. eluent, methanol column temperature, ambient flow rate, 1 ml min -detector A, polarimeter B, refractive index.

In contrast, a number of alkene epoxides (10.3) are chemically quite stable, i.e., intrinsically less reactive than arene oxides. Examples of epoxide metabolites that have proven to be stable enough to be isolated in the absence of degrading enzymes include 1,2-epoxyoctane (10.4), 1,2-epoxycyclohex-ane (10.5), 1-phenyl-1,2-epoxy ethane (styrene oxide, 10.6), and cis- 1,2-diphenyl-1,2-epoxyethane (cfv-stilbene oxide, 10.7) [12], The same is true of alclofenac epoxide (10.8), hexobarbital epoxide (10.9), and a few other epoxides of bioactive compounds. 

The human cytosolic epoxide hydrolase (cytosolic EH, cEH, also known as soluble EH) has 554 amino acids (Mr 62.3 kDa) and is the product of the EPHX2 gene [49]. Its specific substrate is trans-stilbene oxide, and it appears... 

Stilbene oxide (2,3-diphenyloxirane) is another compound of interest. It exists as two diastereoisomers, namely cA-stilbene oxide (10.7, Fig. 10.28) and the trans-(RJi)- and /ra/i.y-(5,5)-stilbene oxides (10.121, Fig. 10.28), which exhibit significant but condition-dependent substrate selectivity. Cytosolic EH purified from mouse liver metabolized racemic tram -sti I bene oxide with high affinity and high velocity, and cA-stilbene oxide with lower affinity and lower... 

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