Styrene oxide synthesis

Unfortunately, the highest enantioselectivity so far obtained for the synthesis of styrene oxide by this route is only 57 % ee with Goodman s sulfide 30 [21]. Thus methylidene transfer is not yet an effective strategy for the synthesis of terminal epoxides. 

Figure 5.6 Cost Indices Cl for the biocatalytic (a) and chemical catalytic (b) synthesis of (S)-styrene oxide (Scheme 5.3), using the software EATOS. The bottom figure shows the cost savings achieved by solvent recycling.

This enantioselective reduction can be used for synthesis of chiral 1-substituted oxiranes.1 2 3 Thus reduction of 2-chloroacetophenone with B2H6 catalyzed by 1 (1 mole %) results in (S)-( + )-(chloromethyl)benzenemethanol, which in the presence of base converts to (S)-( - )-phenyloxirane (styrene oxide). 

Amidocarbonylation methodology can also be applied to the synthesis of N-acclyl- (D,L)-phenylalanine, a key intermediate for aspartame (1-aspartyl-l-phenylalanine methylester), from styrene oxide (via isomerization to phenac-etaldehyde) [24] or benzyl chloride [25] in good yields. 

The ODH of ethylbenzene to styrene is a highly promising alternative to the industrial process of non-oxidative dehydrogenation (DH). The main advantages are lower reaction temperatures of only 300 500 °C and the absence of a thermodynamic equilibrium. Coke formation is effectively reduced by working in an oxidative atmosphere, thus the presence of excess steam, which is the most expensive factor in industrial styrene synthesis, can be avoided. However, this process is still not commercialized so far due to insufficient styrene yields on the cost of unwanted hydrocarbon combustion to CO and C02, as well as the formation of styrene oxide, which is difficult to remove from the raw product. 

Synthesis of Enantiopure (S)-Styrene Oxide by Seiective Oxidation of Styrene 385... 

Synthesis of Enantiopure (5)-Styrene Oxide by Selective Oxidation of Styrene by Recombinant Escherichia coli JMlOl (pSPZlO)... 

The table, which collects representative examples, shows that monosubstituted epoxides afford homoaUyhc alcohols resulting from the attack to the less substituted carbon atom (runs 1, 5 and 7). HomoaUyhc alcohols are useful intermediates in several important total synthesis." Disubstituted epoxides fail to react (run 4). Styrene oxide leads to a mixture of homoaUyhc alcohols (run 2) and ally lie epoxides give mixture of 1,2- and 1,4-opening product, with predominance of the 1,4 product (run 3, 6 and 8). 

Dopamine, the free catechol corresponding to (1-1), plays an important role as a neurotransmitter, particularly in the CNS. The synthesis of a dopamine-related sedative agent starts with the condensation of homoveratramine (1-1) with styrene oxide (1-2) to afford the carbinol (1-3). Treatment of that product with a strong acid leads to an attack on the electron-rich aromatic ring by the resulting carbocation there is thus obtained the benzazocine (1-4). The secondary amine is then methylated by reaction with formaldehyde and formic acid to yield trepipam (1-5) [1]. 

Scheme 7.3 The synthesis of styrene oxides through the enzymatic acylation of chloroalcohols.

A variation of this synthesis involving enamines is the condensation of cyclohexenyl-pyrrolidine (301) with styrene oxide (reflux DMF) to give compound 311 (R2 = Ph) by distillation of the intermediate perhydro derivative 312 from oxalic acid.720... 

Manufacture. Current commercial methods for making PEA include Grignard synthesis. Friedel-Crafts process, and catalytic hydrogenation of styrene oxide. 

Isomerization of substituted styrene oxides allows the synthesis of aldehydes in high yields726 [Eq. (5.275)]. Cycloalkene oxides do not react under these conditions, whereas 2,2,3-trimethyloxirane gives isopropyl methyl ketone (85% yield). Isomerization of oxiranes to carbonyl compounds is mechanistically similar to the pinacol rearrangement involving either the formation of an intermediate carbocation or a concerted mechanism may also be operative. Glycidic esters are transformed to a-hydroxy-/3,y-unsaturated esters in the presence of Nafion-H727 [Eq. (5.276)]. 

Reaction of styrene oxide with sodium ethanethiolate completes the synthesis. 

Two types of asymmetric reactions were conducted synthesis of styrene oxide and reduction of olefinic ketones. 

As demonstrated below, a Lewis acid-mediated reaction was utilized in the synthesis of dihydro[b furan-based chromen-2-one derivatives from l-cyclopropyl-2-arylethanones and allenic esters <070L4017>. The TiCh-catalyzed anti-Markovnikov hydration of alkynes, followed by a copper-catalyzed O-arylation was applied to the synthesis of 2-substituted benzo[6]furan <07JOC6149>. In addition, benzo[6]furan-based heterocycles could be made from chloromethylcoumarins <07SL1951>, substituted cyclopropanes <07AGE1726>, as well as benzyne and styrene oxide <07SL1308>. On the other hand, DBU-mediated dehydroiodination of 2-iodomethyl-2,3-dihydrobenzo[6]furans was also useful in the synthesis of 2-methylbenzo[Z>]furans <07TL6628>. 

Styrenes and styrene oxides can be combined in a highly chemo- and regioselective fashion to yield 2,4-bis-aryl-substituted tetrahydrofurans using an iron catalyst <2005CC1996>. This tetrahydrofuran synthesis developed by Hilt et al. opens an unprecedented way for the one-step synthesis of racemic calyxolane A and calyxolane B with moderate diastereoselectivities. The iron-catalyzed ring-expansion reaction of epoxyalkenes was considerably... 

This reduction is useful for synthesis of optically active styrene oxide (equation I). 

The same differential behavior can be observed with amine nucleophiles. For example, calcium triflate promotes the aminolysis of propene oxide 84 with benzylamine to give 1-(A -benzyl)amino-2-propanol 85, the result of attack at the less substituted site <03T2435>, and which is also seen in the solventless reaction of epoxides with heterocyclic amines under the catalysis of ytterbium(III) triflate <03SC2989>. Conversely, zinc chloride directs the attack of aniline on styrene oxide 34 at the more substituted carbon center <03TL6026>. A ruthenium catalyst in the presence of tin chloride also results in an SNl-type substitution behavior with aniline derivatives (e.g., 88), but further provides for subsequent cyclization of the intermediate amino alcohol, thus representing an interesting synthesis of 2-substituted indoles (e.g., 89) <03TL2975>. 

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