Cinnamyl alcohol asymmetric epoxidation

Via Asymmetric Epoxidation and Related Reactions. Denis et al.35 synthesized the taxol side chain derivative via Sharpless epoxidation. Starting from cw-cinnamyl alcohol, the corresponding epoxide compound was prepared with 76-80% ee. Subsequent azide ring opening gives a product that possesses the side chain skeleton (Scheme 7-78). 

Figure 14.7. Electronic effects in asymmetric epoxidation of cinnamyl alcohols...

The Sharpless synthesis (Scheme 17.13) begins with the asymmetric epoxidation of cinnamyl alcohol (50) using (-l-)-di-isopropyl tartarate (DIPT) as the chiral ligand for the... 

The second stoichiometry consideration is the ratio of catalyst to substrate. As noted in the preceding section, virtually all asymmetric epoxidations can be performed with a catalytic amount of Ti-tartrate complex if molecular sieves are added to the reaction milieu. A study of catalyst/substrate ratios in the epoxidation of cinnamyl alcohol revealed a significant loss in enantioselectivity (Table 6A.2) below the level of 5 mol % catalyst. At this catalyst level, the reaction rate also decreases, with the consequence that incomplete epoxidation of the substrate may occur. Presendy, the recommended catalyst stoichiometry is from 5% Ti and 6% tartrate ester to 10% Ti and 12% tartrate ester [4],... 

The concentration of substrate used in the asymmetric epoxidation must be given consideration because competing side reactions may increase with increased reagent concentration. The use of catalytic quantities of the Ti-tartrate complex has greatiy reduced this problem. The epoxidation of most substrates under catalytic conditions may be performed at a substrate concentration up to 1 M. By contrast, epoxidations using stoichiometric amounts of complex are best run at substrate concentrations of 0.1 M or lower. Even with catalytic amounts of the complex, a concentration of 0.1 M may be maximal for substrates such as cinnamyl alcohol, which produce sensitive epoxy alcohol products [4]. 

Preliminary results for asymmetric epoxidations of ( )-cinnamyl alcohol and geraniol using (15,25)-... 

Preliminary results for asymmetric epoxidations of ( )-cinnamyl alcohol and geraniol using (15,25)-l,2-di(2-methoxyphenyl)ethane-l,2-diol or (15,25)-l,2-di(4-methoxyphenyl)ethane-l,2-diol as chiral auxiliaries with titanium(IV) isopropoxide and TBHP have been described. High enantioselectivity (95% ee) is observed when the 2-methoxyphenyl compound is used, while somewhat lower enantioselectivity (64% ee) and opposite face selectivity is described for the catalyst comprised of the 4-methoxyphenyl analog.Further elaboration of the scope and generality of these observations will be of interest. 

Recently, two other groups have shown that exocyclic iminium salts can be useful mediators in asymmetric epoxidation. Komatsu has developed a system based on ketiminium salts [14], prepared through the condensation of aliphatic cyclic amines with ketones. A chiral variant was also produced, derived from prolinol and cyclohexanone, which gave 70% yield and 39% ee for cinnamyl alcohol (Scheme 5.7). 

Long-range electron transfer is postulated to occur from ferrocene to tris(bipyridine)iron(III) constructed within the pores of a NaY zeolite. The iron bipyridine complex is too large to move throughout the faujasite pores to the surface, thus requiring the long-range transfer. The asymmetric catalyst, titanium tartrate, has been prepared inside NaY and used as an immobilized catalyst for the epoxidation of cinnamyl alcohol. ... 

Bonini C, Righi G (1994) Enantio- and Stereo-selective Route to the Taxol Side Chain via Asymmetric Epoxidation of ran -Cinnamyl Alcohol and Subsequent Epoxide Ring Opening. J Chem Soc Chem Comm 2767... 

Henegar et al. [78] at Pfizer developed an efficient and greener synthesis of the (S, 5)-reboxetine 157, which is being evaluated for the treatment of neuropathic pain and a variety of other indications (Scheme 9.42). The reported chiral synthesis of 157 starts by SAE of cinnamyl alcohol 154 to give R, R)-epoxide 155 in 89% yield (> 98% ee). Reaction of 155 with 2-ethoxyphenol gave crystallized product 156. The overall yield of (S, 5)-reboxetine succinate increased by 9%, compared to resolution method. The catalytic asymmetric process offers use of less solvent and reduces waste generation by approximately 50%, compared to the resolution route. 

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