Asymmetric cinnamyl alcohol

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... 

Asymmetric cyclopropanation of olefins can also be achieved by the Simmons-Smith reaction (231). Reaction of ( )-cinnamyl alcohol and the diiodomethane-diethylzinc mixed reagent in the presence of a small amount of a chiral sulfonamide gives the cyclopropylcarbinol in up to 75% ee (Scheme 97) (232a). ( )-Cinnamyl alcohol can be cyclopro-... 

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. 

Asymmetric Intramolecular Hydrosilation. Intramolecular hydrosilation of allylic alcohols followed by oxidation is a convenient method for the stereoselective preparation of 1,3-diols. An enantioselective version is achieved by use of diene-free BINAP-Rh+ (eq 6). Both silyl ethers derived from cinnamyl alcohol and its cis isomer give (iJ)-l-phenylpropane-l,3-diol in high ee regardless of alkene geometry. 

The scope of the reaction was examined with a catalyst prepared from the benzene sulfonamide and DIBAL, because it was found that essentially the same induction could be obtained as with those obtained from tri-/so-butyl aluminum. Two years earlier the authors had reported that this Simmons-Smith reaction could also be catalyzed by the aluminum-free sulfonamide 132 (optimum with Ar = /7-NO2C6H4) the induction obtained is listed in the far right column of Table 8 [34]. It was proposed that a zinc complex of 132 is generated in-situ. Surprisingly, with the exception of the silyl-substituted allyl alcohol (the last entry in the table) [35], almost identical asymmetric induction obtained by use of the aluminum-containing and aluminum-free catalysts. The main advantage of the diazaaluminolidine catalyst is that it is apparently more soluble than the aluminum-free bis-sulfonamide catalyst, with the result that a tenfold increase in concentration (0.1 m) can be used this might explain the increased rate observed for the diazaaluminolidine catalyst. Finally, it has recently been reported that a catalyst formed from the Ci symmetrical sulfonamide 135 and DIBAL will induce the formation of 131 from cinnamyl alcohol in 68 % ee [36]. 

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). 

Scheme 6.33. Asymmetric catalysts for the Simmons-Smith cyclopropanation of trani-cinnamyl alcohol (a) [123]. (b) [124]. (c) [120,122]. (d) Transition state model for catalyst c [120]. Only one zinc and the transfer methylene are shown other atoms associated with the Simmons-Smith reagent are deleted for clarity.

The addition of alkyllithiums to allylic alcohols, originally described by Felkin and Crandall [83], has recently acquired new interest due to the enantioselective approach of the carbometallation reaction of cinnamyl derivatives. Indeed, asymmetric carbolithiation of ( )-cinnamyl alcohol in hexane or cumene, in the presence of the readily available chiral diamine (—)sparteine, leads to the carbometallated product in 82% ee. Primary as well as secondary alkyllithiums lead to identical enantioselection [128] (Scheme 7-108). 

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... 

Scheme 10.4 The first example of an asymmetric intermolecular carbolithiation of cinnamyl alcohol [7].

Despite tremendous advances in the development of chiral methods, asymmetric alkene dichlorination remains one of the challenges. This reaction was successfully achieved for frans-cinnamyl alcohols as substrates using (dichloroiodo)arenes in combination with dimeric cinchona alkaloid derivatives 41 leading to products with up to 85% ee (Scheme 19) [64]. Chiral iodine(V) reagent 42 in combination with pyridine hydrobromide led to the dibromination of p-methylstyrene in only 3% ee [65]. 

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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