Phenylpropionic acid diastereoselectivity

When dienones such as 55 are subjected to the epoxidation conditions the electron-poorer C=C double bond is selectively epoxidized. The other C=C bond can be functionalized further, for example, it can be dihydroxylated, as shown in the synthesis of the lactone 56 (Scheme 10.11) [82]. Stannyl epoxides such as 57 (Scheme 10.11, see also Table 10.8, R1 = n-Bu3Sn) can be coupled with several electrophiles [72], reduction of chalcone epoxide 58 and ring opening with alkyl aluminum compounds provides access to, e.g., the diol 59 and to phenylpropionic acids (for example 60). Tertiary epoxy alcohols such as 61 can be obtained with excellent diastereoselectivity by addition of Grignard reagents to epoxy ketones [88, 89]. 

In contrast, reaction of diethyl propionylphosphonate with lithium bis-(trimethylsilyl)amide (LiHMDS) at -78 °C gave the expected enolate as evidenced by its highly diastereoselective condensation with benzaldehyde, leading to the formation of 3-hydroxy-2-methyl-3-phenylpropionic acid (equation 91) " . An attempt was made to develop this concept to enantioselective aldol condensation. However, condensation of a cyclic chiral propionylphosphonamidate (31), synthesized from ( S)-A-isopropyl-4-aminobutan-2-ol, with benzaldehyde yielded 3-hydroxy-2-methyl-3-phenylpropionic acid in disappointingly low 47% e.e. (equation 92)... 

Paditaxel, a complex terpene molecule with antimitotic activity (commercialized as Taxol ), is used for various cancer treatments, including ovarian and breast cancer treatments. The isolation of this naturally occurring compound requires the harvesting of a large amount of trees and involves difficult purification. A semisynthetic route has been developed based on the coupling of baccatin III (a diterpenoid that can be isolated from yew leaves) with the chiral side-chain (2R,3S)-N-benzoyl-3-phenylisoserine ethyl ester. The latter could be obtained from the diastereoselective microbial reduction of racemic 2-keto-3-(N-benzoylamino)-3-phenylpropionic acid ethyl ester using whole cells of Hansemda sp. (Figure 13.12). Despite concomitant production of the undesired anti diastereomers (2R,3R)-N-benzoyl-3-phenylisoser-ine ethyl ester and (2S,3S)-N-benzoyl-3-phenylisoserine ethyl ester (up to 20%) due to nonperfect selectivity, the C-13 side-chain synthon required for paclitaxel... 

Figure 13.12 Diastereoselective reduction of2-keto-3-(N-benzoylamino)-3-phenylpropionic acid ethyl ester to chiral C-13 paclitaxel side-chain synthon.

Lalitha, A., Pitchumani, K., and Srinivasan, C., Induced diastereoselectivity in photodecarboxylation of 2-phenylpropionic acid in faujasite zeolites. Tetrahedron, 57,4455, 2001. 

Photodecarboxylation of NSAIDs Inside Cyclodextrin Diastereoselective Photodecarboxylation of 2-Phenylpropionic Acid in Zeolite Medium Photolysis of Ibuprofen and the Methyl Ester of Naproxen 64.5 Conclusion.65-11... 

Diastereoselective Photodecarboxylation of 2-Phenylpropionic Acid in Zeolite Medium... 

Hoshino, T., Ishida, K., Irie, T., Hirayama, E, Uekama, K., and Yamasaki, M., Reduction of pho-tohemolytic activity of benoxaprofen by P-cyclodextrin complexation,/. Incl Phenom.,6,415,1988. Lalitha, A., Pitchumani, K., and Srinivasan, C., Induced diastereoselectivity in photodecarboxylation of 2-phenylpropionic acid in faujasite zeolites. Tetrahedron, 57, 4455, 2001. 

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