Asymmetric reactions 73 propionic acid

The development of enantioselective aldol reactions has been widely studied in conjunction with the synthesis of natural products. Highly enantioselective aldol reactions have been achieved by employing chiral enolates of ethyl ketones and propionic acid derivatives.(1) On the other hand, achieving high asymmetric induction in the asymmetric aldol reaction of methyl ketones is still a problem.(2)... 

A novel class of complexes, Ir-(5 )-26a, with chiral spiro aminophosphine ligands was found to be effective catalyst for the asymmetric hydrogenation of a-substituted acrylic acids (Scheme 11) [62]. Under mild reaction conditions and at ambient pressure, various a-aryl and alkyl propionic acids were produced with extremely high efficiency (TONS up to 10 000 TOFs up to 6000h ) and excellent enantioselectivity (up to 99% ee). This reaction provides a practically useful method for the preparation of a-aryl propionic acids, a popular class of non-steroid anti-inflammtory reagents. 

The aliphatic segment has 8 asymmetric carbons based on propionic acid biogenesis. Masamune reported a strategy based upon aldol reaction [18]. Hanessian retrosynthesized rifamycin ansachain by chiron approach [19]. On the other hand, Kishi demonstrated to provide a general method affording all... 

As one of the enzymic reactions, asymmetric synthesis catalyzed by cyclodextrins has been studied in the past, but gave all the products in a low optical yield. We have already found a strong chiral induction for the chlorination of methacrylic acid in the crystalline cyclodextrin complexes. 100 % enantiomeric excess (e.e.) of (-)-2,3-dichloro-2-methyl-propionic acid and 88 % e.e. of its enantiomer were isolated in a- and 3-cyclodextrins, respectively. This paper describes asymmetric addition of gaseous halogens and hydrogen halides in the crystalline complexes comprising trans-cinnamic acid as a reactant and a- or 3-cyclodextrin as chiral matrix. Asymmetric bromination of menthyl cinnamate and of salts from the acid and several chiral amines have been reported, but gave low chiral inductions up to 2 16 % e.e.. 

Chen, A. Ren, L. Crudden, M. C. Catalytic Asymmetric Carbon-Carbon Bond Forming Reactions Preparation of Optically Enriched 2-aryl Propionic Acids by a Catalytic Asymmetric Hydroboration-Homologation Sequence [Dagger]. Chem. Commun. 1999,611-612. 

The erythromycins are examples of polypropionates , natural products biosynthetically derived largely from propionic acid units via a series of condensation reactions. Many natural products, broadly called polyketides, share this biosynthetic origin. These compounds are decorated with multiple stere-ogenic centers, and acyclic diastereoselection problems that are much more complex than the terpenoid sidechain stereochemistry problem will surface with erythromycin, including the problem of asymmetric synthesis. 

Asymmetric hydroformylation of vinylarenes allows access to the 2-aryl propionic acids, an important family of nonsteroidal anti-inflammatory agents, known as the profen drugs (Scheme 14.6). For the reactions of vinyl arenes, early platinum-based catalysts again provided higher enan-tioselectivities than the rhodium catalysts available up to the early 1990s. However, the platinum complexes suffered from poor chemo- and regioselectivities. 

These first examples of the catalytic asymmetric aldol reaction not only provided first results that could be utilized for such transformations but also highlighted the problems that had to be overcome in further elaborations of this general method. It was shown that truly catalytic systems were required to perform an enantioselective and diastereoselective vinylogous aldol reaction, and it became obvious that y-substituted dienolates that serve as propionate-acetate equivalents provide an additional challenge for diastereoselective additions. To date, the latter problem has only been solved for diastereoselective additions under Lewis acid catalysis (vide infra) (Scheme 4, Table 3). 

As above (eq 1), a major drawback of this reagent is the lack of a readily available enantiomer. There are many alternative methods for the enantioselective propionate aldol reaction. The most versatile chirally modified propionate enolates or equivalents are N-propionyl-2-oxazolidinones, a-siloxy ketones, boron enolates with chiral ligands, as well as tin enolates. Especially rewarding are new chiral Lewis acids for the asymmetric Mukaiyama reaction of 0-silyl ketene acetals. Most of these reactions afford s yw-aldols good methods for the anri-isomers have only become available recently. ... 

One of the most common substrates is vinyl acetate, leading to 2-acetoxypropanal with up to 98% ee125 if the reaction is carried out in the presence of orthoformate. Vinyl propionate and vinyl benzoate can also be used (see Table 7)75,167. All these substrates are prostereogenic building blocks, e.g, as precursors for the asymmetric preparation of a-amino acids, such as threonine. 

The final example illustrates yet another use of the biomimetic approach. Figure 10.9shows a retro-synthetic analysis for Masamune s synthesis of deoxyerythronolide B (213). The biosynthetic building blocks of this and other macrolide antibiotics are known to be acetate and/or propionate units combined head-to-tail, as seen in 213. 7 xhe stereocenters in 213 are clearly shown in the acyclic (seco acid) form of the macrolide 215. The specific biopathway is not utilized but rather modified to include the basic building blocks, seven propionate units (bold lines in 213).Seco acid 215 was constructed by sequential aldol condensation reactions (sec. 9.4.A) of propionaldehyde units, as shown by the disconnections in Figure 10.9. Asymmetric... 

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