Acrylic acid derivatives enantioselective

Table 2 Enantioselective hydrogenation of a-acylamino acrylic acid derivatives...

Enantioselective Diels-Alder reactions proceed smoothly in the presence of a chiral Sc catalyst, prepared in situ from Sc(OTf)3, R)- I )-l,l -bi-2-napluhol [(R)-BINOL], and a tertiary amine in dichloromethane.58 The catalyst is also effective in Diels-Alder reactions of an acrylic acid derivative with dienes (Scheme 14). 

The enantioselective hydrogenation of a,fj- or / ,y-unsaturated acid derivatives and ester substrates including itaconic acids, acrylic acid derivatives, buteno-lides, and dehydrojasmonates, is a practical and efficient methodology for accessing, amongst others, chiral acids, chiral a-hydroxy acids, chiral lactones and chiral amides. These are of particular importance across the pharmaceutical and the flavors and fragrances industries. 

As can be seen in Table 5, various oxazolidones of acrylic acid derivatives react with cyclopentadiene to afford the endo-adducts in good to high (64-91%) enantioselectivity by the combined use of a catalytic amount of the chiral titanium reagent and MS 4A. 

Only limited successful examples of asymmetric hydrogenation of acrylic acids derivatives have included the use of chiral Rh complexes (Scheme 1.17). The diamino phosphine (28) utilizes selective ligation of the amino unit to a Rh center and also exerts electrostatic interaction with a substrate. Its Rh complex catalyzes enantioselective hydrogenation of 2-methylcinnamic acid in 92% optical yield [116], Certain cationic Rh complexes can attain highly enantioselective hydrogenation of trisubstituted acrylic acids [ 1171. 2-(6 -Methoxynaphth-2 -yl)acrylic acid is hydrogenated by an (.S ..S )-BIPNOR- Rh complex in methanol at 4 atm to give (.S)-naproxen with 98% ee but only in 30% yield [26]. 

Cycloalkenyl sulfides 10 are converted into bicyclo[n.2.0] alkane compounds with almost complete enantioselectivity by the reaction with the fumaric or acrylic acid derivatives 2a,c as listed in Scheme 8 and Table 3. As the reactivity of 10 is not as high as that of acyclic alkenyl sulfides, the use of an equimolar amount of the chiral titanium reagent is required to attain a good chemical yield in some cases. Diastereoselectivity is generally excellent and no ene product is detected. 

Asymmetric Catalysts Using Sc(OTf)3. The chiral Sc catalyst prepared from Sc(OTf)3, (i )-BINOL, and a tertiary amine in dichloromethane (eq 22) serves as an asymmetric catalyst for the Diels-Alder reactions of an acrylic acid derivative with dienes (eq 23). The highest enantioselectivities are observed when di -l,2,6-trimethylpiperidine is employed as the amine. Even 3 mol % of the catalyst is enough to complete the reaction yielding the endo adduct in 92% ee. The structure of the chiral Sc catalyst is indicated by C-NMR and IR spectra. A similar Sc(OTf)3/(R)-BINOL/diisopropylethylamine complex serves as an effective catayst for the Diels-Alder reaction of A-benzyloxy-carbonyl-l-aminobutadiene with 3-acyl-l,3-oxazolidin-2-one. ... 

Scheme 5.23 Enantioselective Michael reactions glydnate imines with acrylic acid derivatives catalyzed by 103a.

Another important example of an enantioselective reaction mediated by a chiral catalyst is the hydrogenation of 3-substituted 2-acetamido acrylic acid derivatives. 

The fundamental concepts of enantioselective hydrogenation were introduced in Section 2.5.1 of Part A, and examples of reactions of acrylic acids and the important case of a-acetamido acrylate esters were discussed. The chirality of enantioselective hydrogenation catalysts is usually derived from phosphine ligands. A number of chiral phosphines have been explored in the development of enantioselective hydrogenation catalysts,21 and it has been found that some of the most successful catalysts are derived from chiral 1, l -binaphthyldiphosphines, such as BINAP.22... 

Rhodium-catalyzed enantioselective hydrogenation of acctamido -cinnamic in water was also achieved using pyrphos bound to poly-acrylic acid as ligand.337 Roucoux described some Rh° nanoparticles which function as reusable hydrogenation catalyst for arene derivatives in a biphasic water-liquid system.338... 

A breakthrough in this area came when Dang and Kagan3 synthesized DIOP, a C2 chiral diphosphine obtained from tartaric acid (Fig. 6-1). DIOP-Rh(I) complex catalyzed the enantioselective hydrogenation of a-(acylamino)acrylic acids and esters to produce the corresponding amino acid derivatives with up to 80% ee. These achievements stimulated research on a variety of bidentate chiral diphosphines, and numerous chiral ligands bearing C2 symmetry have been developed as a result (see Fig. 6-1 for examples). 

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