Acrylic acid stereoselectivity

Asymmetric hydrogenation has been achieved with dissolved Wilkinson type catalysts (A. J. Birch, 1976 D. Valentine, Jr., 1978 H.B. Kagan, 1978). The (R)- and (S)-[l,l -binaph-thalene]-2,2 -diylblsCdiphenylphosphine] (= binap ) complexes of ruthenium (A. Miyashita, 1980) and rhodium (A. Miyashita, 1984 R. Noyori, 1987) have been prepared as pure atrop-isomers and used for the stereoselective Noyori hydrogenation of a-(acylamino) acrylic acids and, more significantly, -keto carboxylic esters. In the latter reaction enantiomeric excesses of more than 99% are often achieved (see also M. Nakatsuka, 1990, p. 5586). 

The highly ordered cyclic TS of the D-A reaction permits design of diastereo-or enantioselective reactions. (See Section 2.4 of Part A to review the principles of diastereoselectivity and enantioselectivity.) One way to achieve this is to install a chiral auxiliary.80 The cycloaddition proceeds to give two diastereomeric products that can be separated and purified. Because of the lower temperature required and the greater stereoselectivity observed in Lewis acid-catalyzed reactions, the best diastereoselectivity is observed in catalyzed reactions. Several chiral auxiliaries that are capable of high levels of diastereoselectivity have been developed. Chiral esters and amides of acrylic acid are particularly useful because the auxiliary can be recovered by hydrolysis of the purified adduct to give the enantiomerically pure carboxylic acid. Early examples involved acryloyl esters of chiral alcohols, including lactates and mandelates. Esters of the lactone of 2,4-dihydroxy-3,3-dimethylbutanoic acid (pantolactone) have also proven useful. 

The same group has developed another synthetically useful photochemically induced domino transformation. Irradiation of the enaminecarbaldehydes 5-40a or 5-40b in the presence of acrylic acid ester 5-41a or acrylonitrile 5-41b afforded the quinolizidines 5-45a and 5-45b as well as the pyrido[l,2-a]azepines 5-45c and 5-45d, respectively, with high stereoselectivity [14]. Only very small amounts of the corresponding diastereomers 5-46a-d were detected. 

Alkylation of norbornene with acrylic acid derivatives occurs with ruthenium catalysts like [RuCl2(C6H6)]2/Zn in protic solvent.31 (,E)-o -2-norbonylacrylates are obtained with high regio- and stereoselectivity in good yields. 

The oxazoline ring acts as an electron-withdrawing group for a substituent at the 2-position. Thus, the ot-protons of a 2-alkyloxazoline exhibit some acidity and can be abstracted by a base. A 2-alkenyloxazoline can be viewed as a masked acrylic acid derivative and is capable of undergoing Michael addition and Diels-Alder reactions. These reactions can often be carried out stereoselectively using a chiral oxazoline. Other types of chiral auxilliaries, most notably oxazolidinones, are also very effective for these types of applications. However, they are outside the scope of this chapter. The discussion in this section will focus on the new developments with oxazolines. 

Nickel(0)-catalyzed codimerization of methylenecyclopropanes with electron-deficient olefines are highly regiospedfic, but show a rather poor stereoselectivity. Thus the asymmetric nickel(0)-catalyzed codimerization of methylenecyclopropanes with the chiral bomane derivatives of acrylic acid leads to the optically active 3-methylenecyclopen-... 

Related ligands for catalysis, namely BINAP ligands substituted with Frechet dendrons (5, Fig. 6.34) were prepared by Chan et al. [51]. They form rutheniu-m(II) complexes in situ, whose activity in the stereoselective hydrogenation of 2-[p-(2-methylpropyl)phenyl]acrylic acid was investigated. 

A haloalkene that contains a stereogenic C=C double bond can usually be coupled with alkenes via the Heck reaction without isomerization. This is illustrated with the three reaction pairs in Figure 16.36. As can be seen, both the as- and the /raw-configured iodoalkenes react with acrolein or methyl vinyl ketone or acrylic acid methyl ester with complete retention of the C=C double bond configuration. These coupling reactions are thus stereoselective and— when considered as a pair—stereospecific. 

Asymmetric Hydrogenation. The diene-free cationic rhodium complex of (R)-BINAP catalyzes the enantioselective hydrogenation of dehydroamino acids. a-(Benzoylamino)acrylic acid is hydrogenated at rt to afford (S)-lV-benzoylphenylalanine in 100% ee (eq 1). To obtain maximal stereoselectivity the reaction should be carried out under a low concentration of substrate (100% in 0.013 M vs. 62% in 0.15 M) and low initial hydrogen pressure (100% at 1 atm, but 71% at 50 atm). 

Asymmetric Hydrogenations. Catalytic asymmetric hydrogenations of p-disubstituted-a-phenylacrylic acids have been achieved using the Rh complex of (4) (eq 9). Asymmetric hydrogenation of unsymmetrically substituted trisubstituted acrylic acids leads to the formation of two stereocenters in high ee. The variation of the terminal dialkylamino substituents has little effect on enantioselectivity. A study of a Ru° complex of (1) was reported as a model for understanding the stereoselective transition state of asymmetric hydrogenations. ... 

Hydrostannation of chiral menthyl esters of substituted acrylic acids proceeds stereoselectively, providing a route to optically active alkyl-... 

Af-Unsubstituted pyrazoles and indazoles add to compounds containing activated double and triple bonds (67HC 22)1,B-76MI40402>. Amongst C—C double and triple bonds, maleic anhydride, acrylic acid esters and nitriles, acetylene-carboxylic and -dicarboxylic esters (78AHC(23)263), quinones, and some a,/3-unsaturated ketones have been used with success. Phenylacetylene reacts with pyrazole in the presence of Na/HMPT as catalyst to yield the Z isomer of 1-styrylpyrazole in a highly stereoselective reaction (78JHC1543). 

As far as stereoselectivity is concerned, the key step is the Diels-Alder reaction—in each case the diene (cyclopentadiene, shown in black) adds across the dienophile, an acrylic acid derivative. As you would expect from what we said in Chapter 35, both reactions are diastereoselective in that they generate mainly the endo product. In the hrst example, that is all there is to say the product that is formed is necessarily racemic because all the starting materials in the reaction were achiral. 

Esterification of 19 with acrylic acid chloride made diene 20 available. Subsequent stereoselective Diels-Alder cycloaddition with cyclopentadiene proceeded with complete diastereoselectivity in 55% yield. The asymmetric product 21 was cleaved from the polymer by exposure to light (Scheme 12.11). 

The reaction of nitrone 101 with such olefins 5 as propylene, n-hexene, allyl alcohol, styrene, acrylic acid, methyl acrylate, acrylonitrile, and butadiene are all regiospecific to give S-substituted isoxazolidines of type l.77 The reaction with olefins 6 seems to be regio- and stereo-specific thus, nitrone 101 and methyl methacrylate give cycloadduct lilt as the sole product.77 Similarly, 101 and 1 -methyl-1-phenylethylene gives adduct Hit.77 In the reactions with olefins 7 or 8, the stereospecificity is more evident.77,78 The isoxazolidine obtained is always one of the two possible epimers. The reaction of nitrone 101 with trisubstituted olefins is highly stereoselective.64 Some results are summarized in Table III. 

Chiral samarium (II) complexes have also been applied towards the hydrodimerization of acrylic acid amides [16]. Such reactions involve the ligand-controlled dimerization of conjugated ketyl radicals in the enantioselective formation of 3,4-tra .y-disubstituted adipamides (Eq. 11). Yields were mainly low, often under 40% and enantiocontrol was modest with selectivities ranging from around 50-85% ee. A nine-membered chelated transition state 37 is used to rationalize the stereoselectivity of the dimerization where the ligand-bound conjugated ketyl radicals are oriented cis to each other on the metal assuming an octahedral geometry. 

Among the many stereoselective routes currently employed to prepare enantiomerically pure NS AID a-arylalkanoic acids [63], a pre-eminent position is held by the enantioselective catalytic hydrogenation of a-arylsubstituted acrylic acids. 

The manufacture of optically active L-a-amino acids from racemic amino acid amides was shown by Mitsubishi Gas Chemical, Japan [117]. In this process different microorganisms were immobilized on polymers made from (meth)acrylic acid esters or urethane acrylates and applied for the stereoselective hydrolysis of racemic amides (Scheme 43). o/L-Leucinamide (rac-136), for example, can be hydrolyzed with Mycoplana bullata cells immobilized on polyethylene glycol dimethacrylate-AT,N -methylenebisacrylamide copolymer at 30 C to produce i-leudne (l-137) over 3,000 h. 

In the Diels-Alder reaction of acrylic acid and E-pentadienoic acid, the temperature has a noticeable effect on the stereoselectivity (3.69). At low or moderate temperatures the endo adduct is the major product, but the proportion of the exo isomer increases as the temperature of the reaction increases. 

A heterogeneous cobalt catalyst was employed for arylations of styrene (2) and two acrylates with aryl iodides. Generally, isolated yields were significantly lower than those observed for heterogeneous nickel catalysts [24]. Further, a silica-supported poly-y-aminopropylsilane cobalt(II) complex was reported as a highly active and stereoselective catalyst for Mizoroki-Heck-type reactions of styrene (2) and acrylic acid (16) using aryl iodides [23,25]. 

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