Acrylic acids asymmetric reduction

Novel C2-symmetric thiophene-containing ligands have recently been prepared and utilized in asymmetric synthesis. Dithiophene 158 was utilized as a ligand in the asymmetric reduction of p-ketoesters (prostereogenic carbonyl) and acrylic acids (carbon-carbon double bond) <00JOC2043>. Dibenzo[b]thiophene 159 was utilized as a ligand in enantioselective Heck reactions of 2-pyrrolines <00SL1470>. 

Asymmetric Hydrogenation. Asymmetric hydrogenation with good enantio-selectivity of unfunctionalized prochiral alkenes is difficult to achieve.144 145 Chiral rhodium complexes, which are excellent catalysts in the hydrogenation of activated multiple bonds (first, in the synthesis of a-amino acids by the reduction of ol-N-acylamino-a-acrylic acids), give products only with low optical yields.144 146-149 The best results ( 60% ee) were achieved in the reduction of a-ethylstyrene by a rhodium catalyst with a diphosphinite ligand.150 Metallocene complexes of titanium,151-155 zirconium,155-157 and lanthanides158 were used in recent studies to reduce the disubstituted C—C double bond with medium enantioselectivity. 

An excellent review describing asymmetric transfer hydrogenation has been published156. Many excellent results have been achieved in recent studies of acrylic acid reductions employing the same catalysts of ruthenium or rhodium with a chiral diphosphine as were used in the hydrogen gas process1331157. In this case, however, the most common hydrogen source is the combination of formic acid with an amine. The choice of amine is often critical in the reduction shown in Scheme 30, the use... 

Rhodium-BisP and -MiniPHOS catalysts are capable of high enantioselective reductions of dehydroamino acids in 96-99.9% ee.109 A variety of aryl enamides give optically active amides with 96-99% ee with the exception of ort/jo-substituted substrates.111 Despite the high enantio-selectivity, the rate of reaction in this transformation is slow. Rhodium-BisP and -MiniPHOS catalysts perform excellently in the asymmetric reduction of ( >P-(acylamino)acrylates to the corresponding protected-P-amino esters in 95-99% ee.112 Within the family of BisP and MiniPHOS, the ligands that contain t-Bu groups were found to be the most effective in a variety of asymmetric hydrogenations. 

One of the most common auxiliaries is menthyl, where an acrylic acid derivative is attached to menthol to form a menthyl ester, 255. Morrison and Mosher22l showed that asymmetric induction is possible with 255 when it reacts with cyclopentadiene to give diastereomers 256 and 257, 22 as shown in Table 11.13.221 in the absence of a Lewis acid, however, the % ee is rather poor. Similarly, (-)-dimenthyl fumarate (258) reacted with butadiene to give 259 and 260, after reduction of the ester products with lithium aluminum hydride. Hydride reduction of esters (sec. 4.2.B) is a common method for removing ester auxiliaries. The work of... 

Ruthenium/BINAP complexes have been successfully used in the asymmetric reduction of acrylic acids. This methodology has been used to prepare the antiinflammatory drug (S)-Naproxen (2.78) by reduction of the acrylic acid (2.77). Ruthenium/PQ-Phos species catalyse the same transformation with comparable ee. ... 

The formation of the latter complexes can be followed by infrared spectroscopy, as it involves a proton transfer from the acid of poly (acrylic acid) to the tertiary amine of the mesogens. Complexation results in a significant reduction, or almost complete elimination, for the equimolar complexes, of the acid carbonyl band near 1700 cm and the appearance of a new band near 1550cm attributed to the asymmetric carboxylate stretch. The residual carbonyl absorption that remains in the equimolar mixtures indicates the presence of a small... 

Acrylic acids are also excellent substrates for this asymmetric reduction, as demonstrated by the synthesis of the anti-inflammatory drug (5)-naproxen (77). 

The Fukuyama synthesis commenced with the copper-catalyzed asymmetric reduction of butenolide 26 to give lactone 27 in 98% enantiomeric excess (Scheme 9). Sequential alkylation with CbzCl followed by methyl acrylate provided lactone 28 and installed both of the required contiguous stereocenters. The key Curtius rearrangement was performed by conversion of the benzyl ester to the acyl azide followed by heating. Subsequent treatment with aqueous HCI provided cyclized lactam 8. This compound was then dibromi-nated to lactam 29 using bromine, ZnCl2, and formic acid, which were the only conditions that were able to introduce the orf/to-bromine. The fully elaborated aromatic compound 29 was treated with methylamine followed by PDC to obtain cyclic A -methylimide 23. 

Garbay reported the chemoselective reduction of a a-dehydrophenylala-nine substrate bearing a p-acrylate moiety [105]. Robinson et al. have also used a tandem, one-pot asymmetric hydrogenation-hydroformylation-cyclization approach to generate six- to eight-membered cyclic a-amino acids [136]. 

Asymmetric Hydrogenation.—The asymmetric hydrogenation of a-acylamino-acrylates and cinnamates using chiral rhodium(i) diphosphine complexes as catalysts is now established as one of the best methods for obtaining optically pure a-amino-acids (see previous reviews in this series). In the past year, some new chiral diphosphines have been added to the already considerable number of such ligands. A bis(diphenylphosphino)-derivative of pyrrolidine in conjunction with Rh can be used to hydrogenate a-acetamidocinnamates and itaconic acid with chiral inductions of 90%, whereas an Rh -diphos complex derived from natural tartaric acid effects the reduction of some a-acylaminoacrylic acids to natural (5)-a-acylamino-acids with optical yields of between 80 and 100%. ... 

---