2, propenoic acid, enantioselective

Interestingly, hydrolase-type enzymes could also be employed for enantioselective hydrations79. Yields and enantiomeric excess values obtained in the addition of water to 2-(trifluo-romethyl)propenoic acid (7) are summarized. Unfortunately, the absolute configuration of the product 8 was not determined, the enantiomeric excess values stated rest on 19F-NMR analysis of the Mosher ester. Whereas ethanol and phenol did not react under these conditions, the /V-nucleophiles diethylamine and aniline, and also thiophenol, could be added to 7 in moderate to good yields and enantiomeric excess values. Finally, the bifunctional aniline derivatives 9 afforded the lactams 10 in 52-90% yield and 25-67% ee. Again, the absolute configurations of the products were not determined. 

The first enantioselective total synthesis of (+)-macbecin I was accomplished by R. Baker and co-workers. A key vinyl iodide precursor was prepared stereoselectively using the malonic ester synthesis. Diethyl methylmalonate was treated with in situ generated diiodocarbene in ether at reflux to afford diiodomethylmethylmalonate in good yield. This dialkylated malonic ester then was converted to ( )-3-iodo-2-methyl-2-propenoic acid by reacting it with aqueous KOH. The saponification was accompanied by a concomitant decarboxylation. 

The asymmetric catalytic hydrogenation of 2-(6 -methoxy-2 -naphthyl)propenoic acid to (S)-naproxen was monitored in both methanol- and C02-expanded methanol.f The catalyst used was [dichloro-(S)-(-)-2,2 -bis(diphenyl-phosphino)-1, l -binapthyl]ruthenium(II). Addition of CO2 to the methanol produced strong retardation of the reaction rate. An average reduction in enantioselectivity of 6%i was observed compared to that in methanol. The enantioselectivity was found to increase as the temperature decreased in both neat methanol and C02-expanded methanol systems, indicating that the underlying mechanisms were similar. Insufficient oxygen removal may have prevented the... 

The quinine derived thiourea 12 was found to be the most efficient catalyst, in terms of conversion and enantioselectivity, in the Michael-Michael cascade process between tra y-3-(2-mercaptoaryl)-2-propenoic acid esters and /ra 5-nitroalkenes [39]. The thiochromanes, containing three new stereocenters, were obtained with excellent enantio- and diastereoselectivity irrespective of the electronic namre and substitution pattern of the aromatic ring in the nitroalkene and in the thiol. Although the first sulfa-Michael step of the process was poorly enantioselective, it was also reversible, so that the enantiomeric mixture of the adducts underwent an efficient dynamic kinetic resolution due to a retro-Michael-Michael-Michael sequence (Scheme 14.10). 

---