A,3-Unsaturated acids

Various trifluoromethyl containing a, -unsaturated acids, esters, ketones, and nitriles have been used as dienophiles Details regarding regiochermstry and stereochemistry have been reported [2S, 98, 99] (equations 82-84)... 

Crotonic acid is an example of an a -unsaturated acid, whilst vinylacetic acid is a acid. Upon heating the latter with a solution of an... 

A chiral ruthenium catalyst bearing BINAP-type ligands was used in ILs for enantioselective hydrogenation of prochiral a, -unsaturated acids followed by... 

Analogues of BPPFA and BPPFOH have been prepared, but for many applications these two ligands still prove to be the best for enantioselective hydrogenations [125]. The introduction of another functional group into the side chain, as in 31, provided the first catalysts capable of hydrogenating the tetra-substi-tuted a,/ -unsaturated acids with high enantioselectivity, even though the activity was very low (turnover frequency, TOF, 2 h-1) [132, 133],... 

One of the first applications of the then newly developed Ru-binap catalysts for a,/ -unsaturated acids was an alternative process to produce (S)-naproxen. (S)-Naproxen is a large-scale anti-inflammatory drug and is actually produced via the resolution of a racemate. For some time it was considered to be one of the most attractive goals for asymmetric catalysis. Indeed, several catalytic syntheses have been developed for the synthesis of (S)-naproxen intermediates in recent years (for a summary see [14]). The best results for the hydrogenation route were obtained by Takasago [69] (Fig. 37.15), who recently reported that a Ru-H8-binap catalyst achieved even higher activities (TON 5000, TOF 600 h 1 at 15 °C, 50 bar) [16]. 

In this reaction the carbanion (103) is obtained by removal of an a-H atom from a molecule of an acid anhydride (104), the anion of the corresponding acid acting as the necessary base the carbonyl acceptor is pretty well confined to aromatic aldehydes. The products are a. -unsaturated acids, e.g. 3-phenylpropenoic(cinnamic) acid (105) from PhCHO/excess (MeCOljO/MeCOj at 140° ... 

Use of BF3 etherate as catalyst was suggested by the report of Yamamoto and Maruyama4 that -C,H(iCu complexed with BF3 undergoes conjugate addition to a,/ -unsaturated acids and esters, a reaction that has not been observed with R CuLi, even in the presence of BFj etherate. 

Several instances ore known in which a unsaturated acids yield ./ -dihydroxy acids on treatment with peracetic aoid and alkaline hydrolysis of the resultant 1,2-diol monoesters. 37- Although... 

Deviations between calculated and experimental values are generally smaller than 4 ppm [306], Differences may be attributed partly to varying molecular ground states and partly to varying excited states of a, / -unsaturated acids [306]. 

CIS-a,/ -UNSATURATED ACIDS ISOCROTONIC ACID [(-Z)-Crotonic acid]... 

A retrosynthetic analysis of a,/ -unsaturated acids leading to various methods of synthesis is outlined in Section 5.18.3, p. 804. The following methods are particularly applicable to aromatic aldehydes. 

COOH-> —CHO Reaction of a carboxylic acid with isobutylmagnesium bromide and catalytic amounts of titanocene dichloride affords aldehydes in fair to moderate yield (equation I). The reaction fails with a,/ -unsaturated acids. 

The reaction of 1 -(trimethylsilyl)-2-(phenylthio)ethylene (5) with an a,/ -unsaturated acid chloride such as 6 in the presence of A1C1, involves an unusual rearrangement to give 7. ... 

Asymmetric hydrogenation of a,/ -unsaturated acids is carried out successfully using Ru—BINAP and Ru—Hg— BINAP (XXXIII). (S)-Ibuprofen (33) with 97% ee is... 

Tellier, F. Sauvetre, R. Straightforward synthesis of a,/ -unsaturated acids and derivatives. Tetrahedron Lett. 1993, 34, 5433-5436. 

A number of methods of 2-imino-TA synthesis are based on the cycliza-tion of acylthioureas containing an a,/ -unsaturated acid fragment. In the case of reactions of acryloyl chloride with thiourea (72MI1) or with N-substituted thioureas (73MI2), no A-acryloylthioureas were isolated and hydrochlorides of 3-substituted 5,6-dihydro-TAs 128 were obtained (Scheme 42). 

As for the unsaturated carbonyl compounds, the most significant groups are the a,/ -unsaturated acids or esters. Some of their methods of formation are closely analogous, for example, (a) the Horner-Emmons or Wadsworth-Emmons reaction, and (b) the aldol-type reactions. Rather more specific methods are considered below for the formation of a, -acetylenic acids, and for the conversion of the unsaturated dicarboxylic acid, maleic acid, into its anhydride or into fumaric acid. 

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