Hydrogenation unsaturated carboxylic acids

Tellers DM, McWiUiams JC, Humphrey G, Joumet M, DiMichele L, Hinksmon J, McKeown AE, Rosner T, Sun Y, Tillyer RD. On the mechanism of an asymmetric a,P-unsaturated carboxylic acid hydrogenation application to the synthesis of a PGD2 receptor antagonist. J. Am. Chem. Soc. 2006 128(51) 17063 17073. 

The mechanism of such reactions using unsaturated carboxylic acids and Ru(BINAP)(02CCH3)2 is consistent with the idea that coordination of the carboxy group establishes the geometry at the metal ion.26 The configuration of the new stereocenter is then established by the hydride transfer. In this particular mechanism, the second hydrogen is introduced by protonolysis, but in other cases a second hydride transfer step occurs. 

Prochiral organic acids were hydrogenated on clay-supported Rh-chiral phosphine complexes.205,206 Hectorite-supported chiral Rh(I)-phosphine complexes were used for the asymmetric hydrogenation of a,P-unsaturated carboxylic acids.207 It was found that the interaction between the a-ester group of itaconates and phenyl groups of phosphine can play an important role in the determination of the configuration of products. 

The benzotriazolyl derivative of acrolein acetal, compound 882, is lithiated, treated with chlorodiphenylphosphine, and the obtained intermediate is oxidized with hydrogen peroxide to phosphine oxide 883 (Scheme 145). The relatively acidic proton in derivative 883 is easily removed by a base, and the obtained anion adds to a carbonyl group of aldehyde or ketone. Subsequent rearrangement and elimination of the phosphorane group generates diene 884. For the derivatives of aldehydes (884, R2 = H), (E)-(E) stereoselectivity of the elimination is observed. Acidic alcoholysis of dienes 884 affords esters of P,y-unsaturated carboxylic acids 885 < 1997JOC4131>. 

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

Enantioselective Hydrogenation of Unsaturated Acids and Esters 26.3.5.1 a,/ -Unsaturated Carboxylic Acids... 

Limited progress has been achieved in the enantioselective hydrogenation of a,/ -unsaturated carboxylic acid esters, amides, lactones, and ketones (Scheme 26.10). The Ru-BINAP system is efficient for the hydrogenation of 2-methy-lene-y-butyrolactone, and 2-methylene-cyclopentanone [98]. With a dicationic (S)-di-t-Bu-MeOBIPHEP-Ru complex under a high hydrogen pressure, 3-ethoxy pyr-rolidinone could be hydrogenated in isopropanol to give (R)-4-ethoxy-y-lactam in 98% ee [39]. 

A wide range of a,fi-unsaturated carboxylic acids, including substituted acrylic acids, undergo enantioselective homogeneous hydrogenation when catalyzed by... 

Th effect of pH on the rate of hydrogenation of water-soluble unsaturated carboxylic acids and alcohols catalyzed by rhodium complexes with PNS [24], PTA [29], or MePTA r [32] phosphine ligands can be similarly explained by the formation of monohydride complexes, [RhHPJ, facilitated with increasing basicity ofthe solvent. 

Hydrogenation of unsaturated carboxylic acids, such as acrylic, methacryUc, maleic, fumaric, cinnamic etc. acids was studied in aqueous solutions with a RhCU/TPPTS catalyst in the presence of p-CD and permethylated P-cyclodextrin [7]. In general, cyclodextrins caused an acceleration of these reactions. It is hard to make firm conclusions with regard the nature of this effect, since the catalyst itself is rather undefined (probably a phosphine-stabilized colloidal rhodium suspension, see 3.1.2) moreover the interaction of the substrates with the cyclodextrins was not studied separately. 

The BINAP-Rh catalyzed hydrogenation of functionalized olefins has a mechanistic drawback as described in Section 1.2.1. This problem was solved by the exploitation of BINAP-Ru(ll) complexes.Ru(OCOCH3)2(binap) catalyzes highly enantioselective hydrogenation of a variety of olefinic substrates such as enamides, a, (3- and (3,y-unsaturated carboxylic acids, and allylic and homoallylic alcohols (Figure 1.9). " " Chiral citronellol is produced in 300 ton quantity in year by this reaction. ... 

Ll-Rh complex was employed for the enantioselective synthesis of (S)-2-(4-fluorophe-nyl)-3-mefhylbutanoic acid (98% ee) [107], while the Pr-DuPhos-Rh complex was utilized for the enantioselective hydrogenation of a,/ -unsaturated carboxylic acids, as exemplified by tiglic acid [29]. 

Table 2.1.5.3 Asymmetric hydrogenation of a, P-unsaturated carboxylic acid derivatives.

Evidence for this mechanism is (1) two equivalents of RLi are required (2) the hydrogen in the product comes from the water and not from the adjacent carbon, as shown by deuterium labeling 209 and (3) the intermediates 31-33 have been trapped.210 This reaction, when performed in tetramethylenediamine, can be a synthetically useful method211 of generating vinylic lithium compounds (33), which can be trapped by various electrophiles such as D20 (to give deuterated alkenes), C02 (to give a, 3-unsaturated carboxylic acids—6-34), or DMF (to give a, 3-unsaturated aldehydes—0-105). 

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