Synthesis of Unsaturated Acids

This is the best known alkyne carbonylation reaction. It has been industrialized in the special case of acryhc acid synthesis [129]. 

The reaction has been extended to unsymmetrical alkynes (Table XVI). 

Usually performed at high temperature using nickel (or palladium) catalysts, the reaction is effective at room temperature using stoichiometric quantities of nickel tetracarbonyl  

Use of cobalt instead of nickel catalysts favors succinic derivatives (Table XVI). Use of an alcoholic solvent allows the synthesis of the corresponding esters but yields are generally lower and palladium catalysts seem then preferable. 

Unsaturated diesters can be directly prepared under mild conditions using palladium catalysts in the presence of thiourea (Table XVI). 

Saturated, unsaturated, and functionalized carboxylic acids are important classes of natural products. Moreover, optically active hydroxy carboxylic acids are important biological molecules [ 1 ] as well as intermediates for organic synthesis [2]. 

The synthesis of wide varieties of functionalized [3] and unsaturated carboxylic acids [4] have been achieved through organoboranes. The reaction sequence involves the attack of organoboranes on the dianion of phenoxy acetic acid followed by the alkyl migration as illustrated in Eq. 8.1. 

9-BBN has been elegantly employed for the selective hydroboration to afford the corresponding alkyl boranes, which on treatment with dianion of phenoxy acetic acid, followed by alkaline HjOj oxidation produce in good to moderate yields the corresponding carboxylic acids with two carbon homologation (Eqs. 8.2,8.3). 

P-Amino acids are valuable for the synthesis of peptidomimetics [5], functionalized P-lactams and some naturally occurring materials [6-8]. Burgess and Ohlmeyer [9] have reported that the allylic amines on hydroboration afford 

R R2 Hydroborating agent Syn-.anti Yield of major isomer (%) 

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Another general method of synthesis of unsaturated acids from saturated compounds involves this same reaction as a second step. 

Oxidation by Tollens reagent is useful chiefly for detecting aldehydes, and in particular for differentiating them from ketones (see Sec. 19.17). The reaction is of value in synthesis in those cases where aldehydes are more readily available than the corresponding acids in particular, for the synthesis of unsaturated acids from the unsaturated aldehydes obtained from the aldol condensation (Sec. 21.6), where advantage is taken of the fact that Tollens reagent does not attack carbon-carbon double bonds. 

The specificity of Mo-heteropolycompounds in the synthesis of unsaturated acids starting from paraffins which can not yield heterocyclic compounds (i.e. propane and isobutane). This may arise from the very strong acidity which is typical of these compounds (even when they are not in a protonic form) which favours the desorption of the organic acids, sparing them from consecutive reactions. These compounds also yield maleic anhydride from n-butane and n-pentane (but with remarkably lower selectivity than the vanadyl pyrophosphate), but they lack the surface properties which are necessary for the formation of phthalic anhydride from n-pentane. 

Acrylic Acid, CH2 = CH.COOH.—The synthesis of unsaturated acids may be illustrated by. the methods which can be used to prepare acrylic acid—the first member of the series... 

Synthesis of Unsaturated Acids.—Regioselectivity in the reactions of nucleophiles with p-vinyl-P-propiolactone has been explained by reference to the principle of hard and soft acids and bases (HSAB). The findings are applied in a synthesis... 

Ireland s group has described in detaiF an elegant use of a [3,3] sigmatropic rearrangement in a synthesis of unsaturated acids from allyl esters via the corresponding enolates (Scheme 3). t-Butyldimethylsilyl enolates were found to be most useful, the low temperature transformation normally giving rise to the E-isomer, with yields in the range of 66—88%. 

Processes have been developed separating pure metaxylene from other Cj aromatics.Metaxylene is a raw material for the manufacture of isophthalic acid. The major outlets for the acid are in the synthesis of unsaturated polyester and alkyd resins, and for the production of isophthalic esters (plasticizers). 

Oxidation of n-hutane to maleic anhydride is becoming a major source for this important chemical. Maleic anhydride could also be produced by the catalytic oxidation of n-butenes (Chapter 9) and benzene (Chapter 10). The principal use of maleic anhydride is in the synthesis of unsaturated polyester resins. These resins are used to fabricate glass-fiber reinforced materials. Other uses include fumaric acid, alkyd resins, and pesticides. Maleic acid esters are important plasticizers and lubricants. Maleic anhydride could also be a precursor for 1,4-butanediol (Chapter 9). 

Since anhydrides are much more reactive than carboxylic acids, reaction kinetics is controlled by the second step. The scope and apphcations of this reaction are the same as direct polyesterification but are practically limited to the synthesis of unsaturated polyesters and alkyd resins from phtliahc and maleic anhydrides (see Sections 2.4.2.1 and 2.4.23). 

Warwel, S., Sojka, M., and Rusch, M. Synthesis of Dicarboxylic Acids by Transition-Metal Catalyzed Oxidative Cleavage of Terminal-Unsaturated Fatty Acids. 164, 79-98 (1993). Wexle.r, D., Zink, J. I., and Reber, C. Spectroscopic Manifestations of Potential Surface Coupling Along Normal Coordinates in Transition Metal Complexes. 171,173-204 (1994). Willett, P., see Artymiuk, P. J. 174, 73-104 (1995). 

Warwel, S., Sojka, M., and Rusch, M. Synthesis of Dicarboxylic Acids by Transition-Metal Catalyzed Oxidative Cleavage of Terminal-Unsaturated Fatty Acids. 164, 79-98 (1993). 

The chemicals used in syntheses were used as received from the supplier. The unsaturated polyesters were prepared by standard methods from the diacids and diols using butyl stannoic acid (Fascat 4100) as the catalyst. The water of condensation removed using a xylene azeotrope and after reaching the desired acid value the xylene was removed by distillation. The synthesis of unsaturated polyester A is representative. 

The reactions are related to the incorporation of CO and H20 into alkenes or alkynes leading to the corresponding saturated or unsaturated carboxylic acids. The general equation is shown below. Equation lb is related to the synthesis of acrylic acid discovered by Reppe [11]. 

It has been shown that the Claisen rearrangement of lithium enolates of amino acid enynol esters allows the synthesis of very sensitive y, 5-unsaturated amino acids with conjugated enyne side chains.The chelate-enolate Claisen rearrangement has also been applied to the synthesis of unsaturated polyhydroxylated amino acids, polyhydroxylated piperidines, and unsaturated peptides. ... 

Functionalized y-acyloxy-a,yS-unsaturated esters provided yet another versatile strategy towards paraconic acids as exemplified with the synthesis of protolichesterinic acid ((-i-)-lO) (Scheme 22) [60]. The prerequisite precur-... 

A stereoselective total synthesis of the antifungal mould metabolite ( )-LL-Z1271a (165) from the readily available Wieland-Miescher diketone, via the keto-lactone (164), has been described. A synthesis of grindelic acid (167) from the unsaturated 7-toluene-p-sulphonate (166) utilized an intramolecular solvolysis of the toluene-p-sulphonate to construct the 9—13 ether bridge. 

TABLE 7.32. SYNTHESIS OF UNSATURATED 5(4/T)-OXAZOLONES VIA CYCLIZATION OF a,P-DIDEHYDROAMINO ACIDS OR a,P-UNSATURATED CARBODIIMIDES... 

TABLE 7.34. SYNTHESIS OF UNSATURATED 5(4/f)-OXAZOLONES FROM A-ACYLAMINO ACID DERIVATIVES AND VILSMEIER-HAACK REAGENT... 

During the last two decades, the importance of the dipolarophilic nature of unsaturated 5(4/l/)-oxazolones has been widely recognized and studied with a variety of 1,3-dipoles. Among the systems studied, diazoalkanes, particularly diazomethane, are the most frequently used and have opened the way for the synthesis of aminocyclopropanecarboxyhc acid derivatives. 

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