Unsaturated carboxylic acids, acylation

Azabicyclononenecarboxylate acylated with unsaturated carboxylic acids is converted via tandem olefin metathesis in indolizidine scaffolds <2006OL5553>. 

Phenol esters of a,(3-unsaturated carboxylic acids have an interesting reactivity due to the synthetic utility of the resulting hydroxychalcones (Scheme 19). This aspect will be illustrated in Section IV. However, from the basic point of view, it is worth mentioning that the cis or trans configuration of the olefinic part of the acyl moiety can have a marked influence on the photochemical reactivity of the ester. When para-methoxyphenyl fumarates are irradiated, the normal ortho-rearranged products are obtained. By contrast, irradiation of para-me-thoxyphenyl maleates does not lead to rearrangement. Instead, cyclization products are obtained (Scheme 20). 

Carboxylic acids and their derivatives like esters, amides, anhydrides, and acyl halides are formally synthesized from olefins, carbon monoxide, and compounds represented by Nu-H such as H2O, ROH, RNH2, RCOOH (Equations (4) and (5)). Alkynes also react under similar conditions to afford the corresponding unsaturated carboxylic acid derivatives. These reactions have been named hydrocarboxylation, hydroalkoxycarbonylation, and hydroaminocarbonylation. 

Reactions between A -tosylpyrroles 394 and a-substituted unsaturated carboxylic acids in the presence of TFAA result in smooth 2-acylation of the pyrrole, followed by Nazarov cyclization to give 50-80% yields of 4,5-dihydrocy-clopenta[3]pyrrol-6(lf/)-ones 395 (Equation 93) <20060L163>. The presence of an a-substituent in the unsaturated acid appears to be mandatory. 

The acylation of alkenes can also be similarly effected with SbFs [32], For example, a,/3-unsaturated carboxylic acid fluorides react with perfluoroalkenes to form a,/3-unsaturated ketones (Eq. 16) [32b]. 

Warren has used a variation of his phosphine oxide-based olefination method to synthesise single isomers (E or Z) of unsaturated carboxylic acids.23 a-Diphenylphosphinoyl ketones (32) are reduced by sodium borohydride to give diastereomeric mixtures of the corresponding alcohols (33) and (34). These alcohols can be converted to the lactones (35) and (36) which can be separated and individually converted stereospecifically into (Z)-(37) and (E)-(38) alkenes by base treatment (Scheme 6). In many cases it is possible to reduce p-ketophosphine oxides (39) and enones (41) stereoselectively to the ery/Aro-alcohols (40) and (42), respectively, using sodium borohydride in the presence of cerium chloride (Scheme 7).24 An earlier report that reduction in the presence of cerium salts did not cause reversal of stereochemistry compared to reduction with borohydride alone appears to be true only of the compounds studied in that report. The carbanions of 3-hydroxypropylphosphine oxides (43) have been reported to undergo O- to C-acyl transfer to give the p-ketoalkylphosphine oxides... 

McFadyen and Stevens (cf. Bayer344h) obtained aldehydes from the corresponding carboxylic acids in yields of up to 60% by intramolecular disproportionation of aromatic and heterocyclic l-acyl-2-(benzenesulfonyl)hydrazines induced by an alkali carbonate in ethylene glycol at 160° but this method fails for aliphatic and, / -unsaturated carboxylic acids. 

Nucleophiles react with a, 8-unsaturated carboxylic acid derivatives with reactive carbonyl groups, such as acyl chlorides, to form nucleophilic acyl substitution products. Conjugate addition products are formed from the reaction of nucleophiles with less reactive carbonyl groups, such as ester and amides. 

In Section 18.13, you saw that nucleophiles react with o , 8-unsaturated aldehydes and ketones, forming either direct addition products or conjugate addition products in Section 18.14, you saw that nucleophiles react with o , S-unsaturated carboxylic acid derivatives, forming either nucleophilic acyl substitution products or conjugate addition products. 

Orthoesters seldom appear in organic synthesis but they do occupy one useful niche. In 1%7 Seebach introduced tris(methylthio)methyllithium as an acyl anion equivalent of a carboxyl group. It was sufficiently stable and nucleophilic to react with a range of electrophiles For example, nucleophilic substitution of the allylic chloride 121 1. followed by mercury(Il)-mediated hydrolysis of the 5 5 5-orthoester intermediate 121 2. gives the. y-unsaturated carboxylic acid 121 3 en route to Suspensolide [Scheme 2.121]. ... 

Vinyl azides 498 can be prepared directly from a,p-unsaturated carboxylic acids 497 by treatment with [bis(trifluoroacetoxy)iodo]benzene and sodium azide in dichloromethane under phase-transfer conditions (Scheme 3.197) [574]. This method is also useful for the preparation of acyl azides [574]. 

Metzger, J.O., and U. Biermaim, Alkylaluminium Dichloride Induced Friedel-Crafts Acylation of Unsaturated Carboxylic Acids and Alcohols, Liebigs Ann. Chem. 645-650 (1993). 

Four-Component Synthesis of Pyrrolopyridines If a primary amine were used as an input, the three-component reaction shown in Scheme 15.10 would produce an oxazole bearing a secondary amine. In other words, the so-produced adduct 24 would contain both a diene (oxazole) and a nucleophilic site (amine). Therefore, a dienophile bearing an electrophihc center would pair perfectly with the dual reactivity of 24. In practice, if an activated a,P-unsaturated carboxylic acid derivative were introduced after the three-component reaction, a sequence of N-acylation/intramolecular Diels-Alder reaction (IMDA) might occur to produce the four-component adducts. 

Shin, C., K. Nanjo, E. Ando, and J. Yoshimura a,p-Unsaturated Carboxylic Acid Derivatives. VI. New Synthesis of N-Acyl-a-dehydroamino Acid Esters. Bull. Chem. Soc. Japan 47, 3109 (1974). 

Two alternative pathways have been proposed for the reaction of carbodiimides (127) with activated Q ,j8-unsaturated carboxylic acids (126), based on DFT calculations the reaction, which affords hydantoins (130) and variable amounts of At-acyl ureas (129), may proceed either via imino-oxazolidinones (128) or At-acyl ureas (129), as the overall barriers are similar for both pathways. A second molecule of carboxylic... 

Two alternative pathways featuring IV-acyl ureas and imino-oxazolidinones as intermediates for the formation of the hydantoin from reaction of carbodiimides and activated a,j8-unsaturated carboxylic acids have been studied using computational methods and the overall barriers are similar (Scheme 82)P ... 

Pd is an efficient catalyst for carbonylation of olefinic and acetylenic compounds and aryl halides to form various saturated and unsaturated carboxylic acids, their esters, and lactones. Also, aldehydes are obtained using Pd catalysts. For a long time, Pd has been known as an efficient catalyst for decarbonylation of aldehydes. Acyl halides are also de-carbonylated with Pd catalysts. Now it is well-established that Pd is the efficient catalyst for both carbonylation and decarbonylation as reversible processes. 

Under these conditions nearly all olefins and a great number of dienes, unsaturated carboxylic acid esters, unsaturated and saturated alcohols and diols, reactive cycloparaffins, saturated and unsaturated halogenated compounds, N-tertiary alkyl acyl amines, carboxylic acid esters and saturated... 

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