A,b-Unsaturated acids

TRANSESTERIFICATION OF METHYL ESTERS OF AROMATIC AND a,B-UNSATURATED ACIDS WITH BULKY ALCOHOLS (-)-NENTHYL CINNAHATE AND (-)-MENTHYL NICOTINATE (2-Propeno1c acid, 3-pheity1, 5-BethyI-2-(l- ethyIethyl)cyclohevl ester, [lR-(la,2B.Sa)-) and... 

More typical behavior of ketones is a condensation process yielding p-acylamino ketones. This process was first reported by Bruson et al. who reacted cyclohexanone and nitriles in the presence of anhydrous aluminum chloride and obtained products now known to have the structure (35). Such reactions were later studied in more detail by Khorlin using conventional Ritter conditions. p-Acylamino ketones were obtained only from ketones capable of undergoing condensations to produce a,p-unsaturated ketones or ketols, suggesting the intermediacy of such structures in the reaction. This process is shown for acetophenone in Scheme 14. It is well established that a,B-unsaturated acids, esters and ketones yield similar products under Ritter reaction conditions. - ... 

Dienophiles prepared from a,B-unsaturated acids and 1,3-oxazolidin-2-one react with cyclopentadiene in the presence of catalytic amounts of a chiral alkoxytitanium(IV) complex and molecular sieves to give optically active adducts (Scheme 52) via Carbonylation Reactions. - The temporary incorporation of a co-ordinating phosphine into a tetracyclic phyllanthocin precursor... 

EmoI etiers. In the presence of (C Iii) Ru and P(Bu)) in the molar ratio 1 2, a B-unsaturated acids add to terminal alkynes to fomi enol esters as the major product. 

Note that the Hofmann elimination follows a mechanism typical of an E2 elimination and products such as a,B unsaturated acids are favored. 

Further studies on the site of kinetic deprotonation of a,B-unsaturated acids and esters have been reported. As a rule... 

Sulfur in oxidation state IV can be used to produce a variety of anionic snUbnates, as depicted in Scheme 1.5. Sodium bisulfite can be used to prepare sulfonates of a,b-unsaturated acids and esters, such as those prepared from maleic anhydride. The mechanism involves Michael addition to the activated double bond by the more nucleophilic sulfur atom, and is conducted in an aqueous two-phase system where, for example, a maleate half acid ester or diester is dispersed and heated under narrowly controlled pH conditions to minimize ester hydrolysis and avoid competitive hydroxide addition to the double bond. The resulting classes of surfactants include sulfosuccinates (which are in fact carboxylate sulfonate disalt surfactants) prepared from the maleic half acid esters of fatty alcohols or alcohol ethoxylates. Diesters of maleic are sulfonated by the same type of process to produce surfactants such as the ubiquitous dioctyl sulfosuccinate (DOSS) from the diester of 2-ethylhexyl alcohol and maleic anhydride. 

Esters of [1-(diethoxyphosphinyloxy)perfluoro-l-alkene]-phosphonic acid appear to be effective reagents for the synthesis of perfluoro-a,B-unsaturated carboxylic acids and their derivatives presumably an initially-generated perfluoroketene (166 ) is acted upon by a nucleophile (NuH=RNH2, I NH, or ROH). The ( E) / (Z) ratio of the product components increases with increasing length of R. 2 ... 

Nagao, Y., Hagiwara, Y., Kumagai, T., Ochiai, M., Inoue, T., Hashimoto, K., and Fujita, E. (1986). New C4-chiral l,2-thiazolidine-2-thiones Excellent chiral auxiliaries for highly diastereocontrolled aldol-type reactions of acetic acid and a,b-unsaturated aldehydes. J. Org. Chem. 51, 2391-2393. 

Nicolas, E., Russell, K. C., and Hruby, V. J. (1993). Asymmetric 1,4-addition of organo-cuprates to chiral a, b-unsaturated N-Acyl-4-phenyl-2-oxazolidinones A new approach to the synthesis of chiral b-branched carboxylic acids. J. Org. Chem. 58, 766—770. 

The unified highly convergent total and formal syntheses of ( + )-macro-sphelides B (441 X = O) and A (441 X = a-OH, p-H), respectively, have been described (483). Key features of the syntheses include the concise synthesis of the optically active S-hydroxy-y-keto a, 3-unsaturated acid fragment 442 via the direct addition of a fra/i.s-vinylogous ester anion equivalent to a readily available Weinreb amide, and the facile construction of the 16-membered macrolide core of the macrosphelide series via an INOC. 

However, the two methods of choice for the oxidations of a, (B-unsaturated ketones are based on lanthanoid-BINOL complexes or a biomimetic process based on the use of polyamino acids as catalysts for the oxidation 1"1. 

Wadsworth-Emmons olefination with a variety of aldehydes to afford (E)-a,B-unsaturated and diene acyl tetramic and tetronic acids in good to excellent yields upon treatment with potassium tert-butoxide (2 equiv) in tetrahydrofuran. For readily enolizable substrates use of the N-protected systems is generally required. The following compounds have been prepared, in the indicated yields, in this manner ... 

A double bond forms because the product is a stable, conjugated a./3-unsaturated acid [Problem 16.28(b)]. 

The stereochemical implication for the ejection of a leaving group in the B-position of a carbonyl group which yields an a,B-unsaturated system has been treated elsewhere (see p. 233). It may be pointed out here that double bond formation through the opening of a cyclopropane ring should also take place following the same stereoelectronic principle. One example of such a reaction is the transformation of B,r-cyclopropyl-s-hydroxyketone 299 which is smoothly converted into the dienone 300 (85) under acid conditions. 

Pollini, G. R, Barco, A. and De Giuli, G. Tetramethylguanidine-catalyzed addition of nitromethane to a,b-unsaturated carboxylic acid esters, Synthesis, 1972, id J5. 

Bromolactonization. A key step in a synthesis of ramulosin (4) requires halolac-tonization of the yi.b-unsaturated acid 1, which can result in a "y- or a 8-lactone. Bromolactonization results mainly in the desired 8-lactone (2), which is converted in two steps into 4. lodolactonization of 1 results mainly in the undesired y-lactone and a mixture of isomeric 8-lactones. 

The enamine reaction was introduced by Stork and his co-workers " and is widely used in organic synthesis. Enamines are a,(B-unsaturated amines and are obtained by the reaction of an aldehyde or ketone having a-hydrogen with a secondary amine in the presence of a dehydrating agent (such as catalytic amount of p-toluenesulfonic acid). 

Fleet and coworkers discovered that chromium(VI) oxide in 3 1 dichloromethane/diethylether, in the presence of celite, acts as an efficient oxidant for a range of alcohols, and is tolerant of a wide range of acid labile functionalities. In dichloromethane alone chromium(VI) oxide was reported to be inert due to low solubility. This oxidant is particularly effective for the preparation of ketones, but aldehydes, especially a,B-unsaturated, are found to be prone to overoxidation. The oxidizing species is unstable, and therefore it is better to add chromium(VI) oxide to a solution of the alcohol in 3 1 dichloromethane/diethylether. N.b. Diethyl ether/chlorinated solvent mixtures have been reported elsewhere to inflame spontaneously in the presence of chromium(VI). )... 

Phenylthioalkylation of silyl enol ethers. Silyl enol ethers of ketones, aldehydes, esters, and lactones can be alkylated regiospecifically by a -chloroalkyl phenyl sulfides in fhe presence of a Lewis acid. Zinc bromide and titanium(IV) chloride are the most effective catalysts. The former is more satisfactory for enol ethers derived from esters and lactongs. ZnBr2 and TiCL are about equally satisfactory for enol ethers of ketones. The combination of TiCL and Ti(0-f-Pr)4 is more satisfactory for enol ethers of aldehydes. Since the products can be desulfurized by Raney nickel, this reaction also provides a method for alkylation of carbonyl compounds. Of more interest, sulfoxide elimination provides a useful route to a,B-unsaturated carbonyl compounds. 

It is remarkable diat 0.1 mol equiv. of this chiral acyloxyborane complex induced fast (-78 C) and highly enantioselective Diels-Alder reactions of cyclic or acyclic 1,3- enes widi simple acrylic acid (entry 1), " or a,B-unsaturated aldehydes (entries 2-9)."" Table 32 reveals a striking steieo recting... 

Usually y.B-unsaturated acids (260) are employed in these lactonizations. The initial step involves an electrophilic attack at the double bond, either by a proton or a reagent X—Y (264). An activated species (261) is thus generated, suitable for the nucleophilic addition of the carboxy group, which in principle may close to a six- or five-membered lactone ring (263 or 262 equation 92). Normally, (262) is preferred on the basis of vector approach analysis. 

Boron catalysts bearing the tartaric acid skeleton have received more applications. Borate 3.8 is an efficient catalyst in the cycloaddition of 1-tri-ethylsilyloxydiene 9.43 with quinone 9.41 (X = OH) [778] (Figure 9.16). Acy-loxyborates 3.9 (CAB) introduced by Yamamoto and coworkers [559, 778, 785, 789, 1558, 1561] catalyze the cycloadditions of a, B-unsaturated aldehydes with... 

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