Carboxylic esters a,/3-unsaturated

The Michael acceptor can be an a, -unsaturated carboxylic ester. This possibility is illustrated with the conjugate addition of phenylmagnesium bromide to ethyl arecaidinate, which leads to 4-phenylnipecotic acid (equation 33). 

Two examples of Pd(II)-catalyzed carbomethoxylations of vinyl(phenyl)iodonium salts have been reported (equations 251 and 252)125,126. The mild reaction conditions and stereospecificity of carbonylation recommend further applications of vinyliodonium compounds for the synthesis of a,/ -unsaturated carboxylate esters. By way of comparison, similar carbobutoxylations of vinyl halides (Br, I) typically require higher temperatures (60-100 °C) and longer reaction times, and they sometimes proceed with low stereospecificity151. 

The reductive coupling of aldehydes or ketones with a,/ -unsaturated carboxylic esters by >2 mol samarium(ll) iodide (J.A. Soderquist, 1991) provides a convenient route to y-lactones (K. Otsubo, 1986). Intramolecular coupling of this type may produce trans-2-hy-droxycycloalkaneacetic esters with high stereoselectivity, if the educt is an ( )-isomer (E.J. Enholm, 1989 A, B). 

The reaction was successfully applied to both electron-rich and electron-poor 4-nitrophenyl carboxylates among them, the conversion of the electron-deficient esters was found to be faster and more efficient. Many functional groups are tolerated on both the side of the carboxylic ester (halo, keto, formyl, ester, cyano, nitro and protected amino groups, heterocyclic and a,-unsaturated carboxylic esters) and of the alkene (electron-rich alkyl-substituted alkenes, electron-poor acrylate derivatives, trimethylvinylsilane as an ethylene surrogate). The cinnamate derivatives could become particularly useful substrates, since the availability of the synthetically equivalent vinyl halides is rather limited. In analogy to conventional Mizoroki-Heck chemistry, linear (Zi)-substituted alkenes are predominantly but not exclusively obtained. Selected examples are shown in Table 4.1. 

Formation of carboxylic acids ami their derivatives. Aryl and alkenyl halides undergo Pd-catalyzed carbonylation under mild conditions, offering useful synthetic methods for carbonyl compounds. The facile CO insertion into aryl- or alkenylpalladium complexes, followed by the nucleophilic attack of alcohol or water affords esters or carboxylic acids. Aromatic and a,/ -unsaturated carboxylic acids or esters are prepared by the carbonylation of aryl and alkenyl halides in water or alcohols[30l-305]. 

The prototype of a Knoevenagel reaction shown in the scheme above is the condensation of an aldehyde or ketone 1 with a malonic ester 2, to yield an a ,/3-unsaturated carboxylic ester 4. 

Reaction of a-sulphinyl carboxylic esters 421 with carbonyl compounds has usually been performed using a Grignard reagent as a base. No condensation products are obtained using t-butyllithium or sodium hydride367,496,497 (equation 251). The condensation products formed are convenient starting materials for the synthesis of a, p-unsaturated esters and /1-ketones497. 

The cyclopropane cyclizations by elimination of triflinic acid (CF3S02H) are readily effected by basic treatment of triflones (trifluoromethyl alkyl sulfones) with activated /-protons (equations 46 and 47)39. The cyclopropane diesters 45 are formed on treatment of 44 with potassium hydride in DMSO or sodium methoxide in methanol (equation 48). In contrast, the monoester 46 failed to give the desired cyclopropane40. Addition of carbanions derived from /f, y-unsaturated phenyl sulfones to a, /i-unsaturated carboxylic esters and subsequent elimination of benzenesulfinate ion give cyclopropanes possessing the unsaturated side chain and the ester function in trans positions (equation 49)41. 

Preparation of l-ethoxy-2-phenyl-4,5-dimethoxycarbonyl-A2- 5-phospholene 1-oxide — Reaction of a vinylicphos-phonite diester with an unsaturated carboxylate ester... 

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]. 

In 2006, Zeitler demonstrated the use of alkynyl aldehydes in redox esterification [114]. As in previous examples, the author proposes the formation of an activated carboxylate that acts as an acylating agent Eq. 19. A variety of a,P-unsaturated carboxylic esters 199 are formed in moderate yields with E-selectivity up to >95 5. 

The reaction between a phenol and an unsaturated carboxylic ester has been widely used for the synthesis of chromone-2-carboxylic acids (00JCS1119,1179). There is little restriction on the substituents which may be present in the phenol and the necessary basic conditions have been achieved in various ways. 

Several characteristic recent examples describing the epoxidation of a,/ -unsaturated ketones (equations 26-28) and that of a,/TunsaUirated carboxylic esters (equations 29 and 30) are given below. 

Tetrahydro-7H-oxazolo[3,2-a]pyrimidin-7-ones (275) can be prepared from 2-amino-2-oxazolines and a,/8-unsaturated carboxylic esters. The orientation of the substituents in the reaction product corresponds to Michael addition of the oxazoline nitrogen as the first step (74LA593). 

The UV-spectrum (64, Table III) and high negative rotation ([aD] — 310° in methanol) of tabersonine hydrochloride (64, 65) indicated at once that the alkaloid contained the same chromophore as akuam-micine (CCXXV) and echitamidine (CCXLII, Chapter 8), and this chromophore was subsequently shown (Volume VII, p. 127) to be Ph—NH—C=C—CO2R. The NH (2.95 /a) and a,/3-unsaturated carboxylic ester bands (6.02 /a and 6.2 /a) were also seen in the IR-spectrum. The NH group was not acetylated under usual conditions and the ester group was unusually resistant to hydrolysis (64). 

The ate-complexes (34) also react with benzylic halides aroyl chlorides allyl halides and proj r l halides to afford the (x>rr ponding products, respectively (Eq. 75). (E)-a,P-Unsaturated carboxylic esters can also be obtains by the reaction of such borate complexes with ethyl propiolate The same type of reaction between copper(I) methyltrialkylborates and l-(l-pyrrolidinyl)-6-chloro--1-cyclohexene gives the corresponding alkylation products which are readily hydrolyzed to 2-alkylcyclohexanone... 

---