Unsaturated carboxylic esters formation

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. 

In 2010, Hoveyda and coworkers disclosed a Cu-catalyzed method for enantio-selective boronate conjugate additions to trisubstituted alkenes of acyclic a.P Unsaturated carboxylic esters, ketones, and thioesters, resulting in the formation of p-substituted quaternary carbon stereogenic centers (Scheme 3.65) [94]. By using 5 mol% of a chiral monodentate NHC 103 copper complex at low temperature, the products were obtained in good yields (up to 98%) and enantiose-lectivities (up to 96% ee). Moreover, transformations involving unsaturated thioesters gave the best enantiocontrol. 

Table 4.8 Reactions of diene-magnesium reagents with carboxylic esters formation of 3,y-unsaturated ketones.

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]. 

Heterocyclic carboxylic esters (708) are as reactive as formate and acetate esters. Extended to 1-substituted biguanides, the reaction is promoted by metal alkoxides. Since the heterocyclic ring must be five-or six-membered and contains a conjugated system of double bonds, the reaction resembles formally that involving a,p-unsaturated esters (see below). Several successful examples are on record (599, 606). 

Protodesilylation, A new preparation of -unsaturated carboxylic acids involves the amide acetal Claisen rearrangement of a 3-(trimethylsilyl)allyl alcohol such as 1 to allylsilanes (2). Desilylation of 2 by usual methods results in formation of stereoisomers. However, use of liquid HF at low temperatures results only in (E)-3 in 88% yield. The HF-pyridine complex is not so stereoselective. Amides such as 3 can be converted into carboxylic acid esters by Meerwein s trialkyloxonium salts (—70% yield). 

Formation of a double bond between carbon and a heteroatom or between two heteroatoms can be accomplished by a hetero retro-Diels-Alder reaction. Aldehydes, ketones and carboxylic esters can be obtained by this retrodiene process. A series of ct,3-unsaturated aldehydes (152) was prepared by Funk using the facile bis-hetero retro-Diels-Alder reaction of 4-alky 1-4//-1,3-dioxins (151) as shown in equation (66). This retrodiene process involves exceptionally mild conditions, refluxing in toluene, in order to unmask the a,3-unsaturated aldehyde. The diversity of this process is illustrated by the partial list of reactions shown. The same mild conditions can be used to prepare a,3-unsaturated ketones by reflux-... 

The construction of the naturally derived narbomycin and tylosin-aglycones by Masamune and coworkers employ identical methodology for seco-acid formation. In each case, Peterson alkenadon of a functionalized aldehyde (not shown) and the silyl ketones (96 R = SiMes Scheme 36) or (99 Scheme 37) efficiently introduced the required ( )-a,3-unsaturation. Silyl ketone formation is accomplished in each case through cuprate acylation by an activated carboxylic acid derivative. Formation of an acid chloride was not possible in the sensitive tylosin-aglycone intermediate however, selective acylation of the silylcuprate proceeded at the pyridyl thiol ester moiety of (98) and not with the r-butyl thiol ester. In a related investigation, (97), an advanced intermediate for 6-deoxyerythronolide B, was obtained from (95) via addition of lithium diethylcuprate to the acid chloride (84% yield). In all the above cases, no addition was observed at the f-butyl thiol ester. 

Usually the Knoevenagel condensation yields the unsaturated product, but, with appropriate aldehydes, 3-hydroxymalonates can be isolated. The unusual formation of an a-naphthol (74) has been reported from the reaction of diphenylacetaldehyde (73) with diethyl malonate under Knoevenagel conditions." Condensation of stdicyl dehydes and other aromatic o-hydroxy aldehydes with malonates is still in use for the synthesis of the corresponding coumarin-3-carboxylic esters (75). - " Reduction... 

Hydrocarboxylation is the formal addition of hydrogen and a carboxylic group to double or triple bonds to form carboxylic acids or their derivatives. It is achieved by transition metal catalyzed conversion of unsaturated substrates with carbon monoxide in the presence of water, alcohols, or other acidic reagents. Ester formation is also called hydroesterification or hydrocarb(o)alkoxylation . The transition metal catalyst precursors are nickel, iron or cobalt carbonyls or salts of nickel, iron, cobalt, rhodium, palladium, platinum, or other metals4 5. 

Some properties of diethyl allylphosphonate have been investigated, in particular the behaviour of its anion (500) towards < /t-unsaturated ketones and carboxylic esters. Although in. some cases the conjugate addition of the anion has been observed, e.g. in the formation of (501) and (502), in most ca.ses the reaction leads to carbocyclic products. y-Nucleophilicity, with addition-elimination, has been observed in reactions with e.g. ( )-4-methoxybut-3-en-2-one, when the final product is (503), following expulsion of the methoxy group. A third mode of reaction consists of multiple addition ... 

Alkylative esterification of carboxylic acids with alkyl halides are effected by action with TMG (1) [65]. An ester is given by the TMG (1) mediated reaction of y-hydroxy-a,p-unsaturated carboxylic acid with methyl iodide without lactone formation after isomerization [65a]. Barton s base effectively works in the alkylation of sterically hindered carboxylic acid [3]. Ethanolysis of the acetate of tertiary alcohol occurred easily in 86% yield in the presence of BTMG (2) [66] (Scheme 4.24). 

The ester formation occurs between a phenolic end group of the PPE and a carboxylic group of the methacrylic anhydride. A highly efficient capping with respect to aliphatic unsaturation can be readily achieved. Instead of toluene, the capping reaction can be performed in a styrene monomer. The mixture can be used for further thermosetting. When the capped PPE does not need to be isolated by a further process, a reduction in color is observed [31]. 

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