Amides, reactions with acetylenic esters

Acidic hydrolysis of the reactive enamide led to the corresponding carboxylic acids 14 whereas alcoholysis gave esters 16 and aminolysis amides 15. The mechanism of the hydrolysis was shown to proceed via miinchnone derivatives 20 which, instead of being opened with a nucleophile, reacted as a 1,3-dipole in [3+2] cycloaddition reactions with propiolic esters or acetylene dicarboxylic esters to give after elimination of carbon dioxide protected pyrroles 19 (Scheme 3.2.4)... 

The addition of a base to an acetylenic ester or ketone provides another method of preparation of enaminones594,595. A convenient one-pot synthesis of enaminones from trimethylsilylethynyl ketones and amines was described596. The reaction of activated methylene compounds, such as cycloalkanones, MeCOPh and PhCH2COOMe, with amide acetals gave high yields of enaminones597 (equation 39). 

Both syntheses made the bond between the two alkenes by a Stille coupling. One put the tin on the amide part by a Cu(I) catalysed conjugate addition of Bu3SnLi to the acetylenic ester 212 and Weinreb amide formation. Coupling this vinyl stannane with a single enantiomer of the iodide derived from the rest of the molecule gave crocacin C in good yield. The synthesis of the iodide uses an asymmetric aldol reaction and is described in the workbook.30... 

Reaction of Ta-alkyne complexes with R R2C=0. The Ta complexes formed from TaCls/Zn with unsymmetrical alkynes react with carbonyl compounds to form two rcgioisomcric allylic alcohols with a ratio depending on the substituents on the alkync (both steric and electronic effects) as well as the size of the substituents in the carbonyl group. The complexes from acetylenic esters react with carbonyl compounds mainly at the position or to the ester group, whereas complexes from acetylenic amides react mainly at the position fi to the amide. 

COPPER DINITRATE (3251-23-8) A strong oxidizer. Violent reaction with reducing agents, combustible materials, acetic anhydride, ethers, potassium ferrocyanide, finely divided tin. The aqueous solution is a medium-strong acid. Incompatible with bases, acetylene, ammonia, aliphatic amines, aikanolamines, amides, alkylene oxides, cyanides, epichlorohy-drin, esters, isocyanates, organic anhydrides, vinyl acetate. Attacks metals in the presence of moisture. 

The presence of electron withdrawing groups at the a position (R3) of the acrylate derivative increases the reactivity of the reagent toward conjugate addition, while substituents in the ( position (R4) tend to provide steric constraints that hinder carbon-carbon bond formation (Scheme 3). Of the various acrylate derivatives employed in these reactions, the most frequently used have electron withdrawing functionality such as a carboxylic acid, amide, ester, or nitrile group or a combination of these. Direct pyridone formation can be achieved primarily through the use of either a,(J acetylenic esters or acrylate derivatives with P substituents (Y = SR, OR, NR2) that eliminate under the reaction conditions. 

Q ,/3-Acetylenic esters react with ReSn2 in the presence of Pd(PhsP)4 at room temperature to provide only the (Z)-2,3-distannylalkenoates (eq 31). When heated to 75-95 °C, clean isomerization to the ( )-isomers is observed. The corresponding amides are also useful substrates but provide either the ( )-isomers directly or ( /Z)-distannane mixtures. Surprisingly, under similar reaction conditions, a, -alkynic aldehydes and ketones form (Z)-/3-stannyl enals and enones in excellent yields (eq 32). ... 

Several improvements in acylation techniques were announced. Butyllithium wwas determined to be superior to sodium amide in preparation of amide ions for ammonolysis reactions with esters. Phosgene is more reactive than ethyl chloroformate toward eneamines. The intermediate acyl chlorides may then be converted to a variety of products. a-Acetylenic aldehydes are easily prepared by the action of acetylenic Grignard reagents upon ethyl formate. ... 

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