Enamines amide acetal

The reaction of propargyl alcohols with an amide acetal affords enamine products512. 

In contrast, morpholine enamines from higher alkyl ketones do not dimerise but undergo disproportionation to the reduced enamine and various oxidation products. Aldehyde enamines dimerise, but with more difficulty at higher temperatures544. Cross-conjugated545 and linear dienamines (e.g. 132)546 have been prepared by condensation of amide acetals with alkynyl alcohols (equation 37). 

Synthesis of enamines from carboxylic acid amides via 1-alkoxyazomethi-nium salts and amide acetals—Gyclic enamines via lactam acetals— Easy reaction of amide acetals with nucleophiles, urea acetals s. 16, 785 Enamines from carboxylic acid amides GHg + OG N < G G N <... 

The Claisen rearrangement has been used to prepare j8,y-unsaturated amides, largely as the E-isomers, from 3-(trimethylsilyl)allyl alcohols and amide acetals (Scheme 48). Overall yields and stereoselectivities are excellent. Conditions have been found under which the stereochemical outcome of the related ynamine-Claisen rearrangement can be controlled. Thus, the kinetically favoured intermediate is the E-enamine (140) which leads to the "trans product (142), whereas the Z-isomer (141) is thermodynamically favoured and gives the cw ... 

Heteroring closures with dimethylformamide dimethyl acetal Indoles via trans- -amino-l-nltrostyrenes Enamines from amide acetals... 

Without additional reagents Enamines from amide acetals... 

Synthesis of enamines from carboxylic acid amides via 1-alkoxyazomethinium salts and amide acetals Cyclic enamines via lactam acetals... 

Triethyloxonium fluoroborate added with stirring under anhydrous conditions to a soln. of l-methyl-2-quinolone in methylene chloride, stirring continued for 1 hr. l-methyl-2-ethoxyquinolinium fluoroborate (Y 96%) added during 5 hrs. under anhydrous conditions to an ice-cooled soln. of Na in ethanol 1-methyl-2-quinolone diethyl acetal (Y 87%) dissolved in ethanol, treated with cyclopentadiene, and refluxed 10min.-> (1-methyl-1,2-dihydro-2-quinolylidene)-cyclopentadiene. (Y 94%).—Amide acetals react easily without catalyst with nucleophiles, e. g. giving enamines with active methyl and methylene groups. F. e., also aliphatic amide acetals and urea acetals, as well as their reactions, s. H. Meerwein et al., A. 641, 1 (1961). 

Other isocyanates undergo [2 + 2] cycloaddition, but only with very electron rich alkenes. Thus phenyl isocyanate gives /3-lactams with ketene acetals and tetramethoxyethylene. With enamines, unstable /3-lactams are formed if the enamine has a /3-H atom, ring opened amides are produced 2 1 adducts are also found. Photochemical addition of cis- and traH5-stilbene to phenyl isocyanate has also been reported (72CC362). 

At low temperatures cyclopropenones and enamines or ketene acetals were shown to yield 2-azonia-bicyclo(3,l, 0)hex-3-enolates-3 (371, X=0), which can be isomerized thermally to penta-2,4-diene amides(372, X=0). At elevated temperatures the amides were found to be the principal products arising from C-N-insertion 237) (insertion of the cyclopropenone three-carbon unit into the C-N bond of the enamine). These were accompanied in some cases by 3-aminoenones 373 arising from C-C-insertion 237) (insertion of the cyclopropenone into the C-C double bond of the enamine) and a-amino cyclopentenones 375 formed by Stevens rearrangement of the ylide 369 and cyclopentenones 374 ( condensation 237)). 

Several syntheses of indiplon have been described and two routes are shown in Scheme 15.5 (Sorbera et al., 2003 Dusza et al., 2002). Treatment of acetophenone 26 with refluxing dimethylformamide dimethylacetal (DMF-DMA) provided enamide 27. Alkylation of the amide with methyl iodide using NaH in DMF afforded 28. 3-Ketonitrile 29 was treated with DMF-DMA to give enamide 30. Cychzation with aminoguanidine produced aminopyrazole 31. The condensation of enamide 28 with aminopyrazole 31 in acetic acid furnished indiplon (4). Alternatively, enamine 28... 

A [3+2] cycloaddition of fV-3-thymine-substituted enamine 64 with ethoxycarbonyl nitrile oxide, generated in situ from ethyl chloro(hydroxyimino)acetate, gave the dihydroisoxazole 65. Subsequent aromatization and ester-to-amide... 

The structures of all currently approved gastric acid secretion inhibitors that act as inhibitors of the sodium-potassium pump consists of variously substituted pyiidylsulfonyl-benzimidazoles. A structurally very distinct compound based on a pyrimidine moiety has much the same activity as the benzimidazole-based drugs. In yet another convergent synthesis, reaction of (3-phenethylamine (53) with acetic anhydride affords amide 54. Treatment with polyphosphoric acid (PPA) then leads to ring closure to form the dihydroisoquinoline (55). Sodium borohydride then reduces the enamine function to afford fragment 56. 

There exists a series of compounds which can also be regarded as activated amides, e.g. a-halo-enamines, ketene 0,N-acetals, ketene aminals or ynamines, which are not dealt with in this chapter. To show the scope of the contribution, the formulae of all the types of compounds which are treated in the text, together with references of the relevant reviews are listed in Table 1. 

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