Allylic amides synthesis

Metathesis of N-tosylated ene-amides and yne-amides has been less extensively investigated. An example of the RCM of ene-amides is a new indole synthesis developed by Nishida [79] metathesis precursor 96 (prepared by ruthenium-catalyzed isomerization of the corresponding allyl amide) is cy-clized to indole 97 in the presence of 56d (Eq. 13). 

A concise total synthesis of the indole alkaloid dihydrocorynantheol (101) (Scheme 19), that features two RCM steps and a zirconocene-catalyzed carbo-magnesation [68], is a further example of Martin s interest in applying RCM as a key reaction for the construction of alkaloid frameworks [69]. The first RCM step was applied to bis-allyl amide 96. The resulting intermediate 97 was directly subjected to carbomagnesation and subsequent elimination to deliver 98 in 71% yield from 96. Amide 98 was then transformed into acrylamide 99 in... 

The use of ethylene adduct lb is particularly important when the species added to activate catalyst la is incompatible with one of the reaction components. Iridium-catalyzed monoallylation of ammonia requires high concentrations of ammonia, but these conditions are not compatible with the additive [Ir(COD)Cl]2 because this complex reacts with ammonia [102]. Thus, a reaction between ammonia and ethyl ciimamyl carbonate catalyzed by ethylene adduct lb produces the monoallylation product in higher yield than the same reaction catalyzed by la and [Ir(COD)Cl]2 (Scheme 27). Ammonia reacts with a range of allylic carbonates in the presence of lb to form branched primary allylic amines in good yield and high enantioselectivity (Scheme 28). Quenching these reactions with acyl chlorides or anhydrides leads to a one-pot synthesis of branched allylic amides that are not yet directly accessible by metal-catalyzed allylation of amides. 

The two products 6 and 7 are formed in a 1 1 mixture however, the stereochemistry of the side-chain is controlled effectively, so that after decomplexation and further manipulations both products can be applied in the synthesis of deoxycytochalasin. When pendant dienes were used instead of the allyl amide side-chain after the initial step of the formal [6 + 2]-Alder-ene reaction (Scheme 9.10), the intermediate 8 undergoes another reductive cyclization to the final polycyclic product 9 in quantitative yield as a single diastereomer, as reported by Pearson and Wang [22], The overall process can be seen as a formal [4 + 4]-cycloaddition reaction of the cyclohexadiene with the pendant diene. 

Another interesting sequence is the amidoselenenation of alkenes for the synthesis of allylic amides. The seleniranium ion is trapped by a nitrile group which is first converted to an iminium chloride and then hydrolyzed to the amide (similar to the Ritter amide synthesis). Several differing nitriles (e.g. methyl to phenyl) have been utilized and all provide good yields of amides. The stereochemistry of addition is always trans but mixtures of regioisomers occur with terminal and unsymmetrically substituted oleflns (equation 24). The -seleno amide is easily converted to the allylic amide by oxidation of the phenyl selenide using the standard conditions. ... 

The Pinner reaction is the standard method of preparing imidate salts (the free imidate is obtained upon basification with weak bases) by alcoholysis of nitriles in the presence of mineral acids. However, this method is not suitable for the synthesis of allylic imidates since, under these reaction conditions, allylic amides, the product of the Ritter reaction, are formed. The acetimidates are easily prepared by condensation of the sodium or potassium alcoholate with trichloro- or trifluoroacetonitrile in high yield. For the rearrangement reaction the crude imidates can be used. 

The synthesis of ( )-Epibatidine 23b and analogs thereof was realized by regioselec-tive chloroacetoxylation of 2-aryl-l,3-cyclohexadiene.f" Subsequent stereoselective substitution of the chloro group by tosylamide with either retention or inversion provided both stereoisomers of the aminoalcohol derivative. Highly stereoselective hydrogenation of the allylic amides gave the requisite stereoisomers for synthesis of the exo- and endo-isomers (Scheme 16). 

Arai, Y, Kasai, M., Ueda, K., Masaki, Y. (2003). Asymmetric tandem conjugate addition-allylation of chiral (p-tolylsulfinyl)pyrrolyl cinnamoyl amide. Synthesis, 1511-1516. 

Zero-valent metal complexes cannot be used directly for the synthesis of polypeptide hybrid block copolymers. However, N° -allyloxycarbonyl-amino acid allyl amides can be used as universal precursors for the amido-amidate nickelacycle initiators (Scheme 15.8). As shown in Scheme 15.8, the N°"-allyloxycarbonyl-amino acid derivatives may undergo tandem oxidative additions to nickel(O) giving the nickelacycle initiators. This method was initially employed for the synthesis of block copolypeptides and was then expanded by Deming and coworkers to a variety of hybrid structures. 

The synthesis of allyl-amide complexes containing the amine-substituted oxapentadienyl ligand of the type [Mn(C0)3(ii3 Til-PhCH2CHCHCHC(0)NR2)], (13), (R = H, Et, Pr , CH2Ph, Me) has been reported and the compound stmcturaUy characterised for R = Me. 

Aza-adamantanes.—1-Aza-adamantanes are easily available in a convenient two-step synthesis from a-pinene (Scheme 83)." The synthesis is dependent on the serendipitous discovery that solvomercuration-demercuration of a-pinene with acetonitrile in the presence of mercuric nitrate followed by in situ boro-hydride reduction led not to the expected allylic amide but instead to azabicy-clo[3,3,l]nonene which is readily converted into aza-adamantane by reaction with formaldehyde. Rearrangement of A-chloro-N-acetyl-l-aminoadamantane... 

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