A-amino acetals

Using the chiral a-amino acetal 1-120 ion and two different N-nucleophiles 1-122 and 1-123, the pyrrolidines 1-124 and 1-125, respectively, are obtained in good di-... 

Glycine H2N—CH2—COOH (a-amino acetic acid i.e., and aliphatic amino acid) ... 

Oxidation of sulphonamides in the presence of bromide or iodide ions and sodium methoxide in methanol also leads to formation of the N-halogeno intermediate. The nitrogen-halogen bond in these intermediates is weak and will undergo themiolysis. At -10 °C, reaction proceeds by base catalysed elimination of hydrogen halide and ftirther steps lead to an a-amino acetal 20. The reaction is carried out in an undivided cell and renders a-aminoacetals readily available for the iso-... 

John L. LaMatMna and R. T. Suleske 19 a-AMINO ACETALS 2.2-DIETH0XY-2-(4-PYRIDYL)ETHYLAMINE... 

Thioamides can serve as surrogates for isothiocyanates in the Marckwald synthesis. For example, reaction of a-amino acetals 1278 with thioamides 1277 in the presence of HgClz affords amidine intermediates, which cyclize to form imidazoles under acidic conditions. This method has been applied to synthesize a variety of sugar imidazoles (Scheme 324) <2005HCA10, 2004HCA3035, 2004HCA719, 2000TA435>. 

In the synthesis of various heterocycles from a-amino ketones, pyrazine formation can be a complicating side reaction due to the tendency of the a-amino ketone to dimerize. One way of avoiding this problem would be to generate the a-amino ketone in a protected form, specifically, as an a-amino acetal. Such derivatives allow the manipulation of the amino moiety as desired. Accordingly, the azirine intermediates derived from oxime tosylates by the Neber rearrangement are subsequently treated with acidic ethanol to furnish the corresponding a-amino acetals (equation 65). ° ... 

Tertiary a-halo ketimines 3 reacted with alcohols in the presence of nitrogen bases, e.g. triethylamine, 1,4-diazabicyclo[2.2.2]octane, l,5-diazabicyclo[4.3.0]non-5-ene or 1,8-diaza-bicyclo[5.4.0]undec-7-ene, to afford mainly l-alkoxy-2,2-dialkylcyclopropylamines 4, together with variable amounts of a-alkoxy ketimines 5 and rearranged a-amino acetals 6. The geminal functionalized cyclopropanes 4, obtained in up to 80% yield, and the a-alkoxy ketimines 5, were formed via intermediate 2-(alkylamino)allylcarbenium ions 7. 

The side reactions could be eliminated to a great extent when 1M sodium methoxide in methanol under reflux was used. Under these conditions, a-chloro ketimines 3 (X = Cl) were converted into 2,2-dialkyl-l-methoxycyclopropylamines 4 (R = Me) in 80-92% yield (Table 1). Lower concentrations of sodium methoxide in methanol favored the formation of a-amino acetals 6 by solvolysis via intermediate 2-methoxyaziridines 9 (R = Me), while higher concentrations... 

Metal-mediated approaches to the synthesis of imidazoles have been reported. PaUadium(ll)-catalyzed intermolecular 1,2-diamination of conjugated dienes with ureas led to 4-alk enyl-2-imidazolones in good yields rmder mild conditions <05JA7308>. Palladium-catalyzed cyclization of O-pentafluorobenzoylamidoximes 74 furnished l-benzyl-2-substituted-4-methylimidazoles 75 <050L609>. Direct copper(I)-chloride mediated reaction of nitriles 76 with a-amino acetals 77 followed by acidic reaction led to a variety of 2-substituted imidazoles 78 <05TL8369>. 

This reaction, like all Neber rearrangements, is limited by availability of the appropriate oxime tosylate. Substrates in which the aryl group contain an electron-donating function are unstable, since they have a propensity to undergo Beckmann rearrangement. However, this difficulty can be resolved by subsequent conversion of the a-amino acetals. For example, catalytic hydrogenation of 2,2-diethoxy-2-(p-bromophenyl)ethylaraine yields the known parent compound, 2,2-diethoxy-2-phenylethylamine These two a-amino acetals readily undergo hydrolysis and should be protected from moisture. 

Rapoport reported preparations of amino guanidines for studies of UV-/iH profiles. It was found that the addition of a substituted amine must precede the addition of ammonia, otherwise no desired amino guanidines will be found (eq 21). Finally, another example involved addition of the dianion of a-amino acetic acid to reagent 1 (eq 22). ... 

The Neber rearrangement of oxime 0-sulfonates to 2//-azirines (or a-amino ketones, after aqueous acid workup) has been reviewed, together with the modified Neber , involving /V,/V,A-trimethylhydrazonium iodides.With an excess of base, the a-amino acetal can be formed from the 2//-azirine via the unstable 2-alkoxy aziridine. 

Frutos prepared 2-fluoromethylimidazoles via the cyclization of the amidines formed by the Cu(I)-piomoted addition of a-amino acetals to fluoroacetonitrile (Scheme 19) [29]. The reactions were performed either stepwise or in a one-pot fashion (depending upon the removal of Cu salts before or after the cycUzation) in which the amidine formation was carried out in the absence of any solvent followed by the cyclization using TFA or HQ-MeOH. Thus, the addition of (methylamino) acetaldehyde dimethyl acetal and (benzylamino)acetaldehyde diethyl acetal with fluoroacetonitrile followed by cyclization afforded the corresponding 2-(fluoro-methyl)imidazoles in 96 % and 53 % yields, respectively. 

Muralidharan KR, MokhaUalati MK, Pridgen LN. Enantioselective synthesis of a-amino acetals (aldehydes) via nucleophilic 1,2-addition to chiral 1,3-oxazolidines. Tetrahedron Lett. 1994 35 7489-7492. 

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