A-Amino carbonyls

Alkylation of a-amino esters with 9-bromo-9-phenylf uorene serves as the principal step in the preparation of N-(9-phenylfluoren-9-yl)-a-amino carbonyl compounds which are useful chiral educts for asymmetric synthesis. A discussion of the synthetic utility of N-9-phenylfluoren-9-yl derivatives of amino adds and amino acid esters appears in the procedure following. 

Strecker aldehydes are produced by the Strecker degradation of the initial Schiff base (Figure 5). An a-amino carbonyl compound and... 

A review entitled a-heteroatom-substituted 1-alkenyllithium regents carbanions and carbenoids for C-C bond formation has addressed the methods of generation of such species, illustrated the carbenoid reactivity of a-lithiated vinyl halides and vinyl ethers, and emphasized the synthetic potential of the carbanion species in asymmetric synthesis of a-hydroxy- and a-amino-carbonyl compounds. ... 

Bei beiden Umlagerungen handelt es sich um die Erscheinung, wonach bei der Reaktion einer a-Hydroxycarbonyl-Verbindung mit einem Amin eine a-Amino-carbonyl-Verbindung entsteht. Dabei tragt jedoch das C-Atom der urspriinglichen Carbonylgruppe nach der Reaktion das Amin. 

SCHEME 18. Route to enantiomericaUy pure a-hydroxy and a-amino-carbonyl compounds by addition of chiral d synthons 143 to aldehydes and imines. X = H, OH G = protecting group... 

This methodology is also an important and potentially valuable method for C—N bond formation using the amination of carbon nucleophiles with electrophilic nitrogen transfer reagents (Scheme 1) Amination of ordinary carbanions and a-carbanion derived from carbonyl compounds and nitriles provides an important method for the synthesis of amines and a-amino carbonyl compounds and nitriles", respectively. For this purpose, a number of electrophilic amination reagents, which are synthetic equivalents of the R2N+ synthon, have been developed and the synthetic potential of electrophilic amination of carbon nucleophiles has been studied in detail . ... 

Tardella s group have developed effective protocols for preparation of chiral a-amino-carbonyl compounds using a-A-(ethoxycarbonyl) 0-(p-nitrobenzenesulfonyl)hydroxyl-amine 3n in the presence or absence of a base . A chiral /S-ketocarboxamide carrying... 

Alkylpyrazines are prepared by two main procedures, (1) self-condensation of a-amino carbonyl compounds and (2) alkylation (or acylation) of pyrazines at nuclear or side chain carbons. Condensation of aminoacetone hydrochloride (491) in the presence of the corresponding aldehyde gave the 3- -alkyl-2,5-dimethylpyrazines 20e and 20g (Scheme 61) 36). 2,5-Dimethylpyrazine 20a was prepared from hydroxyiminoacetone (493) by reduction with tin and hydrochloric acid (Scheme 61) 145). 3-Ethyl-2,6-dimethylpyrazine (21b) was prepared along with 20a and 495 by condensation of aminoacetone hydrochloride (491) with 2-aminopentan-3-one hydrochloride (494) in the presence of sodium ethoxide (Scheme 61) 36). 

One of the classical methods for the synthesis of pyrazines involves dimerization of an a-amino carbonyl compound and subsequent aromatization. Cyclic dimerization of the a-amino ketone, which is formed by reduction of a-azido ketone 149 with triphenylphosphine, leads to the formation of a pyrazine derivative 150 (Scheme 40) <1994JOC6828>. Reduced Te also dimerized a-keto azide 149 to give pyrazine 150 <2006JOG2797>. 

SchlieBlich kann man statt Thiocyanaten auch Arylisothiocyanate (s.Bd. IX, S. 883 u. Bd. E4, S.881) oder Alkyl-isothiocyanate172 173 mit a-Aminosauren bzw. a-Amino-carbonyl-Verbin-dungen umsetzen. In diesem Fall erhalt man als Produkte 1-substituierte 4-Hydroxy-2-mer-capto- bzw. 2-Mercapto-imidazole ... 

Durch Umsetzung von Cyanaten bzw. Isocyanaten mit a-Amino-carbonsauren bzw. a-Amino-carbonyl-Verbindungen werden 2,4-Dihydroxy-bzw. 2-Hydroxy-imidazole erhalten. Re-aktionen dieses Typs wurden bereits an anderer Stelle hinreichend besprochen ... 

Diese Methode entspricht der zweiten Stufe der auf S. 49 beschriebenen Umsetzungen von a-Amino-carbonyl-Verbindungen mit Carbonsaure-ester-imiden. Normalerweise werden die aus 2-Amino-O,O-acetalen mit Carbonsaure-ester-imiden hergestellten N-(2,2-Dialkoxy-ethyl)-carbonsaure-amidine mit Halogenwasserstoff in Alkoholen339,34°, Wasser341 oder DMF342 un-ter RiickfluB erhitzt (Arbeitsvorschriften hierzu s. S. 50). 

It was suggested that a-amino carbonyls such as 3-amino-butane-2-one formed a dihydropyrazine which was subsequently oxidized to a pyrazine (30, 311. The conversion of dihydropyrazine to pyrazine occurs with or without oxygen. There are two possible ways to convert dihydropyrazine into pyrazine without oxygen. One is the disproportionation of dihydropyrazine to give pyrazine and tetrahydropyrazine or piperazine. The other is the dehydration of hydroxy dihydropyrazine (32). Recently, a dialkylpyrazine radical was reported as an intermediate of pyrazine formation (33). However, this simple step from dihydropyrazine to pyrazine is not yet thoroughly understood. 

Formation mechanisms of imidazoles in the Maillard reaction are not as well understood as those of other heterocyclic compounds. The role of a-amino carbonyl fragments as intermediates in imidazole formation was suggested in the reaction of sucrose and ammonia (43). In a study of a L-rhamnose/ammonia model system, which produced fifty-two imidazoles, it was proposed that an amino-hydroxy fragment was responsible for imidazole... 

In the following survey, the literature preparations of some pyrazines (and also dihydro derivatives) from preformed a-amino carbonyl compounds (irrespective... 

The reaction of a-chloro carbonyl compounds with ammonia is not always successful, for example, w-chloro-o-methoxyacetophenone and w-chloro-o,p-dimethoxyacetophenone yield only resinous products (236), but in these cases potassium phthalimide may be used for the ammonation to the a-amino carbonyl compound. This last method was developed by Gabriel (116) and co-workers (187). 

A variation of this procedure was introduced by Tota and Elderfield (248), who described a general synthesis for 2,3-disubstituted and 2,3,6-trisubstituted 5-hydroxypyrazines. In this reaction an a-(bromoacetylainino) carbonyl compound (17) [prepared from an a-amino carbonyl compound (15) with a bromoacetyl bromide (16)] was treated with alcoholic ammonia to give the corresponding pyrazine (18). The reaction is discussed in more detail in Section 7. 

Some a-hydroxy carbonyl compounds when heated with ammonia, ammonium acetate or formate, or formamide have been shown to give pyrazines the reaction presumably proceeds through the a-amino carbonyl compound. 

Tota and Elderfield (248) have described a general synthesis for 2,3-disubstituted and 2,3,6-trisubstituted 5-hydroxypyrazines. In this reaction an a-(bromoacetyl-amino) carbonyl compound (prepared from an a-amino carbonyl compound with... 

Detailed discussion of the preparation of a variety of alkyl- and arylpyrazines by primary syntheses, principally from aliphatic components, appears in Chapter II. These include, for example, the preparation of 2,5-disubstituted and 2,3,5,6-tetrasubstituted alkyl- and arylpyrazines from a-amino carbonyl compounds, which may be produced by many methods such as reduction of a-hydroxyimino carbonyl compounds, aminolysis of a-halogeno carbonyl compounds, oxidation of a-amino... 

As described above, the reactions of Grignaid or organolithium reagents to a-hydroxy- or a-amino-carbonyls can proceed with extremely high stereoselectivities (>99 1) when cyclic chelation control is in effect. However, attempts to generate products arising from the Cram-Felkin-Anh mode of addition exclusively have been much less successful. Hiese products are available by the use of conditions which favor nonchelation-controlled processes however, until recently, the selectivities of these reactions (up to 80-90%) never reached those observed in cyclic chelation control additions. 

JV-Boc protected a-amino carbonyl compounds are prepared by treatment of the lithium enolates of ketones, esters, and amides with AT-Boc 3-(4-cyanophenyl)oxaziridine (53b) <93JOC479i>. The modest yields (33-38%) are ascribed to aldol-type reactions of the enolate with the 4-cyano-benzaldehye (62) by-product (Equation (9)). In one example, the lithium enolate of propiophenone gave A-Boc-cathione (61), the pharmacologically active constituent of the leaves of khat. 

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