Carbonyl compounds a-amino

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. ... 

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>. 

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... 

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. 

Immobilized copper-zeolite Y (Cu-HY) bis(oxazolines) were employed as heterogeneous catalysts in carbonyl-ene and imino-ene reactions, allowing the synthesis of a-hydroxy and a-amino carbonyl compounds 163 from 161 and 162 in satisfactory yields and high enantioselection <04AG(E)1685>. The use of a new, insoluble polystyrene-bound Box ligand (IPB-BOX) was also described with good activity (85-95% ee) <04TA3233>. 

This approach was discussed in Chapter 6. The synthesis of the spasmolytic Diphepanol (28) is an example. Disconnection of one or both phenyl groups gives a-amino carbonyl compounds which can be made from the corresponding a-halo compounds (see Chapter S). Halogenation of both (29) and (30) is regioselective as the other side of the carbonyl group cannot enolise. 

Deamination of a-amino carbonyl compounds occurs when they are treated with Sml2 in the presence of HMPA and a sufficient amount of MeOH as a proton source. By this reaction, proline esters are converted to piperidones [and thence application to a synthesis of (—)-adalinine]. Pyridinemethanols are deoxygenated."... 

After H2O addition and enamine hydrolysis (e / ), route II leads to the /-amino aldol intermediate 5. Aldol fission follows (retroanalysis step g) resulting in the formation of a-amino carbonyl compounds 6 and methylene ketones 7. These are possible starting materials for the synthesis of pyrroles. 

The classical pyrazine synthesis involves the self-condensation of two molecules of an a-amino-carbonyl compound furnishing 3,6-dihydropyrazine 24 followed by oxidation, usually under mild conditions, to pyrazine 25 ... 

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