Aminocarbonyl compounds

Dihydropyrazines are formed by the self-condensation of a-aminocarbonyl compounds and they are relatively stable, although again they are easily oxidized to the corresponding pyrazines. Tetrahydropyrazines are less well documented and structures such as (87) appear to be more stable than the enediamine (88). 

These reactions are related to the formation of pyrroles and quinolines from aminocarbonyl compounds and acetylenes (582,583) and may be contrasted with the formation of pyran derivatives by electrophilic attack on an enamine, followed by addition of an oxygen function to the imonium carbon (584-590). 

The simplest systems in which N/C/O cilternative sites of protonation occur are Q ,j3-unsaturated jS-aminocarbonyl compounds... 

Due to the synthetic and biological importance of amines and a-aminoketones, acids and esters, the introduction of amino functionality into carbon nucleophiles provides a convenient and practical route for their synthesis "In addition, a number of electrophilic amination methodologies have been developed for the asymmetric synthesis of amines and a-aminocarbonyl compounds " ". 

For the synthesis of a-aminocarbonyl compounds, a number of O-organylhydroxyl-amine-type reagents have been used. Several 0-alkylhydroxylamines la-e were screened for amination of a-lithiated carboxylic acids (Scheme 11) °. However, the yields are... 

A-Metal derivatives of A-(aUtoxycarbonyl) 0-(arenesulfonyl)hydroxylamines, [alkyl A-metal A-(arenesulfonyloxy)carbamates] 3i-o have been used in the amination of a-metallated carbonyl compounds to give A-Boc [N(COOBu-f)] or A-Alloc [N(COOCH2 CH=CH)] protected a-aminocarbonyl compounds. 

For stereoselective synthesis of a-aminocarbonyl compounds using 0-phosphinyl-hydroxylamines, a few procedures have been developed. Attempted amination of enolates of chiral alkyl 3-hydroxybutanoates with 0-(diphenylphosphinyl)hydroxylamine 4a or with its A,A-diisopropyl derivative 4d were found to be unsuccessful". ... 

Triazaphosphapentalenes, 1,3,2-benzodiazaphospholes, 1,3,2-benzoxazaphospholes, and 1,3,2-benzothiazaphospholes are contained in a review on anellated heterophospholes <9477675). The synthesis of 1,3,2-oxazaphospholes from a-aminocarbonyl compounds has also been reviewed <92RHA25>. 

M. Tramontini, Synthesis 1982, 605-644 . .Stereoselective Synthesis of Diastereomeric Amino Alcohols from Chiral Aminocarbonyl Compounds by Reduction or by Addition of Organometallic Reagents". 

Self-condensation of suitable aminocarbonyl compounds in various forms is a potential route to symmetrically substituted 1,5-diazocines of many kinds, but the successful applications are largely limited to benzo fused derivatives. o-Aminobenzaldehyde, despite earlier... 

Thieno[3,2-fc]pyridines are obtained in 49-87% yield (74JPR169). Application of the Friedlander reaction to 3-amino-2-formylthiophene gives (261) in reasonable yield (Scheme 78) (75ACS(B)224,75 ACS(B)233). As in the case of the synthesis of furo[3,2- >]pyridines (Section 3.17.2.1.1(i)(d), Scheme 17), it was unnecessary to isolate the o-aminocarbonyl compounds. 6-Substituted 7-hydroxythieno[3,2-6]pyridin-5(4/7)-ones (e.g. 295) can be prepared by base-catalyzed cyclization of the amides (294), which were obtained in high yields from readily available 3-amino-2-alkoxycarbonylthiophenes (293 Scheme 79) (80JCR(S)6) for... 

Gronowitz and coworkers prepared (426) by application of the Friedlander reaction (75ACS(B)233). The Friedlander method utilizes the reaction in alkaline or acidic media between an o-aminocarbonyl compound and a carbonyl compound containing an active methylene group. The amino compound used is 3-amino-2-formylselenophene, which is... 

MANNICH REACTION. Reaction ol active methylene compounds with formaldehyde and ammonia of primary or secondary amines to give fj-aminocarbonyl compounds. 

Several benzonaphthyridines of type 53 have been prepared81 by condensing 4-piperidones with /3-aminocarbonyl compounds such as 52.94... 

The isoquinoline system is conveniently prepared from treatment of o-iodobenzylamines with the enolate ions derived from symmetrical ketones (or ketones with one a-position blocked), aldehydes, or the dimethyl acetal of pyruvaldehyde, to give aminocarbonyl compounds which condensed in situ to give 2- and/or 3-substituted 1,2-dihydroisoquinolines. Catalytic dehydrogenation or borohydride reduction of these products then led to the corresponding isoquinolines or tetrahydroisoquinolines in moderate to high... 

Aminocarbonyl compounds have been prepared via Lewis base-catalysed Man-nich reaction of TMS enol ethers and iV-tosylaldimines, ArCH=N-Ts, with excellent anti selectivity in some cases.30... 

In origin, the Mannich reaction is a three-component reaction between an eno-lizable CH-acidic carbonyl compound, an amine, and an aldehyde producing / -aminocarbonyl compounds. Such direct Mannich reactions can encompass severe selectivity problems since both the aldehyde and the CH-acidic substrate can often act as either nucleophile or electrophile. Aldol addition and condensation reactions can be additional competing processes. Therefore preformed electrophiles (imines, iminium salts, hydrazones) or nucleophiles (enolates, enamines, enol ethers), or both, are often used, which allows the assignment of a specific role to each car-... 

Halo-4-methoxybenzynes are generated by reaction of 5-(3-halo-4-methoxy-phenyl)thianthrenium perchlorates, (20), with LDA in THF their reactions with various /J-aminocarbonyl compounds may give a number of heterocyclic compounds.64... 

Azetines 575, synthesized by the reaction of IV-acyl thiazolidinethione enolates with enolizable aldoxime ethers, have been successfully converted into the corresponding iV-acyl-substituted /3-aminocarbonyl compounds 576 by simple exposure to benzoyl chloride <2003JA3690>. The reactions presumably involved an acyliminium salt 577, which hydrolyzed to yield 576 (Scheme 74). 

The Mannich reaction is a useful reaction for the synthesis of [3-aminocarbonyl compounds including (3-amino acids, [3-lactams, and related compounds.24 Because the synthesis of chiral compounds is required for biological study, asymmetric versions of this reaction are in high demand. Several approaches to achieve asymmetric Mannich reactions have been reported. 

Azodicarboxylates are attractive aminating reagents, since a-aminocarbonyl compounds are not only useful building blocks in organic synthesis, but also essential tools for biological studies.33 Hence, the development of general and efficient methods for the preparation of these compounds is an important issue in organic synthesis. 

The Mannich reaction of an aldehyde enol (example Formula C in Figure 12.14) or a ketonic enol (example Formula C in Figure 12.15) often proceeds beyond the hydrochloride of a /l-aminocarbonyl compound or the Mannich base. The reason is that the secondary amine or its hydrochloride, which has previously been incorporated as part of the iminium ion, is relatively easy to eliminate from these two types of product. The elimination product is an a,fi-unsaturated aldehyde (example Formula E in Figure 12.14) or an a,/l-unsaturated ketone (example Formula D in Figure 12.15)—that is, an a,/l-unsaturated carbowyl compound. Figure 13.51 will show how the Mannich reaction of a carboxylated lactonic enol provides access to an a-methylene lactone, that is, an a,/l-unsaturated carboxyl compound. 

---