Amino-carbonyl Compounds

Amino-ketones may be easily prepared by oxidation of suitably 

It has also been shown that chiral N-trifluoroacetyl-a-amino-acid 

The formation of a-amino-carboxy compounds via heterocyclic intermediates is rapidly gaining importance. Optically active 

Oxazole intermediates afford routes to a-amino-carboxy compounds. threo-B-Hydroxy-L-glutamine has been prepared by the 

73) the route involves a face-selective halogenation followed 

Y-unsaturated a-amino acids were prepared by the oxidative rearrangement of allylic selenides using 3,3,6-trichloroethyl 

2-Aminobut-3-enoic acids deuterated at the vinylic positions 

---

The direct preparation of arylboronic esters from aryl halides or triflates now allows a one-pot, two-step procedure for the synthesis of unsymmetrical biaryls (Scheme 1-41) [147]. The synthesis of biaryls is readily carried out in the same flask when the first coupling of the triflate with diboron 82 is followed by the next reaction with another triflate. The synthesis of naturally occurring biflavanoids and the couphng of N-(phenylfluorenyl)amino carbonyl compounds to polymeric supports are reported [154]. 

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... 

The initially formed titanium enolate 80 adds, in a diastereoselective fashion, to the electrophilic center of the activated oxime. The generated adduct 81 cyclizes chemoselectively to afford the desired /f-azetine, which is converted, with retention of configuration, to the corresponding /3-amino carbonyl compounds 82 via 3V-acetylation followed by hydrolysis. 

Mannich and related readions provide one of the most fundamental and useful methods for the synthesis of p-amino carbonyl compounds, which constitute various pharmaceuticals, natural products, and versatile synthetic intermediates.1271 Conventional protocols for three-component Mannich-type readions of aldehydes, amines, and ketones in organic solvents indude some severe side reactions and have some substrate limitations, espedally for enolizable aliphatic aldehydes. The dired synthesis of P-amino ketones from aldehydes, amines, and silyl enolates under mild conditions is desirable from a synthetic point of view. Our working hypothesis was that aldehydes could read with amines in a hydro-phobic reaction fidd created in water in the presence of a catalytic amount of a metal triflate and a surfactant to produce imines, which could then read with hydrophobic silyl enolates. 

T. Akiyama, J. Takaya, H. Kagoshima, One-Pot Mannich-Type Reaction in Water HBF4 Catalyzed Condensation of Aldehydes, Amines, and Silyl Enolates for the Synthesis of (5-Amino Carbonyl Compounds Synlett. 1999,1426-1428. 

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. ... 

P-amino carbonyl compound, and the reaction is now called the Mannich reaction [206, 207],... 

Mannich reactions give rise to (i-amino carbonyl compounds which are amenable to further synthetic manipulations. Numerous stereoselective variants have been achieved by means of different types of catalysts including both metal complexes and organic molecules. In 2004, the groups of Akiyama and Terada independently selected this transformation as a model reaction for the introduction of a novel chiral motif to asymmetric catalysis [14, 15]. 

Three years after the discovery of the asymmetric BINOL phosphate-catalyzed Mannich reactions of silyl ketene acetals or acetyl acetone, the Gong group extended these transformations to the use of simple ketones as nucleophiles (Scheme 25) [44], Aldehydes 40 reacted with aniline (66) and ketones 67 or 68 in the presence of chiral phosphoric acids (R)-3c, (/ )-14b, or (/ )-14c (0.5-5 mol%, R = Ph, 4-Cl-CgH ) to give P-amino carbonyl compounds 69 or 70 in good yields (42 to >99%), flnfi-diastereoselectivities (3 1-49 1), and enantioselectivities (72-98% ee). 

This protocol complements Akiyama s method which provides P-amino carbonyl compounds as i yn-diastereomers [14], It tolerated aromatic, heteroaromatic, and aliphatic aldehydes. Cyclic ketones, acetone, as well as acetophenone derivatives could be employed. The use of aromatic ketones as Mannich donors was up to that time unprecedented in asymmetric organocatalysis. Rueping et al. independently expanded the scope of the asymmetric Brpnsted acid-catalyzed Mannich reaction of acetophenone [45]. 

In 2004, Kobayashi et al. introduced enecarbamates as nucleophiles to asymmetric catalysis [48], The addition of enecarbamates to imines in the presence of a chiral copper complex provides access to P-amino imines which can be hydrolyzed to the corresponding p-amino carbonyl compounds [49],... 

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). 

P-Amino carbonyl compounds containing an a-atkyUdene group are densely functionalized materials, which are widely applied in the synthesis of medicinal reagents and natural products [265]. These products are usually prepared through the classic aza-Morita-Baylis-Hillman reaction [176, 177] of activated imines and electron-deficient alkenes catalyzed by tertiary amines or phosphines. Chen and co-workers, in 2008, identified bis-thiourea 106 as a suitable catalyst for the... 

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>. 

Amino acids, Amino alcohols, Amino carbonyl compounds, Amino nitriles, Enamines, Homoallylic amines)... 

Amino carbonyl compounds see also Amino acids)... 

Keywords Mannich reaction, p-Amino carbonyl compounds, Imine, Enolate... 

The aza-Michael reaction yields, complementary to the Mannich reaction, P-amino carbonyl compounds. If acrylates are applied as Michael acceptors, P-alanine derivatives such as 64 and 65 are obtained. The aza-Michael reaction can be catalyzed by Bronsted acids or different metal ions. Good results are also obtained with FeCl3, as shown in Scheme 8.29. The addition of HNEt2 to ethyl acrylate (41f), for example, requires 10mol% of the catalyst and a reaction time of almost 2 days [94], The addition of piperidine to a-amino acrylate 41g is much faster and yields a,P-diaminocarboxylic acid derivative 65 [95]. 

A related one-pot, three-component synthesis of fi-amino carbonyl compounds has been achieved using a cascade reaction of anilines with aromatic aldehydes and car- (g) bonyl compounds, catalysed by zinc triflate.19... 

Ammonia and its derivatives are very prone to react in this way thus conjugate addition provides a method for the preparation of j8-amino carbonyl compounds. 

Probably the most important reactant in the formation of volatile meat flavor compounds is hydrogen sulfide. It can be formed by several pathways during meat cookery, but one mechanism is Strecker degradation of cysteine in the presence of a diketone as established by Kobayashi and Fujimaki (29). The cysteine condenses with the diketone and the product in turn decarboxylates to amino carbonyl compounds that can be degraded to hydrogen sulfide, ammonia and acetaldehyde. These become very reactive volatiles for the formation of many flavor compounds in meat and other foods. 

The Mannich reaction [18, 19] is a widely applied means of producing /i-amino carbonyl compounds starting from cheap and readily available substrates. In this reaction an aldehyde 20, an amine 21, and a ketone 22 react in a three-component-one-pot synthesis (Scheme 5.12, pathway 1). As a synthetic alternative, the reaction can also be performed as a nucleophilic addition of a C-nucleophile 22 to a preformed imine 24 which is prepared starting from the aldehyde and an amine source (Scheme 5.12, pathway 2). 

In conclusion, this new organocatalytic direct asymmetric Mannich reaction is an efficient means of obtaining optically active //-amino carbonyl compounds. It is worthy of note that besides the enantioselective process, enantio- and diastereose-lective Mannich reactions can also be performed, which makes synthesis of products bearing one or two stereogenic centers possible. Depending on the type of acceptor or donor, a broad range of products with a completely different substitution pattern can be obtained. The range of these Mannich products comprises classic / -amino ketones and esters as well as carbonyl-functionalized a-amino acids, and -after reduction-y-amino alcohols. 

---