Acyl halide-aldehyde

Hydride donor Iminium ion Acyl halide Aldehyde Ketone Ester Amide Carboxy- late salt... 

Secondary amines an easily converted into formamidines reaction with amidines (equation 24). Deprotonation and addition of electrophiles, including alkyl halides, acyl halides, aldehydes and dise-lenides, permit the introduction of various groups adjacent to the amino center, and therefore can be considered as an oxidation. Alkylation with dihalides gives intermediates which lead to new caibocyclic rings after removal of the formamidine group (equation 2S). ... 

The use of Al(III) complexes as catalysts in Lewis acid mediated reactions has been known for years. However, recent years have witnessed interesting developments in this area with the use of ingeiuously designed neutral tri-coordinate Al(lll) chelates. Representative examples involving such chelates as catalysts include (1) asymmetric acyl halide-aldehyde cyclocondensations, " (2) asymmetric Meerwein-Schmidt-Ponndorf-Verley reduction of prochiral ketones, (3) aldol transfer reactions and (4) asymmetric rearrangement of a-amino aldehydes to access optically active a-hydroxy ketones. It is important to point out that, in most cases, the use of a chelating ligand appears critical for effective catalytic activity and enantioselectivity. 

The tin enolates are useful in organic synthesis as a mild source of the nucleophilic enolate group in its reaction with alkyl or acyl halides, aldehydes or enones. The tin enolates are less basic than the lithium enolates, and more reactive though rather less easy to handle than the silicon enolates.105-113... 

The scope of vinyl metals as sources of nucleophilic vinyl groups is very great. As well as the expected electrophiles such as halogens, alkyl and acyl halides, aldehydes and ketones, unsaturated carbonyl compounds and epoxides, they also combine with aryl and alkenyl halides with palladium catalysis. The usual stereochemical course is retention at the vinyl group. It is necessary to decide whether the vinyl metal is reactive enough or whether it must first be transformed into an ate complex. Since most of these vinyl metals can be converted into each other with retention, this is an unusually versatile group of reagents. 

Many types of reactive molecules are well known to medicinal chemists acyl halides, aldehydes, aliphatic esters, aliphatic ketones, alkyl halides, anhydrides, alpha-halocarbonyl compounds, aziridines, 1,2-dicarbonyl compounds, epoxides, halopyrimidines, heteroatom-heteroatom single bonds, imines, Michael acceptors and (l-heterosubstituted carbonyl compounds, perhalo ketones, phosphonate esters, thioesters, sulfonate esters, and sulfonyl halides, to name a few [14]. This is not to say that these functionalities are not useful - some even appear in approved drugs -but all of these can react covalently with proteins, and thus should be regarded with suspicion. However, molecules can react covalently with proteins even if they do not contain functionalities that raise alarm. Jonathan Baell has referred to these as pan assay interference compounds, or PAINS, and has published a list of moieties to watch out for, as well as strategies to detect them [15, 16]. 

CgHiiN4 Unstable, explosive liquid sensitive to heat, temperature increases, friction, impact, and some chemical reaction (Fire Rating 3). Thermal decomposition releases acutely toxic and potentially deadly tetramethylsuccinonitrile (TMSN). Violent reaction or other toxic chemicals may be formed when mixed with strong oxidizers, acids, acyl halides, aldehydes, alkali metals, strong reducing... 

The general answer to this problem is to avoid alkyl halides and to use instead electrophiles which give relatively unreactive products with amines. The best examples are acyl halides, aldehydes, and ketones. The products, amides (7) and imines (9), can be reduced to amines. The amide method inevitably produces a CH2 group (8) next to the nitrogen atom, but the imine route is suitable for amines with branched chains (10). 

Finally, acyl halides, aldehyde imines, and internal alkynes have recently been shown to react in the presence of CO and a palladium catalyst to gener-... 

Acyl Halide-Aldehyde Cyclocondensation (AAC) Reactions. Treatment of ( -symmetric ligand bis(sulfonamide) A with 1 equiv of trimethylaluminum generated the triamine-Al complex (C), which catalyzed the aldehyde ketene [2 + 2] cyclad-dition. 

Scheme 19.57 Asymmetric acyl halide-aldehyde cyclocondensations catalysed by Al-triamine or Al-bissulfonamide.

Nelson SG, Peelen TJ, Wan Z (1999) Catalytic asymmetric acyl halide - aldehyde cyclocondensations. A strategy for enantioselective catalyzed cross Aldol reactions. J Am Chem Soc... 

Nelson SG, Spencer KL (2000) Enantioselective (3-amino acid synthesis based on catalyzed asymmetric acyl halide-aldehyde cyclocondensation reactions. Angew Chem Int Ed 39 1323-1325... 

Nelson SG, Wan Z (2000) Catalytic asymmetric propionate Aldol reactions via acyl halide — aldehyde cyclocondensations. Org Lett 2 1883-1886... 

Nelson SG, Zhu C, Shen X (2004) Catalytic asymmetric acyl halide — aldehyde cyclocondensation reactions of substituted ketenes. J Am Chem Soc 126 14-15... 

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