Secondary amines 1,3-dicarbonyl derivatives

Several interesting reactions have been described for quinolizine-3-diazonium tetrafluoroborate 121. Thus, its treatment with secondary amines gave the corresponding triazenes 122 <2004ZNB380>, while its reaction with 1,3-dicarbonyl compounds gave the corresponding hydrazones. In the case of alkyl 4-chloro-3-oxobutanoates, the intermediate hydrazone 123 furnished a pyrazole derivative 124, as shown in Scheme 17 <2002H(57)2091>. 

The Michael-type addition, a nucleophilic addition of an anion to the carbon-carbon double bond of an a,(3-unsaturated ketone, aldehyde, nitrile, nitro, sulphonyl, or carboxylic acid derivative, provides a powerful tool for carbon-carbon bond formation. The reaction is most successful with relatively nonbasic ( soft ) nucleophiles such as thiols, cyanide, primary and secondary amines, and P-dicarbonyl compounds. There is often a competition between direct attack on the carbonyl carbon (1,2-addition) and conjugate addition (1,4-addition) when the substrate is an a,(3-unsaturated carbonyl compound. 

The dicarbonyl compoimd 51 was oxidized to the anhydride 52, which subsequently reacted with primary or secondary amines to form a-amino acids, a-amino amides and dipeptides 53 (Scheme 14) [48]. 3-Hydroxy j8-lactams obtained from imines derived from carbohydrates [49,50] or prepared via the Sharpless AD reaction [51-53] were directly oxidized to anhydrides by treatment with NaOCl and TEMPO. Anhydrides 54-56 were used for the synthesis of compounds related to the family of polyoxins represented by 57 (Scheme 15) [49-53]. 

After these initial results by Tsuji, this elementary step was incorporated into a catalytic process by Hata and co-workers at Toray Industries and by Atkins and co-workers at Union Carbide. These groups reported reactions of allylic phenyl ethers, allylic alcohols, and allylic acetates with carboxylates, alcohols, primary and secondary amines, and methyl acetoacetate catalyzed by Pd(0) complexes and precursors to Pd(0) complexes (Equation 20.3). - After these initial reports, early developments focused on reactions of "soft" carbanions derived from 3-dicarbonyl compounds, cyanoesters, and related compounds containing two electron-withdrawing groups attached to the nucleophilic carbon. Although these reactions occur with allylic halides in the absence of a catalyst, these reactions are greatly accelerated by palladium catalysts. Thus, the palladium catalyst allows these reactions to occur under mild conditions with allylic acfetates, which are more accessible than allylic halides, and with selectivities that are altered by the metal catalyst. 

Oxidation of Activated C-H Bonds. As shown in eq 13, extensive oxidation adjacent to carbonyl groups is possible with SOCI2 under relatively mild conditions. The process often stops after formation of the a-chlorosulfenyl chloride. Remarkably, these may be easily hydrolyzed back to the carbonyl compounds from which they were derived. Alternatively, they may be treated with a secondary amine such as morpholine followed by hydrolysis to yield the a-dicarbonyl compound. Similar oxidation of acid derivatives during acid chloride formation is possible (see above). 

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