Reductive amination triketones

A reductive amination/cyclization strategy was used by Surya Prakash Rao and coworkers to synthesize the annulated tricyclic compounds 10-93 [34]. These authors employed the microwave irradiation of a cis/trans- mixture of 1,5,9-triketone 10-92 with an excess of ammonium formate for 1 min in 87 % yield (Scheme 10.23). 

Reaction of phenyl vinyl ketone with cyclopentanone under thermal conditions resulted in a diastereomeric mixture of 1,5,9-triketones 374 via a double Michael reaction. Treatment of this mixture with ammonium formate in polyethyleneglycol-200 under microwave irradiation conditions led to the very fast and efficient formation of a 2 1 diastereomeric mixture of cyclopental flquinolizidines 375 and 376 <2002T2189>. When this reductive amination-cyclization procedure was carried out starting from the purified /ra r-isomer of 374, the result was identical to that obtained from the cis-trans mixture, showing the operation of thermodynamic control (Scheme 86). 

The overall carbon-nitrogen framework was confirmed by synthesis. Reductive amination of the triketone (336) (429) with sodium cyanoborohydride and ammonium acetate formed a mixture of four isomeric pyrrolizidines. Pure sam-... 

Stractures of 3-alkyl-5-methylindolizidines, found in thief ants, Solenopsis species (Table II), arrived at by gas chromatographic and mass spectral analysis were confirmed by coinjection and direct comparison with the synthetic sample. Indolizidine 15a from S. conjurata exhibits characteristic peaks at miz 152 (M — CHj) and 138 (M — C2H5, a base peak) as well as a parent peak at m/z 167 in the mass spectram. It corresponds to an isomer of 3-ethyl-5-methylindolizidine (15) which was prepared as a mixture of four stereoisomers by reductive amination of triketone 391 with ammonium acetate-sodium cyanoborohydride and sodium borohydride (Scheme 47). 

Formation of the imine and subsequent reduction can often be achieved in one pot . Thus, a microwave-assisted reductive amination-cyclisation domino reaction was used as the key step in the synthesis of perhydrocyclo-penta[ij]quinolizines from 1,5,9-triketones. This type of heterocycle is an important structural element in a series of alkaloids. The reaction of the triketone with ammonium formate in PEG-200 was performed within 1 min using microwave irradiation of370 W in a domestic microwave oven. Amixture oftwo ofthree possible stereoisomers was obtained in 87% overall yield (Scheme 4.29)52. 

The venomous constituent of the cryptic thief ant, Solenopsis xenovenenum, has been identified as the 3-heptyl-5-methylpyrrolizidine (50) from its mass spectrum and the fact that a related pyrrolidine (51) has been isolated from another species of ant.47 This is the first reported occurrence of a 3,5-dialkyl-pyrrolizidine, and its structure was confirmed by synthesis. Reductive amination of the known triketone (52) with sodium cyanoborohydride and ammonium acetate gave a mixture of four isomers of 3-heptyl-5-methylpyrrolizidine, which were separated by preparative g.l.c. The stereochemistry of the ring-junction of each isomer was established from its i.r. and n.m.r. spectra. 

The two stereoisomers of perhydro-9b-azaphenalene have been synthesized from the readily available perhydroboraphenalene (61) (Scheme 6). Oxidation yielded the triketone (62) which was converted by reductive amination into stereoisomer (63). This compound was transformed in six stages into isomer (64). 

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