Steric factors in the cyclization of 4-azaheptane-2,6-diones to dehydropiperid-3-ones and the stereochemistry of reduction of 2,2-dimethyl- and 5-neopentylpiperid-3-ones

Conclusions

• 1. The neopentyl substituent in the azadiketones of the type (Ib) completely blocks the cyclization to the dehydropiperidine systems with the participation of the acetonyl carbonyl as the electrophile.

• 2. In such azadiketones, the geminal substitution at the carbon atom adjoining the nitrogen is less effective in its influence on the regioselectivity of the cyclization by comparison with the influence of substitution at the nitrogen.

• 3. In the saturated 3-ketopiperidines, the axial substituent at C² largely blocks the e-coordinate of the approach of the hydride nucleophiles to the carbonyl or the e-adsorption In catalytic hydrogenation. The steric influence of the neopentyl substituent at C² on the carbonyl depends on the specificity of the particular reagent and can surpass the influence of the tert-butyl group.