Synthesis of 6- and 7-membered cyclic enaminones: scope and mechanism.

Six- and seven-membered cyclic enaminones can be prepared using common. environmentally benign reagents. Ammo acids are used as synthetic precursors allowing diversification and the incorporation of chirality The key reaction in this multistep process involves deprotection Boc-amino ynones and subsequent treatment with methanolic K2CO3 to induce cyclization. A beta-amino elimination side reaction was identified in a few labile substrates that led to loss of stereochemical purity of degradation. This process can be mitigated in specific cases using mild deprotection conditions NMR and deuteitum-labeling experiments provided valuable insight into the work kings and limitations of this reaction Although disguised as a 6-endo-dig cyclization, the reagents employed in the transformation play a direct role in bond-making and bond-breaking. thus changing die mode of addition to a 6-endo-trig cyclization This method can be used to construct an array of monocyclic and bicyclic scaffolds. many of which me found in well-known natural products (e g indolizidine, quinolizidine, and Stemona alkaloids).