Investigations of α-Siloxy−Epoxide Ring Expansions Forming 1-Azaspirocyclic Ketones

The construction of 1-azaspirocyclic cycloalkanones using a siloxy−epoxide semipinacol ring
expansion process was examined. Functionalized 1-azaspiro[5.5]undecan-7-ones (1-azaspirocyclic
cyclohexanones) proceeded in high chemical yields with complete diastereoselectivity using titanium
tetrachloride as the Lewis acid promoter. The formation of functionalized 6-azaspiro[5.4]-decan-1-ones (1-azaspirocyclic cyclopentanones) proceeded in high chemical yield with little diastereoselectivity. Modification of reaction parameters such as the Lewis acid promoter or the nature of
the silyl ether allowed for the preferential formation of either (“anti” or “syn” 1,2 alkyl shift)
diastereomeric product. An explanation for the different reactivity profiles between the cyclobutanol
silyl ethers and cyclopentanol silyl ethers is provided.