Intermolecular and intramolecular (4+3) cycloadditions of oxetanyl and azetidinyl enolsilanes

Abstract

In this thesis, we described intermolecular (4 + 3) cycloadditions involved oxetanyl and azetidinyl enolsilanes, and intramolecular ones of furan-tethered oxetanyl enolsilanes. Initially, we introduced methodologies for synthesizing 2-acyl oxetanes and azetidines, which were the precursors of the corresponding enolsilanes. An efficient two-step synthetic route to 2-acyl oxetanes was developed by using dithianes and tosyl aldehydes. Other alkylated 2-acyl oxa-heterocycles were successfully synthesized via oxetanyl Weinreb amides and radical α-hydroxylation reactions. For 2-acyl azetidines, we optimized classic synthetic methods and used N-Bn Weinreb amides and N-Boc substrates, enabling the construction of a variety of N-functionalized 2-acyl azetidines. Subsequently, we studied the reactivity of oxetanyl and azetidinyl enolsilanes in intermolecular (4 + 3) cycloaddition reactions with dienes. Unsubstituted oxetanyl and azetidinyl enolsilanes showed limited reactivity, while alkylated ones provided cycloadducts in good yields. Further mechanism investigation showed that the transition states is stabilized by the substitutions on the enolsilanes, thus enhancing the reactivity albeit forming a cationic intermediate. Therefore, enantiomerically enriched substrates could not transfer the chiral information efficiently. Finally, the thesis explores the intramolecular (4 + 3) cycloaddition reactions of furan-tethered oxetanyl enolsilanes. We synthesized geminally- and vicinally-tethered oxetanyl enolsilanes, overcoming synthetic challenges and optimizing reaction conditions. Despite the reduced ring strain and increased steric hindrance compared to their epoxy analogs, the reactions proceeded successfully. The cycloadditions of geminally-tethered substrates were found to proceed in decent yields. For vicinally-tethered substrates, it was found that only “cis”-enolsilanes could undergo cycloadditions, while “trans”-enolsilanes would only desilylate. In addition, alkyl substitutions on “cis”-enolsilanes would promote cycloadditions efficiently. This research presents the first examples of (4 + 3) cycloadditions involving oxetanes and azetidines. It broadens the application of oxetanes and azetidines in cycloaddition chemistry and provides new synthetic methodologies for their preparations.