Novel Hybrid Prins/Aza‐Prins Oxocarbenium/N‐Acyliminium Cascade: Expedient Access to Complex Indolizidines

Heavy silyl enol ethers (mostly TIPS and TBS) combine with cyclic N‐alkenyl N‐acyliminium salts generated in situ from their N,O‐acetal precursors, to furnish highly functionalized indolizidines through an unprecedented double Mukaiyama–Mannich–Prins cascade transformation. This novel cascade annulation process demonstrates a promising scope, and takes place mostly catalytically with interesting stereocontrol. Furthermore, an appealing facet of this chemistry is emphasized with a bicatalytic approach by which the Mannich–Prins cascade follows a Ru‐catalyzed N‐allylamide to N‐(E)‐propenyl isomerization of the aminal counterpart in a one‐pot operation. Follow the leader: An efficient and highly diastereoselective oxocarbenium/N‐Acyliminium ion triggered cascade reaction was developped leading to the one‐step formation of densely functionalized indolizidine derivatives. This novel Mukaiyama–Mannich–Prins sequence, which proceeds under TIPS‐OTf catalysis, can be combined with a prior Ru‐catalyzed N‐allyl to N‐propenyl isomerization in a one‐pot fashion. This variant improves sustainability while revealing fresh opportunities in multicatalytic methodologies.