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

Abstract

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.

A Brønsted Acid‐Catalyzed Michael Addition/Cyclization Sequence for the Diastereoselective Assembly of Chroman‐Bridged Polycyclic Isoindolinones

“…[1f-g] As a consequence, the development of efficient methods for the construction of polycyclic isoindolinones has attracted considerable attention from the synthetic community. So far the existing synthetic methods for polycyclic isoindolinones mainly include dearomatization of indole derivatives, [2] cyclization of N-acyliminium ions, [3] functionalization of indole-derived hydroxylactams, [4] Diels-Alder reaction-inspired cyclization sequence, [5] photo-or electro-induced coupling of phthalimides, [6] and others. [7] However, these elegant approaches are mainly focused on the formation of fused polycyclic isoindolinones; in sharp contrast, the methods for the construction of bridged polycyclic isoindolinones have lagged far behind, and only two examples have been reported so far.…”

Cyclization Strategies Using Imide Derivatives for the Synthesis of Polycyclic Nitrogen‐Containing Compounds

“…Then, a Mannich reaction with silyl enol ether 20 afforded intermediate 21, which underwent an intramolecular enamine-type mediated Aldol reaction to produce a second N-acyliminium ion 22. Again, a Mannich reaction takes place involving silyl enol ether 20 to afford compound 23, typically in overall low or moderate diastereoselectivities [22] (Scheme 4).…”

"Syn-effect” in asymmetric vinylogous alkylation of 3-[4-(N-phthalimide)-but-2-enoyl]oxazolidinone

“…Some protocols are carried out under harsh reaction conditions, giving as reaction products mixtures of Z/E-enamides. [6][7][8][9][10][11][12][13][14] We report herein, the first asymmetric vinylogous alkylation of a chiral N-enoyl oxazolidinone, where the nitrogen atom is linked to the -unsaturated system as phthalimide group. This compound was treated under alkylation reaction conditions to give chiral Zenamides, -alkylated compounds bearing a double bond with a high Z-selectivity (> 98%).…”