Asymmetric N-Acyliminium Cyclization as an Approach to Heterocyclic Natural Product Synthesis

Abstract

Dedicated to Prof. Wilfred R. Chan for his inspiration and dedication to natural products chemistry. This paper describes the development of a highly stereoselective N-acyliminium cyclization protocol for the construction of a range of non-racemic heterocyclic templates. Due to the nature of this review, we have focused primarily on developments made within our own research group, but have included relevant and noteworthy contributions in the same area from others, most notably the research groups of Amat, Bosch and Lete. As a result, we apologize in advance for the omission of much excellent work carried out by many other talented researchers in this field.

Synthesis of Bridged Heterocycles via Sequential 1,4- and 1,2-Addition Reactions to α,β-Unsaturated N-Acyliminium Ions: Mechanistic and Computational Studies

“…N -Acyliminium ions are well recognized as important reactive intermediates in C–C and C–heteroatom bond forming reactions . Both intramolecular − , and intermolecular ,,, variants have been extensively developed, with the aforementioned versions providing synthetic access to novel polycyclic, spirocyclic, and bridged heterocyclic ring structures.…”

Lewis Acid-Catalyzed Carbofunctionalization of Uncommon C,N-Diacyliminium Ions: Controlling Regio- and Enantioselectivity

“…4 Their elegant use as key intermediates in natural product synthesis has also been demonstrated. 5 The genus of N-acyliminium ions can be subdivided into several classes (Scheme 1a). In addition to the prototypical mono-Nacylated iminium ions, the closely related N-alkoxycarbonyl-, N-carbamoyl-, N-phosphoryl, and N-sulfonyliminium ions have iteratively been introduced.…”

Total Synthesis of (+)-3-Demethoxyerythratidinone and (+)-Erysotramidine via the Oxidative Amidation of a Phenol

“…Such entities are found, for example, at the level of the spiro carbon of aromatic Erythrina alkaloids such as (+)-3-demethoxyerythridatinone, 1 , and (+)-erysotramidine, 2 (Figure ). Past syntheses of these alkaloids have addressed the problem by deriving key portions of the targets from chiral educts (L-DOPA, malic acid, certain lactams, tartaric acid, or other materials obtained by resolution); by desymmetrization of a meso -imide with a chiral base; by relaying axial chirality to the spiro center; or by nucleophilic addition of organometallic agents to Ellman sulfinylimines derived from quinone monoketals …”