An Aza-Prins Cyclization Approach to Functionalized Indolizidines from 2-Allylpyrrolidines

Liu, Xiaoxi; McCormack, Michael P.; Waters, Stephen P.

doi:10.1021/ol302693u

Cited by 35 publications

(12 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reddy 20 , Saikia 21,22 , Overman 23 and Waters 24 have all prepared azabicyclic systems using a Prins or related cyclisation process, but have either started from an intact or commercial mono-cyclic system, 24 or have required the sequential formation and purification of the mono-cyclic precursors, followed by a second cyclisation process. 23 Thus the uniqueness and advantage of this approach in the one-pot double cyclisation, forming both rings in a single transformation.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Azabicycles via Cascade Aza-Prins Reactions: Accessing the Indolizidine and Quinolizidine Cores

et al. 2015

View full text Add to dashboard Cite

The first detailed study of intramolecular aza-Prins and aza-silyl-Prins reactions, starting from acyclic materials, are reported. The methods allow rapid and flexible access towards an array of [6,5] and [6,6] aza-bicycles, which form the core skeletons of various alkaloids. Based upon our findings on the aza-Prins and aza-silyl-Prins cyclisations, herein we present simple protocols for the intramolecular preparation of the azabicyclic cores of the indolizidines and quinolizidines using a one pot cascade process of N-acyliminium ion formation followed by aza-Prins cyclisation and either elimination or carbocation trapping. It is possible to introduce a range of different substituents into the heterocycles through a judicial choice of Lewis acid and solvent(s), with halo-, phenyl-and amido-substituted azabicyclic products all being accessed through these highly diastereoselective processes.2

show abstract

Section: Methodsmentioning

confidence: 99%

Synthesis of Azabicycles via Cascade Aza-Prins Reactions: Accessing the Indolizidine and Quinolizidine Cores

et al. 2015

View full text Add to dashboard Cite

show abstract

“…To achieve the indolizidine core, two approaches have been developed: aza‐Prins cyclization from allylpyrrolidines and an intramolecular aza‐silyl‐Prins cascade that can eventually afford even the quinolizidine skeleton. Waters's group described the synthesis of functionalized indolizidines from 2‐allylpyrrolidines 48 . The reactions between the endocyclic amine and either formaldehyde or highly activated aldehydes such as glyoxylate derivatives led to the formation of iminium ions 49 , which underwent nucleophilic attack from the embedded allyl substituent (Scheme ).…”

Section: Synthesis Of Natural Products and Bioactive Moleculesmentioning

confidence: 99%

The Aza‐Prins Reaction in the Synthesis of Natural Products and Analogues

et al. 2017

View full text Add to dashboard Cite

International audienceThe classical Prins cyclization reaction has been one of the most studied reactions during the last two decades and it has found many applications in key steps of natural product syntheses, especially for products containing pyran units and related structures in their core skeletons. The nitrogen-based version of the Prins reaction, aza-Prins cyclization, has found its own relevance in organic synthesis owing to the fact that it gives direct access to piperidines, which are even more widespread in natural products and in drugs. Even though the potential scope of the reaction is vast, and despite it having afforded significant progress in the synthesis of various azaheterocycles, its applications in the field of natural product synthesis is massively underdeveloped in comparison with the classical Prins reaction. A compilation of the applications of azaPrins cyclization in the preparation of natural products and selected analogues, especially compounds of potential biological interest, is presented, with emphasis placed on the key roles of this reaction in the total synthesis of these products

show abstract

“… 2 In many examples, an aldehyde was used as the substrate, and other carbonyl compounds such as 1,2-dicarbonyl compounds have been occasionally employed as the substrates. 3 , 4 …”

Section: Introductionmentioning

confidence: 99%

The Aza-Prins Reaction of 1,2-Dicarbonyl Compounds with 3-Vinyltetrahydroquinolines: Application to the Synthesis of Polycyclic Spirooxindole Derivatives

et al. 2021

View full text Add to dashboard Cite

The aza-Prins reaction of 6,7-dimethoxy-3-vinyl-1,2,3,4-tetrahydroquinoline ( 1 ) with 1,2-dicarbonyl compounds proceeded smoothly in the presence of HCl, and the corresponding tricyclic benzazocines were isolated in yields of 20–86%. The reaction proceeded in a stereoselective manner, and the formation of the 2,4- trans isomer was observed. The reaction of 1 with an enantiopure ketoester gave the corresponding tricyclic benzazocine as a mixture of diastereomers. The diastereomers were easily separated and converted to enantiopure tricyclic benzazocines. The synthesis of spirooxindole derivatives was achieved by the reaction of 1 with isatin derivatives.

show abstract

An Aza-Prins Cyclization Approach to Functionalized Indolizidines from 2-Allylpyrrolidines

Cited by 35 publications

References 30 publications

Synthesis of Azabicycles via Cascade Aza-Prins Reactions: Accessing the Indolizidine and Quinolizidine Cores

Synthesis of Azabicycles via Cascade Aza-Prins Reactions: Accessing the Indolizidine and Quinolizidine Cores

The Aza‐Prins Reaction in the Synthesis of Natural Products and Analogues

The Aza-Prins Reaction of 1,2-Dicarbonyl Compounds with 3-Vinyltetrahydroquinolines: Application to the Synthesis of Polycyclic Spirooxindole Derivatives

Contact Info

Product

Resources

About