Tandem Prins Strategy for the Synthesis of Spiropyrrolidine and Spiropiperidine Derivatives

Reddy, B. V. Subba; Yarlagadda, Suresh; Reddy, Cheruku Ravindra; Reddy, M. M.; Sridhar, B.; Satyanarayana, Dayaka; Jagadeesh, B.

doi:10.1002/ejoc.201500215

Cited by 15 publications

(9 citation statements)

References 32 publications

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“…Reddy and co-workers presented one example of the synthesis of 3-spiropiperidines with a Prins/ene cascade process. 30…”

Section: -Spiropiperidine Formation On a Preformed Piperidine Ringmentioning

confidence: 99%

“…Wang demonstrated the use of substituted fulvenes 85 as 6π dipolarophiles in a [6+3] cycloaddition with azomethine ylides generated from precursor 86 (Scheme 25). 30 Catalysed by Cu(I) with chiral ligand 87, the enantioselective reaction allowed the synthesis of 3-spiropiperidines 88 in good to high yields with high enantioselectivity. The reaction was reported with a range of fulvene derivatives which consequently accessed different sized carbocyclic spirocycles.…”

Section: Scheme 22 Tandem Prins Cyclisation Strategy For the Synthesimentioning

confidence: 99%

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Strategies for the synthesis of spiropiperidines – a review of the last 10 years

2018

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Spiropiperidines have gained in popularity in drug discovery programmes as medicinal chemists explore new areas of three-dimensional chemical space. This review focuses on the methodology used for the construction of 2-, 3- and 4-spiropiperidines, covering the literature from the last 10 years. It classifies the synthesis of each of the types of spiropiperidine by synthetic strategy: the formation of the spiro-ring on a preformed piperidine ring, and the formation of the piperidine ring on a preformed carbo- or heterocyclic ring. While 3- and 4-spiropiperidines are predominantly synthesised for drug discovery projects, 2-spiropiperidines are synthesised en route to natural products. The lack of 2-spiropiperidines in drug discovery is presumably due to limited general procedures for their synthesis.

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“…Reddy and co-workers presented one example of the synthesis of 3-spiropiperidines with a Prins/ene cascade process. 30…”

Section: -Spiropiperidine Formation On a Preformed Piperidine Ringmentioning

confidence: 99%

Section: Scheme 22 Tandem Prins Cyclisation Strategy For the Synthesimentioning

confidence: 99%

Strategies for the synthesis of spiropiperidines – a review of the last 10 years

2018

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“…Cyclopropanecarbaldehyde is an apparently problematic aldehyde due to presence of an acid-sensitive motif, 55 but to our delight it reacted properly to yield 5k in 63% yield (entry 7). Cyclohexanone was also tested as carbonylic compound in the EAP cyclization to study the obtaining of spirotetrahydropyrans, 56 Afterwards, benzaldehyde (entry 9) and several electron-poor aromatic aldehydes (entries 10-12) were evaluated. An electron-rich aromatic aldehyde carrying a MeO group in para-position also provided a similar good yield (entry 13), though a drop in the yield was observed when the same donor group was located in the orto-position (entry 14).…”

Section: Scheme 3 Synthesis Of Bicycles With Different Stereochemicamentioning

confidence: 99%

Stereoselective Synthesis of Highly Substituted Tetrahydropyrans through an Evans Aldol–Prins Strategy

et al. 2018

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A direct and general method for the synthesis of naturally occurring 2,3,4,5,6-pentasubstituted tetrahydropyrans has been developed, employing β,γ-unsaturated N-acyl oxazolidin-2-ones as key starting materials. The combination of the Evans aldol addition and the Prins cyclization allowed the diastereoselective and efficient generation of the desired oxacycles in two fashions: a one-pot Evans aldol-Prins protocol, in which five new σ bonds and five contiguous stereocenters were straightforwardly generated, and a two-step version, which additionally permitted the isolation of β,γ-unsaturated alcohol precursors bearing an N-acyl oxazolidin-2-one in the α position. From these alcohols were also obtained halogenated pentasubstituted tetrahydropyrans as well as 2,3,4,5-tetrasubstituted tetrahydrofurans, shedding light on the mechanism of the process. Computational studies were consistent with the experimental findings, and this innovative Evans aldol-Prins strategy was performed for the preparation of a battery of more than 30 densely substituted tetrahydropyrans, unprecedentedly fused to a 1,3-oxazinane-2,4-dione ring, both in a racemic fashion and in an enantiomeric fashion. These novel molecules were successfully submitted to several transformations to permit simple access to a variety of differently functionalized tetrahydropyrans. Most of these unique molecules were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria and the yeast Candida albicans, and some structure-activity relationships were established.

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“…Spiropyrrolidine and spiropiperidine scaffolds were synthesized by tandem Prins spirocyclization through treatment of aldehydes 26 with 3‐[(3‐methylbut‐2‐enylamino)methyl]but‐3‐en‐1‐ol ( 25 ; Scheme ) and 3‐[(4‐methylpent‐3‐enylamino)methyl]but‐3‐en‐1‐ol ( 29 ; Scheme ), respectively, in the presence of TMSOTf …”

Section: Domino Prins Reaction: Bicyclizationmentioning

confidence: 99%

Recent Advances in Prins Spirocyclization

et al. 2017

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The classical Prins cyclization has been one of the most intensively studied reactions during the last two decades, and it has found many applications in key steps of natural product syntheses, especially for products containing tetrahydropyran motifs and related structures in their core skeletons. The application of this reaction to the synthesis of spirocylic networks has made substantial progress recently. Spiro motifs are found in many natural products with promising biorelevance and are increasingly being incorporated in drug candidates. Further, various spirocyclic chiral ligands have shown promising efficiency in asymmetric synthesis. Here a compilation of recent spiroannulation reactions by Prins cyclization is presented, focusing on the scope and versatility of this method.

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Tandem Prins Strategy for the Synthesis of Spiropyrrolidine and Spiropiperidine Derivatives

Cited by 15 publications

References 32 publications

Strategies for the synthesis of spiropiperidines – a review of the last 10 years

Strategies for the synthesis of spiropiperidines – a review of the last 10 years

Stereoselective Synthesis of Highly Substituted Tetrahydropyrans through an Evans Aldol–Prins Strategy

Recent Advances in Prins Spirocyclization

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