Trianion Synthon Approach to Spirocyclic Heterocycles

Perry, Matthew A.; Hill, R. R.; Rychnovsky, Scott D.

doi:10.1021/ol400788q

Cited by 27 publications

(22 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2013, Perry and co-workers described a reductive cyclization of α-amino nitrile derivatives mediated by lithium di- tert -butyl biphenylide (LiDBB), which were made by double alkylation of aminoacetonitrile derivatives (method B). 13 In 2016, Um et al developed an intermolecular Cu-catalyzed carboamination of cyclic vinylarenes with potassium N -carbamoyl-β-aminoethyltrifluoroborate (method C). 20 At the same time, Yu et al applied the gold-catalyzed tandem reductive cycloisomerization of cyclic homopropargyl sulfonamides for the synthesis of N -tosyl-protected compound 1c (method D).…”

Section: Introductionmentioning

confidence: 99%

Scalable Synthesis of Biologically Relevant Spirocyclic Pyrrolidines

et al. 2019

View full text Add to dashboard Cite

Synthetic approaches toward multigram preparation of spirocyclic α,α-disubstituted pyrrolidines from readily available starting materials are discussed. It was shown that although a number of synthetic methodologies have been known to date, many of the title compounds remain hardly accessible. The most appropriate literature method (which relied on reaction of imines and allyl magnesium halide, followed by bromocyclization) was identified and optimized. It was found that the method is most fruitful for simple non-functionalized substrates. Two novel approaches based on the Sakurai or Petasis reactions of cyclic ketones, followed by hydroboration–oxidation at the allyl moiety thus introduced, were elaborated. The latter method had the largest scope and was beneficial for the substrates containing organosulfur or protected amino functions. For the synthesis of 4-azaspiro[2.4]heptane, an alternative synthetic scheme commencing from tert -butyl cyclopropanecarboxylate (instead of the corresponding ketone) was developed. It was shown that the whole set of the methodologies developed can be used for the synthesis of various spirocyclic α,α-disubstituted pyrrolidines—advanced building blocks of potential importance to medicinal and agrochemistry—at up to a 100 g scale.

show abstract

Section: Introductionmentioning

confidence: 99%

Scalable Synthesis of Biologically Relevant Spirocyclic Pyrrolidines

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Rychnovsky's approach to the synthesis of spirocyclic heterocycles was reversed in later studies, forming the carbocyclic ring prior to the heterocyclic ring. 14…”

Section: Methodsmentioning

confidence: 99%

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

2018

View full text Add to dashboard Cite

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.

show abstract

“…As a consequence, there is considerable interest in the development of synthetic routes to access small chiral saturated rings including cyclopropanes,2 oxetanes3–4 and azetidines,5 as well as benzofused heterocyclic systems, such as indolines6 and dihydrobenzofurans 7. In addition, the incorporation of these motifs into spirocyclic frameworks can lead to increased molecular complexity whilst maintaining a relatively low molecular weight 4, 8. Such systems can potentially provide a structurally rigid three-dimensional core, which can be functionalised at several sites to provide a library of drug-like compounds.…”

Section: Introductionmentioning

confidence: 99%

Rapid Assembly of Functionalised Spirocyclic Indolines by Palladium‐Catalysed Dearomatising Diallylation of Indoles with Allyl Acetate

Dhankher

Benhamou

Sheppard

2014

Chemistry A European J

View full text Add to dashboard Cite

Herein, we report the application of allyl acetate to the palladium-catalysed dearomatising diallylation of indoles. The reaction can be carried out by using a readily available palladium catalyst at room temperature, and can be applied to a wide range of substituted indoles to provide access to the corresponding 3,3-diallylindolinines. These compounds are versatile synthetic intermediates that readily undergo Ugi reactions or proline-catalysed asymmetric Mannich reactions. Alternatively, acylation of the 3,3-diallylindolinines with an acid chloride or a chloroformate, followed by treatment with aluminium chloride, enables 2,3-diallylindoles to be prepared. By using ring-closing metathesis, functionalised spirocyclic indoline scaffolds can be accessed from the Ugi products, and a dihydrocarbazole can be prepared from the corresponding 2,3-diallylindole.

show abstract

Trianion Synthon Approach to Spirocyclic Heterocycles

Cited by 27 publications

References 30 publications

Scalable Synthesis of Biologically Relevant Spirocyclic Pyrrolidines

Scalable Synthesis of Biologically Relevant Spirocyclic Pyrrolidines

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

Rapid Assembly of Functionalised Spirocyclic Indolines by Palladium‐Catalysed Dearomatising Diallylation of Indoles with Allyl Acetate

Contact Info

Product

Resources

About