334. Quinolizines. Part III. The synthesis of 1-alkyl- and 1-aryl-quinolizinium salts

Four decades ago, we noted that for delocalized carbanions and enols the protonation transition state is close to sp(2) hybridized and that, as a consequence, under kinetic control protonation takes place from the less hindered approach, most often with formation of the less stable of two possible stereoisomers. The initial report was followed by an extensive series of examples. Nevertheless, a major question remained, namely whether it was possible to deliver the proton to the more hindered face of such a species using intramolecular proton transfer. To this end, silyl ether precursors to the enols of 3-benzoyl-endo-6-phenyl-exo-6-pyridylbicyclo[3.1.0]hexane and its endo-6-pyridyl-exo-6-phenyl stereoisomer were synthesized. The corresponding enols were generated with fluoride anion. The endo-phenyl enol stereoisomers, on kinetic protonation, led stereoselectively to the endo-3-benzoyl product resulting from the less hindered protonation. In stark contrast, the endo-6-pyridyl enol isomer led stereoselectively to the exo-3-benzoyl ketone by intramolecular proton delivery. However, the kinetic orders of the stereochemistries differ; the intramolecular process requires additional proton donor molecules. The log of the ratio of the two stereochemistries is linear with the log of the proton donor concentration with the slope giving the difference in kinetic orders. An aromatic cyclic 14 electron Hückel transition state is proposed. Additionally, the roles of acyl, nitro and cyano delocalizing groups were analyzed with ab initio computations.

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“…mp 242−244 °C); TLC R f 0.30 (hexane−ethyl acetate 10:1). The NMR spectrum is in agreement with the literature data …”

Section: Methodssupporting

confidence: 90%

“…(3) 1,2-Di(pyridyl-2)-1,2-diphenylethane as colorless crystals: 0.40 g (24%); mp 242−244 °C (lit . mp 242−244 °C); TLC R f 0.30 (hexane−ethyl acetate 10:1).…”

Section: Methodsmentioning

confidence: 99%

Control of the Stereochemistry of Kinetic Protonation: Intramolecular Proton Delivery¹^,²

Zimmerman

Ignatchenko

1999

J. Org. Chem.

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“…Attempts to improve this yield using the second generation Grubbs catalyst ( G-II ) and Hoveyda−Grubbs catalyst ( H-G , see below in Table ) were unsuccessful. It is noteworthy that this is the first route that allows the synthesis of the parent 1,2-dihydroquinolizinium system in a synthetically useful overall yield (18%), and this enabled the first full characterization of this system as the previously reported synthesis of the 1,2-dihydroquinolizinium picrate gave a very poor yield (overall yield not given) . Finally, the oxidation of 8a under the optimized conditions used for 10a gave 7a in almost quantitative yield.…”

Section: Resultsmentioning

confidence: 82%

“…While most of the 3,4-dihydroquinolizinium derivatives 10 synthesized here are unknown, most of the corresponding quinolizinium salts obtained from their oxidation have been reported previously. It is worth noting the preparation for the first time of the 1,2-dimethylquinolizinium salt 7q with an overall yield of 10% (entry 11) and the significant improvement achieved for 1-bromo-, 3-bromo-, and 1-phenylquinolizinium salts 7b (29 vs 2%), 7d (17 vs 9%), and 7i (15 vs 0.04%) (entries 2, 3, and 6, respectively). By contrast, 3-methyl-, 2-methyl-, and 2-phenylquinolizinium triflates 7e , 7l , and 7m were obtained in lower yields than those previously reported (entries 4, 9, and 10, respectively).…”

Section: Resultsmentioning

confidence: 99%

Ring-Closing Metathesis Reactions on Azinium Salts: Straightforward Access to Quinolizinium Cations and Their Dihydro Derivatives

et al. 2009

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The ring-closing metathesis reaction of 1-butenyl-2-vinylpyridinium salts and 2-butenyl-1-vinylpyridinium salts using Grubbs second generation and Hoveyda-Grubbs catalysts proved to be an efficient approach to 3,4-dihydro- and 1,2-dihydroquinolizinium salts and the corresponding quinolizinium derivatives by an improved thermal oxidation in the presence of Pd/C without solvent. A comparative study showed that the quinolizinium system was obtained in better yields through the 3,4-dihydroquinolizinium route, thus allowing the synthesis of quinolizinium derivatives or improvements in the yields of some examples reported previously.

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Heterocycles Containing a Ring‐Junction Nitrogen

Vaquero

Alvárez‐Builla

2011

Modern Heterocyclic Chemistry

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334. Quinolizines. Part III. The synthesis of 1-alkyl- and 1-aryl-quinolizinium salts

Cited by 9 publications

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Control of the Stereochemistry of Kinetic Protonation: Intramolecular Proton Delivery¹^,²

Control of the Stereochemistry of Kinetic Protonation: Intramolecular Proton Delivery¹^,²

Ring-Closing Metathesis Reactions on Azinium Salts: Straightforward Access to Quinolizinium Cations and Their Dihydro Derivatives

Heterocycles Containing a Ring‐Junction Nitrogen

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334. Quinolizines. Part III. The synthesis of 1-alkyl- and 1-aryl-quinolizinium salts

Cited by 9 publications

References 0 publications

Control of the Stereochemistry of Kinetic Protonation: Intramolecular Proton Delivery1,2

Control of the Stereochemistry of Kinetic Protonation: Intramolecular Proton Delivery1,2

Ring-Closing Metathesis Reactions on Azinium Salts: Straightforward Access to Quinolizinium Cations and Their Dihydro Derivatives

Heterocycles Containing a Ring‐Junction Nitrogen

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Product

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Control of the Stereochemistry of Kinetic Protonation: Intramolecular Proton Delivery¹^,²

Control of the Stereochemistry of Kinetic Protonation: Intramolecular Proton Delivery¹^,²