Asymmetric Deprotonation with Alkyllithium–(−)‐Sparteine

Hoppe, Dieter; Christoph, Guido

doi:10.1002/9780470682531.pat0313

Cited by 2 publications

(3 citation statements)

References 392 publications

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“…The synthesis of enantiomerically or diastereomerically enriched alkyllithium compounds, in which the metalated carbon atom is a stereogenic center, has been studied vigorously for more than 20 years . In general, they have been synthesized in deprotonation reactions employing strong alkyllithium bases such as butyllithium.…”

Section: Introductionmentioning

confidence: 99%

“…In general, they have been synthesized in deprotonation reactions employing strong alkyllithium bases such as butyllithium. Although the configuration of the metalated stereogenic carbon atom is stable only at low temperatures (−78 °C) for most of these compounds, Hoppe et al and Strohmann et al were able to characterize key compounds that proved to have a stable configuration at higher temperatures for at least minutes. , A frequently proposed mechanism for the racemization implies a planar sp 2 -hybridized intermediate carbanion ( C ), which proceeds via a separated ion pair ( B and ent - B ) in Scheme .…”

Section: Introductionmentioning

confidence: 99%

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Structure/Reactivity Studies on an α-Lithiated Benzylsilane: Chemical Interpretation of Experimental Charge Density

et al. 2008

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Modern organic synthesis (e.g., of natural products) is virtually impossible without employment of enantiomerically enriched compounds. In many cases, alkyllithium compounds are key intermediates for the generation of these stereogenic substances. In recent years, the lithiated carbon atom in silicon-substituted benzyllithium compounds has become a focus of interest because it is possible to maintain its stereogenic information. Starting from a highly enantiomerically enriched benzylsilane, (R,S)-2 x quinuclidine could be obtained, and the absolute configuration at the metalated carbon atom was determined by X-ray diffraction analysis. In solution, a quartet was found in the (13)C NMR spectrum for the metalated carbon atom because of coupling between carbon and lithium, indicating a fixed lithium carbon contact at room temperature. After reaction of (R,S)-2 x quinuclidine with trimethylchlorostannane, the trapped product (S,S)-4 was obtained with a dr > or = 98:2 with inversion of the configuration at the metalated carbon. Multipole refinement against high-resolution diffraction data and subsequent topological analysis of the benchmark system (R,S)-2 x quinuclidine provide insight in the electronic situation and thus the observed stereochemical course of the transformations. Surprisingly, the negative charge generated at the carbanion hardly couples into the phenyl ring. The neighboring silicon atom counterbalances this charge by a pronounced positive charge. Therefore, the alpha-effect of the silicon atom is caused not just by a polarization of the electron density but also by an electrostatic bond reinforcement. Furthermore, the experimentally determined electrostatic potential unequivocally explains the observed back side attack of an electrophile under inversion of the stereogenic center with high diastereomeric ratios.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structure/Reactivity Studies on an α-Lithiated Benzylsilane: Chemical Interpretation of Experimental Charge Density

et al. 2008

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“…A recent review cites several examples of quantitative studies on the inversion dynamics of tertiary benzylic organolithiums where free energy barriers ranging from 9 to 14 kcal/mol at −80 °C were measured . Such low barriers indicate a high degree of configurational instability of benzylic organolithiums (half-life for inversion ≤10 min), which provides a challenge to stereoselective synthesis . Approaches to lithiation/alkylation sequences at benzylic sites often employ chiral auxiliaries or chiral ligands such as (−)-sparteine or a bisoxazoline , to impose configurational stability in the ground state or diastereomeric bias in the transition state, thus leading to diastereomerically or enantiomerically enriched products.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Applications and Inversion Dynamics of Configurationally Stable 2-Lithio-2-arylpyrrolidines and -piperidines

2012

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In diethyl ether, N-Boc-2-lithio-2-arylpiperidines have been found to be configurationally stable at −80 °C whereas N-Boc-2-lithio-2-arylpyrrolidines are configurationally stable at −60 °C. Several tertiary benzylic carbanions derived from enantioenriched 2-aryl heterocycles have been successfully alkylated or acylated with little to no loss of enantiopurity. The scope of the reactions has been explored. The enantiomerization dynamics of N-Boc-2-lithio-2-phenylpyrrolidine and N-Boc-2-lithio-2-phenylpiperidine have been studied in the presence of different solvents and achiral ligands.

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Asymmetric Deprotonation with Alkyllithium–(−)‐Sparteine

Cited by 2 publications

References 392 publications

Structure/Reactivity Studies on an α-Lithiated Benzylsilane: Chemical Interpretation of Experimental Charge Density

Structure/Reactivity Studies on an α-Lithiated Benzylsilane: Chemical Interpretation of Experimental Charge Density

Synthetic Applications and Inversion Dynamics of Configurationally Stable 2-Lithio-2-arylpyrrolidines and -piperidines

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