Overview of Carbanion Dynamics and Electrophilic Substitutions in Chiral Organolithium Compounds

Gawley, Robert E.

doi:10.1002/9783906390628.ch3

Cited by 36 publications

(13 citation statements)

References 127 publications

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“…These compounds have low inversion barrier (~15 kcal/mol) and much effort has therefore been carried out to increase their stability toward racemization. Despite of all research devote to this field, understanding the origin of configuration stability and the mechanism of inversion of the organolithiums are still unclear. In the so‐called “conducted‐tour” mechanism, the lithium ion travels (guided by the adjacent heteroatom) from one side of the enantiotopic carbanion to the other during the inversion in a concerted manner.…”

Section: Resultsmentioning

confidence: 99%

Intramolecular carbolithiation‐cyclization‐electrophilic substitution: solvent effect and mechanistic study

Rodríguez

Nudelman

2013

J of Physical Organic Chem

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The intramolecular carbolithiation‐cyclization‐electrophilic substitution sequence proves to be a promising strategy for synthetic organic chemists. Our current research in this area focuses on the one‐pot halogen/lithium exchange of 2‐bromophenyl‐3‐phenylprop‐2‐enyl ether, followed by intramolecular carbolithiation, and trapping of the new lithiated cyclic intermediate by several electrophiles, affording 3‐substituted 2,3‐dihydrobenzofurans with some diastereoselectivity. Within this context, a study on the product distribution solvent dependence was carried out using different types of solvents, namely: polar coordinating, polar non‐coordinating, and non‐polar solvents. The results show that the coordinating features of the solvent affect specially the carbolithiation step, whereas the halogen/lithium exchange seems to be barely affected. Theoretical calculations were carried out to investigate the unexpected diastereoselectivity of the tandem reaction, where two stereocenters are generated. Insights gained from our mechanistic investigations enabled us to propose an inversion of configuration at the lithiated intermediate prior to the reaction, being the electrophile the likely cause for the observed distereoselectivity. Copyright © 2013 John Wiley & Sons, Ltd.

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Section: Resultsmentioning

confidence: 99%

Intramolecular carbolithiation‐cyclization‐electrophilic substitution: solvent effect and mechanistic study

Rodríguez

Nudelman

2013

J of Physical Organic Chem

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“…Intercepting the lithiated nitrile derived from 12a with the heteroatom electrophiles diphenyl disulfide, S -phenyl benzenesulfonothioate, 2-chloro-2-fluoro-2-phenylacetonitrile (Table , entries 1–3), and primary alkyl halides (Table , entries 4, 5, and 8) proceeded with high diastereoselectivity. Diastereoselective alkylations with BnBr and cyclopropylmethyl iodide (Table , entries 5 and 8) implicate alkylation via S N 2 displacement rather than through single electron transfer processes . Alkylation of 12a with isopropyl iodide, a secondary electrophile, was reasonably efficient but not selective (Table , entry 11).…”

Section: Resultsmentioning

confidence: 99%

Electrophile-Dependent Alkylations of Lithiated 4-Alkoxyalk-4-enenitriles

Pitta¹,

Steward

Fleming

2018

J. Org. Chem.

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Alkylations of acyclic, lithiated 4-alkoxyalk-4-enenitriles are highly diastereoselective with an unusual electrophile-dependent preference. Alkyl halides, sulfur, chlorine, and acyl cyanide electrophiles intercept a series of lithiated 4-alkoxyalk-4-enenitriles to install contiguous tertiary-quaternary stereocenters with high diastereoselectivity, whereas acylations with ester and carbonate electrophiles are modestly selective. The diastereoselectivity is consistent with electrophilic attack on the most accessible face of the lithated nitrile for most electrophiles except ester and carbonate electrophiles, which likely precoordinate the lithiated nitrile before acylation. Intercepting the lithiated 4-alkoxyalk-4-enenitriles with a range of electrophiles provide insight into the criteria for otherwise challenging diastereoselective alkylations and acylations of acyclic nitriles.

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“…On deuteration, the appearance of the multiplet due to H-3 at the carbinol carbon changed from a triplet of triplets ( 3 J = 6.6 and 3.9 Hz) for 12 to a triplet of doublets ( 3 J = 6.6 and 3.9 Hz) for cis - 13a , indicating the loss of a 3.9 Hz coupling, corresponding to loss of a proton cis to the alcohol. These observations prompted an investigation into the stereoselectivity of the lithiation and electrophile trapping steps, using cis - 13a and the inverted deuterium adduct trans - 13a . The latter was synthesized by inversion of the alcohol in cis - 13a through acetate displacement of the derived triflate 16 to give acetate 17 , followed by deacetylation (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

α-Lithiation–Electrophile Trapping of N-Thiopivaloylazetidin-3-ol: Stereoselective Synthesis of 2-Substituted 3-Hydroxyazetidines

2013

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α-Lithiation of N-thiopivaloylazetidin-3-ol and subsequent electrophile trapping provides access to a range of 2-substituted 3-hydroxyazetidines with generally good trans-diastereoselectivity, aside from deuteration, which gives the cis-diastereoisomer. Deuterium labeling studies indicate that the initial α-deprotonation occurs preferentially, but not exclusively, in a trans-selective manner. These studies also suggest that the stereochemical outcome of the electrophile trapping depends on the electrophile used but is independent of which α-proton (cis or trans to the hydroxyl group) is initially removed.

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Overview of Carbanion Dynamics and Electrophilic Substitutions in Chiral Organolithium Compounds

Cited by 36 publications

References 127 publications

Intramolecular carbolithiation‐cyclization‐electrophilic substitution: solvent effect and mechanistic study

Intramolecular carbolithiation‐cyclization‐electrophilic substitution: solvent effect and mechanistic study

Electrophile-Dependent Alkylations of Lithiated 4-Alkoxyalk-4-enenitriles

α-Lithiation–Electrophile Trapping of N-Thiopivaloylazetidin-3-ol: Stereoselective Synthesis of 2-Substituted 3-Hydroxyazetidines

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