Developing lithium chemistry of 1,2-dihydropyridines: from kinetic intermediates to isolable characterized compounds

David R. Armstrong, Catriona M. M. Harris, Alan R. Kennedy, John J. Liggat, Ross McLellan, Robert E. Mulvey, Matthew D. T. Urquhart, Stuart D. Robertson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Generally considered kinetic intermediates in addition reactions of alkyllithiums to pyridine, 1-lithio-2-alkyl-1,2-dihydropyridines have been rarely isolated or characterized. This study develops their "isolated" chemistry. By a unique stoichiometric (that is 1:1, alkyllithium:pyridine ratios) synthetic approach using tridentate donors we show it is possible to stabilize and hence crystallize monomeric complexes where alkyl is tert-butyl. Theoretical calculations probing the donor-free parent tert-butyl species reveal 12 energetically similar stereoisomers in two distinct cyclotrimeric (LiN)3 conformations. NMR studies (including DOSY spectra) and thermal volatility analysis compare new sec-butyl and iso-butyl isomers showing the former is a hexane soluble efficient hydrolithiation agent converting benzophenone to lithium diphenylmethoxide. Emphasizing the criticalness of stoichiometry, reaction of nBuLi/Me6TREN with two equivalents of pyridine results in non-alkylated 1-lithio-1,4-dihydropyridine·Me6TREN and 2-n-butylpyridine, implying mechanistically the kinetic 1,2-n-butyl intermediate hydrolithiates the second pyridine.
LanguageEnglish
Pages14410-14420
Number of pages11
JournalChemistry - A European Journal
Volume21
Issue number41
Early online date31 Aug 2015
DOIs
Publication statusPublished - 2015

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Dihydropyridines
Lithium
Pyridine
Kinetics
Addition reactions
Stereoisomerism
Hexanes
Hexane
Stoichiometry
Isomers
Thermoanalysis
Conformations
Nuclear magnetic resonance
pyridine
tris(2-(dimethylamino)ethyl)amine

Keywords

  • hydrides
  • lithium
  • nucleophilic addition
  • pyridine
  • structure elucidation

Cite this

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title = "Developing lithium chemistry of 1,2-dihydropyridines: from kinetic intermediates to isolable characterized compounds",
abstract = "Generally considered kinetic intermediates in addition reactions of alkyllithiums to pyridine, 1-lithio-2-alkyl-1,2-dihydropyridines have been rarely isolated or characterized. This study develops their {"}isolated{"} chemistry. By a unique stoichiometric (that is 1:1, alkyllithium:pyridine ratios) synthetic approach using tridentate donors we show it is possible to stabilize and hence crystallize monomeric complexes where alkyl is tert-butyl. Theoretical calculations probing the donor-free parent tert-butyl species reveal 12 energetically similar stereoisomers in two distinct cyclotrimeric (LiN)3 conformations. NMR studies (including DOSY spectra) and thermal volatility analysis compare new sec-butyl and iso-butyl isomers showing the former is a hexane soluble efficient hydrolithiation agent converting benzophenone to lithium diphenylmethoxide. Emphasizing the criticalness of stoichiometry, reaction of nBuLi/Me6TREN with two equivalents of pyridine results in non-alkylated 1-lithio-1,4-dihydropyridine·Me6TREN and 2-n-butylpyridine, implying mechanistically the kinetic 1,2-n-butyl intermediate hydrolithiates the second pyridine.",
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author = "Armstrong, {David R.} and Harris, {Catriona M. M.} and Kennedy, {Alan R.} and Liggat, {John J.} and Ross McLellan and Mulvey, {Robert E.} and Urquhart, {Matthew D. T.} and Robertson, {Stuart D.}",
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Developing lithium chemistry of 1,2-dihydropyridines : from kinetic intermediates to isolable characterized compounds. / Armstrong, David R.; Harris, Catriona M. M.; Kennedy, Alan R.; Liggat, John J.; McLellan, Ross; Mulvey, Robert E.; Urquhart, Matthew D. T.; Robertson, Stuart D.

In: Chemistry - A European Journal, Vol. 21, No. 41, 2015, p. 14410-14420.

Research output: Contribution to journalArticle

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AU - Urquhart, Matthew D. T.

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