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

Armstrong, David R. and Harris, Catriona M. M. and Kennedy, Alan R. and Liggat, John J. and McLellan, Ross and Mulvey, Robert E. and Urquhart, Matthew D. T. and Robertson, Stuart D. (2015) Developing lithium chemistry of 1,2-dihydropyridines : from kinetic intermediates to isolable characterized compounds. Chemistry - A European Journal, 21 (41). pp. 14410-14420. ISSN 1521-3765 (https://doi.org/10.1002/chem.201501880)

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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.

ORCID iDs

Armstrong, David R., Harris, Catriona M. M., Kennedy, Alan R. ORCID logoORCID: https://orcid.org/0000-0003-3652-6015, Liggat, John J. ORCID logoORCID: https://orcid.org/0000-0003-4460-5178, McLellan, Ross ORCID logoORCID: https://orcid.org/0000-0001-9700-0258, Mulvey, Robert E. ORCID logoORCID: https://orcid.org/0000-0002-1015-2564, Urquhart, Matthew D. T. and Robertson, Stuart D. ORCID logoORCID: https://orcid.org/0000-0002-9330-8770;
  • Item type:Article
    ID code:54112
    Dates:
    Date
    Event
    2015
    Published
    31 August 2015
    Published Online
    1 July 2015
    Accepted
    Notes:This is the peer reviewed version of the following article: Armstrong, D. R., Harris, C. M. M., Kennedy, A. R., Liggat, J. J., McLellan, R., Mulvey, R. E., ... Robertson, S. D. (2015). Developing lithium chemistry of 1,2-dihydropyridines: from kinetic intermediates to isolable characterized compounds. Chemistry - A European Journal, which has been published in final form at http://dx.doi.org/10.1002/chem.201501880. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:31 Aug 2015 09:10
    Last modified:21 Nov 2024 01:10
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/54112
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