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

Chemistry : a European Journal
David R ArmstrongStuart D Robertson

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 spectroscopy 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/Me6 TREN with two equivalents of pyridine results in non-alkylated 1-lithio-1,4-dihydropyridine⋅Me6 TREN and 2-n-butylpyridine, implying mechanistically the kinetic 1,2-n-butyl intermediate hydrolithiates the second pyridine.

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Apr 29, 2014·Dalton Transactions : an International Journal of Inorganic Chemistry·Alan R KennedyStuart D Robertson
Jun 27, 2014·Dalton Transactions : an International Journal of Inorganic Chemistry·David R ArmstrongJoshua J Trivett
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Sep 23, 2014·Chemical Communications : Chem Comm·Stuart D RobertsonRobert E Mulvey
Feb 25, 2015·Chemical Communications : Chem Comm·Andreas Stasch

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Citations

Jun 1, 2017·The Journal of Organic Chemistry·Onkei TaiPaul G Williard
Dec 17, 2015·Dalton Transactions : an International Journal of Inorganic Chemistry·Samantha A OrrStuart D Robertson
May 22, 2018·Chemical Communications : Chem Comm·Sumanta BanerjeeAjay Venugopal
Jan 29, 2019·Chemical Communications : Chem Comm·Raju ChambenahalliAjay Venugopal
Feb 27, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Sumanta BanerjeeAjay Venugopal
Oct 8, 2016·Chemistry : a European Journal·Sergio FombonaLucía Riera
May 31, 2017·Journal of the American Chemical Society·Russell F AlgeraDavid B Collum

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