Atom-efficient regioselective 1,2-dearomatization of functionalized pyridines by an earth-abundant organolanthanide catalyst

Abstract

Developing earth-abundant, non-platinum metal catalysts for high-value chemical transformations is a critical challenge to contemporary chemical synthesis. Dearomatization of pyridine derivatives is an important transformation to access a wide range of valuable nitrogenous natural products, pharmaceuticals and materials. Here, we report an efficient 1,2-regioselective organolanthanide-catalysed pyridine dearomatization process using pinacolborane, which is compatible with a broad range of pyridines and functional groups and employs equimolar reagent stoichiometry. Regarding the mechanism, derivation of the rate law from NMR spectroscopic and kinetic measurements suggests first order in catalyst concentration, fractional order in pyridine concentration and inverse first order in pinacolborane concentration, with C=N insertion into the La-H bond as turnover-determining. An energetic span analysis affords a more detailed understanding of experimental activity trends and the unusual kinetic behaviour, and proposes the catalyst 'resting' state and potential deactivation pathways.

Highly Enantioselective Nucleophilic Dearomatization of Pyridines by Anion‐Binding Catalysis

“…Interestingly,t he tetrakistriazole 1a was superior in terms of reactivity,regio-and enantioselectivity compared to the NHbased thiourea or squaramide catalysts 2 ( Table 1, entries 1-7), leading to ah ighly selective C2 addition [18] (for example, 5:6 ratio 92:8 (1a)v s. 11:89 (2a); entries 1a nd 5, respectively). It is important to mention that abackground reaction was observed in the absence of ac atalyst, providing the 1,4dihydropyridine 6 as the major product (entry 8).…”

Lanthanides and actinides: Annual survey of their organometallic chemistry covering the year 2014

“…Regarding the mechanism, derivation of the rate law from NMR spectroscopic and kinetic measurements suggested first order in catalyst concentration, fractional order in pyridine concentration and inverse first order in pinacolborane concentration, with C=N insertion into an La-H bond as turnover-determining. An energetic span analysis afforded a more detailed understanding of experimental activity trends and the unusual kinetic behavior, and proposed the catalyst "resting" state and potential deactivation pathways [120]. 2.10.…”

β‐Hydroxy‐tetrahydroquinolines from Quinolines Using Chloroborane: Synthesis of the Peptidomimetic FISLE‐412

“…Quinoline is a polarized heterocyclic moiety where the pyridine ring is susceptible to hydride nucleuphilic attacks at α or γ positions. [10] Formation of the quinolinium-borane complex is expected to facilitate such reduction leaving the resulting dihydroquinoline prone to further hydroboration under thermodynamic conditions. Herein, we wish to report that β -functionalized THQ and especially β -hydroxy THQ could be accessed directly in a one-step operation using chloroborane reagents followed by appropriate work up.…”