Calcium‐Mediated Dearomatization, CH Bond Activation, and Allylation of Alkylated and Benzannulated Pyridine Derivatives

Abstract

A facile and general synthetic pathway for the production of dearomatized, allylated, and C-H bond activated pyridine derivatives is presented. Reaction of the corresponding derivative with the previously reported reagent bis(allyl)calcium, [Ca(C(3)H(5))(2)] (1), cleanly affords the product in high yield. The range of N-heterocyclic compounds studied comprised 2-picoline (2), 4-picoline (3), 2,6-lutidine (4), 4-tert-butylpyridine (5), 2,2'-bipyridine (6), acridine (7), quinoline (8), and isoquinoline (9). Depending on the substitution pattern of the pyridine derivative, either carbometalation or C-H bond activation products are obtained. In the absence of methyl groups ortho or para to the nitrogen atom, carbometalation leads to dearomatized products. C(sp(3))-H bond activation occurs at ortho and para situated methyl groups. Steric shielding of the 4-position in pyridine yields the ring-metalated product through C(sp(2))-H bond activation instead. The isolated compounds [Ca(2-CH(2)-C(5)H(4)N)(2)(THF)] (2b⋅(THF)), [Ca(4-CH(2)-C(5)H(4)N)(2)(THF)(2)] (3b⋅(THF)(2)), [Ca(2-CH(2)-C(5)H(3)N-6-CH(3))(2)(THF)(n)] (4b⋅(THF)(n); n=0, 0.75), [Ca{2-C(5)H(3)N-4-C(CH(3))(3)}(2)(THF)(2)] (5c⋅(THF)(2)), [Ca{4,4'-(C(3)H(5))(2)-(C(10)H(8)N(2))}(THF)] (6a⋅(THF)), [Ca(NC(13) H(9)-9-C(3)H(5))(2)(THF)] (7a⋅(THF)), [Ca(4-C(3) H(5)-C(9) H(7)N)(2)(THF)] (8b⋅(THF)), and [Ca(1-C(3)H(5)-C(9)H(7) N)(2)(THF)(3)] (9a⋅(THF)(3)) have been characterized by NMR spectroscopy and metal analysis. 9a⋅(THF)(4) and 4b⋅(THF)(3) were additionally characterized in the solid state by X-ray diffraction experiments. 4b⋅(THF)(3) shows an aza-allyl coordination mode in the solid state. Based on the results, mechanistic aspects are discussed in the context of previous findings.

Halide‐Free Diarylcalcium Complexes—Syntheses, Structures, and Stability

“…On this connection, a disagreeing exception should be mentioned. The synthesis of the structurally not characterized diarylcalcium compound [Ca(2‐C 5 H 3 N‐4‐CMe 3 ) 2 (thf) 2 ],24 containing a metallated pyridine derivative, was described recently. Here, an upfield shift of the calcium bound carbon atom to δ =120.3 ppm was mentioned.…”

Structurally Defined Allyl Compounds of Main Group Metals: Coordination and Reactivity

“…A 2‐metalated pyridine compound is the thermodynamically controlled product when a sterically demanding tert‐ butyl group is the γ substituent of the pyridine substrate (Scheme ). 1,2‐ and 1,4‐addition products were observed as intermediates 149…”

Strukturell definierte Allylverbindungen der Hauptgruppenmetalle: Koordination und Reaktivität

“…Eine in 2‐Position metallierte Pyridinverbindung ist das Reaktionsprodukt unter thermodynamischer Kontrolle, wenn der γ‐Substituent des Pyridinsubstrats eine tert ‐Butylgruppe und damit sterisch anspruchsvoll ist (Schema ). 1,2‐ und 1,4‐Additionsprodukte wurden als Intermediate beobachtet 149…”