Generation of N-Acylpyridinium Ions from Pivaloyl Chloride and Pyridine Derivatives by Means of Silyl Triflates

Nickel-catalyzed enantioselective arylation of pyridine

“…While this obstacle was surmountable with 4-methoxypyridine, pyridine is acylated less efficiently than 4-methoxypyridine, so a greater amount of free pyridine would be expected to be present in the reaction mixture. 18 Another principal concern was whether the catalyst could enforce high regioselectivity for 1,2-addition in the absence of a blocking group installed at the C4 position of the ring. Indeed, only two nucleophile classes have succumbed to coupling with unsubstituted pyridinium ions in an asymmetric fashion: copper acetylides, 19 and most recently, silyl ketene acetals, though poor regioselectivity for the 1,2-dihydropyridine over the 1,4-dihydropyridine was observed in the latter case.…”

Nickel‐Catalyzed Enantioselective Arylation of Pyridinium Ions: Harnessing an Iminium Ion Activation Mode

“…Chemie provides an exciting indication of the generality of this mode of activation and its amenability to asymmetric catalysis. Received: May 9, 2013 Published online: July 10,2013 . Keywords: asymmetric catalysis · cross-coupling · Negishi reaction · nickel · nitrogen heterocycles…”

“…To address this issue, we chose to use 4-methoxypyridine as a substrate, because it shows substantial formation of a pyridinium salt with chloroformates at À78 8C. [10] To enable facile transmetalation at low temperature, a Negishi reaction platform was selected. [11] Notably, when we initiated the reaction at À78 8C with warming to RT, the combination of [{(methallyl)NiCl} 2 ] (7.5 mol %) and (R)-Monophos (L1; 18 mol %) was found to promote arylation of 4-methoxypyridine in the presence of phenyl chloroformate and 4-FC 6 H 4 ZnBr with low but measurable ee ( Table 1, entry 1).…”

Nickel‐Catalyzed Enantioselective Arylation of Pyridinium Ions: Harnessing an Iminium Ion Activation Mode

“…One challenge apparent at the outset of our endeavors was potential catalyst poisoning in the presence of free pyridine. To address this issue, we chose to use 4‐methoxypyridine as a substrate, because it shows substantial formation of a pyridinium salt with chloroformates at −78 °C 10. To enable facile transmetalation at low temperature, a Negishi reaction platform was selected 11.…”