Premium
Functionalization of Oxazolo[4,5‐ b ]pyrazines by Deprotometallation
Author(s) -
Bisballe Niels,
Hedidi Madani,
Demmer Charles S.,
Chevallier Floris,
Roisnel Thierry,
Dorcet Vincent,
Halauko Yury S.,
Ivashkevich Oleg A.,
Matulis Vadim E.,
BentabedAbabsa Ghenia,
Bunch Lennart,
Mongin Florence
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201800481
Subject(s) - chemistry , deprotonation , pyrazine , oxazole , suzuki reaction , surface modification , medicinal chemistry , regioselectivity , ring (chemistry) , stereochemistry , derivative (finance) , palladium , organic chemistry , catalysis , ion , financial economics , economics
Different 2‐arylated oxazolo[4,5‐ b ]pyrazines, obtained by palladium(II)‐catalyzed domino reaction from 2,3‐dichloropyrazine and the corresponding carboxamides, were functionalized by deprotometallation. Employing lithium 2,2,6,6‐tetramethylpiperidine, in order to form a lithio derivative, and then trapping it by iodolysis, proved to be inefficient. However, the presence of a zinc‐based in situ trap allowed most substrates to be functionalized. Deprotonation of the pyrazine ring was observed in the presence of tolyl and anisyl groups at the oxazole 2‐position. In contrast, with chlorophenyl and thienyl groups in this 2‐position, deprotonation rather occurred on these groups either competitively or exclusively. The regioselectivities were discussed in the light of calculated p K a values of the substrates in THF. Finally, in the case of 2‐phenyloxazolo[4,5‐ b ]pyrazine, we converted the mixture of 5‐ and 6‐iodinated products into the corresponding 5,6‐diiodide, which was further functionalized by a double Suzuki coupling.